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Nogueira de Sa P, Narayanan M, Lim MAC. Electrolyte and Acid-Base Abnormalities After Kidney Transplantation. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:450-457. [PMID: 39232615 DOI: 10.1053/j.akdh.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 03/14/2024] [Accepted: 03/25/2024] [Indexed: 09/06/2024]
Abstract
Kidney transplantation is the optimal therapeutic approach for individuals with end-stage kidney disease. The Scientific Registry of Transplant Recipients has reported a continuous rise in the total number of kidney transplants performed in the United States, with 25,500 new kidney recipients in 2022 alone. Despite an improved glomerular filtration rate, the post-transplant period introduces a unique set of electrolyte abnormalities that differ from those encountered in chronic kidney disease. A variety of factors contribute to the high prevalence of hypomagnesemia, hyperkalemia, metabolic acidosis, hypercalcemia, and hypophosphatemia seen after kidney transplantation. These include the degree of allograft function, immunosuppressive medications and their diverse mechanisms of action, and metabolic changes after transplant. This article aims to provide a comprehensive review of the key aspects surrounding the most commonly encountered electrolyte and acid-base abnormalities in the post-transplant setting.
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Affiliation(s)
- Patricia Nogueira de Sa
- Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
| | - Mohanram Narayanan
- Division of Nephrology and Hypertension, Department of Medicine, Baylor Scott & White, Medical Center, Temple, TX
| | - Mary Ann C Lim
- Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA
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Kubota M, Hamasaki Y, Hashimoto J, Aoki Y, Kawamura T, Saito A, Yuasa R, Muramatsu M, Komaba H, Toyoda M, Fukagawa M, Shishido S, Sakai K. Fibroblast growth factor 23-Klotho and mineral metabolism in the first year after pediatric kidney transplantation: A single-center prospective study. Pediatr Transplant 2023; 27:e14440. [PMID: 36471536 DOI: 10.1111/petr.14440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND The role of fibroblast growth factor 23 (FGF23) levels in mineral metabolism before and after kidney transplantation in pediatric patients is poorly understood. METHODS We prospectively evaluated 24 patients under 18 years of age (4.5 [3.3-9.8] years) who underwent living kidney transplantation between July 2016 and March 2018, and measured intact FGF23 and serum αKlotho levels, and other parameters of mineral metabolism before and after transplantation (Day 7, 1 and 4 months, and 1 year). Relationships between parameters were examined by linear analysis. RESULTS FGF23 level was 440.8 [63.4-5916.3] pg/ml pre-transplant and decreased significantly to 37.1 [16.0-71.5] pg/ml at Day 7 post-transplant (-91.6%, p < .001). Thereafter, it remained at normal levels until 1 year. αKlotho level was 785 [568-1292] pg/ml pre-transplant and remained low at Day 7 and 1 month post-transplant, with an increasing trend at 4 months. Post-transplant phosphorus levels were significantly decreased compared with pre-transplant, with a lowest level of 1.7 [1.3-2.9] mg/dl, -5.7 [-6.8, -3.8] SD at Day 4, followed by gradual recovery. Phosphorus levels and the ratio of tubular maximum phosphate reabsorption were significantly and negatively associated with pre-transplant FGF23 until 4 months of post-transplant. Pre-transplant αKlotho was negatively associated with pre-transplant FGF23 but not FGF23 or other parameters after transplantation. CONCLUSION FGF23 in pediatric kidney transplant patients decreased rapidly after transplantation and associated with post-transplant hypophosphatemia and increased phosphorus excretion. Post-transplant αKlotho was low early post-transplant but tended to increase subsequently. Post-transplant αKlotho was unaffected by pre-transplant FGF23 or other factors, suggesting pre-transplant chronic kidney disease status has no effect.
