Development and validation of a nomogram to predict kidney survival at baseline in patients with C3 glomerulopathy

Abstract

Background C3 glomerulopathy is a rare and heterogeneous complement-driven disease. It is often challenging to accurately predict in clinical practice the individual kidney prognosis at baseline. We herein sought to develop and validate a prognostic nomogram to predict the long-term kidney survival. Methods Retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the GLOSEN group. The dataset was randomly divided into training group (n = 87) and validation group (n = 28). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of kidney outcome, and used to build the nomogram. Accuracy of the nomogram was assessed by discrimination and risk calibration, in the training and validation sets. Results The study group comprised 115 patients, of whom 46 patients (40%) reached kidney failure in a median follow-up of 49 months (range 24–112). No significant differences were observed in baseline estimated glomerular filtration rate (eGFR), proteinuria or total chronicity score of kidney biopsy, between patients in the training versus those in the validation set. The selected variables by LASSO were eGFR, proteinuria and total chronicity score. Based on Cox model a nomogram was developed for the prediction of kidney survival at 1-, 2-, 5- and 10-years from diagnosis. The C-index of the nomogram was 0.860 (95% confidence interval 0.834–0.887), and calibration plots showed optimal agreement between predicted and observed outcomes. Conclusions We constructed and validated a practical nomogram with good discrimination and calibration, to predict the risk of kidney failure in C3G patients at 1-, 2-, 5- and 10-years.

Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

“…Consequently, we need to identify clinical and kidney biopsy parameters of progressive disease. Our study confirms previous findings that eGFR at presentation associates with progression to kidney failure in C3 glomerulopathy (10,21,25,26) and membranoproliferative GN type 1 (8). Proteinuria at presentation and longitudinal change associated with progression in our study.…”

“…IFTA, cellular/fibrocellular crescents, and segmental sclerosis were associated with higher risk of progression to our composite outcome. The central pathology review of all biopsies overcame previous limitations (e.g., potential inter-report variation in identifying and quantitating lesions) where biopsy data have been extracted from clinical reports (10,25,26).…”

“…In contrast to the Columbia study (10), the chronicity (but not the activity score) associated with the outcome. Parameters associated with kidney failure were chronicity score greater than or equal to four, baseline eGFR, and 24-hour proteinuria (26). Longitudinal change in proteinuria also associated with kidney failure.…”

Clinical Profiles and Patterns of Kidney Disease Progression in C3 Glomerulopathy

“…Since we previously found that baseline eGFR, proteinuria, and histologic total chronicity score were the main predictors of kidney failure, 19 the study population was divided into different clinical profiles by combining these predictors: eGFR under/above 30, proteinuria under/ above 3.5 g/d, and total chronicity score under/above 4.…”

Prognostication for C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

“…The development of prediction tools to provide both patients and treating physicians with very relevant information is crucial for clinical and research purposes. Our group has recently proposed a simple and easy to use nomogram to predict the risk of kidney failure in C3 glomerulopathy (8) on the basis of the eGFR, proteinuria, and total chronicity score at baseline, although these results have not yet been validated in independent cohorts. The study by Lomax-Browne et al (6) is undoubtedly one of the most important cohorts published to date and sheds light on the main histologic determinants of outcomes in C3 glomerulopathy/Ig-mediated MPGN.…”