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Kalantari K, Sullivan MM, Herrera Hernandez LP, Bu L, Cornell LD, Nasr SH, Fervenza FC, Montes D, Mangaonkar AA, Go RS, Kusne YN, Patnaik MM, Lasho TL, Olteanu H, Reichard KK, Warrington KJ, Koster MJ. Acute kidney injury, an underrecognized feature of VEXAS syndrome. Rheumatology (Oxford) 2025; 64:2027-2033. [PMID: 39186250 DOI: 10.1093/rheumatology/keae465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 07/29/2024] [Accepted: 08/03/2024] [Indexed: 08/27/2024] Open
Abstract
OBJECTIVES Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic mutation of UBA1 and affects multiple organ systems. Involvement of the kidneys is not well characterized. We aimed to investigate the incidence, risk factors and histopathologic features of acute kidney injury (AKI) in VEXAS syndrome. METHODS Patients with genetically confirmed UBA1 mutation consistent with VEXAS were included. Charts were manually reviewed. Cox regression analysis was used to identify variables associated with time-to-first AKI event. For patients with a kidney biopsy, histopathologic findings were reviewed. RESULTS Eighty-one patients were included, all white men, with a mean age of 66.3 ± 8.6 years. Median (IQR) follow up was 3.5 (2.1-5.2) years during which 20 (25%) developed AKI and 22% died. AKI relapsed in 90% of cases for a median of 6 times during the follow up period. Cumulative incidence estimates (95% CI) for AKI at 1, 3 and 5 years were 6.2% (0.80-11.3%), 16.7% (7.5-25.0%) and 27.9% (14.9-38.9%), respectively. Age and baseline C-reactive protein (CRP) were significantly associated with time-to-first AKI event. Six patients underwent a kidney biopsy. Findings included, plasma cell-rich interstitial nephritis (n = 3), neutrophilic-rich interstitial inflammation (n = 1), leukocytoclastic peritubular capillaritis (n = 1) and acute tubular injury (n = 1). AKI responded well to treatment with glucocorticoids but had relapse upon tapering. CONCLUSION AKI is an underrecognized feature of VEXAS occurring in 25% of patients in this cohort. Age at diagnosis and CRP were associated with time to first AKI event during follow up. Plasma cell-rich interstitial nephritis was the most common histopathologic finding.
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Affiliation(s)
- Kambiz Kalantari
- Department of Internal Medicine, Division of Nephrology, Mayo Clinic, Rochester, MN, USA
| | - Megan M Sullivan
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Scottsdale, AZ, USA
| | | | - Lihong Bu
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Lynn D Cornell
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Samih H Nasr
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Fernando C Fervenza
- Department of Internal Medicine, Division of Nephrology, Mayo Clinic, Rochester, MN, USA
| | - Daniel Montes
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Abhishek A Mangaonkar
- Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Ronald S Go
- Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Yael N Kusne
- Department of Internal Medicine, Division of Hematology, Mayo Clinic, Scottsdale, AZ, USA
| | - Mrinal M Patnaik
- Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Terra L Lasho
- Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Horatiu Olteanu
- Department of Hematopathology, Mayo Clinic, Rochester, MN, USA
| | | | - Kenneth J Warrington
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
| | - Matthew J Koster
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
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Yeboah EK, Seshan SV, Pariya F, Khan S, Azhar M, Salifu M, Saggi S. Collapsing Focal Segmental Glomerulosclerosis With Concurrent IgG4 Nephropathy. Cureus 2025; 17:e81031. [PMID: 40264599 PMCID: PMC12013533 DOI: 10.7759/cureus.81031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Accepted: 03/22/2025] [Indexed: 04/24/2025] Open
Abstract
A 41-year-old male with a history of chronic kidney disease, hypertension, and psoriasis was referred to the nephrologist for worsening kidney function associated with nephrotic range proteinuria. The patient had no symptoms, but the initial workup showed elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), positive double-stranded DNA antibody(anti-DsDNA) but normal complement levels, normal antinuclear antibody (ANA) and negative beta-glycoprotein-1 IgG, IgM, and IgA. Further, the workup revealed the patient had elevated total immunoglobulin as well as elevated IgG subsets 2, 3, and 4. He was also found to have a high variant of apolipoprotein L1 (APOL1). A renal biopsy revealed diffuse active, subacute, and chronic interstitial inflammation, plasma cell-rich (25% IgG4 positive), confirming IgG4-related tubulointerstitial nephritis with concomitant IgG4 dominant, PLA2R negative membranous glomerulonephritis. There was also a severe podocytopathy in the form of diffuse segmental/global collapsing glomerulopathy with sclerosing changes as well as global glomerulosclerosis, extensive tubular atrophy with mild interstitial changes suggestive of a variant of focal segmental glomerulosclerosis (FSGS). A diagnosis of APOL-1 collapsing glomerulopathy with IgG4 nephropathy was made based on clinical and pathological findings. The patient's kidney function stabilized, and IgG4 levels returned to normal after the patient was initiated on 60 mg daily prednisolone. The steroid was tapered off and the patient was started on mycophenolate mofetil 1000 mg twice daily. To our knowledge, this is the first reported case of IgG4-related kidney disease with concurrent severe APOL1-associated collapsing glomerulopathy.
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Affiliation(s)
- Eugene K Yeboah
- Internal Medicine, State University of New York Downstate Medical Center, Brooklyn, USA
| | - Surya V Seshan
- Pathology and Laboratory Medicine, Weil Cornell Medicine, New York, USA
| | - Fnu Pariya
- Nephrology, State University of New York Downstate Medical Center, Brooklyn, USA
| | - Sulayman Khan
- Internal Medicine, State University of New York Downstate Medical Center, Brooklyn, USA
| | - Muhammad Azhar
- Internal Medicine, State University of New York Downstate Medical Center, Brooklyn, USA
| | - Moro Salifu
- Nephrology, State University of New York Downstate Medical Center, Brooklyn, USA
| | - Subodh Saggi
- Nephrology, State University of New York Downstate Medical Center, Brooklyn, USA
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Gurevich E, Landau D. Tubulointerstitial nephritis in children and adolescents. Pediatr Nephrol 2025; 40:319-328. [PMID: 39320551 DOI: 10.1007/s00467-024-06526-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 08/26/2024] [Accepted: 08/26/2024] [Indexed: 09/26/2024]
Abstract
The tubulointerstitial compartment comprises most of the kidney parenchyma. Inflammation in this compartment (tubulointerstitial nephritis-TIN) can be acute and resolves if the offending factor is withdrawn or may enter a chronic process leading to irreversible kidney damage. Etiologic factors differ, including different exposures, infections, and autoimmune and genetic tendency, and the initial damage can be acute, recurrent, or permanent, determining whether the acute inflammatory process will lead to complete healing or to a chronic course of inflammation leading to fibrosis. Clinical and laboratory findings of TIN are often nonspecific, which may lead to delayed diagnosis and a poorer clinical outcome. We provide a general review of TIN, with special mention of the molecular pathophysiological mechanisms of the associated kidney damage.
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Affiliation(s)
- Evgenia Gurevich
- Pediatrics Department, Barzilai University Medical Center, Ashqelon, Israel.
- Ben Gurion University of Negev, Faculty of Health Sciences, Beer Sheva, Israel.
| | - Daniel Landau
- Department of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
- School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Vaquer-Grimalt P, García IM, Antón E, Escarda A, Vanrell M, Bonet L, Sastre L. IgG4-related disease mimicking a liver abscess. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:707-708. [PMID: 38305673 DOI: 10.1007/978-3-031-60855-1_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
IgG4-related disease (IGRD) is a complex medical condition affecting multiple organs, including the liver. The condition is characterized by excessive production of IgG4 antibodies, leading to chronic inflammation and tissue damage. We present a case of a 37-year-old man with a history of chronic pancreatitis was diagnosed with a liver mass. Initial treatment included piperacillin and tazobactam, but the patient's condition worsened. An ultrasound-guided biopsy revealed increased IgG4 positive cells, leading to the diagnosis of an inflammatory pseudotumor associated with IGRD. The patient was treated with prednisone taper therapy, and the liver mass resolved after six months of corticoid treatment.
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Affiliation(s)
| | | | - Ester Antón
- Aparato Digestivo, Hospital Universitario Son Espases, España
| | - Aina Escarda
- Hepatología, Hospital Universitario Son Espases, España
| | | | - Lucía Bonet
- Hepatología, Hospital Universitario Son Espases, España
| | - Lydia Sastre
- Hepatología, Hospital Universitario Son Espases, España
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Shaheen M, Bharat A, Friedman AN, Guo S. ALECT2 amyloidosis with concurrent IgG4-related interstitial nephritis, membranous nephropathy and diabetic kidney disease: a case report and literature review. J Nephrol 2024; 37:2363-2369. [PMID: 38630340 DOI: 10.1007/s40620-024-01924-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 02/24/2024] [Indexed: 12/18/2024]
Abstract
Leukocyte chemotactic factor-2 amyloidosis (ALECT2) is a recently described subtype of amyloidosis. IgG4-related disease is a rare fibroinflammatory condition characterized by dense interstitial lymphoplasmacytic infiltrates and fibrosis. Membranous nephropathy and diabetic nephropathy are common causes of nephrotic syndrome. Here we report a 49-year-old Hispanic male patient with diabetes mellitus who presented with jaundice and pruritus. IgG4-related autoimmune pancreatitis was diagnosed through laboratory workup and ampulla biopsy. He subsequently presented with marked lower extremity edema and nephrotic syndrome. Kidney biopsy showed severe interstitial IgG4-positive plasma cell-rich inflammatory infiltrates and interstitial storiform fibrosis. Immunofluorescence microscopy revealed diffuse and finely granular glomerular capillary wall staining for IgG and the glomeruli were negative for anti-phospholipase A2 receptor. Congo red stain was positive for birefringent deposits in the interstitium, arteriolar walls, and glomeruli. Electron microscopy demonstrated subepithelial immune complex-type electron-dense deposits, thickening of glomerular basement membranes (GBM), and randomly oriented fibrils in the mesangium, GBM, and interstitium. Mass spectrometry identified a peptide profile consistent with ALECT2 amyloidosis. This is the first report of a case with concurrence of ALECT2 amyloidosis, IgG4-related disease involving the kidney, membranous nephropathy, and early diabetic kidney injury.
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Affiliation(s)
- Muhammad Shaheen
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Anchit Bharat
- Division of Critical Care Medicine, Advocate Aurora Health, St. Luke's Medical Center, Milwaukee, WI, USA
| | - Allon N Friedman
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Shunhua Guo
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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Buglioni A, Jenkins SM, Nasr SH, Zhang P, Gibson IW, Alexander MP, Herrera Hernandez LP, Fidler ME, Takahashi N, Hogan MC, Cornell LD. Clinicopathologic Features of IgG4-Related Kidney Disease. Kidney Int Rep 2024; 9:2462-2473. [PMID: 39156178 PMCID: PMC11328570 DOI: 10.1016/j.ekir.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 04/29/2024] [Accepted: 05/06/2024] [Indexed: 08/20/2024] Open
Abstract
Introduction IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that can involve nearly any organ. IgG4-RD can affect the kidney in different disease patterns, collectively referred to as IgG4-related kidney disease (IgG4-RKD). Methods We conducted a tissue-based cohort study with clinicopathological correlation in 125 patients with IgG4-RKD. Results The mean age at biopsy (n = 120) or nephrectomy (n = 5) was 63 years; 80% were male. One hundred eighteen patients (94%) had IgG4-related tubulointerstitial nephritis (IgG4-TIN); 20 patients (16%) had IgG4-related membranous glomerulonephritis (IgG4-MGN; 13 with concurrent IgG4-TIN). The primary clinical indication for biopsy/nephrectomy was acute or chronic renal failure in 78%, proteinuria in 17%, and mass lesion(s) in 15% (with overlap in primary indication). Fifty-two percent patients (41/79) had abnormal radiographic findings, including masses in 30% (24/79). All patients with IgG4-MGN had proteinuria. Extrarenal involvement by IgG4-RD was present in 79%. Median serum creatinine at presentation was 2.5 mg/dl (range 0.7-12). Serum IgG and/or IgG4 was increased in 91% (53/58); hypocomplementemia was present in 56% (43/77). Light microscopy showed plasma cell-rich interstitial nephritis in all cases of IgG4-TIN. Ninety-two percent of patients showed increased IgG4+ plasma cells. Seven percent showed an acute interstitial nephritis (AIN) pattern, and 5% showed non-necrotizing arteritis. Tubular basement membrane immune deposits were present in 83% of IgG4-TIN. Treatment information was available for 71 patients; 62 were treated with immunosuppression. Of those with elevated creatinine, 72% (41/57) showed a treatment response. Conclusion This largest tissue-based series more clearly defines the disease phenotype of IgG4-RKD.
