One-Year estimated GFR Slope Independently Predicts Clinical Benefit in Immunoglobulin A Nephropathy.
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SUBMITTER: Lafayette RA
PROVIDER: S-EPMC9727523 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
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One-Year estimated GFR Slope Independently Predicts Clinical Benefit in Immunoglobulin A Nephropathy.
Lafayette Richard A RA Reich Heather N HN Stone Andrew M AM Barratt Jonathan J
Kidney international reports 20220929 12
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Project description:Rationale & objectivePrimary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism that results in early-onset kidney stone disease, nephrocalcinosis, and kidney failure. There is an unmet need for reliable markers of disease progression to test effectiveness of new treatments for patients with PH. In this study, we assessed the rate of estimated glomerular filtration rate (eGFR) decline across chronic kidney disease (CKD) glomerular filtration rate (GFR) categories (CKD G2-G5) in a cohort of patients with PH1.Study designRetrospective observational study.Setting & participantsPatients with PH1 enrolled in the Rare Kidney Stone Consortium (RKSC) registry who did not have kidney failure at diagnosis and who had at least 2 eGFR values recorded from within 1 month of diagnosis until their last contact date or incident kidney failure event.PredictorsCKD GFR category, baseline patient and laboratory characteristics.OutcomeAnnualized rate of eGFR decline.Analytical approachGeneralized estimating equations and linear regression were used to evaluate the associations between CKD GFR category, baseline patient and laboratory characteristics, and annual change in eGFR during follow-up.ResultsCompared with the slope in CKD G2 (-2.3 mL/min/1.73 m2 per year), the mean annual eGFR decline was nominally steeper in CKD G3a (-5.3 mL/min/1.73 m2 per year) and statistically significantly more rapid in CKD G3b and G4 (-14.7 and -16.6 mL/min/1.73 m2 per year, respectively). In CKD G2, older age was associated with a more rapid rate of eGFR decline (P = 0.01). A common PH1-causing variant of alanine glyoxylate aminotransferase, a glycine to arginine substitution at amino acid 170 (G170R), appeared to be associated with less severe annual decline in eGFR.LimitationsData at regular time points were not available for all patients due to reliance on voluntary reporting in a retrospective rare disease registry.ConclusionsThe eGFR decline was not uniform across CKD GFR categories in this PH1 population, with a higher rate of eGFR decline in CKD G3b and G4. Thus, CKD GFR category needs to be accounted for when analyzing eGFR change in the setting of PH1.
| S-EPMC9398980 | biostudies-literature
Project description:Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease. In 42 kidney grafts undergoing protocol biopsies at reperfusion, we estimated the renal metabolome from RNAseq data. The estimated metabolites' abundance was further used to predict the renal function within the first year of transplantation through a random forest machine learning algorithm. Using repeated K-fold cross-validation we first built and then tuned our model on a training dataset. The optimal model accurately predicted the one-year eGFR, with an out-of-bag root mean square root error (RMSE) that was 11.8 ± 7.2 mL/min/1.73 m2. The performance was similar in the test dataset, with a RMSE of 12.2 ± 3.2 mL/min/1.73 m2. This model outperformed classic statistical models. Reperfusion renal metabolome may be used to predict renal function one year after allograft kidney recipients.
| S-EPMC8778290 | biostudies-literature
Project description:We previously observed reduced graft survival for kidney transplants having interstitial fibrosis with subclinical inflammation, but not fibrosis alone, on 1-year protocol biopsy. The current study aimed to determine whether fibrosis with inflammation at 1 year is associated with renal functional decline in a low-risk transplant cohort and to characterize the nature of the inflammation. Subjects were living-donor, tacrolimus/mycophenolate-treated transplant recipients without overt risk factors for reduced graft survival (n=151). Transplants with normal histology (n=86) or fibrosis alone (n=45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, while those having fibrosis with inflammation (n=20) had declining glomerular filtration rate and reduced graft survival. Immunohistochemistry confirmed increased interstitial T-cells and macrophages/dendritic cells in the fibrosis with inflammation group. Gene expression was performed on a subset of biopsies in each group and demonstrated increased expression of transcripts related to innate and cognate immunity in transplants having fibrosis with inflammation. Pathway- and pathological process-specific analyses of microarray profiles revealed that, in fibrosis with inflammation, over-expressed transcripts were enriched for potentially damaging immunological activities including Toll-like receptor signaling, antigen presentation/dendritic cell maturation, interferon gamma-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes. Thus, fibrosis with inflammation in 1-year protocol biopsies is associated with reduced graft survival and function and with a rejection-like gene expression signature even in recipients with no clinical risk for inferior outcome. Early interventions aimed at altering rejection-like inflammation may favor improved long-term KTx survival.
