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Cervantes CE, Atta MG. Updates on HIV and Kidney Disease. Curr HIV/AIDS Rep 2023; 20:100-110. [PMID: 36695948 DOI: 10.1007/s11904-023-00645-1] [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] [Accepted: 10/17/2022] [Indexed: 01/26/2023]
Abstract
PURPOSE OF REVIEW With the advent of antiretroviral therapy, HIV infection has become a chronic disease in developed countries. RECENT FINDINGS Non-HIV-driven risk factors for kidney disease, such as APOL1 risk variants and other genetic and environmental factors, have been discovered and are better described. Consequently, the field of HIV-associated kidney disease has evolved with greater attention given to traditional risk factors of CKD and antiretroviral treatment's nephrotoxicity. In this review, we explore risk factors of HIV-associated kidney disease, diagnostic tools, kidney pathology in HIV-positive individuals, and antiretroviral therapy-associated nephrotoxicity.
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Affiliation(s)
- C Elena Cervantes
- Department of Medicine, Division of Nephrology, Johns Hopkins University, 1830 E. Monument Street, Suite 416, Baltimore, MD, 21218, USA
| | - Mohamed G Atta
- Department of Medicine, Division of Nephrology, Johns Hopkins University, 1830 E. Monument Street, Suite 416, Baltimore, MD, 21218, USA.
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Olabisi OA, Freedman BI. APOL1-associated kidney disease in northern Nigerians with treated HIV infection. Kidney Int 2021; 100:19-21. [PMID: 34154709 PMCID: PMC9827565 DOI: 10.1016/j.kint.2021.04.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/05/2021] [Accepted: 04/14/2021] [Indexed: 01/11/2023]
Abstract
Apolipoprotein L1 (APOL1) high-risk genotypes strongly associate with HIV-associated nephropathy, and antiretroviral therapy reduces the incidence of HIV-associated nephropathy and progression to end-stage kidney disease. Wudil et al. report cross-sectional APOL1 associations with proteinuria and estimated glomerular filtration rate in a northern Nigerian sample with HIV infection on antiretroviral therapy. Multiple ethnic groups with different APOL1 risk variant frequencies were included. Overall, APOL1 was associated with proteinuric chronic kidney disease; however, relationships with underlying causes of nephropathy and progression rates require further study.
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Affiliation(s)
- Opeyemi A Olabisi
- Department of Medicine, Division of Nephrology and Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Barry I Freedman
- Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
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Correa-Rotter R, Saldivar S, Soto LE, De Leon SP, Ojeda F, Ruiz-Palacios G, Pena JC. Recovery of HIV Antigen in Peritoneal Dialysis Fluid. Perit Dial Int 2020. [DOI: 10.1177/089686089001000118] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
We investigated the presence of HIV antigen in dialysis fluid of patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD), previously known to be infected with this virus. Sixteen adult patients and 6 adult volunteers were included in the study in 4 groups as follows: Group A: 3 patients on CAPD, previously known to be positive for serum HIV antibodies; Group B: 7 patients on CAPD, serum HIV negative; Group C: 6 AIDS patients without renal disease; and Group D: 6 healthy volunteers. Of the 3 patients of Group A, the HIV-1 Ag was positive in dialysis fluid in only 2. In 1, serum Ab and Ag were present, while in the others only serum Ab was detected. The samples from Group B were all negative for the viral antigen in dialysis fluid. We conclude that dialysis fluid of HIV-infected patients may contain the Ag and is therefore potentially infective. The presence of the HIV antigen was not constant, and was not related to antigenemia. It is possible that the presence of the Ag depends on local factors that influence viral replication or to alterations in the permeability of the peritoneal membrane. We discuss other possible factors that could influence the presence of viral Ag in peritoneal dialysis fluid.
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Affiliation(s)
- Ricardo Correa-Rotter
- Departments of Nephrology and Infectology of the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Sergio Saldivar
- Departments of Nephrology and Infectology of the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Luis E. Soto
- Departments of Nephrology and Infectology of the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Samuel Ponce De Leon
- Departments of Nephrology and Infectology of the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Francisco Ojeda
- Departments of Nephrology and Infectology of the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Guillermo Ruiz-Palacios
- Departments of Nephrology and Infectology of the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Jose Carlos Pena
- Departments of Nephrology and Infectology of the Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City, Mexico
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Abstract
Human immunodeficiency virus (HIV) infection continues to be a leading cause of morbidity and mortality. HIV-infected individuals are now surviving for a relatively longer period and this is because of easy accessibility to antiretroviral therapy these days. As a result, chronic disease-related complications are now being recognized more often. Kidney disease in HIV-infected children can vary from glomerular to tubular-interstitial involvement. We searched the database to identify various kidney diseases seen in HIV-infected children. We describe the epidemiology, pathogenesis, pathology, clinical and laboratory manifestations, management and outcome of commonly seen kidney disease in HIV-infected children. We also provide a brief overview of toxicity of antiretroviral drugs seen in HIV-infected children. Kidney involvement in HIV-infected children may arise because of HIV infection per se, opportunistic infections, immune mediated injury and drug toxicity. HIV-associated nephropathy is perhaps the most common and most severe form of kidney disease. Proteinuria may be a cost-effective screening test in the long-term management of HIV-infected children, however, there are no definite recommendations for the same. Other important renal diseases are HIV immune complex kidney disease, thrombotic microangiopathy, interstitial nephritis and vasculitis.
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Affiliation(s)
- Ankur Kumar Jindal
- a Department of Paediatrics, Allergy Immunology and Nephrology Unit , Advanced Paediatrics Centre, Postgraduate Institute of Medical Education and Research , Chandigarh , India
| | - Karalanglin Tiewsoh
- a Department of Paediatrics, Allergy Immunology and Nephrology Unit , Advanced Paediatrics Centre, Postgraduate Institute of Medical Education and Research , Chandigarh , India
| | - Rakesh Kumar Pilania
- a Department of Paediatrics, Allergy Immunology and Nephrology Unit , Advanced Paediatrics Centre, Postgraduate Institute of Medical Education and Research , Chandigarh , India
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Cisplatin-Induced Nephrotoxicity and HIV Associated Nephropathy: Mimickers of Myeloma-Like Cast Nephropathy. Case Rep Nephrol 2017; 2017:6258430. [PMID: 28770116 PMCID: PMC5523540 DOI: 10.1155/2017/6258430] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/23/2017] [Accepted: 05/30/2017] [Indexed: 12/03/2022] Open
Abstract
Myeloma cast nephropathy is an obstructing disorder of renal tubules, caused by precipitation of Bence Jones proteins. Myeloma-like cast nephropathy (MLCN) has been reported in the literature to occur in various primary renal and nonrenal diseases. We present a series of three rare cases of cast nephropathy, two of which are HIV patients, and the third patient is receiving cisplatin-based chemotherapy. However, in all three patients plasma cell dyscrasia has been ruled out. A 30-year-old male was admitted to the hospital with facial cellulitis. The second patient is a 31-year-old male who presented with Pneumocystis jiroveci pneumonia. The third patient was treated with cisplatin-based chemotherapy for carcinoma. First two cases revealed foci of diffuse tubular dilatation containing hyaline casts and interstitial inflammatory infiltrate, in addition to globally sclerotic glomeruli with ultrastructural foot process fusion and mesangium expansion. The third case showed acute tubular injury and cast formation of irregular casts composed of amorphous or granular material of low density admixed with scattered high electron-dense globules. Myeloma-like cast nephropathy and true myeloma cast nephropathy pose similar destructive effects on renal parenchyma. This new pattern of HIV-related nephropathy should be considered in HIV patients with MLCN, once monoclonal gammopathy is ruled out.
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Brief Report: APOL1 Renal Risk Variants Are Associated With Chronic Kidney Disease in Children and Youth With Perinatal HIV Infection. J Acquir Immune Defic Syndr 2017; 73:63-8. [PMID: 27035887 DOI: 10.1097/qai.0000000000001010] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2 to 10.0]. We report an unadjusted incidence of 1.2 CKD cases/100 person-years (95% CI: 0.5 to 2.5) in PHIV youth carrying APOL1 high-risk genotypes, with important implications for sub-Saharan Africa.