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Affiliation(s)
- Alessia Buglioni
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Sarah M. Jenkins
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota, USA
| | - Samih H. Nasr
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Pingchuan Zhang
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ian W. Gibson
- Department of Pathology, University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada
| | - Mariam P. Alexander
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Loren P. Herrera Hernandez
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Mary E. Fidler
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Naoki Takahashi
- Division of Abdominal Imaging, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Marie C. Hogan
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Minnesota, USA
| | - Lynn D. Cornell
- Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
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Lanzillotta M, Culver E, Sharma A, Zen Y, Zhang W, Stone JH, Della-Torre E. Fibrotic phenotype of IgG4-related disease. THE LANCET. RHEUMATOLOGY 2024; 6:e469-e480. [PMID: 38574746 DOI: 10.1016/s2665-9913(23)00299-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 10/13/2023] [Accepted: 10/31/2023] [Indexed: 04/06/2024]
Abstract
A prompt response to glucocorticoids is a clinical hallmark of IgG4-related disease. However, manifestations characterised by prominent tissue fibrosis on histological examination can be less responsive to glucocorticoid therapy than other types of IgG4-related disease. These manifestations include retroperitoneal fibrosis, fibrosing mediastinitis, Riedel thyroiditis, orbital pseudotumor, and hypertrophic pachymeningitis, among others. To explain this discrepancy, a preliminary distinction into proliferative and fibrotic phenotypes of IgG4-related disease has been proposed on the basis of clinical presentation, pathological features, and response to immunosuppressive therapy. Implications of this classification for patient management remain an important area of investigation. In this Series paper, we aim to dissect the pathophysiology of tissue fibrosis in IgG4-related disease and discuss how clinicians should approach the management of fibrotic manifestations of IgG4-related disease based on the most recent diagnostic and therapeutic developments.
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Affiliation(s)
- Marco Lanzillotta
- Università Vita-Salute San Raffaele, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emma Culver
- Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Amita Sharma
- Thoracic Imaging and Intervention Division, Massachusetts General Hospital, Boston, MA, USA
| | - Yoh Zen
- Institute of Liver Studies, King's College Hospital and King's College London, London, UK
| | - Wen Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
| | - John H Stone
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Emanuel Della-Torre
- Università Vita-Salute San Raffaele, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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8
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Hyodo T, Hara S, Goto S, Fujii H, Nishi S, Horinouchi T, Nozu K, Yoshikawa N, Yoshimoto A, Itoh T. Immunohistological analysis reveals IgG1-dominant immunophenotype of tubulointerstitial nephritis unassociated with IgG4-related diseases. Int Urol Nephrol 2024; 56:2363-2369. [PMID: 38381285 PMCID: PMC11189997 DOI: 10.1007/s11255-024-03966-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 01/29/2024] [Indexed: 02/22/2024]
Abstract
PURPOSE Tubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis. METHODS The study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry. RESULTS IgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group. CONCLUSION The present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.
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Affiliation(s)
- Toshiki Hyodo
- Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Shigeo Hara
- Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Shunsuke Goto
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinichi Nishi
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoko Horinouchi
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kandai Nozu
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | | | - Akihiro Yoshimoto
- Department of Nephrology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Tomoo Itoh
- Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
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9
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Katz G, Hernandez-Barco Y, Palumbo D, Guy TV, Dong L, Perugino CA. Proliferative features of IgG4-related disease. THE LANCET. RHEUMATOLOGY 2024; 6:e481-e492. [PMID: 38574744 DOI: 10.1016/s2665-9913(24)00022-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 01/17/2024] [Accepted: 01/18/2024] [Indexed: 04/06/2024]
Abstract
IgG4-related disease is an immune-mediated disease that can lead to substantial morbidity and organ damage. Capable of affecting nearly any organ system or anatomic site, and showing considerable overlap in clinical presentation with various other diseases, IgG4-related disease often poses a diagnostic challenge for clinicians. Furthermore, there are no diagnostic biomarkers with high specificity for IgG4-related disease, and histopathological examination is nuanced and requires clinical correlation for accurate diagnosis. Therefore, it is crucial for clinicians to recognise the clinical phenotypes of IgG4-related disease. The disease is generally considered to have predominantly fibrotic and proliferative (or inflammatory) manifestations, with distinct clinical, serological and histopathological findings associated with each manifestation. However, the fibrotic and proliferative manifestations of this disease frequently occur together, thereby blurring this dichotomous distinction. In this Series paper, we provide a detailed overview of the clinical manifestations typical of the proliferative features of IgG4-related disease, with an emphasis on the diagnostic evaluation and differential diagnosis of each proliferative disease manifestation. In addition, we summarise the immune mechanisms underlying IgG4-related disease, suggest a framework for how to approach management and monitoring after the diagnosis is established, and highlight current unmet needs for patient care surrounding this disease.
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Affiliation(s)
- Guy Katz
- Rheumatology Unit, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Yasmin Hernandez-Barco
- Pancreatology Unit, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Diego Palumbo
- San Raffaele Scientific Institute, Radiology, Milan, Italy
| | - Thomas V Guy
- Royal Prince Alfred Hospital, Camperdown, NSW, Australia; School of Medical Sciences, The University of Sydney, Camperdown, NSW, Australia; Ragon Institute of Massachusetts Gneral Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
| | - Lingli Dong
- Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cory A Perugino
- Rheumatology Unit, Massachusetts General Hospital, Boston, MA, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
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10
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Towheed ST, Zanjir W, Ren KYM, Garland J, Clements-Baker M. Renal Manifestations of IgG4-Related Disease: A Concise Review. Int J Nephrol 2024; 2024:4421589. [PMID: 38957780 PMCID: PMC11217581 DOI: 10.1155/2024/4421589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 04/28/2024] [Accepted: 06/10/2024] [Indexed: 07/04/2024] Open
Abstract
IgG4-related disease (IgG4-RD) is an immune-mediated disorder marked by fibro-inflammatory masses that can infiltrate multiple organ systems. Due to its relatively recent discovery and limited understanding of its pathophysiology, IgG4-related disease may be difficult to recognize and is consequently potentially underdiagnosed. Renal involvement is becoming regarded as one of the key features of this disease. To date, the most well-recognized renal complication of IgG4-related disease is tubulointerstitial nephritis, but membranous glomerulonephritis, renal masses, and retroperitoneal fibrosis have also been reported. This concise review has two objectives. First, it will briefly encapsulate the history, epidemiology, and presentation of IgG4-related disease. Second, it will examine the reported renal manifestations of IgG4-related disease, exploring the relevant histology, imaging, clinical features, and treatment considerations. This synthesis will be highly relevant for nephrologists, rheumatologists, general internists, and renal pathologists to raise awareness and help improve early recognition of IgG4-related kidney disease (IgG4-RKD).
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11
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Luo S, Guo L, Yang Z, Shen R, Zhang T, Wang M, Zhou Q, Wang H, Li X, Chen J, Wang R. Deciphering three predominant biopsy-proven phenotypes of IgG4-associated kidney disease: a retrospective study. Clin Kidney J 2024; 17:sfae111. [PMID: 38783966 PMCID: PMC11114465 DOI: 10.1093/ckj/sfae111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Indexed: 05/25/2024] Open
Abstract
Background IgG4-associated kidney disease (IgG4-RKD) encompasses a spectrum of disorders, predominantly featuring tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). The limited understanding of the co-occurrence of IgG4-RD-TIN with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) poses a diagnostic and therapeutic challenge. Methods We examined 49 cases, comprising 21 cases of IgG4-RD-TIN (group A), 10 cases of IgG4-RD-TIN accompanied with MGN (group B), and 18 cases of IgG4-RD-TIN concurrent with AAV (group C), at the First Affiliated Hospital of Zhejiang University, China, from June 2015 to December 2022. Results The mean age and gender of the three IgG4-RKD subtypes were not statistically significant. IgG4-RD-TIN exhibited higher serum creatinine and a higher incidence of hypocomplementemia (group A 47.6%, group B 30%, group C 16.7%). IgG4-RD-TIN-MGN was characterized by proteinuria (group A 0.3 g/d, group B 4.0 g/d, group C 0.8 g/d, P < 0.001) and hypoalbuminemia. IgG4-RD-TIN-AAV exhibited hypohemoglobinemia (group A 103.45 g/l, group B 119.60 g/l, group C 87.94 g/l, P < 0.001) and a high level of urine erythrocytes. The primary treatment for IgG4-RD-TIN was steroids alone, whereas IgG4-RD-TIN-MGN and IgG4-RD-TIN-AAV necessitated combination therapy. Group A experienced two relapses, whereas groups B and C had no relapses. There was no significant difference in patient survival among the three groups, and only two cases in group C suffered sudden death. Conclusions This study provides valuable insights into clinical manifestations, auxiliary examination features, pathological characteristics, and prognosis of IgG4-RD-TIN, IgG4-RD-TIN-MGN, and IgG4-RD-TIN concurrent AAV. Large-scale studies are required to validate these findings.
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Affiliation(s)
- Sulin Luo
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Luying Guo
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Zhenzhen Yang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Nephrology, Huzhou Central Hospital, Huzhou, Zhejiang Province, China
| | - Rongfang Shen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, China
| | - Tianlu Zhang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Meifang Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Qin Zhou
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Huiping Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Xiayu Li
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Rending Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
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12
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Needleman A, Sheaff M, Pepper RJ, Evans RDR. Immunoglobulin G4-related disease presenting with nephrotic syndrome due to minimal change disease: a case report. J Med Case Rep 2024; 18:192. [PMID: 38641649 PMCID: PMC11031906 DOI: 10.1186/s13256-024-04494-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 03/06/2024] [Indexed: 04/21/2024] Open
Abstract
BACKGROUND Immunoglobulin G4-related disease is an inflammatory disease affecting multiple organs including the kidney. Immunoglobulin G4-related kidney disease most commonly manifests as a tubulointerstitial nephritis and is associated with glomerular disease in a proportion of cases. Membranous nephropathy is the most frequent glomerular lesion. Herein, we report the first documented case of immunoglobulin G4-related disease presenting with nephrotic syndrome owing to minimal change disease. CASE PRESENTATION A 67-year-old South Asian male presented to our service with systemic upset and leg swelling. He had heavy proteinuria (urine protein:creatinine ratio 1042 mg/mmol) and was hypoalbuminemic (17 g/L) and hypercholersterolemic (9.3 mmol/L), consistent with the nephrotic syndrome. His serum creatinine was 140 μmol/L, and he was hypocomplementemic (C3 0.59 g/L, C4 < 0.02 g/L) with raised immunoglobulin G4 subclass levels (5.29 g/L). Kidney biopsy demonstrated minimal change disease alongside a plasma-cell-rich tubulointerstitial nephritis with strong positive staining for immunoglobulin G4. A diagnosis of minimal change disease in the setting of immunoglobulin G4-related disease was made. He was commenced on oral prednisolone at 60 mg daily but suffered infectious complications, including necrotizing fasciitis within 3 weeks of starting treatment, ultimately resulting in his death 52 days after initial presentation. CONCLUSION This case highlights the potential for immunoglobulin G4-related disease to be associated with a spectrum of glomerular pathologies including minimal change disease. It adds to the differential diagnosis of secondary causes of minimal change disease, and moreover, aids as an important reminder of the potential complications of high-dose steroids used in its treatment.