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Affiliation(s)
- Mai Kubota
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Yuko Hamasaki
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Junya Hashimoto
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Yujiro Aoki
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Takeshi Kawamura
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Akinobu Saito
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Rena Yuasa
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Masaki Muramatsu
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Hirotaka Komaba
- Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan
| | - Masao Toyoda
- Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan
| | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan
| | - Seichiro Shishido
- Department of Pediatric Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
| | - Ken Sakai
- Department of Nephrology, Toho University, Faculty of Medicine, Tokyo, Japan
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Ralston MR, Stevenson KS, Mark PB, Geddes CC. Clinical factors associated with severe hypophosphataemia after kidney transplant. BMC Nephrol 2021; 22:407. [PMID: 34886802 PMCID: PMC8656060 DOI: 10.1186/s12882-021-02624-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 11/24/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The mechanism by which hypophosphataemia develops following kidney transplantation remains debated, and limited research is available regarding risk factors. This study aimed to assess the association between recipient and donor variables, and the severity of post-transplantation hypophosphataemia. METHODS We performed a single-centre retrospective observational study. We assessed the association between demographic, clinical and biochemical variables and the development of hypophosphataemia. We used linear regression analysis to assess association between these variables and phosphate nadir. RESULTS 87.6% of patients developed hypophosphataemia. Patients developing hypophosphataemia were younger, had a shorter time on renal replacement therapy, were less likely to have had a parathyroidectomy or to experience delayed graft function, were more likely to have received a living donor transplant, from a younger donor. They had higher pre-transplantation calcium levels, and lower alkaline phosphatase levels. Receipt of a living donor transplant, lower donor age, not having had a parathyroidectomy, receiving a transplant during the era of tacrolimus-based immunosuppression, not having delayed graft function, higher pre-transplantation calcium, and higher pre-transplantation phosphate were associated with lower phosphate nadir by multiple linear regression. CONCLUSIONS This analysis demonstrates an association between variables relating to better graft function and hypophosphataemia. The links with biochemical measures of mineral-bone disease remain less clear.
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Affiliation(s)
- Maximilian R Ralston
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK.
| | - Karen S Stevenson
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK
| | - Patrick B Mark
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK.,Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Colin C Geddes
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK
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Torregrosa JV, Ferreira AC, Cucchiari D, Ferreira A. Bone Mineral Disease After Kidney Transplantation. Calcif Tissue Int 2021; 108:551-560. [PMID: 33765230 DOI: 10.1007/s00223-021-00837-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 03/09/2021] [Indexed: 12/18/2022]
Abstract
Chronic kidney disease-mineral bone disorder (CKD-MBD) after kidney transplantation is a mix of pre-existing disorders and new alterations. The final consequences are reflected fundamentally as abnormal mineral metabolism (hypercalcemia, hypophosphatemia) and bone alterations [high or low bone turnover disease (as fibrous osteitis or adynamic bone disease), an eventual compromise of bone mineralization, decrease bone mineral density and bone fractures]. The major cause of post-transplantation hypercalcemia is the persistence of severe secondary hyperparathyroidism, and treatment options include calcimimetics or parathyroidectomy. On turn, hypophosphatemia is caused by both the persistence of high blood levels of PTH and/or high blood levels of FGF23, with its correction being very difficult to achieve. The most frequent bone morphology alteration is low bone turnover disease, while high-turnover osteopathy decreases in frequency after transplantation. Although the pathogenic mechanisms of these abnormalities have not been fully clarified, the available evidence suggests that there are a number of factors that play a very important role, such as immunosuppressive treatment, persistently high levels of PTH, vitamin D deficiency and hypophosphatemia. Fracture risk is four-fold higher in transplanted patients compared to general population. The most relevant risk factors for fracture in the kidney transplant population are diabetes mellitus, female sex, advanced age (especially > 65 years), dialysis vintage, high PTH levels and low phosphate levels, osteoporosis, pre-transplant stress fracture and high doses or prolonged steroids therapy. Treatment alternatives for CKD-MBD after transplantation include minimization of corticosteroids, use of calcium and vitamin D supplements, antiresorptives (bisphosphonates or Denosumab) and osteoformers (synthetic parathyroid hormone). As both mineral metabolism and bone disorders lead to increased morbidity and mortality, the presence of these changes after transplantation has to be prevented (if possible), minimized, diagnosed, and treated as soon as possible.
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Affiliation(s)
- Josep-Vicent Torregrosa
- Nephrology & Renal Transplant Department - Hospital Clínic, Barcelona, Spain.