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Shabbal DM, Jamda MA, Dalhatu IT, Abdulrahman MB, Isichei C. Comparison of microalbuminuria among treatment naïve HIV sero-positive and negative adult clients in Faith Alive Foundation Hospital, Jos. Niger Med J 2014; 55:508-11. [PMID: 25538372 PMCID: PMC4262850 DOI: 10.4103/0300-1652.144711] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND This study is to determine microalbuminuria in human immunodeficiency virus (HIV) infected patients before commencement of highly active anti-retroviral treatment (HAART). PATIENTS AND METHODS Consecutive patients with the HIV infection seen in the HIV counselling and testing (HCT) unit of the Faith Alive Foundation Hospital, Jos, and a similar group of healthy uninfected patients were evaluated for renal disease: Urinary albumin and urinary creatinine were analysed. RESULTS Of the 200 patients with HIV infection and 100 uninfected controls studied, increased urinary albumin excretion (UAE) was present in 39 (19.5%) of the subjects and 5.0 (5.0%) of controls. The difference between the mean values for the UAE for both subjects and controls [182.3 ± 54.3 and 163.9 ± 39.3 mg/l, respectively (P = 0.006)] was statistically significant. On the other hand the urinary creatinine for both the subjects and controls [11.7 ± 5.2 and 12.0 ± 4.8 mmol/L, respectively (P = 0.6)] was not statistically significant. The difference between the mean urinary albumin/creatinine ratio (UACR) for both subjects and controls [1.8 ± 1.2 mg/mmol and 1.4 ± 0.4 mg/mmol respectively (P = 0.001)] was statistically significant. CONCLUSION/RECOMMENDATION Increase UAE is a common complication of HIV infection due to a number of factors other than HAART. Early screening for renal disease using microalbuminuria is very useful since the use of medications such as angiotensin converting enzyme inhibitors, which could help reverse progression to end-stage renal disease.
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Affiliation(s)
- Dalili Mohammed Shabbal
- Department of Chemical Pathology, University of Abuja Teaching Hospital, Gwagwalada Federal Capital Territory, Nigeria
| | - Mustapha Abubakar Jamda
- Department of Community Medicine, University of Abuja Teaching Hospital, Gwagwalada Federal Capital Territory, Nigeria
| | - Ibrahim Tijjani Dalhatu
- Department of Public Health, State House Clinic Abuja, Federal Capital Territory, Abuja, Nigeria
| | | | - Chris Isichei
- Department of Chemical Pathology, University of Jos, Plateau State, Nigeria
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Kidney disease in children and adolescents with perinatal HIV-1 infection. J Int AIDS Soc 2013; 16:18596. [PMID: 23782479 PMCID: PMC3687339 DOI: 10.7448/ias.16.1.18596] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 04/14/2013] [Accepted: 04/16/2013] [Indexed: 12/20/2022] Open
Abstract
Introduction Involvement of the kidney in children and adolescents with perinatal (HIV-1) infection can occur at any stage during the child's life with diverse diagnoses, ranging from acute kidney injury, childhood urinary tract infections (UTIs), electrolyte imbalances and drug-induced nephrotoxicity, to diseases of the glomerulus. The latter include various immune-mediated chronic kidney diseases (CKD) and HIV-associated nephropathy (HIVAN). Discussion The introduction of highly active anti-retroviral therapy (HAART) has dramatically reduced the incidence of HIVAN, once the commonest form of CKD in children of African descent living with HIV, and also altered its prognosis from eventual progression to end-stage kidney disease to one that is compatible with long-term survival. The impact of HAART on the outcome of other forms of kidney diseases seen in this population has not been as impressive. Increasingly important is nephrotoxicity secondary to the prolonged use of anti-retroviral agents, and the occurrence of co-morbid kidney disease unrelated to HIV infection or its treatment. Improved understanding of the molecular pathogenesis and genetics of kidney diseases associated with HIV will result in better screening, prevention and treatment efforts, as HIV specialists and nephrologists coordinate clinical care of these patients. Both haemodialysis (HD) and peritoneal dialysis (PD) are effective as renal replacement therapy in HIV-infected patients with end-stage kidney disease, with PD being preferred in resource-limited settings. Kidney transplantation, once contraindicated in this population, has now become the most effective renal replacement therapy, provided rigorous criteria are met. Given the attendant morbidity and mortality in HIV-infected children and adolescents with kidney disease, routine screening for kidney disease is recommended where resources permit. Conclusions This review focuses on the pathogenesis and genetics, clinical presentation and management of kidney disease in children and adolescents with perinatal HIV-1 infection.
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Purswani M, Patel K, Kopp JB, Seage GR, Chernoff MC, Hazra R, Siberry GK, Mofenson LM, Scott GB, Van Dyke RB. Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection. Pediatr Infect Dis J 2013; 32:495-500. [PMID: 23249917 PMCID: PMC3800277 DOI: 10.1097/inf.0b013e31827f4eff] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Tenofovir is associated with renal proximal tubule injury. Such toxicity has not been extensively studied in HIV-1-infected children, in whom tenofovir is increasingly used. METHODS History, urine and blood were collected at regular intervals from 448 children and adolescents with perinatal HIV-1 infection followed in the Pediatric HIV/AIDS Cohort study. Relationships between tenofovir use and proteinuria and chronic kidney disease (CKD) outcomes were examined using multivariable logistic regression models. Proteinuria was defined as at least one urine protein/creatinine ratio (uPCR) ≥ 0.2, and CKD as ≥ 2 sequential uPCR ≥ 0.2 or estimated glomerular filtration rates <60 mL/min/1.73 m with no subsequent resolution, or a clinical diagnosis not contradicted by a normal uPCR. Subjects with ≥ 2 uPCR <0.2, and no abnormal uPCR and eGFR comprised the comparison group. RESULTS Subjects were 47% male, 72% black, 24% Hispanic, with entry mean age (± standard deviation) of 11.5 ± 2.5 years. Proteinuria prevalence at entry, and annually during 3 years, ranged from 10.3% to 13.7%. The cumulative prevalence of proteinuria was 22% (94/434, 95% confidence interval: 18%-26%) and CKD 4.5% (20/448, 95% confidence interval: 2.7%-6.8%). Duration of tenofovir use was an independent predictor of proteinuria, with >3 years of exposure having the highest risk compared with no exposure (odds ratio: 2.53, 95% confidence interval: 1.23-5.22, overall P = 0.01). Overall, duration of tenofovir use did not significantly predict the presence of CKD. CONCLUSIONS Rates of proteinuria and CKD were lower than those seen in the pre-highly active antiretroviral therapy era. However, prolonged exposure to tenofovir increases risk of renal injury.
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Affiliation(s)
- Murli Purswani
- Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY 10457, USA.
| | - Kunjal Patel
- Department of Epidemiology, Harvard School of Public Health, Boston, MA,Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA
| | | | - George R. Seage
- Department of Epidemiology, Harvard School of Public Health, Boston, MA,Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA
| | - Miriam C. Chernoff
- Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA
| | - Rohan Hazra
- Pediatric Adolescent Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD
| | - George K. Siberry
- Pediatric Adolescent Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD
| | - Lynne M. Mofenson
- Pediatric Adolescent Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD
| | - Gwendolyn B. Scott
- Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL
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Giacomet V, Erba P, Di Nello F, Coletto S, Viganò A, Zuccotti G. Proteinuria in paediatric patients with human immunodeficiency virus infection. World J Clin Cases 2013; 1:13-18. [PMID: 24303454 PMCID: PMC3845933 DOI: 10.12998/wjcc.v1.i1.13] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 03/15/2013] [Indexed: 02/05/2023] Open
Abstract
In human immunodeficiency virus (HIV)-infected people kidney disease is as an important cause of morbidity and mortality. Clinical features of kidney damage in HIV-infected patients range from asymptomatic microalbuminuria to nephrotic syndrome. The lack of specific clinical features despite the presence of heavy proteinuria may mask the renal involvement. Indeed, it is important in HIV patients to monitor renal function to early discover a possible kidney injury. After the introduction of antiretroviral therapy, mortality and morbidity associated to HIV-infection have shown a substantial reduction, although a variety of side effects for long-term use of highly active antiretroviral therapy, including renal toxicity, has emerged. Among more than 20 currently available antiretroviral agents, many of them can occasionally cause reversible or irreversible nephrotoxicity. At now, three antiretroviral agents, i.e., indinavir, atazanavir and tenofovir disoproxil fumarate have a well established association with direct nephrotoxicity. This review focuses on major causes of proteinuria and other pathological findings related to kidney disease in HIV-infected children and adolescents.
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Vali PS, Ismal K, Gowrishankar S, Sahay M. Renal disease in human immunodeficiency virus - Not just HIV-associated nephropathy. Indian J Nephrol 2012; 22:98-102. [PMID: 22787310 PMCID: PMC3391831 DOI: 10.4103/0971-4065.97117] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
The aim of the study was to determine the various histopathological lesions in human immunodeficiency virus (HIV) patients with renal dysfunction and to establish clinicopathological correlation. Over a period of two years from January 2008 to March 2010, 27 HIV positive patients with renal dysfunction were subjected to renal biopsy. Of the 27 patients, 23 were males and four were females (85.2% males, 14.8% females). Mean age was 38.2 ± 10.36 (range 20 – 60) years. The probable mode of acquisition of HIV infection was sexual in 22 patients (81.5%). Thirteen patients (48%) had nephrotic proteinuria. The CD4 count ranged from 77 to 633/microliter. The kidneys were of normal size in 19 (70.4%) and bulky in eight (29.6%) patients. Thirteen patients required renal replacement therapy. Eleven patients had acute tubule-interstitial lesions (40.7%) while 15 (55.5%) had glomerular lesions. The various glomerular lesions were, focal segmental glomerulosclerosis in five, amyloidosis in three, diffuse proliferative GN in two, and membranoproliferative glomerulonephritis (GN), membranous GN, minimal change disease, diabetic nephropathy, crescentic GN, and thrombotic microangiopathy were seen in one each. None of the clinical or laboratory variables, except hypertension, was found to predict glomerular versus non-glomerular lesions on biopsy. In conclusion we show that a variety of glomerular and tubulointerstitial lesions can be seen on renal histology. Hence, renal biopsy is indicated in renal dysfunction associated with HIV for making proper diagnosis and therapy.