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Affiliation(s)
- Amy Needleman
- UCL Centre for Kidney and Bladder Health, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
| | - Michael Sheaff
- Department of Histopathology, Bart's Health NHS Trust, London, UK
| | - Ruth J Pepper
- UCL Centre for Kidney and Bladder Health, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
| | - Rhys D R Evans
- UCL Centre for Kidney and Bladder Health, Royal Free Hospital, Pond Street, London, NW3 2QG, UK.
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13
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L’Imperio V, Ceola S, Cerbelli B, Barreca A, Pagni F. Systemic vasculitis involving the kidney: the nephropathologist's point of view. Pathologica 2024; 116:104-118. [PMID: 38767543 PMCID: PMC11138762 DOI: 10.32074/1591-951x-990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 03/01/2024] [Indexed: 05/22/2024] Open
Abstract
Kidneys are often targets of systemic vasculitis (SVs), being affected in many different forms and representing a possible sentinel of an underlying multi-organ condition. Renal biopsy still remains the gold standard for the identification, characterization and classification of these diseases, solving complex differential diagnosis thanks to the combined application of light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). Due to the progressively increasing complexity of renal vasculitis classification systems (e.g. pauci-immune vs immune complex related forms), a clinico-pathological approach is mandatory and adequate technical and interpretative expertise in nephropathology is required to ensure the best standard of care for our patients. In this complex background, the present review aims at summarising the current knowledge and challenges in the world of renal vasculitis, unveiling the potential role of the introduction of digital pathology in this setting, from the creation of hub-spoke networks to the future application of artificial intelligence (AI) tools to aid in the diagnostic and scoring/classification process.
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Affiliation(s)
- Vincenzo L’Imperio
- Department of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano-Bicocca, Italy
| | - Stefano Ceola
- Department of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano-Bicocca, Italy
| | - Bruna Cerbelli
- Department of Medical Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Antonella Barreca
- Pathology Unit, Città della Salute e della Scienza di Torino University Hospital, Turin, Italy
| | - Fabio Pagni
- Department of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano-Bicocca, Italy
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14
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Czarnywojtek A, Agaimy A, Pietrończyk K, Nixon IJ, Vander Poorten V, Mäkitie AA, Zafereo M, Florek E, Sawicka-Gutaj N, Ruchała M, Ferlito A. IgG4-related disease: an update on pathology and diagnostic criteria with a focus on salivary gland manifestations. Virchows Arch 2024; 484:381-399. [PMID: 38316669 DOI: 10.1007/s00428-024-03757-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/12/2024] [Accepted: 01/29/2024] [Indexed: 02/07/2024]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality. Given its broad clinical spectrum, physicians of all specialties may be the first clinicians facing this diagnostic challenge. Outside the pancreatobiliary system, the head and neck represents the major site of IgG4-RD with variable organ-specific diffuse or mass-forming lesions. In up to 75% of cases, elevated serum IgG4 levels are observed, but this figure possibly underestimates the fraction of seronegative cases, as the disease manifestations may present metachronously with significant intervals. Together with negative serology, this can lead to misdiagnosis of seronegative cases. A standardized nomenclature and diagnostic criteria for IgG4-RD were established in 2012 and revised in 2020 facilitating scientific research and expanding the range of diseases associated with IgG4 abnormalities. In addition to orbital pseudotumor, dacryoadenitis, Riedel thyroiditis, sinonasal manifestations, and rare miscellaneous conditions, IgG4-related sialadenitis is one of the most frequent presentations in the head and neck region. However, controversy still exists regarding the relationship between sialadenitis and IgG4-RD. This review focuses on the clinicopathological features of IgG4-related sialadenitis and its contemporary diagnostic criteria.
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Affiliation(s)
- Agata Czarnywojtek
- Department of Pharmacology, Poznan University of Medical Sciences, 60-806, Poznan, Poland
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Abbas Agaimy
- Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany
| | | | - Iain J Nixon
- Department of Otorhinolaryngology Head and Neck Surgery, NHS Lothian, Edinburgh, EH8 9YL, UK
| | - Vincent Vander Poorten
- Otorhinolaryngology-Head and Neck Surgery, KU Leuven University Hospitals, 3000, Leuven, Belgium
- Department of Oncology, Section Head and Neck Oncology, KU Leuven, 3000, Leuven, Belgium
| | - Antti A Mäkitie
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, and the Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland
| | - Mark Zafereo
- Department of Head & Neck Surgery, MD Anderson Cancer Center, Houston, TX, 77005, USA
| | - Ewa Florek
- Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, 60-806, Poznan, Poland.
| | - Nadia Sawicka-Gutaj
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Alfio Ferlito
- International Head and Neck Scientific Group, 35100, Padua, Italy
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15
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Oleson I, Fecker A, Richardson K, Bauer A, Andeen NK, Kung VL. ANCA-associated kidney disease preceded by orbital pseudotumor. Pediatr Nephrol 2024; 39:741-744. [PMID: 37855995 DOI: 10.1007/s00467-023-06172-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/14/2023] [Accepted: 09/14/2023] [Indexed: 10/20/2023]
Abstract
INTRODUCTION Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ACR/EULAR classification, this criterion is not uniformly applied, and AAV can form inflammatory masses in various organs and show increase in IgG4 + plasma cells, similar to IgG4-RD. CASE DIAGNOSIS/TREATMENT A 5-year-old female with history of orbital mass diagnosed as IgG4-RD presents with acute kidney injury. She has a myeloperoxidase ANCA, and kidney biopsy shows pauci-immune crescentic glomerulonephritis and acute tubulointerstitial nephritis with increased IgG4 + plasma cells and tubular basement membrane (TBM) deposits. CONCLUSION In isolation, TBM deposits and increased IgG4 + plasma cells are suggestive of IgG4-RD. In the context of a positive ANCA and pauci-immune crescentic glomerulonephritis, however, increased IgG4 + plasma cells due to AAV are favored. In cases with features of IgG4-RD, ANCA positivity suggests an alternate diagnosis of AAV to be more likely.
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Affiliation(s)
- Ileisa Oleson
- School of Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Adeline Fecker
- School of Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Kelsey Richardson
- Division of Pediatric Nephrology and Hypertension, Oregon Health & Science University, Portland, OR, USA
| | - Abbie Bauer
- Division of Pediatric Nephrology and Hypertension, Oregon Health & Science University, Portland, OR, USA
| | - Nicole K Andeen
- Department of Pathology and Laboratory Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA
| | - Vanderlene L Kung
- Department of Pathology and Laboratory Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA.
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16
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Gilani SI, Buglioni A, Cornell LD. IgG4-related kidney disease: Clinicopathologic features, differential diagnosis, and mimics. Semin Diagn Pathol 2024; 41:88-94. [PMID: 38246802 DOI: 10.1053/j.semdp.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 12/11/2023] [Indexed: 01/23/2024]
Abstract
IgG4-related kidney disease (IgG4-RKD) encompasses all forms of kidney disease that are part of IgG4-related disease (IgG4-RD). First recognized as IgG4-related tubulointerstitial nephritis (IgG4-TIN), and then IgG4-related membranous glomerulonephritis (IgG4-MGN), we now recognize additional patterns of interstitial nephritis, glomerular disease, and vascular disease that can be seen as part of IgG4-RKD. The clinical presentation is variable and can include acute or chronic kidney injury, proteinuria or nephrotic syndrome, mass lesion(s), and obstruction. While usually associated with other organ involvement by IgG4-RD, kidney-alone involvement is present in approximately 20 % of IgG4-RKD. Compared to IgG4-RD overall, patients with IgG4-RKD are more likely to show increased serum IgG4 or IgG, and more likely to have hypocomplementemia. In this review, we extensively cover other types of autoimmune and plasma cell-rich interstitial nephritis, mass forming inflammatory diseases of the kidney, and other mimics of IgG4-TIN, in particular ANCA-associated disease.
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Affiliation(s)
- Sarwat I Gilani
- Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at San Antonio, TX, USA
| | - Alessia Buglioni
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Lynn D Cornell
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
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17
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Guo L, Yang Z, Cheng Y, Wang X, Ren X, Wang M, Yan P, Shen J, Sun K, Wang H, Wu J, Chen J, Wang R. Clinical phenotypes and prognosis of IgG4-related diseases accompanied by deteriorated kidney function: a retrospective study. Clin Rheumatol 2024; 43:315-324. [PMID: 37642763 DOI: 10.1007/s10067-023-06748-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 08/07/2023] [Accepted: 08/18/2023] [Indexed: 08/31/2023]
Abstract
INTRODUCTION IgG4-related disease (IgG4-RD) is a multiorgan autoimmune disorder that causes irreversible injury. Deteriorated kidney functions are common but easily ignored complications associated with IgG4-RD. Yet the clinical manifestations and prognosis of this specific entity have not been fully illustrated. METHOD Three hundred fifty patients with IgG4-RD were retrospectively enrolled and divided into 119 IgG4-RD with chronic kidney disease (IgG4-RD CKD+) and 231 IgG4-RD without CKD (IgG4-RD CKD-). Demographic clinical and laboratory characteristics and survival of two cohorts were compared using restricted cubic splines, logistic and Cox regression, and Kaplan-Meier analysis. A nomogram was generated for calculating the probability of CKD in IgG4-RD. RESULTS The spectrum of organ involvement was different between IgG4-RD CKD+ and CKD- cohorts (p<0.001). Lung (26.89%) and retroperitoneum (18.49%) involvement were more common in the IgG4-RD CKD+ cohort. Increased serum potassium and phosphorus, reduced calcium levels, and hypocomplementemia (all p<0.05) were observed in IgG4-RD CKD+. Restricted cubic splines revealed a U-shaped plot regarding associations between serum potassium and CKD. Kaplan-Meier analysis demonstrated significantly lower long-term survival rates in IgG4-RD patients with kidney function at CKD stages 4-5. Cox regression revealed declined kidney functions (G4 HR 6.537 (95% CI: 1.134-37.675)) associated with increased all-cause mortality in IgG4-RD patients. A nomogram was constructed to predict CKD in IgG4-RD promptly with a discrimination (C-index) of 0.846. CONCLUSIONS CKD in IgG4-RD was associated with poor outcomes and electrolyte disturbances. Patients with IgG4-RD should be aware of possible deterioration in kidney function. The nomogram proposed would help to identify the subtle possibility of CKD in IgG4-RD. Key points • IgG4-related diseases with deteriorated kidney function have specific clinical and laboratory characteristics. • It is crucial to recognize and address the negative impact of deteriorating kidney function in IgG4-related diseases to prevent further harm. • The nomogram proposed would help to identify subtle kidney involvement by evaluating the possibility of CKD in IgG4-related diseases.
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Affiliation(s)
- Luying Guo
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Zhenzhen Yang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Nephrology, Huzhou Central Hospital, Huzhou, Zhejiang Province, China
| | - Yamei Cheng
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Xingxia Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Nephrology, 903rd Hospital of PLA, Hangzhou, China
| | - Xue Ren
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Nephrology, Huzhou Central Hospital, Huzhou, Zhejiang Province, China
| | - Meifang Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Pengpeng Yan
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Jia Shen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Ke Sun
- Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Huiping Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Jianyong Wu
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China
- National Key Clinical Department of Kidney Diseases, Hangzhou, China
- Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China.
- National Key Clinical Department of Kidney Diseases, Hangzhou, China.
- Institute of Nephrology, Zhejiang University, Hangzhou, China.
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China.
| | - Rending Wang
- Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, Zhejiang Province, China.
- National Key Clinical Department of Kidney Diseases, Hangzhou, China.
- Institute of Nephrology, Zhejiang University, Hangzhou, China.
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China.
