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Mortality and Allograft Loss Trends Among US Pediatric Kidney Transplant Recipients With and Without Focal Segmental Glomerulosclerosis.

ABSTRACT: BACKGROUND:Pediatric patients with focal segmental glomerulosclerosis (FSGS) have high rates of disease recurrence and allograft failure after kidney transplantation, but there are few data for long-term survival posttransplantation. STUDY DESIGN:Retrospective cohort study. SETTING & PARTICIPANTS:12,303 pediatric patients (aged <18 years), including 1,408 (11%) patients with FSGS, who received a first kidney transplant in 1990 through 2009 and were followed up through June 2015 were identified from the US Renal Data System database. PREDICTORS:Primary cause of end-stage renal disease, FSGS or other. OUTCOMES:All-cause patient mortality and allograft loss. RESULTS:All-cause mortality significantly improved for patients with FSGS who underwent transplantation in the 2000s versus the 1990s (6.72 vs 12.24 deaths/1,000 patient-years; HR, 0.55; 95% CI, 0.39-0.78; P<0.001). Reductions in allograft loss were less dramatic (75.91 vs 89.05 events/1,000 patient-years; HR, 0.85; 95% CI, 0.74-0.98; P=0.02). After adjusting for baseline characteristics at the time of transplantation, patients with FSGS had similar rates of death compared with patients without FSGS (HRs of 0.81 [P=0.6] and 1.06 [P=0.2] among those who underwent transplantation in the 2000s and 1990s, respectively) despite higher rates of allograft loss (HRs of 1.17 [P=0.03] and 1.27 [P<0.001], respectively). Among patients who underwent transplantation in the 2000s, further adjustment for allograft failure as a time-varying covariate demonstrated a lower rate of death among patients with FSGS compared with those without FSGS (HR, 0.70; P=0.02). LIMITATIONS:Lack of information about certain risk factors for mortality, including duration of chronic kidney disease; missing data; and potential primary disease misclassification. CONCLUSIONS:Survival of pediatric kidney transplant recipients with FSGS improved between the 1990s and 2000s and was similar to that of recipients without FSGS. Interestingly, adjustment for allograft failure showed greater survival for pediatric patients with FSGS who underwent transplantation in the 2000s as compared with others, suggesting that effective interventions to decrease allograft loss due to disease recurrence may improve patient survival.

SUBMITTER: Wang CS

PROVIDER: S-EPMC5828873 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Mortality and Allograft Loss Trends Among US Pediatric Kidney Transplant Recipients With and Without Focal Segmental Glomerulosclerosis.

Wang Chia-Shi CS Gander Jennifer J Patzer Rachel E RE Greenbaum Larry A LA

American journal of kidney diseases : the official journal of the National Kidney Foundation 20171223 3

<h4>Background</h4>Pediatric patients with focal segmental glomerulosclerosis (FSGS) have high rates of disease recurrence and allograft failure after kidney transplantation, but there are few data for long-term survival posttransplantation.<h4>Study design</h4>Retrospective cohort study.<h4>Setting & participants</h4>12,303 pediatric patients (aged <18 years), including 1,408 (11%) patients with FSGS, who received a first kidney transplant in 1990 through 2009 and were followed up through June ...[more]

PMID: 29277509

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Project description:INTRODUCTION:We qualitatively examined the symptoms and impact of recurrent primary focal segmental glomerulosclerosis (rpFSGS) in kidney transplant recipients, compared with two related FSGS populations, to characterize the experience of patients with rpFSGS. METHODS:A literature review identified 58 articles concerning the experience of patients with pFSGS and/or rpFSGS in three groups: pre-transplant pFSGS, post-transplant rpFSGS, or post-transplant non-recurrent pFSGS. Literature findings were used to construct a preliminary conceptual model incorporating the symptoms and impact of rpFSGS, which was refined on the basis of qualitative interviews with clinicians. Twenty-five patients (rpFSGS: n?=?15; pre-transplant pFSGS: n?=?5; post-transplant non-recurrent pFSGS: n?=?5) were interviewed to characterize the experience of patients with rpFSGS and compare it with other FSGS populations, and findings were used to finalize the conceptual model. RESULTS:The impact of pFSGS/rpFSGS described in the literature was diverse. Treatment-related symptoms, along with anxiety and depression, were considered important features of rpFSGS in addition to the findings from the literature review, according to clinicians. Patient-reported tiredness and swelling were the most common/disturbing symptoms associated with rpFSGS, while physical activity restrictions and adverse effects on work/social life were considered the most profound impact concepts. The collective disease experience was different for patients with rpFSGS and non-recurrent pFSGS, although psychological impact, including treatment-related anxiety and depression, were common to both groups. CONCLUSIONS:Post-transplant recipients with rpFSGS display a greater symptom burden and experience a more diverse impact than those with non-recurrent pFSGS, highlighting the importance of effective patient monitoring and introducing effective treatments for the prevention and management of pFSGS recurrence. FUNDING:Astellas Pharma Global Development, Inc.

Project description:Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele-associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g, glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g, to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.

Project description:Rationale & objectiveRemission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival.Study designCohort analysis of clinical trial participants.Setting & participantsPatients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone.PredictorsReduction in proteinuria measured during 26 weeks after initiating treatment.OutcomesRepeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization.Analytical approachMultivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome.Results138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44).LimitationsLimited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years.ConclusionsThese findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.

Dataset Information

Mortality and Allograft Loss Trends Among US Pediatric Kidney Transplant Recipients With and Without Focal Segmental Glomerulosclerosis.

Publications

Mortality and Allograft Loss Trends Among US Pediatric Kidney Transplant Recipients With and Without Focal Segmental Glomerulosclerosis.

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