Novel Urinary Biomarkers For Improved Prediction Of Progressive eGFR Loss In Early Chronic Kidney Disease Stages And In High Risk Individuals Without Chronic Kidney Disease

Abstract

Chronic kidney disease is associated with increased risk of CKD progression and death. Therapeutic approaches to limit progression are limited. Developing tools for the early identification of those individuals most likely to progress will allow enriching clinical trials in high risk early CKD patients. The CKD273 classifier is a panel of 273 urinary peptides that enables early detection of CKD and prognosis of progression. We have generated urine capillary electrophoresis-mass spectrometry-based peptidomics CKD273 subclassifiers specific for CKD stages to allow the early identification of patients at high risk of CKD progression. In the validation cohort, the CKD273 subclassifiers outperformed albuminuria and CKD273 classifier for predicting rapid loss of eGFR in individuals with baseline eGFR > 60 ml/min/1.73 m2. In individuals with eGFR > 60 ml/min/1.73 m2 and albuminuria <30 mg/day, the CKD273 subclassifiers predicted rapid eGFR loss with AUC ranging from 0.797 (0.743–0.844) to 0.736 (0.689–0.780). The association between CKD273 subclassifiers and rapid progression remained significant after adjustment for age, sex, albuminuria, DM, baseline eGFR, and systolic blood pressure. Urinary peptidomics CKD273 subclassifiers outperformed albuminuria and CKD273 classifier for predicting the risk of rapid CKD progression in individuals with eGFR > 60 ml/min/1.73 m2. These CKD273 subclassifiers represented the earliest evidence of rapidly progressive CKD in non-albuminuric individuals with preserved renal function.

Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

“…These tools could let early intervention or prediction of therapy response, leading to a personalized therapeutic approach [3,4,23,24]. One of these tools is urine proteomics, which is a promising strategy for predicting rapid disease progression before albuminuria becomes pathological [25]. Recently, a kidney risk inflammatory signature consisting of 17 circulating proteins was associated with the 10-year risk of ESRD in type 1 and type 2 DN with pathological albuminuria and low estimated glomerular filtration rate [26].…”

Urinary Proteomics and Precision Medicine for Chronic Kidney Disease: Current Status and Future Perspectives

“…Recent developments may change this however, since there are now efforts to assign different subclassifiers of the CKD273 peptides to different eGFR strata. Rodriguez‐Ortiz et al . showed that these specifically developed subclassifiers can outperform albuminuria and CKD273 at several stages of eGFR and may thus refine the clinical use of this approach.…”

Urinary Peptidomic Biomarkers in Kidney Diseases

“…When peptide overlap with CKD273 was examined, common peptides varied according to the eGFR stratum. The highest number of common peptides was found for stratum 1 (eGFR ≥ 80 mL/min/1.73 m 2 ), whereas in stratum 6 (eGFR 30-39 mL/min/1.73 m 2 ) there was no peptide overlapping [44].…”

“…More recently, CKD subclassifiers specific for CKD stages were generated, allowing early identification of patients at high risk of CKD progression [44]. Urinary peptidomics CKD273 subclassifiers outperformed CKD classifier and urinary albumin for predicting rapid loss of eGFR in individuals with baseline eGFR > 60 mL/min/1.73 m 2 , and even predicted a rapid CKD progression in individuals with eGFR > 60 mL/min/1.73 m 2 and albuminuria < 30 mg/day.…”