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18
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Mizushima I, Saeki T, Kobayashi D, Sawa N, Hayashi H, Taniguchi Y, Nakata H, Yamada K, Matsui S, Yasuno T, Masutani K, Nagasawa T, Takahashi H, Ubara Y, Yanagita M, Kawano M. Improved Renal Function in Initial Treatment Improves Patient Survival, Renal Outcomes, and Glucocorticoid-Related Complications in IgG4-Related Kidney Disease in Japan. Kidney Int Rep 2024; 9:52-63. [PMID: 38312790 PMCID: PMC10831353 DOI: 10.1016/j.ekir.2023.10.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/26/2023] [Accepted: 10/16/2023] [Indexed: 02/06/2024] Open
Abstract
Introduction We aimed to clarify long-term renal prognosis, complications of malignancy, glucocorticoid (GC) toxicity, and mortality in immunoglobulin G4 (IgG4)-related kidney disease (IgG4-RKD). Methods Reviewing the medical records of 95 patients with IgG4-RKD, we investigated clinical and pathologic features at baseline, the course of renal function, complications of malignancy, GC toxicity, and mortality during follow-up (median 71 months). The standardized incidence ratio (SIR) of malignancy and standardized mortality ratio were calculated using national statistics. Factors related to outcomes were assessed by Cox regression analyses. Results At diagnosis, the median estimated glomerular infiltration rate (eGFR) was 46 ml/min per 1.73 m2. GC achieved initial improvement. Additional renal function recovery within 3-months of initial treatment occurred in patients with highly elevated serum IgG and IgG4 levels and hypocomplementemia. During follow-up, 68%, 17%, and 3% of the patients had chronic kidney disease (CKD), >30% eGFR decline, and end-stage renal disease (ESRD), respectively. Age-adjusted and sex-adjusted Cox regression analyses indicated that eGFR (hazard ratio [HR], 0.71) and extensive fibrosis (HR, 2.58) at treatment initiation had a significant impact on the time to CKD. Ten patients died, and the standardized mortality ratio was 0.94. The SIR of malignancy was 1.52. The incidence rate (IR) of severe infection was 1.80/100 person-years. Cox regression analyses showed that the best eGFR within 3 months after treatment initiation were associated with lower mortality (HR 0.67) and fewer severe infections (HR 0.63). Conclusion This study suggests that more renal function recovery through early treatment initiation may improve patient survival, renal outcomes, and some GC-related complications in IgG4-RKD.
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Affiliation(s)
- Ichiro Mizushima
- Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
| | - Takako Saeki
- Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Daisuke Kobayashi
- Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan
| | - Naoki Sawa
- Department of Nephrology Center, Toranomon Hospital, Kawasaki, Japan
| | - Hiroki Hayashi
- Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Japan
| | - Yoshinori Taniguchi
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi University, Nankoku-shi, Japan
| | - Hirosuke Nakata
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto City, Japan
| | - Kazunori Yamada
- Department of Hematology and Immunology, Kanazawa Medical University, Kahoku-gun, Japan
| | - Shoko Matsui
- Health Administration Center, University of Toyama, Toyama City, Japan
| | - Tetsuhiko Yasuno
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Jonan-Ku, Japan
| | - Kosuke Masutani
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Jonan-Ku, Japan
| | - Tasuku Nagasawa
- Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan
| | - Hiroki Takahashi
- Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Yoshifumi Ubara
- Department of Nephrology Center, Toranomon Hospital, Kawasaki, Japan
| | - Motoko Yanagita
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto City, Japan
| | - Mitsuhiro Kawano
- Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
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19
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Groh M, Habert P, Ebbo M, Muller R, Gaigne L, Gaubert JY, Schleinitz N. [IgG4-related disease: A proteiform pathology with frequent chest manifestations]. Rev Mal Respir 2023; 40:768-782. [PMID: 37858433 DOI: 10.1016/j.rmr.2023.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/11/2023] [Indexed: 10/21/2023]
Abstract
INTRODUCTION While IgG4-related disease (IgG4-RD) was initially described in the early 2000s, its polymorphic clinical manifestations were previously reported under different names ; they have in common the presence of IgG4+ oligoclonal plasma cells and fibrosis. STATE OF THE ART Ruling out certain differential diagnoses, the diagnosis of IgG4-RD is based on a bundle of clinical, biological and histological features. Chest involvement is variable and can affect the mediastinum, bronchi, parenchyma, pleura and/or, more rarely, bones and (pericardium, aorta, coronary…) vascular structures. The most frequent radiological manifestations are peribronchovascular thickening, mediastinal lymphadenopathy, and nodular or interstitial patterns. Pleural involvement and posterior mediastinal fibrosis are less frequent, while thoracic paravertebral tissue thickening is highly specific. Systemic corticosteroids are the cornerstone of treatment. In case of relapse or as frontline therapy in case of risk factors for relapse and/or poor tolerance of corticosteroids), a steroid-sparing agent (most often rituximab) is added, and biannual maintenance infusions are associated with a lower risk of relapse. PERSPECTIVES An international consensus has recently led to the development of classification criteria that should standardize the diagnostic approach and homogenize the enrolment of patients in epidemiological as well as therapeutic studies. Other treatments are also under evaluation, including biologics targeting T2 inflammation, CD-19 (inebilizumab, obexelimab), SLAMF7 (elotuzumab) surface proteins, Bruton's tyrosine kinase, and the JAK/STAT pathway. CONCLUSIONS Substantial progress has been made over recent years in understanding IgG4-RD pathophysiology, and personalized patient care seems to be an achievable medium-term goal.
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Affiliation(s)
- M Groh
- Centre de références des syndromes hyperéosinophiliques (CEREO), service de médecine Interne, hôpital Foch, 92150 Suresnes, France; Inserm, U1286 - INFINITE-Institute for Translational Research in Inflammation, Université de Lille, CHU de Lille, 59000 Lille, France
| | - P Habert
- Service de radiologie, hôpital Nord, APHM, Aix-Marseille université, Marseille, France; LIIE (Experimental Interventional Imaging Laboratory), Aix-Marseille Université, 13000 Marseille, France
| | - M Ebbo
- Service de médecine Interne, hôpital La Timone, APHM, Aix-Marseille Université, 13005 Marseille, France
| | - R Muller
- Service de médecine Interne, hôpital La Timone, APHM, Aix-Marseille Université, 13005 Marseille, France
| | - L Gaigne
- Service de médecine Interne, hôpital La Timone, APHM, Aix-Marseille Université, 13005 Marseille, France
| | - J-Y Gaubert
- Service de radiologie, hôpital La Timone, APHM, Aix-Marseille université, 13005 Marseille, France
| | - N Schleinitz
- Service de médecine Interne, hôpital La Timone, APHM, Aix-Marseille Université, 13005 Marseille, France.
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20
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Kurata S, Nawata A, Morinishi T, Ohta K, Katafuchi E, Hisano S, Tanaka S, Hisaoka M, Koike J, Nishikomori R, Nakayama T. Immunoglobulin G deposition on proximal tubules and the tubular basement membrane in acute tubular injury complicated with focal segmental glomerulosclerosis (FSGS): A possible prediction tool for subclinical FSGS. Ann Diagn Pathol 2023; 66:152154. [PMID: 37216712 DOI: 10.1016/j.anndiagpath.2023.152154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/28/2023] [Accepted: 05/02/2023] [Indexed: 05/24/2023]
Abstract
Immunofluorescent deposition of immunoglobulin G (IgG) in the tubular basement membrane (TBM) has been evaluated in the diagnosis of various diseases; however, few studies have investigated the immunofluorescence of acute tubular injury (ATI). Herein, we attempted to clarify IgG expression in the proximal tubular epithelium and TBM in ATI due to various causes. Patients with ATI with nephrotic-range proteinuria, including focal segmental glomerulosclerosis (FSGS, n = 18) and minimal change nephrotic syndrome (MCNS, n = 8), ATI with ischemia (n = 6), and drug-induced ATI (n = 7), were enrolled. ATI was evaluated by light microscopy. CD15 and IgG double staining and IgG subclass staining were performed to evaluate immunoglobulin deposition in the proximal tubular epithelium and TBM. IgG deposition was identified in the proximal tubules only in the FSGS group. Furthermore, IgG deposition in the TBM was observed in the FSGS group showing severe ATI. IgG3 was predominantly deposited by the IgG subclass study. Our results indicate that IgG deposition in the proximal tubular epithelium and TBM suggests the leaking of IgG from the glomerular filtration barrier and its reabsorption by proximal tubules, which may predict disruption of the glomerular size barrier, including subclinical FSGS. FSGS with ATI should be included as a differential diagnosis when IgG deposition in TBM is observed.
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Affiliation(s)
- Satoko Kurata
- Department of Pediatrics and Child Health, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan; Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Aya Nawata
- Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
| | - Takuya Morinishi
- Department of Nephrology, Graduate School of Medicine, Kyoto University, Shogoin-Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
| | - Keisuke Ohta
- Advanced Imaging Research Center, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan
| | - Eisuke Katafuchi
- Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Satoshi Hisano
- Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Seiji Tanaka
- Department of Pediatrics and Child Health, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan
| | - Masanori Hisaoka
- Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
| | - Junki Koike
- Department of Pathology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
| | - Ryuta Nishikomori
- Department of Pediatrics and Child Health, School of Medicine, Kurume University, 67, Asahimachi, Kurume 830-0011, Japan
| | - Toshiyuki Nakayama
- Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
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21
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Mima A, Lee R, Murakami A, Gotoda H, Akai R, Lee S. Case Report: IgG4-related kidney disease complicated by interstitial pneumonia. F1000Res 2023; 12:1045. [PMID: 37744768 PMCID: PMC10511842 DOI: 10.12688/f1000research.131818.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/22/2023] [Indexed: 09/26/2023] Open
Abstract
Immunoglobulin G4 (IgG4)-related disease is a systemic inflammatory disorder characterized by tubulointerstitial nephritis with IgG4-positive plasma cell infiltration. We report the case of an 84-year-old male who presented with a history of dyspnea on exertion and cough. The lymph nodes were palpated in the axilla. Urinalysis revealed mild proteinuria and increased levels of NAG and β2-microglobulin. Blood tests showed hyperglobulinemia with a marked elevation of serum IgG4 levels. Chest computed tomography showed bilateral ground-glass and reticular opacities in the lower and peripheral portions of the lungs. Ga-67 scintigraphy showed kidney uptake. The patient was diagnosed with IgG4-related kidney disease based on the renal pathology indicative of typical tubulointerstitial nephritis with extensive IgG4-positive plasma cell infiltration. The patient was treated with prednisolone and showed a prompt response in his clinical condition. The patient achieved normalization of serum IgG4 levels 6 months after the initiation of treatment. Although IgG4-related disease is thought to be potentially associated with organ fibrosis, there are few reports on combination of interstitial pneumonia and IgG4-related kidney disease. Our case report presents a possible pattern of IgG4-related disease.
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Affiliation(s)
- Akira Mima
- Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Rina Lee
- Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Ami Murakami
- Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Hidemasa Gotoda
- Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Ryosuke Akai
- Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Shinji Lee
- Department of Nephrology, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
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22
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Shankar M, Gurusiddaiah SC, Mutalik S, Aralapuram K. Changing Tides of Acute Interstitial Nephritis: A Retrospective Observational Study from South India. Indian J Nephrol 2023; 33:362-365. [PMID: 37881735 PMCID: PMC10593296 DOI: 10.4103/ijn.ijn_142_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 05/08/2022] [Accepted: 05/21/2022] [Indexed: 10/27/2023] Open
Abstract
Introduction The incidence of acute interstitial nephritis (AIN) has been increasing in recent years. The causes and outcomes of AIN have been changing with time and vary widely based on geographical region. Methods A retrospective observational study was conducted in a tertiary care center. All (n = 6234) native kidney biopsies were reviewed from January 2016 to December 2021. All biopsy-proven AIN cases were included in the study. AIN associated with systemic diseases (such as SLE, Sjogren's, sarcoidosis, plasma cell dyscrasias), proliferative glomerulonephritis, and allograft biopsies were excluded. Results Among 6234 biopsies analyzed, there were 156 biopsy-proven AIN cases. The majority were in the 6th decade of life (24.4%) and males (80.8%). 50% of the patients had a history of drug intake, the most common being tenofovir (12.3%) followed by alternate forms of medications (10.3%). The majority (96.2%) presented with acute kidney injury (AKI). At the end of six months, 79.5% recovered completely, 19.2% progressed to chronic kidney disease. The presence of nephrotic range proteinuria at presentation was associated with progression to chronic kidney disease. Conclusion AIN is an important cause of AKI, especially in the elderly population. Drugs are the most common cause, especially HAART follwed by alternate forms of medication. The presence of nephrotic range proteinuria was associated with increased risk of progression to chronic kidney disease.