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Affiliation(s)
- P S Vali
- Department of Nephrology, Osmania General Hospital, Hyderabad, India
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Chronic kidney disease associated with perinatal HIV infection in children and adolescents. Pediatr Nephrol 2012; 27:981-9. [PMID: 22366874 PMCID: PMC3715373 DOI: 10.1007/s00467-011-2097-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2011] [Revised: 12/01/2011] [Accepted: 12/02/2011] [Indexed: 12/20/2022]
Abstract
BACKGROUND This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. METHODS Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. RESULTS Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. CONCLUSIONS A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.
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Abstract
HIV-1 associated nephropathy (HIVAN) is a clinical and renal histological disease characterized by the presence of heavy proteinuria associated with focal segmental glomerulosclerosis and microcystic tubular dilatation. These renal lesions lead to renal enlargement and rapid progression to kidney failure. People from African ancestry show a unique susceptibility to develop HIVAN. The study by Wearne and colleagues, which includes the largest group of patients of African ancestry with HIVAN studied so far, describes a novel renal histological variant of HIVAN, and suggests that antiretroviral therapies improve the clinical outcome of all HIV-associated renal diseases. These findings, when interpreted in the context of recent advances in our understanding of the molecular pathogenesis and genetics of HIVAN, will facilitate the recognition of all clinical variants of HIVAN as well the planning of better screening, prevention, and treatment programs for all HIV nephropathies.
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Ramsuran D, Bhimma R, Ramdial PK, Naicker E, Adhikari M, Deonarain J, Sing Y, Naicker T. The spectrum of HIV-related nephropathy in children. Pediatr Nephrol 2012; 27:821-7. [PMID: 22205506 DOI: 10.1007/s00467-011-2074-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2011] [Revised: 11/11/2011] [Accepted: 11/15/2011] [Indexed: 11/26/2022]
Abstract
BACKGROUND Despite the burden of human immunodeficiency virus (HIV) disease in Southern Africa, there have been few reports of HIV-related nephropathy in children. This study outlines the spectrum of HIV-1-related kidney diseases of children in KwaZulu-Natal, South Africa. METHODS A review of the clinical presentation, laboratory and histopathological findings of children diagnosed with HIV-related nephropathy. RESULTS Forty-nine out of 71 children (1-16 years old) with HIV-1 related nephropathy underwent kidney biopsy. The most common histopathological finding was focal segmental glomerulosclerosis (FSGS), which was present in 32 (65.3%) children; 13 (26.5%) having collapsing glomerulopathy and 19 (38.8%) classic FSGS. The majority of patients showed haematological (86.4%) and electrolyte abnormalities (69.4%). Renal impairment was present in 41% of patients on initial presentation. However, end-stage kidney disease was present in only 4% of these patients. All patients were treated with highly active anti-retroviral therapy (HAART), the majority (79.6%) showed decreased proteinuria with 38.8% having complete remission. CONCLUSIONS This study, one of the largest series of children reported from Africa, demonstrates that nephrotic syndrome due to HIV-associated nephropathy (HIVAN) is the commonest presentation of HIV-related nephropathy in childhood. Highly active anti-retroviral therapy in combination with angiotensin-converting enzyme antagonists is highly effective in decreasing proteinuria and preserving renal function.
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Affiliation(s)
- Duran Ramsuran
- Optics and Imaging Centre, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, KwaZulu-Natal, South Africa
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Ekulu PM, Nseka NM, Aloni MN, Gini JLE, Makulo JR, Lepira FB, Sumaili EK, Mafuta EM, Nsibu CN, Shiku JD. [Prevalence of proteinuria and its association with HIV/AIDS in Congolese children living in Kinshasa, Democratic Republic of Congo]. Nephrol Ther 2011; 8:163-7. [PMID: 22056079 DOI: 10.1016/j.nephro.2011.09.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2011] [Revised: 09/24/2011] [Accepted: 09/26/2011] [Indexed: 01/17/2023]
Abstract
CONTEXT In Sub-Saharian Africa, the extent of the HIV-related kidney diseases is less known. Even so, that region is supposed to be the epicentre of such complications. This study aimed to determine the prevalence of proteinuria in Congolese children living in Kinshasa and to study its association with the HIV infection. METHODS By a cross-sectional and multicentric study (in six hospitals of Kinshasa), 194 children were consecutively recruited from August 2008 to February 2009. Among these, 101 naives HIV-infected children and 93 HIV-uninfected children like a control group. Proteinuria was assessed using urine dipstick completed by the 24-hour proteinuria assessment (Esbach method). Determinants of proteinuria were assessed by logistic regression. RESULTS The median age of all children recruited was 84 months (9-221 months). Concerning the HIV-infected children, the median age was 76 months (9-221 months) with a male/female ratio of 1/1. The prevalence of proteinuria in this group was in order to 23.8%. HIV infected children have seven times more probability to present proteinuria than non infected children (OR 6.9; IC 95%: 2.3-20.8; P<0.001). Important immunosuppression was the main determinant of proteinuria (OR 10.4; IC 95%: 3.34-32.48; P<0.001). CONCLUSION Proteinuria is common in Congolese children. The HIV infection rises significantly the probability to present proteinuria in children of this study, more so among those with important immunosuppression. This raises the question about the ideal time to initiate HAART in order to reduce the prevalence of kidney injury and to provide the best outcome.
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Affiliation(s)
- Pépé Mfutu Ekulu
- Unité de néphrologie, département de pédiatrie, cliniques universitaires de Kinshasa, Kinshasa, République démocratique du Congo.
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Abstract
A wide clinical spectrum of renal diseases affects individuals with HIV. These conditions include acute kidney injury, electrolyte and acid-base disturbances, HIV-associated glomerular disease, acute-on-chronic renal disease and adverse side effects related to treatment of HIV. Studies employing varying criteria for diagnosis of kidney disease have reported a variable prevalence of these diseases in patients with HIV in sub-Saharan Africa: 6% in South Africa, 38% in Nigeria, 26% in Côte d'Ivoire, 28% in Tanzania, 25% in Kenya, 20-48.5% in Uganda and 33.5% in Zambia. Results from these studies also suggest that a broader spectrum of histopathological lesions in HIV-associated kidney disease exists in African populations than previously thought. Strategies to prevent or retard progression to end-stage renal disease of HIV-associated kidney conditions should include urinalysis and measurement of kidney function of all people with HIV at presentation. Renal replacement in the form of dialysis and transplantation should be implemented as appropriate. This Review focuses on the available evidence of renal diseases in patients with HIV infection in sub-Saharan Africa and offers practical guidelines to treat these conditions that also take into consideration challenges and obstacles that are specific to sub-Saharan Africa.
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Abstract
Before the era of highly active antiretroviral therapy, more than 40% of human immunodeficiency virus (HIV)-infected children experienced renal complications. In sub-Saharan Africa, approximately 2.1 million children are infected with HIV-1. In the absence of antiretroviral therapy, young African children frequently died of AIDS-related complications before renal diseases could be manifested or diagnosed. As antiretroviral therapy has become more available, and their survival has increased, our experience in treating kidney disease in HIV-infected children has improved. This article discusses relevant clinical and pathologic findings related to kidney disease in HIV-infected children.
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Wyatt CM, Morgello S, Katz-Malamed R, Wei C, Klotman ME, Klotman PE, D'Agati VD. The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy. Kidney Int 2008; 75:428-34. [PMID: 19052538 DOI: 10.1038/ki.2008.604] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications.