- Universidad de Barcelona, Barcelona, Spain.
| | - Ana Carina Ferreira
- Nephrology Department, Centro Hospitalare, Universitário de Lisboa Central, Lisbon, Portugal
- Nova Medical School, Nova University, Lisbon, Portugal
| | - David Cucchiari
- Nephrology & Renal Transplant Department - Hospital Clínic, Barcelona, Spain
| | - Aníbal Ferreira
- Nephrology Department, Centro Hospitalare, Universitário de Lisboa Central, Lisbon, Portugal
- Nova Medical School, Nova University, Lisbon, Portugal
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Podestà MA, Cucchiari D, Ciceri P, Messa P, Torregrosa JV, Cozzolino M. Cardiovascular calcifications in kidney transplant recipients. Nephrol Dial Transplant 2021; 37:2063-2071. [PMID: 33620476 DOI: 10.1093/ndt/gfab053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 12/15/2022] Open
Abstract
Vascular and valvular calcifications are highly prevalent in kidney transplant recipients and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uremia-associated metabolic derangements, kidney transplant recipients are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in kidney transplant recipients, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.
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Affiliation(s)
- Manuel Alfredo Podestà
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Italy
| | - David Cucchiari
- Nephrology and Renal Transplant Department, Hospital Clínic, Barcelona, Spain
| | - Paola Ciceri
- Department of Nephrology, Dialysis and Renal Transplant, Renal Research Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Piergiorgio Messa
- Department of Nephrology, Dialysis and Renal Transplant, Renal Research Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Mario Cozzolino
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Italy
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Law JP, Price AM, Pickup L, Radhakrishnan A, Weston C, Jones AM, McGettrick HM, Chua W, Steeds RP, Fabritz L, Kirchhof P, Pavlovic D, Townend JN, Ferro CJ. Clinical Potential of Targeting Fibroblast Growth Factor-23 and αKlotho in the Treatment of Uremic Cardiomyopathy. J Am Heart Assoc 2020; 9:e016041. [PMID: 32212912 PMCID: PMC7428638 DOI: 10.1161/jaha.120.016041] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor-23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor-23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end-stage renal disease.
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Affiliation(s)
- Jonathan P. Law
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of NephrologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Anna M. Price
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of NephrologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Luke Pickup
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Ashwin Radhakrishnan
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
| | - Chris Weston
- Institute of Immunology and ImmunotherapyUniversity of BirminghamUnited Kingdom
- NIHR Birmingham Biomedical Research CentreUniversity Hospitals Birmingham NHS Foundation Trust and University of BirminghamUnited Kingdom
| | - Alan M. Jones
- School of PharmacyUniversity of BirminghamUnited Kingdom
| | | | - Winnie Chua
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Richard P. Steeds
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of CardiologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Larissa Fabritz
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of CardiologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Paulus Kirchhof
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Davor Pavlovic
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
| | - Jonathan N. Townend
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of CardiologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
| | - Charles J. Ferro
- Birmingham Cardio‐Renal GroupUniversity Hospitals BirminghamUniversity of BirminghamUnited Kingdom
- Institute of Cardiovascular SciencesUniversity of BirminghamUnited Kingdom
- Department of NephrologyUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUnited Kingdom
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Pochineni V, Rondon-Berrios H. Electrolyte and Acid-Base Disorders in the Renal Transplant Recipient. Front Med (Lausanne) 2018; 5:261. [PMID: 30333977 PMCID: PMC6176109 DOI: 10.3389/fmed.2018.00261] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 08/29/2018] [Indexed: 12/17/2022] Open
Abstract
Kidney transplantation is the current treatment of choice for patients with end-stage renal disease. Innovations in transplantation and immunosuppression regimens have greatly improved the renal allograft survival. Based on recently published data from the Scientific Registry of Transplant recipients, prevalence of kidney transplants is steadily rising in the United States. Over 210,000 kidney transplant recipients were alive with a functioning graft in mid-2016, which is nearly twice as many as in 2005. While successful renal transplantation corrects most of the electrolyte and mineral abnormalities seen in advanced renal failure, the abnormalities seen in the post-transplant period are surprisingly different from those seen in chronic kidney disease. Multiple factors contribute to the high prevalence of these abnormalities that include level of allograft function, use of immunosuppressive medications and metabolic changes in the post-transplant period. Electrolyte disturbances are common in patients after renal transplantation, and several studies have tried to determine the clinical significance of these disturbances. In this manuscript we review the key aspects of the most commonly found post-transplant electrolyte abnormalities. We focus on their epidemiology, pathophysiology, clinical manifestations, and available treatment approaches.