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Affiliation(s)
- Mythri Shankar
- Department of Nephrology, Institute of Nephro-Urology, Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Sreedhara C. Gurusiddaiah
- Department of Nephrology, Institute of Nephro-Urology, Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Seeta Mutalik
- Department of Nephrology, Institute of Nephro-Urology, Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
| | - Kishan Aralapuram
- Department of Nephrology, Institute of Nephro-Urology, Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India
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23
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Peyronel F, Vaglio A. IgG4-Related Kidney Disease. Clin J Am Soc Nephrol 2023; 18:994-996. [PMID: 37418275 PMCID: PMC10564360 DOI: 10.2215/cjn.0000000000000235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/08/2023]
Affiliation(s)
- Francesco Peyronel
- Nephrology and Dialysis Unit, Meyer Children's University Hospital—IRCCS, Firenze, Italy
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Augusto Vaglio
- Nephrology and Dialysis Unit, Meyer Children's University Hospital—IRCCS, Firenze, Italy
- Department of Biomedical, Experimental and Clinical Sciences “Mario Serio,” University of Firenze, Firenze, Italy
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24
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Chaba A, Devresse A, Audard V, Boffa JJ, Karras A, Cartery C, Deltombe C, Chemouny J, Contamin C, Courivaud C, Duquennoy S, Garcia H, Joly D, Goumri N, Hanouna G, Halimi JM, Plaisier E, Hamidou M, Landron C, Launay D, Lebas C, Legendre M, Masseau A, Mathian A, Mercadal L, Morel N, Mutinelli-Szymanski P, Palat S, Pennaforte JL, Peraldi MN, Pozdzik A, Schleinitz N, Thaunat O, Titeca-Beauport D, Mussini C, Touati S, Prinz E, Faller AL, Richter S, Vilaine E, Ferlicot S, Von-Kotze C, Belliere J, Olagne J, Mesbah R, Snanoudj R, Nouvier M, Ebbo M, Zaidan M. Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease. Clin J Am Soc Nephrol 2023; 18:1031-1040. [PMID: 37283461 PMCID: PMC10564355 DOI: 10.2215/cjn.0000000000000193] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 05/31/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.
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Affiliation(s)
- Anis Chaba
- Departement of Nephrology-Dialysis-Transplantation, Assistance Publique des Hôpitaux de Paris (AP-HP), Bicêtre University Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France
| | - Arnaud Devresse
- Department of Nephrology, Cliniques universitaires Saint-Luc, Bruxelles, Belgium
| | - Vincent Audard
- Nephrology and Renal Transplantation Department, Assistance Publique des Hôpitaux de Paris (AP-HP), Henri Mondor Hospital University, Rare Disease Center « Idiopathic Nephrotic syndrome », Fédération Hospitalo-Universitaire « Innovative therapy for immune disorders, Créteil, France
- Univ Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France
| | | | | | - Claire Cartery
- Department of Nephrology, CH Valenciennes, Valenciennes, France
| | - Clément Deltombe
- Institute for Transplantation, Urology and Nephrology (ITUN) Nantes University Hospital, Nantes, France
| | | | | | | | - Simon Duquennoy
- Department of Nephrology, Fondation AUB Santé Avranches, France
| | - Hugo Garcia
- Department of Nephrology, Hôpitaux Sorbonne Université, Paris, France
| | | | - Nabila Goumri
- Department of Nephrology, CH Chartres, Chartres, France
| | | | | | | | | | - Cédric Landron
- Department of Internal Medicine, CHU Poitier, Poitier, France
| | - David Launay
- Univ. Lille, Inserm, CHU Lille, Service de Médecine Interne et Immunologie Clinique, Centre de référence des maladies autoimmunes systémiques rares du Nord et Nord-Ouest de France (CeRAINO), U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
| | - Celine Lebas
- Department of Nephrology, CHU Valenciennes, Valenciennes, France
| | | | - Agathe Masseau
- Department of Internal Medicine, CHU Nantes, Nantes, France
| | - Alexis Mathian
- Department of Internal Medicine, Hôpital Cochin, APHP, Paris, France
| | - Lucile Mercadal
- Department of Nephrology, Hôpitaux Sorbonne Université, Paris, France
| | - Nathalie Morel
- Department of Internal Medicine, Hôpital Cochin, APHP, Paris, France
| | | | - Sylvain Palat
- Department of Internal Medicine, CHU Limoges, Limoges, France
| | | | | | | | | | | | | | - Charlotte Mussini
- Departement of Pathology, Assistance Publique des Hôpitaux de Paris (AP-HP), Bicêtre University Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France
| | - Sonia Touati
- Department of Nephrology, CH Pontoise, Pontoise, France
| | - Eric Prinz
- Department of Nephrology, NHC Strasbourg, France
| | | | - Sarah Richter
- Department of Nephrology, Clinique Sainte Anne, Strasbourg, France
| | - Eve Vilaine
- Department of Nephrology, CHU Ambroise Paré, France
| | - Sophie Ferlicot
- Departement of Pathology, Assistance Publique des Hôpitaux de Paris (AP-HP), Bicêtre University Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France
| | | | - Julie Belliere
- Departement of Nephrology, CHU Toulouse, Toulouse, France
| | | | - Rafik Mesbah
- Department of Nephrology, Hopital Boulogne-sur-mer, Boulogne-sur-mer, France
| | - Renaud Snanoudj
- Departement of Nephrology-Dialysis-Transplantation, Assistance Publique des Hôpitaux de Paris (AP-HP), Bicêtre University Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France
| | | | - Mikael Ebbo
- Department of Internal Medicine, CHU Timone, Marseille, France
| | - Mohamad Zaidan
- Departement of Nephrology-Dialysis-Transplantation, Assistance Publique des Hôpitaux de Paris (AP-HP), Bicêtre University Hospital, Paris-Saclay University, Le Kremlin Bicêtre, France
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Soma Y, Kato M, Shimura G, Kamio M, Iida M. Renal biopsy diagnosis of IgG4-related kidney disease with minor hematuria and mild renal dysfunction: lessons for the clinical nephrologist. J Nephrol 2023; 36:639-642. [PMID: 36441499 DOI: 10.1007/s40620-022-01506-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 10/13/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Yu Soma
- Department of Nephrology, Yokosuka General Uwamachi Hospital, Yokosuka, Japan.
| | - Miku Kato
- Department of Nephrology, Yokosuka General Uwamachi Hospital, Yokosuka, Japan
| | - Gaku Shimura
- Department of Nephrology, Yokosuka General Uwamachi Hospital, Yokosuka, Japan
| | - Manabu Kamio
- Department of Internal Medicine, Yokosuka General Uwamachi Hospital, Yokosuka, Japan
| | - Maki Iida
- Department of Pathology, Yokosuka General Uwamachi Hospital, Yokosuka, Japan
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He PH, Liu LC, Zhou XF, Xu JJ, Hong WH, Wang LC, Liu SJ, Zeng JH. IgG4-related kidney disease complicated with retroperitoneal fibrosis: A case report. World J Clin Cases 2023; 11:1656-1665. [PMID: 36926395 PMCID: PMC10011980 DOI: 10.12998/wjcc.v11.i7.1656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/11/2023] [Accepted: 02/15/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND IgG4-related disease (IgG4-RD) is a chronic fibrotic disease mediated by immunity recognized by clinicians in recent years. When the kidney is involved, it is called IgG4-related kidney disease (IgG4-RKD). IgG4-related tubulointerstitial nephritis (IgG4-TIN) is a representative manifestation of IgG4-RKD. IgG4-TIN can cause obstructive nephropathy complicated by retroperitoneal fibrosis (RPF). Cases of IgG4-TIN complicated with RPF are rare. Glucocorticoids are the first-line therapeutic medication for IgG4-RD and can significantly improve renal function.
CASE SUMMARY Herein, we report the case of a 56-year-old man with IgG4-RKD complicated with RPF. The patient presented to the hospital with complaints of elevated serum creatinine (Cr), nausea, and vomiting. During hospitalization, Cr was 1448.6 µmol/L, and serum IgG4 was increased. A total abdominal computed tomography (CT) scan and enhanced CT scan obviously indicated RPF. Although this patient had a long course and renal insufficiency, we performed a kidney biopsy. Renal biopsy showed that the renal tubulointerstitium had focal plasma cell infiltration and increased lymphocyte infiltration accompanied by fibrosis. After combining the biopsy results with immunohistochemistry, it was found that the absolute number of positive IgG4+ cells per high power field exceeded 10, and the ratio of IgG4/IgG was over 40%. Finally, the patient was diagnosed with IgG4-TIN complicated with RPF and given glucocorticoids as long-term maintenance therapy, helping him keep out of dialysis. After a follow-up of 19 mo, the patient had recovered well. Previous literature on IgG4-RKD and RPF was retrieved from PubMed to characterize the clinical and pathological features and to identify the diagnosis and treatment of IgG4-RKD.
CONCLUSION Our case report demonstrates the clinical characteristics of IgG4-RKD complicated with RPF. Serum IgG4 is a favorable indicator for screening. Performing renal biopsy actively plays a vital role in diagnosis and treatment, even if the patient has a long course and manifests with renal insufficiency. It is remarkable to treat IgG4-RKD with glucocorticoids. Hence, early diagnosis and targeted therapy are essential for reversing renal function and improving extrarenal manifestations in patients with IgG4-RKD.
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Affiliation(s)
- Pei-Hua He
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Li-Chang Liu
- Department of Nephrology, Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine, Zhuhai 519015, Guangdong Province, China
| | - Xing-Fu Zhou
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Jun-Jie Xu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Wei-Hong Hong
- Department of Nephrology, Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine, Zhuhai 519015, Guangdong Province, China
| | - Li-Chun Wang
- Department of Nephrology, Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine, Zhuhai 519015, Guangdong Province, China
| | - Su-Jun Liu
- Department of Nephrology, Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine, Zhuhai 519015, Guangdong Province, China
| | - Jia-Hao Zeng
- Department of Nephrology, Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine, Zhuhai 519015, Guangdong Province, China
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Kawano M, Saeki T, Ubara Y, Matsui S. Recent advances in IgG4-related kidney disease. Mod Rheumatol 2023; 33:242-251. [PMID: 35788361 DOI: 10.1093/mr/roac065] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/01/2022] [Accepted: 06/21/2022] [Indexed: 11/14/2022]
Abstract
Recent advances in the management and understanding of immunoglobulin (Ig)G4-related kidney disease (RKD) have emphasized the importance of urgent treatment in IgG4-related tubulointerstitial nephritis. On the other hand, to avoid long-term glucocorticoid toxicity, strategies for early withdrawal of steroids or combination of immunosuppressants, such as rituximab, and the minimum dose of steroids have been pursued. However, disease recurrence after reducing or stopping steroid therapy hampers early withdrawal of glucocorticoid maintenance therapy. In addition, knowledge has accumulated in diagnostic approaches including differential diagnosis of anti-neutrophil cytoplasmic antibodies-associated vasculitis, idiopathic multicentric Castleman's disease, and Rosai-Dorfman disease with kidney lesion, which leads to earlier and precise diagnosis of IgG4-RKD. This review summarizes recent progress in the differential diagnosis of IgG4-RKD and related treatment strategies and recent topics of hypocomplementaemia, membranous glomerulonephritis, and IgG4-related pyelitis and periureteral lesion.