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Affiliation(s)
- Christina M Wyatt
- Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
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Symeonidou C, Standish R, Sahdev A, Katz RD, Morlese J, Malhotra A. Imaging and Histopathologic Features of HIV-related Renal Disease. Radiographics 2008; 28:1339-54. [DOI: 10.1148/rg.285075126] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Fine DM, Perazella MA, Lucas GM, Atta MG. Renal disease in patients with HIV infection: epidemiology, pathogenesis and management. Drugs 2008; 68:963-80. [PMID: 18457462 DOI: 10.2165/00003495-200868070-00006] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
With the introduction of highly active antiretroviral therapy, we have witnessed prolonged survival with the potential for normal life expectancy in HIV-infected individuals. With improved survival and increasing age, HIV-infected patients are increasingly likely to experience co-morbidities that affect the general population, including kidney disease. Although HIV-associated nephropathy, the most ominous kidney disease related to the direct effects of HIV, may be prevented and treated with antiretrovirals, kidney disease remains an important issue in this population. In addition to the common risk factors for kidney disease of diabetes mellitus and hypertension, HIV-infected individuals have a high prevalence of other risk factors, including hepatitis C, cigarette smoking and injection drug use. Furthermore, they have exposures unique to this population, including antiretrovirals and other medications. Therefore, the differential diagnosis is vast. Early identification (through efficient screening) and definitive diagnosis (by kidney biopsy when indicated) of kidney disease in HIV-infected individuals are critical to optimal management. Earlier interventions with disease-specific therapy, often with the help of a nephrologist, are likely to lead to better outcomes. In those with chronic kidney disease, interventions, such as aggressive blood pressure control with the use of ACE inhibitors or angiotensin receptor antagonists where tolerated, tight blood glucose control in those with diabetes, and avoidance of potentially nephrotoxic medications, can slow progression and prevent end-stage renal disease. Only with greater awareness of kidney-disease manifestations and their implications in this particularly vulnerable population will we be able to achieve success in confronting this growing problem.
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Affiliation(s)
- Derek M Fine
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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Chaparro AI, Mitchell CD, Abitbol CL, Wilkinson JD, Baldarrago G, Lopez E, Zilleruelo G. Proteinuria in children infected with the human immunodeficiency virus. J Pediatr 2008; 152:844-9. [PMID: 18492529 DOI: 10.1016/j.jpeds.2007.11.007] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2007] [Revised: 09/11/2007] [Accepted: 11/05/2007] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To determine the prevalence of proteinuria in a large cohort of children infected with the human immunodeficiency virus (HIV) and their longitudinal progression during treatment with highly active antiretroviral therapy. STUDY DESIGN In a retrospective cohort study, 286 children infected with HIV were monitored with quantitative assays of proteinuria from January 1998 through January 2007, with monitoring of viral load, lymphocyte profiles, kidney function, and mortality rates. Proteinuria was quantitated by urine protein to creatinine ratio (Upr/cr). RESULTS Ninety-four (33%) had proteinuria at baseline. Of these, 32 (11.2%) had nephrotic range proteinuria (Upr/cr > or = 1.0). Initial screening was at 11 +/- 0.3 years of age, with an average follow-up of 5.6 +/- 0.1 years. The mortality rate was significantly greater in those with proteinuria. During the period of observation, 15 patients with nephrotic proteinuria died or had development of end-stage renal disease, and 16 showed improvement. Of those with intermediate range proteinuria (Upr/cr > or = 0.2 < 1.0), 3 progressed to nephrotic range proteinuria, and 39 (63%) showed resolution of the proteinuria (Upr/cr < 0.2). Improvement in proteinuria was correlated with decreasing viral load (r = 0.5; P < .01). CONCLUSIONS Control of viral load with highly active antiretroviral therapy appears to prevent the progression of HIV-associated renal disease and improve survival rates in infected children.
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Affiliation(s)
- Aida I Chaparro
- Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, University of Miami, Miami, FL, USA
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Gonzalez C, Ariceta G, Langman CB, Zibaoui P, Escalona L, Dominguez LF, Rosas MA. Hypercalciuria is the main renal abnormality finding in Human Immunodeficiency Virus-infected children in Venezuela. Eur J Pediatr 2008; 167:509-15. [PMID: 17593389 DOI: 10.1007/s00431-007-0538-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2007] [Accepted: 05/30/2007] [Indexed: 11/25/2022]
Abstract
Kidney involvement in children with Human Immunodeficiency Virus (HIV) infection is increasing in prevalence in parallel with the longer survival of HIV-infected patients and the side-effects of new antiretroviral drugs. However, there are only a few reports describing renal tubular disorders in HIV+ children. This is a cross-sectional, case series study evaluating kidney disease in 26 Venezuelan HIV-infected children. The study cohort consisted of 15 girls and 11 boys, with a median age of 5.9 years (25-75th percentile: 3.6-7.8), who had been treated with antiretrovirals for 2.8 +/- 0.4 years, Overall, the patients were short for their age and gender (Z-height: -3.1; 25-75th percentile: -4.94 to -1.98), and 15 showed signs of mild to moderate malnutrition. All of the children had a normal estimated glomerular filtration rate (136 +/- 22.6 ml/min/1.73 m2), and glomerular involvement was only observed in one patient with isolated proteinuria. None had nephromegaly. In contrast, tubular disorders were commonly found. Hypercalciuria was detected in 16 of the patients (UCa/Cr = 0.28; 25-75th percentile: 0.17-0.54 mg/mg), with five of these showing crystalluria. Eight children showed hyperchloremia, and three had frank metabolic acidosis. Kidney stones were absent in all, but one boy had bilateral medullary nephrocalcinosis. Conclusion, in Venezuelan children, HIV infection per se, or its specific treatment, was commonly associated with renal tubular dysfunction, especially hypercalciuria and acidosis, potentially leading to nephrocalcinosis and growth impairment. We recommend renal tubular evaluation during the follow-up of children with HIV infection.
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Affiliation(s)
- Corina Gonzalez
- Department of Pediatric Infectology, Hospital Doctor Enrique Tejera, University of Carabobo, Valencia, Venezuela
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23
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Ramezani A, Mohraz M, Banifazl M, Jam S, Gachkar L, Yaghmaie F, Eslamifar A, Zadsar M, Kalantar N, Nemati K, Haghighi M, Rezaie M, Aghakhani A. Frequency and associated factors of proteinuria in Iranian HIV-positive patients. Int J Infect Dis 2008; 12:490-4. [PMID: 18394943 DOI: 10.1016/j.ijid.2008.01.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2007] [Revised: 12/24/2007] [Accepted: 01/15/2008] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Screening HIV-positive patients for proteinuria would result in early recognition of HIV-associated nephropathy (HIVAN). This would allow diagnosis and treatment of HIVAN at an early stage and hence prevent further disease progression. This study was undertaken to determine the frequency of proteinuria and its associated factors in Iranian HIV-positive patients. METHODS In this study, 171 HIV-positive patients were screened for proteinuria. Proteinuria was defined as > or =1+ protein on the urine dipstick. A questionnaire was used to collect patient sociodemographic and clinical data. Hepatitis B surface antigen (HBsAg), hepatitis C antibody (anti-HCV), serum albumin, and creatinine were tested in all patients. CD4 counts were obtained by flow cytometry. RESULTS Out of 171 HIV-positive patients, 21 (12.3%) had proteinuria. There were no significant differences between patients with and without proteinuria with regard to age, sex, risk behaviors for HIV acquisition, stage of infection, concurrent antiretroviral therapy, systolic and diastolic blood pressure, serum albumin and creatinine, glomerular filtration rate (GFR), and presence of anti-HCV or HBsAg. Patients with proteinuria had a lower CD4 count and creatinine clearance than those without proteinuria. CONCLUSION Proteinuria was relatively high in Iranian HIV-positive patients. The group at higher risk was that of patients with lower CD4 counts and creatinine clearance.
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Affiliation(s)
- Amitis Ramezani
- Clinical Research Department, Pasteur Institute of Iran, No. 69, Pasteur Ave., Tehran, Iran
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25
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26
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Jaffe JA, Kimmel PL. Chronic nephropathies of cocaine and heroin abuse: a critical review. Clin J Am Soc Nephrol 2006; 1:655-67. [PMID: 17699270 DOI: 10.2215/cjn.00300106] [Citation(s) in RCA: 97] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Renal disease in cocaine and heroin users is associated with the nephrotic syndrome, acute glomerulonephritis, amyloidosis, interstitial nephritis, and rhabdomyolysis. The pathophysiologic basis of cocaine-related renal injury involves renal hemodynamic changes, glomerular matrix synthesis and degradation, and oxidative stress and induction of renal atherogenesis. Heroin is the most commonly abused opiate in the United States. Previous studies identified a spectrum of renal diseases in heroin users. The predominant renal lesion in black heroin users is focal segmental glomerulosclerosis and in white heroin users is membranoproliferative glomerulonephritis. Although the prevalence of heroin use in the United States has increased, the incidence of "heroin nephropathy" has declined. Because reports of heroin nephropathy predated the surveillance of hepatitis C virus and HIV, the varied findings might be related to the spectrum of viral illnesses that are encountered in injection drug users. Socioeconomic conditions, cultural and behavioral practices, or differences in genetic susceptibilities may be more associated with the development of nephropathy in heroin users than the drug's pharmacologic properties. Administration of cocaine in animal models results in nonspecific glomerular, interstitial, and tubular cell lesions, but there is no animal model of heroin-associated renal disease. The heterogeneity of responses that are associated with heroin is not consistent with a single or simple notion of nephropathogenesis. There are no well-designed, prospective, epidemiologic studies to assess the incidence and the prevalence of renal disease in populations of opiate users and to establish the validity of a syndrome such as heroin nephropathy. It is concluded although there is a paucity of evidence to support a heroin-associated nephropathy, the evidence from in vitro cellular and animal studies to support the existence of cocaine-induced renal changes is more convincing.