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Affiliation(s)
- Vaishnavi Pochineni
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
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Abstract
Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular mortality, infections, and impaired cognitive function. It is characterized by excessively increased levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23) and a deficiency of its co-receptor Klotho. Despite the important physiological effect of FGF23 in maintaining phosphate homeostasis, there is increasing evidence that higher FGF23 levels are a risk factor for mortality and cardiovascular disease. FGF23 directly induces left ventricular hypertrophy via activation of the FGF receptor 4/calcineurin/nuclear factor of activated T cells signaling pathway. By contrast, the impact of FGF23 on endothelial function and the development of atherosclerosis are poorly understood. The results of recent experimental studies indicate that FGF23 directly impacts on hippocampal neurons and may thereby impair learning and memory function in CKD patients. Finally, it has been shown that FGF23 interferes with the immune system by directly acting on polymorphonuclear leukocytes and macrophages. In this review, we discuss recent data from clinical and experimental studies on the extrarenal effects of FGF23 with respect to the cardiovascular, central nervous, and immune systems.
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Wolf M, Weir MR, Kopyt N, Mannon RB, Von Visger J, Deng H, Yue S, Vincenti F. A Prospective Cohort Study of Mineral Metabolism After Kidney Transplantation. Transplantation 2016; 100:184-93. [PMID: 26177089 PMCID: PMC4683035 DOI: 10.1097/tp.0000000000000823] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Kidney transplantation corrects or improves many complications of chronic kidney disease, but its impact on disordered mineral metabolism is incompletely understood. The prevalence of posttransplant hyperparathyroidism was 86% at 12 months (PTH >65 pg/ml) but only 40% (PTH >130 mg/dL) in the absence of cinacalcet, vitamin D sterols, or parathyroidectomy. Intact fibroblast growth factor 23 decreased rapidly to G40 pg/ml by 3 months posttransplant. Supplemental digital content is available in the text.
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Affiliation(s)
- Myles Wolf
- 1 Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. 2 Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD. 3 Lehigh Valley Hospital, Allentown, PA. 4 University of Alabama at Birmingham, Birmingham, AL. 5 The Ohio State University Medical Center, Columbus, OH. 6 Amgen Inc., Thousand Oaks, CA. 7 Kidney Transplant Service, University of California San Francisco, San Francisco, CA
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Taweesedt PT, Disthabanchong S. Mineral and bone disorder after kidney transplantation. World J Transplant 2015; 5:231-242. [PMID: 26722650 PMCID: PMC4689933 DOI: 10.5500/wjt.v5.i4.231] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 09/11/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
After successful kidney transplantation, accumulated waste products and electrolytes are excreted and regulatory hormones return to normal levels. Despite the improvement in mineral metabolites and mineral regulating hormones after kidney transplantation, abnormal bone and mineral metabolism continues to present in most patients. During the first 3 mo, fibroblast growth factor-23 (FGF-23) and parathyroid hormone levels decrease rapidly in association with an increase in 1,25-dihydroxyvitamin D production. Renal phosphate excretion resumes and serum calcium, if elevated before, returns toward normal levels. FGF-23 excess during the first 3-12 mo results in exaggerated renal phosphate loss and hypophosphatemia occurs in some patients. After 1 year, FGF-23 and serum phosphate return to normal levels but persistent hyperparathyroidism remains in some patients. The progression of vascular calcification also attenuates. High dose corticosteroid and persistent hyperparathyroidism are the most important factors influencing abnormal bone and mineral metabolism in long-term kidney transplant (KT) recipients. Bone loss occurs at a highest rate during the first 6-12 mo after transplantation. Measurement of bone mineral density is recommended in patients with estimated glomerular filtration rate > 30 mL/min. The use of active vitamin D with or without bisphosphonate is effective in preventing early post-transplant bone loss. Steroid withdrawal regimen is also beneficial in preservation of bone mass in long-term. Calcimimetic is an alternative therapy to parathyroidectomy in KT recipients with persistent hyperparathyroidism. If parathyroidectomy is required, subtotal to near total parathyroidectomy is recommended. Performing parathyroidectomy during the waiting period prior to transplantation is also preferred in patients with severe hyperparathyroidism associated with hypercalcemia.