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Affiliation(s)
- Mitsuhiro Kawano
- Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
| | - Takako Saeki
- Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - Yoshifumi Ubara
- Department of Nephrology and Rheumatology, Toranomon Hospital, Kawasaki, Japan
| | - Shoko Matsui
- Health Administration Center, University of Toyama, Toyama, Japan
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Dong HF, Huang X, Wu JY, Li XH. [A case of skin ulcers secondary to extensive burns caused by flame and heavy metal-containing hydrothermal fluids]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2023; 39:71-74. [PMID: 36740429 DOI: 10.3760/cma.j.cn501120-20211115-00386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
On May 13, 2020, a 56-year-old man with extensive burns caused by flames and heavy metal-containing hydrothermal fluids was admitted to the General Hospital of Western Theater Command. After being admitted to the hospital, most of the burn wounds healed after treatments such as debridement, expansion, skin grafting, anti-shock, anti-infection, fluid replacement, and wound dressing change, etc. However, in the middle and late stages of treatment, the patient's burn wounds gradually showed repeated skin ulceration and inflammation. After excluding the cause of physical, bacterial infection and others, IgG4-related skin diseases was finally diagnosed by histopathological examination of tissue biopsy and concentration measurement of IgG4 in interstitial fluid, and the condition was improved after hormone treatment. This suggests that extensive burns may lead to the occurrence of autoimmune skin diseases. For the diagnosis of such diseases, it is necessary to combine clinical manifestations, serological examinations, and histopathological biopsy, etc. to avoid diagnostic pitfalls and draw correct conclusions.
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Affiliation(s)
- H F Dong
- Department of Burn Plastic Surgery, General Hospital of Western Theater Command, Chengdu 610083, China
| | - X Huang
- Department of Burn Plastic Surgery, General Hospital of Western Theater Command, Chengdu 610083, China
| | - J Y Wu
- Department of Burn Plastic Surgery, General Hospital of Western Theater Command, Chengdu 610083, China
| | - X H Li
- Department of Burn Plastic Surgery, General Hospital of Western Theater Command, Chengdu 610083, China
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He R, Ma M, Luo P, Guo Q. An overlap of IgG4-related tubulointerstitial nephritis and microscopic polyangiitis-associated glomerulonephritis: a case-based review. Clin Rheumatol 2023; 42:1459-1467. [PMID: 36593364 DOI: 10.1007/s10067-022-06493-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/03/2022] [Accepted: 12/22/2022] [Indexed: 01/04/2023]
Abstract
Because of some similarities in organ involvement, clinical manifestations, and histopathological features, IgG4-related disease (IgG4-RD) may occur concurrently with some clinicopathologic variants of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). An overlap syndrome of IgG4-RD and AAV has recently been proposed in clinical and/or histopathological studies, indicating that there may be some potential pathophysiological associations between the two disease entities; however, the mechanisms underlying these are incompletely understood. Here, we describe a rare case of a 63-year-old man with IgG4-related tubulointerstitial nephritis (IgG4-TIN) and microscopic polyangiitis-associated glomerulonephritis (MPA-GN) overlap syndrome. The clinical diagnosis of MPA was based on the 2022 American College of Rheumatology (ACR)/European League Against Rheumatology (EULAR) classification criteria. Remission induction therapy with intravenous methylprednisolone was initiated, followed by oral prednisone maintenance therapy with gradual tapering. The patient remained asymptomatic and his renal function was essentially normalized within 3.5 months of follow-up. The serum IgG4 levels decreased to 5 g/L. We also conducted a literature review to identify clinical findings, treatment options, and outcomes of patients with concurrent IgG4-RD and MPA and briefly discussed the potential pathophysiological association between IgG4-RD and MPA. Our findings enrich the database of this rare overlap syndrome and provide a basis for the diagnosis and early intervention in both diseases. These results provide some insights for clinicians to recognize and treat this overlap syndrome.
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Affiliation(s)
- Ronghua He
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Mingqi Ma
- Department of Nephrology and Rheumatology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Ping Luo
- Department of Nephrology and Rheumatology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China
| | - Qiaoyan Guo
- Department of Nephrology and Rheumatology, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China.
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Falk GE, Cornell LD, Brake M, Ford R, Todd K, Fox C. Unique Challenges in Diagnosing IgG4-Related Tubulointerstitial Nephritis with Arteritis. Kans J Med 2022; 15:443-445. [PMID: 36578454 PMCID: PMC9778723 DOI: 10.17161/kjm.vol15.18510] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/14/2022] [Indexed: 12/23/2022] Open
Affiliation(s)
- Grace E. Falk
- Department of Laboratory Medicine and Pathology, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Lynn D. Cornell
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Mona Brake
- Robert J. Dole Veterans Affairs Medical Center, Wichita, KS,Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Ryan Ford
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Kaleb Todd
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Christopher Fox
- Robert J. Dole Veterans Affairs Medical Center, Wichita, KS,Department of Pathology, University of Kansas School of Medicine-Wichita, Wichita, KS
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Kurašová E, Orság J, Klementa V, Marešová K, Tichý T, Hraboš D, Krejčí K. TUBULOINTERSTITIAL NEPHRITIS WITH UVEITIS (TINU SYNDROME). A CASE REPORT. CESKA A SLOVENSKA OFTALMOLOGIE : CASOPIS CESKE OFTALMOLOGICKE SPOLECNOSTI A SLOVENSKE OFTALMOLOGICKE SPOLECNOSTI 2022; 78:315-318. [PMID: 36543598 DOI: 10.31348/2022/31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
In this case report, we describe the case of a 50-year-old woman referred by her general practitioner to a pulmonologist in order to investigate persistent fever and elevation of C-reactive protein despite antibiotic treatment following a respiratory infection. The patient was examined extensively, during which rheumatology, gastroenterology, nephrology, ophthalmology, laboratory and imaging tests were performed. Due to a rapid progression of renal insufficiency with active urinary sediment, the patient was referred for a renal biopsy, which confirmed tubulointerstitial nephritis, followed by a diagnosis of bilateral anterior uveitis two months later - genetic testing was also conducted, which confirmed the diagnosis of tubulointerstitial nephritis with uveitis syndrome. Steroid treatment brought about a gradual reduction of proteinuria and a stabilisation of renal function.
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Ten Cases of Biopsy-Proven Acute Tubulointerstitial Nephritis: Report from a Single Center in a Rural Area from 2008 to 2021. Case Rep Nephrol 2022; 2022:6203803. [PMID: 36032631 PMCID: PMC9411007 DOI: 10.1155/2022/6203803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 11/17/2022] Open
Abstract
Acute tubulointerstitial nephritis (ATIN) can be caused by any number of factors, and it accounts for several percent of renal biopsy cases. In Japan, case reports exist, but there are few single-center series of ATIN cases. Case 1. A teenage male patient developed fever and cough on day X-61 and was found to have normal renal function and positive C-reactive protein (CRP) by his primary care physician. On day X-20, he presented with cough and nasal discharge in addition to low-grade fever, and his doctor noted renal dysfunction with serum creatinine of 2.12 mg/dL, negative urine occult blood, and positive urine glucose. Renal biopsy results showed diffuse interstitial nephritis with scarce glomerular involvement. There was no concurrent uveitis. Renal function normalized after 4 months of treatment with moderate-dose prednisolone. Cases 2–10. Of the 422 cases for which renal biopsies were performed at our institution from 2008 to 2021, acute tubulointerstitial nephritis was confirmed clinically and pathologically in 9 cases in addition to case 1, accounting for 2.4% of all biopsy cases. In the analysis of the 10 patients, the median age was 40 years old, eGFR at diagnosis was 19.4 (3.2–49.1) mL/min/1.73 m2, and 2 of them underwent hemodialysis, but both were weaned from dialysis, and the eGFR after treatment was 53.6 (20.8–110.0) mL/min/1.73 m2; all patients showed improvement (P < 0.001). Treatment consisted of steroids in 8 patients and no steroids in 2 patients, the latter being treated by discontinuation of the suspect drugs and treatment of infection; 7 of the 10 patients were examined for ocular uveitis, and uveitis was diagnosed in 5 patients. The causes and clinical course of ATIN are diverse, but it is treated according to individual judgment in addition to standard treatment, and it generally has a good renal prognosis.
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Nasr SH, Leung N, Said SM, Alkhateeb HB, Madden BJ, Charlesworth MC, Beck LH, Larsen CP, Sethi S. Membranous Nephropathy With Extensive Tubular Basement Membrane Deposits Following Allogeneic Hematopoietic Cell Transplant: A Report of 5 Cases. Am J Kidney Dis 2022; 79:904-908. [PMID: 34508832 DOI: 10.1053/j.ajkd.2021.07.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 07/20/2021] [Indexed: 12/24/2022]
Abstract
Tubular basement membrane (TBM) deposits are very uncommon in non-lupus membranous nephropathy. We report 5 patients with membranous nephropathy and extensive TBM deposits following allogeneic hematopoietic cell transplant. Patients presented with nephrotic syndrome (3 also had acute kidney injury) late post-transplant in association with chronic graft-versus-host disease (cGVHD). Kidney biopsies revealed global subepithelial and extensive TBM immune complex deposits, accompanied by acute tubular injury (n = 4) and tubulointerstitial inflammation (n = 4). Proteomic analysis of glomeruli in 4 cases identified PLA2R in 1, with no significant protein spectra for PLA2R, THSD7A, EX1/2, NELL-1, PCDH7, NCAM1, or SEMA3B detected in the remaining 3. On follow-up (for a mean 42 months), 4 patients had complete and 1 partial remission following prednisone and/or rituximab therapy. We propose that membranous nephropathy with extensive TBM deposits is a distinctive clinicopathologic lesion associated with allogeneic hematopoietic cell transplant. Pathogenesis likely involves cGVHD-driven antibodies against glomerular and TBM components, the identity of which remains to be elucidated.
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Affiliation(s)
- Samih H Nasr
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Nelson Leung
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Division of Hematology, Mayo Clinic, Rochester, Minnesota.
| | - Samar M Said
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | | | - Benjamin J Madden
- Medical Genome Facility, Proteomics Core, Mayo Clinic, Rochester, Minnesota
| | | | | | | | - Sanjeev Sethi
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
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Abstract
A woman in her 70s presented to the hospital being generally unwell 8 days following the first dose of the AstraZeneca COVID-19 vaccination. She was in stage III acute kidney injury (AKI) with hyperkalaemia and metabolic acidosis. Urinalysis showed haematoproteinuria. Renal immunology screen was negative. She subsequently underwent two renal biopsies. The second biopsy showed features consistent with acute tubulointerstitial nephritis. She was commenced on oral steroids, which led to marked improvement of her renal function.There are reasons why AKI can occur post vaccination such as prerenal AKI from reduced oral intake postvaccination due to feeling unwell or developing vomiting or diarrhoea. Intravenous fluids were given to this patient but with no meaningful improvement in renal function. She developed a possible reaction to the AstraZeneca COVID-19 vaccine, which led to AKI as supported by the interstitial inflammation and presence of eosinophils on renal biopsy.
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Affiliation(s)
- Felicia Sc Tan
- Renal Medicine, Hull University Teaching Hospitals NHS Trust, Hull, UK
| | - Mohammad E Kabir
- Renal Medicine, Hull University Teaching Hospitals NHS Trust, Hull, UK
| | - Sunil Bhandari
- Renal Medicine, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK
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Nakaosa N, Tsuboi N, Okabayashi Y, Haruhara K, Sasaki T, Tanno Y, Hirano K, Ikeda M, Miyazaki Y, Shimizu A, Yokoo T. Tubulointerstitial nephritis: a biopsy case series of 139 Japanese patients. Clin Exp Nephrol 2022; 26:435-444. [PMID: 35132512 DOI: 10.1007/s10157-021-02178-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 12/24/2021] [Indexed: 01/13/2023]
Abstract
BACKGROUND Tubulointerstitial nephritis (TIN) is an important cause of acute kidney injury (AKI) and advanced CKD. Only a limited number of studies have reported etiology-based differences in the clinical and/or histopathological properties and kidney outcomes of the biopsy-proven TIN. METHODS Patients with biopsy-proven TIN identified from 2005 to 2016 in five hospitals were categorized based on the etiologies and were retrospectively analyzed in relation to the clinicopathological findings and kidney outcomes. RESULTS Among 4815 biopsy cases screened, 153 Japanese TIN patients were identified, of whom 139 patients with ≥ 6 months of follow-up data (median 58 years old, 45.3% female, median 31.5 months follow-up) were further analyzed. TIN was drug-induced in 32.4%, autoimmune-related in 24.5%, of unknown etiology in 27.3% and other disease-related in 15.8%. Non-steroidal anti-inflammatory drugs and antibiotics were major causative drugs in drug-induced TIN, and IgG4-related disease, Sjögren's syndrome and sarcoidosis were common in autoimmune-related TIN. Among etiology groups, drug-induced TIN showed advanced AKI with elevated serum creatinine (sCr) and increased C-reactive protein levels at the diagnosis. TIN patients with autoimmune diseases showed less-severe AKI, but were more frequently treated with corticosteroids than others. Tubulointerstitial injury expansion in biopsy specimens was comparable among the groups. Complete or partial kidney function recovery at 6 months was more frequent in drug-induced and autoimmune-related TIN than in others. sCr levels at 6 months were similar among the groups. CONCLUSIONS This largest case series study of the biopsy-proven TIN in Japan provides detailed information regarding both etiology-based clinicopathological properties and kidney outcomes.