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Affiliation(s)
- Jared A Jaffe
- Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA
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Han TM, Naicker S, Ramdial PK, Assounga AG. A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa. Kidney Int 2006; 69:2243-50. [PMID: 16672914 DOI: 10.1038/sj.ki.5000339] [Citation(s) in RCA: 165] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the most common finding on renal biopsy in HIV-infected black patients and is also the commonest cause of end-stage renal disease in these patients. Early detection of HIVAN may be beneficial in evaluating early treatment. This study examined the pattern of renal diseases in HIV-infected South Africans and also attempted to diagnose HIVAN at an early stage. In this single-center cross-sectional study, 615 HIV-infected patients were screened for proteinuria. Thirty patients with varying degrees of proteinuria underwent renal biopsy. Patients with diabetes mellitus, uncontrolled hypertension, known causes of chronic kidney disease, and serum creatinine above 250 mumol/l were excluded. Patients in this study were not on antiretroviral therapy. HIVAN was found in 25 (83%) patients. Six of them (24%) had microalbuminuria. Altogether, seven patients with persistent microalbuminuria were biopsied and six (86%) showed HIVAN. Other biopsy findings included membranoproliferative nephropathy in two (7%) and interstitial nephritis in three (10%). Four patients with HIVAN had associated membranous nephropathy. HIVAN is the commonest biopsy finding among our study patients with HIV infection who present with varying degrees of proteinuria. Microalbuminuria is a manifestation of HIVAN in our study patients. Therefore, microalbuminuria may be an early marker of HIVAN, and screening for its presence may be beneficial. Renal biopsy may be considered in seropositive patients who present with persistent microalbuminuria, especially with low CD4 counts irrespective of good renal function. This will allow diagnosis and treatment of HIVAN at an early stage and may prevent further disease progression.
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Affiliation(s)
- T M Han
- Department of Nephrology, Division of Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
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28
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Behar DM, Shlush LI, Maor C, Lorber M, Skorecki K. Absence of HIV-associated nephropathy in Ethiopians. Am J Kidney Dis 2006; 47:88-94. [PMID: 16377389 DOI: 10.1053/j.ajkd.2005.09.023] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2005] [Accepted: 09/20/2005] [Indexed: 01/14/2023]
Abstract
BACKGROUND Population-based epidemiological surveys in several countries have shown approximately 10- to 15-fold increased susceptibility to human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) for populations of recent African ancestry. Accordingly, we sought to determine whether a similar or different pattern of susceptibility was evident among Ethiopians followed up in an HIV clinic in Israel. METHODS One hundred seventy-six consecutive patients (126 Ethiopians, 50 non-Ethiopian Israelis) followed up at the HIV clinic of Rambam Medical Center in northern Israel were examined for the presence of proteinuria and/or decreased glomerular filtration rate. HIV viral load, CD4 count, and treatment modality also were determined. RESULTS Overall, 73% of patients were treated with highly active antiretroviral therapy, and there was no difference between Ethiopians and non-Ethiopian Israelis in this regard. Mean CD4 count in Ethiopians was 288 +/- 140/microL, significantly less than the corresponding CD4 count of 398 +/- 190/microL for non-Ethiopian Israelis. Mean viral loads were greater in Ethiopians compared with non-Ethiopian Israelis. None of 176 HIV-infected patients fulfilled clinical criteria for HIVAN as delineated in this study. CONCLUSION HIV-infected individuals of Ethiopian descent have a level of susceptibility to HIVAN similar to that of non-Ethiopian Israelis, which is strikingly less than that reported for other populations for recent African ancestry. This does not appear to be attributable to differences in HIV infection control or viral subtype and most likely represents population-based differences in host genetic factors. This finding emphasizes the importance of avoiding generalizations with respect to phylogeographic ancestry in disease-susceptibility studies.
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Affiliation(s)
- Doron M Behar
- Department of Critical Care Medicine, The Bruce Rappaport Faculty of Medicine and Research Institute, Haifa, Israel
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Atta MG, Choi MJ, Longenecker JC, Haymart M, Wu J, Nagajothi N, Racusen LC, Scheel PJ, Brancati FL, Fine DM. Nephrotic range proteinuria and CD4 count as noninvasive indicators of HIV-associated nephropathy. Am J Med 2005; 118:1288. [PMID: 16271919 DOI: 10.1016/j.amjmed.2005.05.027] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2004] [Accepted: 05/03/2005] [Indexed: 12/23/2022]
Abstract
PURPOSE Human immunodeficiency virus (HIV)-associated nephropathy is a common and serious cause of progressive renal insufficiency in patients with HIV, frequently presenting with nephrotic range proteinuria. The purpose of this study is to document the histopathologic diagnoses seen in HIV-positive patients with and without nephrotic range proteinuria and to evaluate the predictive value of both nephrotic range proteinuria and CD4 count in diagnosing HIV-associated nephropathy. METHODS We performed a cross-sectional, single-center study of all 107 HIV-positive patients who had both a renal biopsy and urine protein measurement between 1995 and 2002. Nephrotic range proteinuria was defined as a urine protein-to-creatinine ratio > 3 or a 24-hour urine protein > 3 g. Clinical and laboratory characteristics of those patients with and without HIV-associated nephropathy were compared. Sensitivity, specificity, and positive and negative predictive values of nephrotic range proteinuria in the diagnosis of HIV-associated nephropathy were determined. RESULTS Fifty-five biopsied patients had nephrotic range proteinuria, among whom 29 (53%) were diagnosed with HIV-associated nephropathy. Among the remaining patients, 12 had non-HIV-associated nephropathy focal segmental glomeruloscerlosis, 3 had membranoproliferative glomerulonephritis, 2 had AA Amyloid, 2 had diabetic nephropathy, and 7 had other diagnoses. Sensitivity, specificity, and positive and negative predictive values of nephrotic proteinuria in the diagnosis of HIV-associated nephropathy were 73%, 61%, 53%, and 79%, respectively. The patients with HIV-associated nephropathy had a significantly higher creatinine (8.2 mg/dL vs 2.5 mg/dL, P < .001) and a lower CD4 count (158 count/mm3 vs 349 count/mm3, P < .01) at the time of biopsy. Although significantly more patients with HIV-associated nephropathy had a CD4 count below 200 (P = .03), among those with a CD4 count below 200, 10 of 30 patients (33%) had diagnoses other than HIV-associated nephropathy. Injection drug use, presence of hepatitis C, and hypertension were not associated with HIV-associated nephropathy. CONCLUSION Our results suggest that HIV patients with nephrotic range proteinuria warrant a kidney biopsy because the presence of nephrotic range proteinuria, even in the presence a low CD4 count, does not establish the diagnosis of HIV-associated nephropathy.
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Affiliation(s)
- Mohamed G Atta
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA.
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Kumar MSA, Sierka DR, Damask AM, Fyfe B, McAlack RF, Heifets M, Moritz MJ, Alvarez D, Kumar A. Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients. Kidney Int 2005; 67:1622-9. [PMID: 15780120 DOI: 10.1111/j.1523-1755.2005.00245.x] [Citation(s) in RCA: 180] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Human immunodeficiency virus-associated nephropathy (HIVAN) has become the third leading cause of end-stage renal disease (ESRD) in African Americans, and is expected to grow exponentially. Highly active antiretroviral therapy (HAART) has significantly prolonged the survival of patients with HIV infection. Despite the growing number of HIV-positive dialysis patients with prolonged life expectancy, kidney transplantation with immunosuppression has been declined because it is considered a waste of scarce donor kidneys due to potential increases in morbidity and mortality. METHODS The institutional review board of Drexel University College of Medicine and Hahnemann University Hospital approved this prospective study. The aim was to find out safety and success of kidney transplantation, and the effect of immunosuppression on HIV infection. Forty HIV-positive dialysis patients received kidney transplantation between February 2001 and January 2004. Patient inclusion criteria were maintenance of HAART, plasma HIV-1 RNA of <400 copies/mL, absolute CD4 counts of 200 cells/muL or more. Immunosuppression was basiliximab induction and maintenance with cyclosporine, sirolimus, and steroids. HAART was continued post-transplant. Acute rejections were diagnosed by biopsy and treated with methylprednisolone. Surveillance biopsies were completed at 1, 6, 12, and 24 months, and evaluated for subclinical acute rejection, chronic allograft nephropathy, and HIVAN. RESULTS One- and 2-year actuarial patient survival was 85% and 82%, respectively, and graft survival was 75% and 71%, respectively. Plasma HIV-1 RNA remained undetectable, and CD4 counts remained in excess of 400 cells per muL with no evidence of AIDS for up to 2 years. CONCLUSION One- and 2-year graft survival is comparable to other high-risk populations receiving kidney transplantation. One- and 2-year patient survival is higher than HIV patients maintained on dialysis. Immunosuppression does not adversely affect HIV recipients maintained on HAART in the short term.