2010-11-01 | GSE22459 | GEO
Project description: Not available
| S-EPMC10851060 | biostudies-literature
Project description:Background and objectivesImmunoglobulin A Nephropathy (IgAN) is the most common type of glomerulonephritis with variable renal outcome. The association between IgAN and patient survival is limited. The effect of crescents on patient survival was never studied.MaterialsWe conducted a retrospective cohort study between January 2003 and December 2013. All patients with the biopsy-proved IgAN was enrolled for the analysis of patient survival and renal survival. Cox regression model was used analyze the associated factors for patient survival.ResultsAll 388 participants with IgAN were enrolled, in which 45 patients with crescents. The mean percentage of glomeruli involvement was 23±18.9%. After long-term follow-up, crescents group had both worse renal (p = 0.034) and patient survivals (p = 0.016). In univariate Cox regression model, the age (HR = 1.08, 95% CI = 1.05-1.12, p<0.001), crescents (HR = 3.93, 95% CI = 1.18-13.07, p = 0.025), serum albumin (HR = 0.023, 95%CI = 0.11-0.50, p<0.001), blood total protein (HR = 0.46, 95%CI = 0.28-0.75, p = 0.002), HDL (HR = 0.95, 95%CI = 0.91-0.99, p = 0.009), daily urine protein (HR = 1.14, 95%CI = 1.01-1.29, p = 0.038), urine PCR (HR = 1.07, 95%CI = 1.02-1.12, p = 0.003), serum IgM (HR = 0.98, 95%CI = 0.96-1.00, p = 0.036), BUN (HR = 1.02, 95%CI = 1.01-1.02, p = 0.005), and eGFR (HR = 0.097, 95%CI = 0.94-0.99, p = 0.0011) were associated with patient survival. After multivariate Cox regression analysis, age (HR = 1.08, 95%CI = 1.01-1.13, p = 0.013), crescents (HR = 5.57, 95%CI = 1.14-29.05, p = 0.034), and HDL (HR = 0.94, 95%CI = 0.90-0.99, p = 0.026) were associated with patient survival. Crescents IgAN is with the highest risk (up to 5.75 of HR) for patient mortality.ConclusionsThe major strengths of the present study is that crescents IgAN had worse patient survival compared to non-crescents IgAN. Clinicians should be more careful to care patients with crescents IgAN.
| S-EPMC7394392 | biostudies-literature
Project description:Automated reporting of estimated GFR (eGFR) with serum creatinine measurement is now common. We surveyed nephrologists in four countries to determine whether eGFR reporting influences nephrologists' recommendations for dialysis initiation. Respondents were randomly allocated to receive a survey of four clinical vignettes that included either serum creatinine concentration only or serum creatinine and the corresponding eGFR. For each scenario, the respondent was asked to rank his or her likelihood of recommending dialysis initiation on a modified 8-point Likert scale, ranging from 1 ("definitely not") to 8 ("definitely would"). Analysis of the 822 eligible responses received showed that the predicted likelihood of recommending dialysis increased by 0.55 points when eGFR was reported (95% confidence interval, 0.33 to 0.76), and this effect was larger for eGFRs >5 ml/min per 1.73 m(2) (P<0.001). Subgroup analyses suggested that physicians who had been in practice ?13 years were more affected by eGFR reporting (P=0.03). These results indicate that eGFR reporting modestly increases the likelihood that dialysis is recommended, and physicians should be aware of this effect when assessing patients with severe CKD.
| S-EPMC3810082 | biostudies-other
Project description:BackgroundDespite cardiovascular disease (CVD) and chronic kidney disease sharing similar causes and interplay, it is unknown if a broader relationship between these diseases exists across generations. We investigated the association between parental CVD history and estimated glomerular filtration rate (eGFR) in the community.Study designCross-sectional and longitudinal analyses.Setting & participants13,241 community-based adults with serum creatinine measurement and follow-up visits (from 1-8 visits ~2 years apart) from the Aerobics Center Longitudinal Study.PredictorsPremature parental CVD history (before age 50 years).OutcomeseGFR, decreased eGFR (<60 mL/min/1.73 m(2)), and rate of eGFR decline.MeasurementsInformation for parental history was collected by protocol-standardized questionnaires. eGFR was assessed with serum creatinine.Results3,339 (25.2%) participants reported a history of parental CVD. Individuals with parental CVD had significantly lower eGFRs compared with those without parental CVD (69.4 ± 12.9 vs 74.8 ± 14.2 mL/min/1.73 m(2); P<0.001). After multivariable adjustment, parental CVD was associated independently with higher odds of having decreased eGFR (adjusted OR, 1.68; 95% CI, 1.52-1.86). Random-coefficient models showed that individuals with parental CVD had a faster decline in eGFR compared with those without parental CVD (sex- and ethnicity-adjusted annual change of -0.47 vs -0.41 mL/min/1.73 m(2); P=0.06).Limitations~70% of participants did not attend a second examination.ConclusionsParental history of CVD was associated with lower baseline eGFR, higher odds of decreased eGFR, and a nominally faster rate of eGFR decline in the offspring. Such findings may imply previously unrecognized cross-generational links between both diseases and be of support in community screening programs.