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Affiliation(s)
- Naoko Nakaosa
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
| | - Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan.
| | - Yusuke Okabayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
| | - Kotaro Haruhara
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
| | - Takaya Sasaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
| | - Yudo Tanno
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
| | - Keita Hirano
- Division of Nephrology, Department of Internal Medicine, Ashikaga Red Cross Hospital, Ashikaga, Japan
| | - Masato Ikeda
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
| | - Yoichi Miyazaki
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
| | - Akira Shimizu
- Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8641, Japan
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Faz-Muñoz D, Hinojosa-Azaola A, Mejía-Vilet JM, Uribe-Uribe NO, Rull-Gabayet M, Muñoz-Castañeda WR, Vargas-Parra NJ, Martín-Nares E. ANCA-associated vasculitis and IgG4-related disease overlap syndrome: a case report and literature review. Immunol Res 2022; 70:550-559. [PMID: 35449491 PMCID: PMC9023041 DOI: 10.1007/s12026-022-09279-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 04/09/2022] [Indexed: 12/11/2022]
Abstract
Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides are infrequent autoimmune diseases characterized by inflammation of the walls of small vessels leading to tissue and endothelial damage. On the other hand, IgG4-related disease is a fibroinflammatory disease characterized histologically by lymphoplasmacytic infiltrates with IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis that may affect nearly every organ of the body. There are similarities in clinical, serological, radiological, and histopathological features between both diseases, and hence, they usually mimic each other complicating the differential diagnosis. Furthermore, reports of patients with the coexistence of both conditions (overlap syndrome) have been reported. We herein report a patient with an unequivocal diagnosis of ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (posterior uveitis, polyneuropathy, pauci-immune glomerulonephritis with crescent formation and granulomas, and MPO-ANCA positivity) and IgG4-related disease (thoracic aortitis, tubulointerstitial nephritis with prominent IgG4+ plasma cell infiltration, fibrosis, and obliterative arteritis, high levels of serum IgG4, and eosinophilia) overlap syndrome.
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Affiliation(s)
- David Faz-Muñoz
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, Mexico City, Mexico, 14080
| | - Andrea Hinojosa-Azaola
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, Mexico City, Mexico, 14080
| | - Juan M Mejía-Vilet
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Norma O Uribe-Uribe
- Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Marina Rull-Gabayet
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, Mexico City, Mexico, 14080
| | - Wallace Rafael Muñoz-Castañeda
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, Mexico City, Mexico, 14080
| | - Nancy Janeth Vargas-Parra
- Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Eduardo Martín-Nares
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Sección XVI, Tlalpan, Mexico City, Mexico, 14080.
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Tawhari M, Al Oudah N, Al Zahrani Y, Radwi M. IgG4-Related Kidney Disease Associated With End-Stage Kidney Disease, Renal Pseudotumor, and Renal Vein Thrombosis. Cureus 2022; 14:e22837. [PMID: 35281583 PMCID: PMC8906446 DOI: 10.7759/cureus.22837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/04/2022] [Indexed: 11/05/2022] Open
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Ishibuchi K, Iwakura T, Ema C, Nakagami D, Uchiyama Y, Kaneko M, Fukasawa H, Matsuyama T, Yasuda H, Furuya R. A Case of M-Type Phospholipase A2 Receptor-Associated Membranous Nephropathy With IgG4-Positive Cells Infiltration in the Interstitium. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2022; 15:11795476221078635. [PMID: 35221739 PMCID: PMC8874188 DOI: 10.1177/11795476221078635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 12/30/2021] [Indexed: 11/16/2022]
Abstract
A 70-year-old man was referred to our department for evaluation of nephrotic syndrome. Renal biopsy revealed membranous nephropathy (MN). Immunohistochemical analysis demonstrated IgG4-positive staining in the glomeruli and interstitial cells. The presence of serum anti-phospholipase A2 receptor (PLA2R) antibody and enhanced staining of PLA2R in the glomeruli was noted. Computed tomography unidentified the extrarenal lesions of IgG4-related disease. He was diagnosed with PLA2R-associated MN possibly complicated with IgG4 related kidney disease (IgG4-RKD). Storiform fibrosis, a typical manifestation of IgG4-RKD, was not apparent. We herein describe a case of serologically and histologically confirmed PLA2R-associated MN with IgG4+ cell infiltration into the interstitium without any signs of IgG4-RD.
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Affiliation(s)
- Kento Ishibuchi
- Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
| | - Takamasa Iwakura
- Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
- First Department of Internal medicine, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Chiemi Ema
- First Department of Internal medicine, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Daisuke Nakagami
- Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
| | - Yuri Uchiyama
- Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
| | - Mai Kaneko
- Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
| | - Hirotaka Fukasawa
- Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
| | - Takashi Matsuyama
- First Department of Internal medicine, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hideo Yasuda
- First Department of Internal medicine, Division of Nephrology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Ryuichi Furuya
- Renal Division, Department of Internal Medicine, Iwata City Hospital, Iwata, Japan
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Persistent enlargement of the pancreatic gland after glucocorticoid therapy increases the risk of relapse in IgG4-related autoimmune pancreatitis. Clin Rheumatol 2022; 41:1709-1718. [PMID: 35175447 DOI: 10.1007/s10067-022-06091-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/26/2022] [Accepted: 01/31/2022] [Indexed: 11/03/2022]
Abstract
OBJECTIVES This study aims to clarify the relationship between the changes of pancreatic size after glucocorticoid (GC) therapy and relapse in IgG4-related autoimmune pancreatitis (AIP). METHODS We prospectively enrolled 205 newly diagnosed IgG4-related AIP patients. 145 patients were followed up for more than 3 years. These patients were divided into three groups according to the changes of pancreatic size after treatment of 6 months: pancreatic swelling, normal size, and pancreatic atrophy. Baseline clinical and laboratory parameters were compared among three groups. Kaplan-Meier survival analysis was performed in the 134 patients based on GC therapy. Besides, Cox regression analysis and logistic regression analysis were performed to identify risk factors associated with relapse and the potential variables affecting changes of pancreatic size after treatment. RESULTS Age at diagnosis, white blood cell count, and serum IgG1 level at baseline were significantly different among the three groups. After treatment of 6 months, the pancreas of most patients (n = 81, 55.9%) could return to normal size, while persistent pancreatic swelling was found in 24.1% patients (n = 35), and atrophy was observed in 20.0% of the patients (n = 29). Kaplan-Meier survival analysis presented patients with pancreatic swelling after 6 months of GC therapy were more likely to relapse in the follow-up of 3 years. Persistent pancreatic swelling after treatment and salivary gland involvement at baseline were independent risk variables associated with relapse in IgG4-related AIP patients, while GC-based therapy was a protective factor of relapse. Logistic regression analysis revealed that older age at diagnosis was associated with pancreatic atrophy and higher baseline serum IgG1 level was associated with pancreatic swelling after treatment of 6 months. CONCLUSIONS Patients with persistent pancreatic swelling after GC-based therapy of 6 months were more likely to relapse in the follow-up of 3 years. Older age at diagnosis and higher baseline serum IgG1 level were potential variables associated with pancreatic atrophy or swelling after treatment of 6 months. Key Points • Patients with persistent pancreatic swelling after glucocorticoid-based therapy were more likely to relapse in IgG4-related autoimmune pancreatitis. • Older age at diagnosis was associated with pancreatic atrophy after glucocorticoid-based therapy. • Higher baseline serum IgG1 level was associated pancreatic swelling after glucocorticoid-based therapy.
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40
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Update on classification, diagnosis, and management of immunoglobulin G4-related disease. Chin Med J (Engl) 2022; 135:381-392. [PMID: 34985023 PMCID: PMC8869566 DOI: 10.1097/cm9.0000000000001891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, its prognosis prediction, as well as therapy response monitoring. Although recurrence is very common in IgG4-RD, glucocorticoid is still the first-line treatment for the majority of patients. The factors that affect the likelihood of disease relapse are multifaceted. The selection strategy of various steroid-sparing agents is still being explored. Besides, when patients have special sites involvement leading to severe clinical conditions, surgical operation or interventional therapy should also be considered. An update on classification, diagnosis, and management of IgG4-RD is provided in the current study to fully elucidate the recommended clinical practice of this mysterious disease.
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Muthuppalaniappan VM, Ball S. Acute Tubulointerstitial Nephritis. PRIMER ON NEPHROLOGY 2022:585-597. [DOI: 10.1007/978-3-030-76419-7_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
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Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020. J Gastroenterol 2022; 57:225-245. [PMID: 35192048 PMCID: PMC8938398 DOI: 10.1007/s00535-022-01857-9] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/28/2022] [Indexed: 02/04/2023]
Abstract
In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.
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Della-Torre E, Zen Y, Stone JH. IgG4-Related Disease Overview: Pathology, Clinical Picture, and Treatment. PARAPROTEINEMIA AND RELATED DISORDERS 2022:229-250. [DOI: 10.1007/978-3-031-10131-1_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Momoniat T, Jacob D, Duhli N, Jorna T. IgG4-related tubulointerstitial nephritis. BMJ Case Rep 2021; 14:e241942. [PMID: 34764107 PMCID: PMC8586881 DOI: 10.1136/bcr-2021-241942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/02/2021] [Indexed: 11/04/2022] Open
Abstract
A 67-year-old man was referred to the renal team following an episode of acute kidney injury on a background of chronic kidney disease. He had a 9-year history of steroid-sensitive arthritis, epigastric pain and isolated submandibular gland enlargement. He was noted to have a raised eosinophil count, total serum protein and total immunoglobulin G4 (IgG4) level as well as a serum hypocomplementaemia. A renal biopsy showed a tubulointerstitial nephritis with lymphoplasmacytic infiltrates, fibrosis and IgG4-positive plasma cells on immunohistochemistry. A diagnosis of IgG4-related disease was made based on clinical presentation and pathology. Renal function improved with glucocorticoids and the patient was successfully transitioned to azathioprine as a steroid-sparing agent.