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Rapid calcitriol increase and persistent calcidiol insufficiency in the first 6 months after kidney transplantation. Nucl Med Commun 2015; 36:489-93. [PMID: 25603274 DOI: 10.1097/mnm.0000000000000265] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Vitamin D deficiency or insufficiency is prevalent in kidney transplant recipients. Little is known about post-transplantation changes in vitamin D forms, which are essential for bone health and other health outcomes. The aim was to measure the levels of calcidiol and calcitriol during the first 6 months after kidney transplantation and examine their relation with other bone mineral metabolic parameters. PATIENTS AND METHODS A prospective study was performed on 98 patients recruited between April 2010 and June 2011. Calcidiol and calcitriol levels were measured at baseline and at days 15, 30, 90, and 180 after kidney transplantation. RESULTS Serum calcidiol levels remained persistently low: 14.3 (9-22) ng/ml at baseline and 16.3 (10.1-20.6) ng/ml at 6 months (P=0.641). At 6 months, calcidiol levels showed an inverse correlation with simultaneously measured parathyroid hormone levels. Calcidiol showed a trend to be higher in patients transplanted in spring but with no statistically significant difference. Calcitriol levels increased from 17 (13-23.7) pg/ml at baseline to 24 (16-32) pg/ml (P=0.002) in the first 2 weeks after transplantation and reached 37 (25-50) pg/ml (P=0.000) after 6 months. During the follow-up, calcitriol levels showed a significant inverse correlation with baseline fibroblast growth factor-23 levels. At month 6, calcitriol levels were inversely correlated with baseline fibroblast growth factor-23 levels and directly correlated with calcidiol levels. CONCLUSION In most patients, calcidiol levels remain low 6 months after kidney transplantation, whereas calcitriol levels rapidly return to normal. Lower calcidiol blood levels promoted lower calcitriol blood levels and higher parathyroid hormone concentrations.
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Barros X, Fuster D, Paschoalin R, Oppenheimer F, Rubello D, Perlaza P, Pons F, Torregrosa JV. Changes in bone mineral metabolism parameters, including FGF23, after discontinuing cinacalcet at kidney transplantation. Endocrine 2015; 49:267-73. [PMID: 25154517 DOI: 10.1007/s12020-014-0400-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Accepted: 08/18/2014] [Indexed: 12/11/2022]
Abstract
Little is known about the effects of the administration of cinacalcet in dialytic patients who are scheduled for kidney transplantation, and in particular about the changes in FGF23 and other mineral metabolism parameters after surgery compared with recipients not on cinacalcet at kidney transplantation. We performed a prospective observational cohort study with recruitment of consecutive kidney transplant recipients at our institution. Patients were classified according to whether they were under treatment with cinacalcet before transplantation. Bone mineral metabolism parameters, including C-terminal FGF23, were measured at baseline, on day 15, and at 1, 3, and 6 months after transplantation. In previously cinacalcet-treated patients, cinacalcet therapy was discontinued on the day of surgery and was not restarted after transplantation. A total of 48 kidney transplant recipients, 20 on cinacalcet at surgery and 28 cinacalcet non-treated patients, completed the follow-up. Serum phosphate declined significantly in the first 15 days after transplantation with no differences between the two groups, whereas cinacalcet-treated patients showed higher FGF23 levels, although not significant. After transplantation, PTH and serum calcium were significantly higher in cinacalcet-treated patients. We conclude that patients receiving cinacalcet on dialysis presented similar serum phosphate levels but higher PTH and serum calcium levels during the initial six months after kidney transplantation than cinacalcet non-treated patients. The group previously treated with cinacalcet before transplantation showed higher FGF23 levels without significant differences, so further studies should investigate its relevance in the management of these patients.
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Affiliation(s)
- Xoana Barros
- Nephrology and Renal Transplant Department, Hospital Clinic, Barcelona, Spain
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