| S-EPMC4414720 | biostudies-literature
Project description:The error of estimated glomerular filtration rate (eGFR) and its consequences in predialysis are unknown. In this prospective multicentre study, 315 predialysis patients underwent measured GFR (mGFR) by the clearance of iohexol and eGFR by 52 formulas. Agreement between eGFR and mGFR was evaluated by concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). In a sub-analysis we assessed the impact of eGFR error on decision-making as (i) initiating dialysis, (ii) preparation for renal replacement therapy (RRT) and (iii) continuing clinical follow-up. For this sub-analysis, patients who started RRT due to clinical indications (uremia, fluid overload, etc.) were excluded. eGFR had scarce precision and accuracy in reflecting mGFR (average CCC 0.6, TDI 70% and cp 22%) both in creatinine- and cystatin-based formulas. Variations -larger than 10 ml/min- between mGFR and eGFR were frequent. The error of formulas would have suggested (a) premature preparation for RTT in 14% of stable patients evaluated by mGFR; (b) to continue clinical follow-up in 59% of subjects with indication for RTT preparation due to low GFRm and (c) to delay dialysis in all asymptomatic patients (n = 6) in whom RRT was indicated based on very low mGFR. The error of formulas in predialysis was frequent and large and may have consequences in clinical care.
| S-EPMC10909958 | biostudies-literature
Project description:BackgroundThis study aimed to develop a machine learning-based 2-year risk prediction model for early identification of patients with rapid progressive immunoglobulin A nephropathy (IgAN). We also assessed the model's performance to predict the long-term kidney-related outcome of patients.MethodsA retrospective cohort of 1,301 patients with biopsy-proven IgAN from two tertiary hospitals was used to derive and externally validate a random forest-based prediction model predicting primary outcome (30% decline in estimated glomerular filtration rate from baseline or end-stage kidney disease requiring renal replacement therapy) and secondary outcome (improvement of proteinuria) within 2 years after kidney biopsy.ResultsFor the 2-year prediction of primary outcomes, precision, recall, area-under-the-curve, precision-recall-curve, F1, and Brier score were 0.259, 0.875, 0.771, 0.242, 0.400, and 0.309, respectively. The values for the secondary outcome were 0.904, 0.971, 0.694, 0.903, 0.955, and 0.113, respectively. From Shapley Additive exPlanations analysis, the most informative feature identifying both outcomes was baseline proteinuria. When Kaplan-Meier analysis for 10-year kidney outcome risk was performed with three groups by predicting probabilities derived from the 2-year primary outcome prediction model (low, moderate, and high), high (hazard ratio [HR], 13.00; 95% confidence interval [CI], 9.52-17.77) and moderate (HR, 12.90; 95% CI, 9.92-16.76) groups showed higher risks compared with the low group. From the 2-year secondary outcome prediction model, low (HR, 1.66; 95% CI, 1.42-1.95) and moderate (HR, 1.42; 95% CI, 0.99-2.03) groups were at greater risk for 10-year prognosis than the high group.ConclusionOur machine learning-based 2-year risk prediction models for the progression of IgAN showed reliable performance and effectively predicted long-term kidney outcome.
| S-EPMC11615444 | biostudies-literature
Project description:Rationale & objectiveAn early change in proteinuria is considered a reasonably likely surrogate end point in immunoglobulin A nephropathy (IgAN) and can be used as a basis for accelerated approval of therapies, with verification in a postmarketing confirmatory trial. Glomerular filtration rate (GFR) slope is a recently validated surrogate end point for chronic kidney disease progression and may be considered as the end point used for verification. We undertook a meta-analysis of clinical trials in IgAN to compare treatment effects on change in proteinuria versus change in estimated GFR (eGFR) slope.Study designIndividual patient-level meta-analysis.Setting & study populationsIndividual data of 1,037 patients from 12 randomized trials.Selection criteria for studiesRandomized trials of IgAN with proteinuria measurements at baseline and 6 (range, 2.5-14) months and at least a further 1 year of follow-up for the clinical outcome.Analytical approachFor each trial, we estimated the treatment effects on proteinuria and on the eGFR slope, computed as the total slope starting at baseline or the chronic slope starting 3 months after randomization. We used a Bayesian mixed-effects analysis to relate the treatment effects on proteinuria to effects on GFR slope across these studies and developed a prediction model for the treatment effect on the GFR slope based on the effect on proteinuria.ResultsAcross all studies, treatment effects on proteinuria accurately predicted treatment effects on the total slope at 3 years (median R2 = 0.88; 95% Bayesian credible interval [BCI], 0.06-1) and on the chronic slope (R2 = 0.98; 95% BCI, 0.29-1). For future trials, an observed treatment effect of approximately 30% reduction in proteinuria would confer probabilities of at least 90% for nonzero treatment benefits on the total and chronic slopes of eGFR. We obtained similar results for proteinuria at 9 and 12 months and total slope at 2 years.LimitationsStudy population restricted to 12 trials of small sample size, leading to wide BCIs. There was heterogeneity among trials with respect to study design and interventions.ConclusionsThese results provide new evidence supporting that early reduction in proteinuria can be used as a surrogate end point for studies of chronic kidney disease progression in IgAN.
| S-EPMC8384669 | biostudies-literature