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Affiliation(s)
| | - Deepa Jacob
- Histopathology Department, Hull Royal Infirmary, Hull, UK
| | | | - Tom Jorna
- Renal Department, Hull Royal Infirmary, Hull, UK
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Su T, Wang H, Wang S, Yang L. Clinicopathological Patterns and Predictors of the Functional Restoration of Immunoglobulin G4-Related Kidney Disease: A Chinese Single-Center Cohort Study. Front Med (Lausanne) 2021; 8:736098. [PMID: 34692728 PMCID: PMC8526789 DOI: 10.3389/fmed.2021.736098] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 09/06/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immunoreactivity-based fibro-inflammatory disease. Immunoglobulin G4-related kidney disease (IgG4-RKD) is a frequently overlooked diagnosis. This study aimed to describe IgG4-RKD and examine the factors relevant to the renal outcomes of IgG4-RD. Methods: We studied a prospective IgG4-RKD cohort between January 2012 and December 2020 with close follow-up. Clinicopathologic data at kidney biopsy were collected and analyzed. We aimed to explore independent risk factors for long-term renal outcome and disease relapse. Patients with an eGFR<45 ml/min per 1.73m2 at 12 months were defined as having poor outcomes. Results: The included 42 patients with IgG4-RKD had a mean age of 58.5 ± 8.7 years (male-to-female ratio = 5:1). The IgG4-RD responder index (RI) was 12.2 ± 3.3. A total of 66.7% of the patients presented with acute on kidney disease or acute on chronic kidney disease. Eight patients (19.0%) showed nephrotic-range proteinuria, and nine (21.4%) had high-titer IgG4-autoantibodies, including antineutrophil cytoplasmic antibody and anti-phospholipase A2 receptor. A kidney biopsy was conducted in 40 patients. Thirty-seven (90.0%) patients were diagnosed with IgG4-related tubulointerstitial nephritis, and 19 (47.5%) of them had concurrent glomerular diseases (membranous nephropathy [MN], n = 3; crescentic glomerulonephritis [CrGN], n = 11; diabetic kidney disease, n = 3; and both MN and CrGN, n = 2). IgG4-RD RI had a close relationship with serum C3 (R = -0.509, P = 0.001), C4 (R = -0.314, P = 0.049) levels, and peripheral blood eosinophil count (PBEC; R = 0.377, P = 0.024), factors that were not included in RI scores. Correlation analysis disclosed that IgG4-RD RI (R = 0.422, P = 0.007), organs involved (R = 0.452, P = 0.003), and C3 (R = -0.487, R = 0.002) were correlated with the percentage decrease of serum creatinine at 1 month. However, multivariate regression analysis failed to identify any clinicopathological parameters that could predict short-term renal restoration and IgG4-RKD relapse. Ten out of 29 variables, of most importance, were identified by the least absolute shrinkage and selection operator (LASSO) regression analysis. By multivariate logistic regression a higher serum IgG4 (OR = 0.671, P = 0.010), IgG1 (OR = 1.396, P = 0.049), IgG3 (OR = 19.154, P = 0.039), and erythrocyte sedimentation rate (ESR; OR = 1.042, P = 0.032) were found to be independent factors for poor long-term outcome. Conventional immunosuppressive medications and/or rituximab were prescribed, and in 83.3% of the patients, the kidney function improved. Repeat kidney biopsies confirmed the remission of interstitial inflammation in two patients under immunosuppressive therapy. However, the disease relapse rate was as high as 31.0%. Conclusions: We strongly recommend a kidney biopsy in active IgG4-RD, especially when there is proteinuria and renal dysfunction, because concurrent glomerular involvement and active interstitial inflammation should be assessed. A higher serum IgG1, IgG3, and ESR were independent factors for the poor long-term renal outcome; however, elevated IgG4 predicted a good renal prognosis, and appropriate and timely immunosuppressive therapy can help achieve a better prognosis.
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Affiliation(s)
- Tao Su
- Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China
- Renal Pathology Center, Institute of Nephrology, Peking University, Beijing, China
| | - Hui Wang
- Renal Pathology Center, Institute of Nephrology, Peking University, Beijing, China
- Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China
| | - Suxia Wang
- Renal Pathology Center, Institute of Nephrology, Peking University, Beijing, China
- Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, China
| | - Li Yang
- Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China
- Renal Pathology Center, Institute of Nephrology, Peking University, Beijing, China
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Liu J, Yin W, Westerberg LS, Lee P, Gong Q, Chen Y, Dong L, Liu C. Immune Dysregulation in IgG 4-Related Disease. Front Immunol 2021; 12:738540. [PMID: 34539675 PMCID: PMC8440903 DOI: 10.3389/fimmu.2021.738540] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 08/09/2021] [Indexed: 12/26/2022] Open
Abstract
Immunoglobin G4-related disease (IgG4-RD) is one of the newly discovered autoimmune diseases characterized by elevated serum IgG4 concentrations and multi-organ fibrosis. Despite considerable research and recent advances in the identification of underlying immunological processes, the etiology of this disease is still not clear. Adaptive immune cells, including different types of T and B cells, and cytokines secreted by these cells play a vital role in the pathogenesis of IgG4-RD. Antigen-presenting cells are stimulated by pathogens and, thus, contribute to the activation of naïve T cells and differentiation of different T cell subtypes, including helper T cells (Th1 and Th2), regulatory T cells, and T follicular helper cells. B cells are activated and transformed to plasma cells by T cell-secreted cytokines. Moreover, macrophages, and some important factors (TGF-β, etc.) promote target organ fibrosis. Understanding the role of these cells and cytokines implicated in the pathogenesis of IgG4-RD will aid in developing strategies for future disease treatment and drug development. Here, we review the most recent insights on IgG4-RD, focusing on immune dysregulation involved in the pathogenesis of this autoimmune condition.
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Affiliation(s)
- Jiachen Liu
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Yin
- Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lisa S Westerberg
- Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Pamela Lee
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Quan Gong
- Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China
| | - Yan Chen
- The Second Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Lingli Dong
- Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chaohong Liu
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Osuorji C, Master K, Osuorji I. IgG4-Related Disease With Renal and Pulmonary Involvement. Cureus 2021; 13:e17071. [PMID: 34522549 PMCID: PMC8428951 DOI: 10.7759/cureus.17071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2021] [Indexed: 12/04/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a rare immune-mediated disease affecting multiple organs and tissues. There is often the presence of elevated serum Ig4 subtype with histological evidence of lymphoplasmacytic infiltration, fibrosis, and phlebitis. The mainstay of treatment is steroids therapy. We report the case of a 66-year-old man presenting with acute on chronic renal failure and pulmonary nodules seen on PET-CT scan. He also had elevated serum IgG4 subclass and histological features in keeping with IgG4-RD. He failed steroid therapy but responded subsequently to rituximab with complete resolution of his symptoms.
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Affiliation(s)
- Chinenye Osuorji
- Internal Medicine, Burrell College of Osteopathic Medicine, Las Cruces, USA
| | - Kiron Master
- Radiology, Hospitals of Providence Sierra Campus, El Paso, USA
| | - Ikenna Osuorji
- Hematology and Oncology, Burrell College of Osteopathic Medicine, Las Cruces, USA
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Tian M, Luan J, Jiao C, Chang Q, Kopp JB, Zhou H. Co-occurrence of IgA nephropathy and IgG4-Tubulointersitial nephritis effectively treated with tacrolimus: a case report. BMC Nephrol 2021; 22:279. [PMID: 34384379 PMCID: PMC8358553 DOI: 10.1186/s12882-021-02477-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/19/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Cases of concurrent immunoglobulin A nephropathy (IgAN) and IgG4-related tubulointerstitial nephritis (IgG4-TIN) are rare and previous case reports have lacked important data. KDIGO suggests a treatment with systemic glucocorticoids in IgAN patients. Glucocorticoids are recommended as the first-line therapy for IgG4-TIN. The use of tacrolimus as a long-term maintenance treatment has not been described. We report the case of a man who developed IgAN and IgG4-TIN without abnormalities in extra-renal tissue, without renal function abnormalities or impairment as well, and was treated by tacrolimus as a long-term maintenance during 45 months follow-up. CASE PRESENTATION A 56-year-old Chinese man first presented to our hospital with the chief complaint of foamy urine for 1 year and hematuria for 3 months, with a medical history of hypertension. Testing revealed a notable increase in serum IgG4 level without abnormalities in renal function or imaging, or in dysfunction other organs. Renal biopsy showed mesangial extracellular matrix proliferation, increased mesangial cell numbers and infiltration of plasma cells. Immunofluorescence showed mesangial positivity for IgA and C3. Immunohistochemistry staining showed widespread IgG4 and increased CD38 and CD138 expression. Electron microscopy showed immune complexes located on the tubular basement membrane. He was diagnosed with IgAN and IgG4-TIN. He received glucocorticoids, leflunomide and tacrolimus to induce remission. He was given tacrolimus as long-term maintenance treatment. When tacrolimus was temporarily withdrawn, proteinuria recurred. After resuming tacrolimus therapy, he again entered complete remission. After 45 months of therapy, he remains in complete remission and the serum IgG4 level is normal. CONCLUSIONS The finding of concurrent IgAN and IgG4-TIN without abnormalities in renal function, imaging or extra-renal tissue is rare and their coexistence may be coincidental. Long-term treatment with tacrolimus proved effective and he has remained in remission during 45 months follow-up.
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Affiliation(s)
- Mi Tian
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao St, Shenyang, 110004, Liaoning, China
| | - Junjun Luan
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao St, Shenyang, 110004, Liaoning, China
| | - Congcong Jiao
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao St, Shenyang, 110004, Liaoning, China
| | - Qing Chang
- Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jeffrey B Kopp
- Renal Diagnostics and Therapeutics Unit, NIDDK/NIH, Bethesda, MD, USA
| | - Hua Zhou
- Department of Nephrology, Shengjing Hospital of China Medical University, 36 Sanhao St, Shenyang, 110004, Liaoning, China.
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Mizushima I, Kawano M. Renal Involvement in Retroperitoneal Fibrosis: Prevalence, Impact and Management Challenges. Int J Nephrol Renovasc Dis 2021; 14:279-289. [PMID: 34349543 PMCID: PMC8328390 DOI: 10.2147/ijnrd.s239160] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/23/2021] [Indexed: 01/01/2023] Open
Abstract
Retroperitoneal fibrosis (RPF) is a rare disorder consisting of idiopathic and various secondary forms and characterized by chronic inflammatory infiltrates and marked fibrosis in the retroperitoneal space. In idiopathic RPF (IRPF), 35–60% of cases have been reported to be IgG4-related RPF, the retroperitoneal lesions of IgG4-related disease (IgG4-RD). IRPF can frequently lead to renal insufficiency mediated by urinary tract obstruction and hydronephrosis irrespective of being IgG4-related or not. Clinical pictures, laboratory and imaging findings, and location of the urinary tract obstruction are generally similar in IgG4-related and non-IgG4-related IRPF although multiple organ involvement and serum IgG4 elevation may be characteristic of the IgG4-related forms. Periaortic/periarterial lesions are the most frequent cause of renal insufficiency. Although the response to glucocorticoids is generally good, relapse does occur in a considerable proportion of patients, and may require an additional immunosuppressive agent and/or urological intervention in cases with multiple relapses or refractory obstructive uropathy. In general, the prognosis of patients with IRPF is good, but careful attention needs to be paid to chronic kidney disease as a major complication and rupture of the affected aorta/artery as a life-threatening one. Further studies are necessary to better understand the pathogenesis of the disease and to establish the optimal diagnostic and therapeutic strategies for it.
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Affiliation(s)
- Ichiro Mizushima
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
| | - Mitsuhiro Kawano
- Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan
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Reyes JVM, Maldonado D, Stern AS, Brown M. A Case of IgG4-Related Kidney Disease Developing While on Steroid Treatment for Autoimmune IgG4 Pancreatitis. J Investig Med High Impact Case Rep 2021; 9:23247096211026500. [PMID: 34151624 PMCID: PMC8216373 DOI: 10.1177/23247096211026500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
IgG4 (immunoglobulin G4)-related systemic disease is an autoimmune process affecting multiple organ systems. This inflammatory process can present as but not limited to pancreatitis, cholangitis, or unspecified kidney disease. In this case, our patient developed IgG4-related kidney disease while already on a prolonged steroid course for IgG4-related pancreatitis. The patient ultimately had renal recovery after starting a higher dose of prednisone, but also developed steroid-related complications. This case further highlights the relationship between IgG4 diseases now termed IgG4-related systemic disease. This case brings to light the need for further investigative research into ideal steroid dosing, as well as steroid-sparing agents for IgG4-related systemic disease.
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Affiliation(s)
| | - Dawn Maldonado
- Icahn School of Medicine at Mount Sinai Hospital (Elmhurst Hospital Center), New York, NY, USA
| | - Aaron S Stern
- Icahn School of Medicine at Mount Sinai Hospital (Elmhurst Hospital Center), New York, NY, USA
| | - Maritza Brown
- Icahn School of Medicine at Mount Sinai Hospital (Elmhurst Hospital Center), New York, NY, USA
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