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Affiliation(s)
- Mysore S Anil Kumar
- Department of Surgery/Transplantation, Drexel University College of Medicine and Hahnemann University Hospital, Philadelphia, PA 19102, USA.
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Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, Tashima KT, Roland M, Franceschini N, Palella FJ, Lennox JL, Klotman PE, Nachman SA, Hall SD, Szczech LA. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005; 40:1559-85. [PMID: 15889353 DOI: 10.1086/430257] [Citation(s) in RCA: 399] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2005] [Accepted: 03/07/2005] [Indexed: 01/06/2023] Open
Affiliation(s)
- Samir K Gupta
- Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
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Ray PE, Xu L, Rakusan T, Liu XH. A 20-year history of childhood HIV-associated nephropathy. Pediatr Nephrol 2004; 19:1075-92. [PMID: 15300477 DOI: 10.1007/s00467-004-1558-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2004] [Revised: 05/13/2004] [Accepted: 05/24/2004] [Indexed: 12/16/2022]
Abstract
In 1984, physicians in New York and Miami reported HIV-infected adult patients with heavy proteinuria and rapid progression to end-stage renal disease. These patients showed large edematous kidneys with a combination of focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions. This renal syndrome, named HIV-associated nephropathy (HIVAN), was found predominantly in African Americans. Subsequent studies confirmed the presence of HIVAN in children, who frequently develop nephrotic syndrome in association with FSGS and/or mesangial hyperplasia with microcystic tubular dilatation. Since then, substantial progress has been made in our understanding of the etiology and pathogenesis of HIVAN. This article reviews 20 years of research into the pathogenesis of HIVAN and discusses how these concepts could be applied to the treatment of children with HIVAN. HIV-1 infection plays a direct role in the pathogenesis of childhood HIVAN, at least partially by affecting the growth and differentiation of glomerular and tubular epithelial cells and enhancing the renal recruitment of infiltrating mononuclear cells and cytokines. An up-regulation of renal heparan sulfate proteoglycans seems to play a relevant role in this process, by increasing the recruitment of heparin-binding growth factors (i.e., FGF-2), chemokines, HIV-infected cells, and viral proteins (i.e., gp120, Tat). These changes enhance the infectivity of HIV-1 in the kidney and induce injury and proliferation of intrinsic renal cells. Highly active anti-retroviral therapy (HAART) appears to be the most promising treatment to prevent the progression of childhood HIVAN. Hopefully, in the near future, better education, prevention, and treatment programs will lead to the eradication of this fatal childhood disease.
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Affiliation(s)
- Patricio E Ray
- Division of Nephrology, Children's National Medical Center, Washington, DC 20010, USA.
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Giner V, Esteban MJ, Fernández C, Galindo MJ, Oltra MR, Oliver V, Rodríguez JC, Forner MJ, Alcácer F, Guix J, Redón J, Monteagudo C. [Renal involvement in the human immunodeficiency virus infection]. Med Clin (Barc) 2004; 122:601-4. [PMID: 15142506 DOI: 10.1016/s0025-7753(04)74325-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE Although renal pathologies are becoming an emergent problem in the population infected by the human immunodeficiency virus (HIV), there is very scarce information about the natural course of this problem. The objective of the present study is to describe renal lesions in an autopsy series of HIV-infected patients never treated with antiretroviral therapies. PATIENTS AND METHOD Autopsy information has been retrospectively retrieved from 61 HIV-infected subjects (mean age, 36,9 [8,4] years; 58,6% drug abusers, 84% males) died in our hospital between 1984 and 1997. None of the patients received antiretroviral therapy. All autopsy and clinical reports were considered, as well as basic analytical parameters about renal function. Renal autopsy samples were specifically reviewed. RESULTS At the time of the last admission, 9.8% of patients had renal insufficiency, who made up 44.3% of patients having renal insufficiency anytime. Infections were the main cause of death (76%). The majority of patients (93.4%) showed histopathological renal abnormalities, which were highly heterogeneous. Renal lesions were mainly located on the tubules (96.7%) and the interstitium (60.7%). Moreover, glomeruli were affected in 55.7% of patients. Most frequent histopathological diagnosis was acute tubular necrosis (16.4%) and septic nephritic abscesses (16.4%), followed by tubulointerstitial nephritis (9%). HIV-associated nephropathy was present in two patients (3.3%). There were no significant differences when considering the existent of renal failure. CONCLUSIONS Renal histological abnormalities are frequent in the natural evolution of HIV infection. There is an important heterogeneity of lesions, mainly involving tubules, interstitium and mesangium. The cause of renal lesions is predominantly septic, according to the chief systemic process. It does not exist any relationship between renal analytical parameters and the presence of renal damage.
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Affiliation(s)
- Vicente Giner
- Servicio de Medicina Interna, Hospital Clínico Universitario, Universidad de Valencia, Valencia, España.
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Abstract
HIV is generally regarded as an acceptable reason to exclude a potential recipient from consideration for transplantation. Most of the data in the literature regarding transplantation of HIV sero-positive individuals pertains to the time prior to the administration of Highly Active Anti-Retroviral Therapy (pre-HAART). This data, therefore, provides little guidance for the management of HIV-positive individuals in the current era. The development of HAART has resulted in a decreased mortality. With prolonged survival more HIV-infected individual are developing end stage organ disease from co-existing conditions such as HCV and HBV, and diseases common in the general population such as diabetes mellitus and hypertension. This has lead to clinicians, researchers and patients to actively investigate the role of solid organ transplantation in HIV-infected individuals. In this article We review the literature to date in liver and renal transplantation, including more recent data in patients receiving HAART.
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Affiliation(s)
- Suzanne El Sayegh
- Division of Nephrology, Mount Sinai School of Medicine, New York 10029, USA
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35
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Delaney V, Sumrani N, Hong J, Davis R, Sommer B. The course of HIV disease in renal allograft recipients. Transpl Int 2003; 5 Suppl 1:S129-32. [PMID: 14621755 DOI: 10.1007/978-3-642-77423-2_41] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/27/2023]
Abstract
The clinical course of HIV seropositive renal allograft recipients is ill defined. Thus, a retrospective analysis of mortality, morbidity and graft survival was performed in two groups of HIV-positive patients. Group 1 (nine patients), seropositive for an indefinite period of time prior to transplantation (eight i.v. drug abusers, one homosexual), all lost their grafts after a mean period of 23 +/- 11 months from chronic rejection (six), complicated by focal glomerular sclerosis and nephrotic syndrome in three cases, sepsis (two) and death with a functioning graft (one). Four patients died, two from sepsis, one from Kaposi's sarcoma and one from fluid overload. Of the remaining five patients, all on hemodialysis, one had AIDS and four were asymptomatic after a mean period of 44 months following graft failure. Prolonged hospitalizations for both infections and acute rejection were common. Group 2 (six patients) seroconverted in the perioperative period, and two had functioning allografts at 78 and 100 months post-transplant. Causes of allograft loss, patient death and infection-related complications were similar to those of group 1, but acute rejection was rare. In conclusion, HIV infection in renal allograft recipients was associated with poor allograft survival due mainly to rejection, mostly chronic, often complicated by glomerular sclerosis and nephrotic syndrome. Infectious complications requiring hospitalization were also increased.
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Affiliation(s)
- V Delaney
- Department of Surgery, Division of Transplantation, State University of New York Health Science Center at Brooklyn, New York 11203, USA
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36
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Ray PE, Liu XH, Robinson LR, Reid W, Xu L, Owens JW, Jones OD, Denaro F, Davis HG, Bryant JL. A novel HIV-1 transgenic rat model of childhood HIV-1-associated nephropathy. Kidney Int 2003; 63:2242-53. [PMID: 12753314 DOI: 10.1046/j.1523-1755.2003.00028.x] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND A characteristic finding of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the presence of heavy proteinuria, focal or global glomerulosclerosis, and microcystic tubular dilatation leading to renal enlargement, and rapid progression to end-stage renal disease (ESRD). METHODS We have recently developed the first HIV-1 transgenic rat model that carry a noninfectious HIV-1 DNA construct lacking 3.1 kb of sequence overlapping the gag and pol sequences, and develop many of the clinical lesions seen in HIV-infected patients, including HIVAN. To gain further insight into the pathogenesis of childhood HIVAN, we followed the clinical and renal pathologic outcome of 165 HIV-1 transgenic (HIV-Tg) rats and their respective control littermates for a period of 18 months. RESULTS HIV-1 Tg rats progressively developed proteinuria and renal histologic lesions similar to those seen in children with HIVAN, leading to chronic renal failure. By in situ hybridization, HIV-1 genes were detected in glomerular and tubular epithelial cells and infiltrating mononuclear cells, which also expressed the HIV-1 envelop protein gp120. The development of HIVAN was associated with the accumulation of basic fibroblast growth factor (bFGF) in the kidney. CONCLUSION These data support the notion that HIV-1 plays a direct role in the pathogenesis of HIVAN, by affecting the function and growth of renal epithelial cells, inducing the recruitment of mononuclear cells, and accumulating bFGF in the kidney, even in the absence of viral replication. These rats may provide an excellent model system to study the pathogenesis of childhood HIVAN.
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Affiliation(s)
- Patricio E Ray
- Children's Research Institute, Center for Genetic Medicine, Children's National Medical Center, Washington, D.C. 20010, USA.
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38
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Hedayati SS, Reddan DN, Szczech LA. HIV-associated nephropathy: a review of the epidemiology and clinical course in the HAART era. AIDS Patient Care STDS 2003; 17:57-63. [PMID: 12639288 DOI: 10.1089/108729103321150782] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- S Susan Hedayati
- Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, North Carolina 27710, USA
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39
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Szczech LA. Renal diseases associated with human immunodeficiency virus infection: epidemiology, clinical course, and management. Clin Infect Dis 2001; 33:115-9. [PMID: 11389504 DOI: 10.1086/320893] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2000] [Revised: 01/31/2001] [Indexed: 11/03/2022] Open
Abstract
Human immunodeficiency virus (HIV)--associated nephropathy (HIVAN) and other glomerular lesions (e.g., immunoglobulin A nephropathy and immune complex glomerulonephritis) are frequent complications of HIV infection. These renal diseases usually present as a nephrotic syndrome with progressive loss of renal function and an increased risk of mortality. The prevalence and epidemiology of these renal lesions remain largely undefined; however, most studies agree that black race is a major risk factor for HIVAN. Observational studies have suggested that antiretroviral medications and angiotensin-converting enzyme inhibitors have beneficial effects on slowing the progression of renal disease among patients with HIVAN; however, little is known about the effect of these therapies on other renal lesions. Future research should focus on gaining a better understanding of the distribution and determinants of renal disease among HIV-infected patients as well as on performing controlled studies to test treatment strategies.
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Affiliation(s)
- L A Szczech
- Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, NC 27710, USA.
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40
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Saulsbury F. Resolution of organ-specific complications of human immunodeficiency virus infection in children with use of highly active antiretroviral therapy. Clin Infect Dis 2001; 32:464-8. [PMID: 11170955 DOI: 10.1086/318493] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2000] [Revised: 06/13/2000] [Indexed: 11/04/2022] Open
Abstract
Opportunistic infections are a major source of morbidity and mortality in children and adults infected with human immunodeficiency virus (HIV). In addition, organ-specific complications of HIV infection, such as cardiomyopathy, nephropathy, encephalopathy, and others, contribute substantially to the morbidity and mortality associated with HIV infection. Highly active antiretroviral therapy (HAART) has produced a dramatic decline in the incidence of opportunistic infections among patients with HIV infection. Nevertheless, there is very little information concerning the value of HAART for organ-specific complications of HIV infection. In this report, we describe 3 children with HIV infection in whom the dominant clinical manifestations were cardiomyopathy, red cell aplasia, and nephropathy. HAART produced a decrease in the HIV ribonucleic acid level, an increase in the CD4 cell count, and resolution of the organ-specific complications in all patients. These cases add to our knowledge concerning the benefits of HAART for children with HIV infection.
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Affiliation(s)
- F Saulsbury
- Department of Pediatrics, University of Virginia Health System, Charlottesville, VA, USA.
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41
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Fishman JA, Rubin RH. Solid organ transplantation in HIV-infected individuals: obstacles and opportunities. Transplant Proc 2001; 33:1310-4. [PMID: 11267303 DOI: 10.1016/s0041-1345(00)02488-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- J A Fishman
- Transplant Infectious Disease Program, Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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42
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Shahinian V, Rajaraman S, Borucki M, Grady J, Hollander WM, Ahuja TS. Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients. Am J Kidney Dis 2000; 35:884-8. [PMID: 10793023 DOI: 10.1016/s0272-6386(00)70259-9] [Citation(s) in RCA: 90] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Previous studies have reported that approximately 10% of the patients with human immunodeficiency virus (HIV) infection develop HIV-associated nephropathy (HIVAN). However, over the last decade, morbidity and mortality as a result of HIV-1 infection has remarkably decreased with the availability of potent new antiretroviral drugs. We therefore determined the prevalence of HIVAN from autopsy data of HIV-infected patients in more recent years (1992 to 1997). Autopsy reports of 389 patients were reviewed. In reports suggestive of possible HIVAN, slides of renal tissue were retrieved and reviewed again to ensure appropriate classification. The criteria for the diagnosis of HIVAN were focal segmental glomerulosclerosis with collapse of the glomerular tuft in some glomeruli, extensive tubular ectasia, and significant tubulointerstitial disease. Of 389 autopsy reports, 54% of the patients were black, 35% were white, and 11% were Hispanic. Thirty-three percent of the patients had a history of intravenous drug abuse. The mean CD4 count of the patients was 54 +/- 91/microL (mean +/- SD). In 27 cases, typical features of HIVAN were found based on the criteria used, accounting for an overall HIVAN prevalence of 6.9% (27 of 389 autopsies). Because the overwhelming majority of these patients were black (93%), the prevalence in blacks was 12% (25 of 209 autopsies). We conclude that although mortality and morbidity from HIV infection is decreasing, HIVAN remains an important complication of HIV infection in blacks, even in recent years.
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Affiliation(s)
- V Shahinian
- Department of Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
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43
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Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int 1999; 56:2203-13. [PMID: 10594796 DOI: 10.1046/j.1523-1755.1999.00769.x] [Citation(s) in RCA: 129] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
UNLABELLED Collapsing glomerulopathy in HIV and non-HIV patients: A clinicopathological and follow-up study. BACKGROUND Collapsing glomerulopathy (CG) is a pattern of renal injury that is seen in association with HIV infection and that is increasingly recognized in non-HIV patients. METHODS A review of native kidney biopsies with CG that were diagnosed between 1979 and 1997 in 18 HIV and 42 non-HIV patients is provided. RESULTS HIV and non-HIV patients with CG were similar in terms of age, sex ratio, serum creatinine, proteinuria, the extent of collapsing and sclerosing glomerular lesions, and interstitial damage. A slight female predominance was found in both groups. In contrast to non-HIV patients, the HIV group was characterized by a high prevalence of blacks (94 vs. 57%), frequent tubuloreticular inclusions (76 vs. 29%), and microcystic tubular changes (72 vs. 40%). In 13 non-HIV patients, CG was associated with a systemic lupus erythematosus (SLE)-like disease (5), hepatitis C virus (HCV) infection (3), HTLV-I infection, MCTD, acute monoblastic leukemia, multiple myeloma, and cerebral arteritis. Overall, the renal survival of human immunodeficiency virus (HIV) and non-HIV patients with CG was not significantly different. Cox regression revealed that HIV infection had an adverse effect on short-term renal survival, with other significant risk factors being extensive interstitial fibrosis, high serum creatinine, proteinuria, and a low percentage of glomeruli with collapse. The slope of reciprocal creatinine was best predicted by the degree of proteinuria. Serum creatinine correlated with the extent of interstitial fibrosis, the male gender, and the percentage of glomeruli with collapse. Proteinuria was best predicted by the extent of effacement of podocyte foot processes. CONCLUSIONS CG shares many clinicopathological similarities in HIV and non-HIV patients. In some non-HIV patients, CG was associated with autoimmune diseases, lymphoproliferative disorders, and viral infections.
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Affiliation(s)
- A Laurinavicius
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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44
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Affiliation(s)
- P E Klotman
- Mt. Sinai School of Medicine, New York, New York 10029, USA
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45
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Praditpornsilpa K, Napathorn S, Yenrudi S, Wankrairot P, Tungsaga K, Sitprija V. Renal pathology and HIV infection in Thailand. Am J Kidney Dis 1999; 33:282-6. [PMID: 10023639 DOI: 10.1016/s0272-6386(99)70301-x] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
The existence of a human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) as a distinct disease entity characterized by glomerulosclerosis is well established in North America and Western Europe. Although the large number of HIV-infected cases overwhelm the Asian countries, no cases of HIVAN are documented in the literature. We studied 26 cases of HIV-infected Thai patients with proteinuria greater than 1.5 g/d of protein during 1995 and 1996. None of the patients were treated with antiretroviral drugs at the time of renal biopsy. Intravenous drug addiction and sexual transmission were risk factors in 11 and 15 patients, respectively. Pathological examinations were performed by light microscopic and immunoperoxidase study. Mesangial proliferative glomerulonephritis was found in 17 cases, immunoglobulin A (IgA) nephropathy in 2 cases, and diffuse proliferative glomerulonephritis and interstitial nephritis secondary to cryptococcal infection in 2 cases each. One case each had membranous glomerulopathy, membranoproliferative glomerulonephritis, and granulomatous interstitial nephritis secondary to tuberculosis. The renal pathological findings of HIVAN with the unique features described in previous literature were not evident in these patients. Although the data in this study are limited to 26 HIV-infected Thai patients, we believe that HIVAN is uncommon in the Asian HIV-infected population.
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46
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Abstract
HIV-associated nephropathy is rare in children. Proteinuria can be its first sign. In the black child, it often presents as focal and segmental glomerulosclerosis. White children are mostly affected with mesangial hyperplasia, rarely with IgA nephropathy. Its etiology is probably multifactorial: presence of the virus itself in the glomeruli, hemodynamic alterations and drug toxicity. There is no specific treatment at the moment.
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Affiliation(s)
- F Cachat
- Département médicochirurgical de pédiatrie, CHUV, Lausanne, Suisse
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47
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Mochel A, Rosa TT, Veiga JP. [Renal function aspects in carriers of the human immunodeficiency virus]. Rev Soc Bras Med Trop 1998; 31:179-86. [PMID: 9608236 DOI: 10.1590/s0037-86821998000200003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The occurrence of alterations was verified in some parameters of the asymptomatic individuals' renal function infected by the virus of the human immunodeficiency (HIV). Forty seven individuals were studied, taking place renal functional tests, as: creatinine clearance, clearance of free water, clearance osmolar, reabsorption tubular proximal and distal of sodium and potassium and urinary pH. The results revealed significant differences (p < 0.05) in the urinary pH, larger in the group with HIV (6.36 +/- 0.41), that in the controls (6.02 +/- 0.41); in the clearance of free water, that indicated reabsorption of larger water in the group with HIV (1.00 +/- 0.64 ml/min) and in the clearance osmolar, that was 2.00 +/- 0.83 ml/min in the group with HIV and 1.57 +/- 0.48 ml/min. The remaining of the indicators of renal function was not shown statistically different between an and other group. It was ended that those differences are significant, in spite of the absolute values they be inside of the normality, because could be associated to late evolutionary alterations of the disease, such as the increase of the frequency of infections of the urinary treatment and the dilution hyponatremia. More studies are necessary for if they confirm those hypotheses.
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Affiliation(s)
- A Mochel
- Fundação Hospitalar do Distrito Federal, Nefrologia da Universidade de Brasilia, DF
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48
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Mattana J, Siegal FP, Schwarzwald E, Molho L, Sankaran RT, Gooneratne R, Ahuja TS, Singhal PC. AIDS-associated membranous nephropathy with advanced renal failure: response to prednisone. Am J Kidney Dis 1997; 30:116-9. [PMID: 9214410 DOI: 10.1016/s0272-6386(97)90573-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We report the case of a patient with acquired immunodeficiency syndrome (AIDS) who developed nephrotic syndrome and progressive renal failure mimicking human immunodeficiency virus (HIV)-associated focal segmental glomerulosclerosis (FSGS) who required initiation of hemodialysis and was found on renal biopsy to have membranous nephropathy. Hepatitis B and C serologies were negative. Although she required hemodialysis, she was treated with prednisone and experienced a progressive decline in her serum creatinine from 10.1 mg/dL to 1.9 mg/dL, which permitted the discontinuation of hemodialysis. After she abruptly discontinued prednisone, her creatinine level increased to 4.8 mg/dL, and she experienced marked worsening of her nephrotic syndrome. Resumption of prednisone resulted in normalization of serum creatinine and reduction in urine protein excretion. No adverse effects of prednisone occurred during this time. She remains off of hemodialysis for 1 year with a serum creatinine level of 1.0 mg/dL and urine protein excretion of 0.4 g/d. Although most patients with HIV infection, nephrotic-range proteinuria, and renal failure have FSGS, a minority may have membranous nephropathy. Although typically not a steroid-responsive lesion in the setting of advanced renal failure, membranous nephropathy may be a highly steroid-responsive lesion in the HIV-infected patient, and treatment may help avert the need for dialysis in a patient population that generally has a poor outcome on dialysis.
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MESH Headings
- Acquired Immunodeficiency Syndrome/complications
- Adult
- Anti-Inflammatory Agents/therapeutic use
- Diagnosis, Differential
- Female
- Glomerulonephritis, Membranous/complications
- Glomerulonephritis, Membranous/diagnosis
- Glomerulonephritis, Membranous/drug therapy
- Glomerulonephritis, Membranous/pathology
- Glomerulonephritis, Membranous/virology
- Glomerulosclerosis, Focal Segmental/diagnosis
- Humans
- Kidney Failure, Chronic/drug therapy
- Kidney Failure, Chronic/etiology
- Kidney Failure, Chronic/pathology
- Prednisone/therapeutic use
- Renal Dialysis
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Affiliation(s)
- J Mattana
- Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA
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Stokes MB, Chawla H, Brody RI, Kumar A, Gertner R, Goldfarb DS, Gallo G. Immune complex glomerulonephritis in patients coinfected with human immunodeficiency virus and hepatitis C virus. Am J Kidney Dis 1997; 29:514-25. [PMID: 9100039 DOI: 10.1016/s0272-6386(97)90332-2] [Citation(s) in RCA: 72] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, "collapsing" glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and "collapsing" glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group.
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Affiliation(s)
- M B Stokes
- Department of Pathology, New York University Medical Center, New York, NY 10016, USA
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50
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Alpers CE, Tsai CC, Hudkins KL, Cui Y, Kuller L, Benveniste RE, Ward JM, Morton WR. Focal segmental glomerulosclerosis in primates infected with a simian immunodeficiency virus. AIDS Res Hum Retroviruses 1997; 13:413-24. [PMID: 9075483 DOI: 10.1089/aid.1997.13.413] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Focal and segmental glomerulosclerosis (FSG) with endothelial tubuloreticular inclusions (TRIs) is the typical lesion of human HIV-associated glomerulopathy. Autopsy studies showed the presence of FSG in 3 of 15 macaques dying 15-120 weeks after experimental infection with a simian immunodeficiency virus (SIVMne). Ultrastructural studies generally revealed numerous endothelial TRIs (also present in normals), mesangial expansion, and evidence of mesangial cell injury. One additional animal had a small-vessel polyarteritis with a proliferative and focally crescentic glomerulonephritis; seven animals had mild, multifocal interstitial nephritis. All animals had documented viremia after infection; 14 of 15 developed antibodies to SIV postinoculation. Additional postmortem findings included severe enterocolitis, encephalitis, and opportunistic infections. In contrast, autopsy studies of macaques infected with a type D simian retrovirus (SAIDS-D/Washington, SRV-2) for similar periods of time (n = 40) showed no evidence of FSG. One SRV-infected animal had a mild proliferative glomerulonephritis. These studies indicate SIV-infected primates may provide a relevant model for study of human HIV-associated nephropathy. They also indicate the variable pathology that can be seen in primate infections of distinct retrovirus types, each of which produces a simian immunodeficiency state that resembles human AIDS.
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MESH Headings
- AIDS-Associated Nephropathy
- Animals
- Antibodies, Viral/blood
- CD4 Lymphocyte Count
- Disease Models, Animal
- Endothelium/virology
- Glomerulonephritis, Membranoproliferative/pathology
- Glomerulonephritis, Membranoproliferative/virology
- Glomerulosclerosis, Focal Segmental/pathology
- Glomerulosclerosis, Focal Segmental/virology
- Humans
- Kidney/pathology
- Kidney/virology
- Macaca
- Nephritis, Interstitial/pathology
- Nephritis, Interstitial/virology
- Polyarteritis Nodosa/pathology
- Polyarteritis Nodosa/virology
- RNA, Messenger/analysis
- RNA, Viral/analysis
- Retroviruses, Simian
- Simian Acquired Immunodeficiency Syndrome/immunology
- Simian Acquired Immunodeficiency Syndrome/pathology
- Simian Acquired Immunodeficiency Syndrome/virology
- Simian Immunodeficiency Virus/immunology
- Simian Immunodeficiency Virus/isolation & purification
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Affiliation(s)
- C E Alpers
- Department of Pathology, School of Medicine, University of Washington, Seattle 98195, USA
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