Abstract Background and Aims Chronic kidney disease (CKD) represents a major global healthcare challenge, affecting approximately 850 million people worldwide [1], and is an independent risk factor for the progression to kidney replacement therapy (KRT) and all-cause mortality [2]. However, CKD encompasses various causes, each with unique pathophysiology and rates of progression [3]. Here we describe the outcomes from NURTuRE-CKD, an ongoing, multicenter prospective cohort study of 2996 non-dialysis CKD patients, by primary renal diagnosis, aiming to describe the differing rates of progression, ESKD and mortality by CKD cause and provide insights into those at greatest risk. Method Patients with an eGFR of 15–59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a uACR >30 mg/mmol were enrolled, in addition to 86 controls. The full study design and methods of NURTuRE-CKD have previously been reported [4]. Outcomes: ESKD, eGFR <15 mL/min/1.73 m2, Transplantation, initiation of KRT, all-cause mortality and serial eGFR data were sourced from the UK Renal Registry. ESKD was defined as initiation of KRT or eGFR <15 mL/min/1.73 m2. Rate of progression was determined via eGFR slope. ERA diagnostic categories were used for primary renal diagnoses, with ‘glomerular diseases’ split into glomerulonephritis (GN) and vasculitis. The Chi-squared test was used to compare categorical variables, and the Kruskal-Wallis test for continuous variables. A multivariable Cox proportional hazards regression analysis predicting the time to ESKD by primary diagnosis was undertaken, using vasculitis as the reference category. Model 2 included adjustments for baseline eGFR. Results Table 1 depicts both the baseline characteristics and outcomes by the 8 diagnosis categories. Average follow-up duration was 53.8 months, not significantly different between the groups, but all other baseline variables differed significantly. The hypertensive/renovascular group were oldest and familial group youngest at 71 and 53 years, respectively. At baseline the diabetic nephropathy (DN) group had the lowest eGFR 28 ml/min/1.73 m2 and highest uACR 88.3 mg/mmol. However, the familial group had the steepest pre-enrolment eGFR decline slope. Delta eGFR during the follow-up period was steepest in the familial group and DN groups at −3.4 and −3.0 ml/min/1.73 m2, respectively, whereas the vasculitis group had slowest progression −0.7 ml/min/1.73 m2. Overall rate of ESKD was 24.7%; lower in the vasculitis (14%), systemic disease (17.7%) and tubulointerstitial (18.8%) groups, and higher in the DN (36.7%) and familial (31.6%) groups. All-cause mortality was greatest in the DN group at 40.4%. Despite being the fastest progressors defined by eGFR slope, the familial group had the lowest mortality rate (5.2%), but they were of younger age and had a high rate of kidney transplantation (10.1%). Unadjusted HRs for ESKD, were significantly higher for all diagnoses except tubulointerstitial and systemic diseases compared to the vasculitis group; DN evidenced the highest hazard ratio at 3.15 (2.18-4.55). When adjusted for baseline eGFR, HRs for the glomerulonephritis 2.04 (1.89-4.03), diabetes 1.5 (1.04-2.16) and familial 2.76 (1.89-4.03) remained significantly higher. Conclusion Rates of progression and incidence of clinically meaningful outcomes differ between CKD causes in NURTuRE. Those with DN and familial conditions had faster eGFR decline and had higher rates of ESKD, with associations persisting despite controlling for baseline eGFR. Recognising that CKD progresses at different rates is crucial, not only for providing personalised care, but also key to understanding differing pathophysiologic mechanisms of progression. NURTuRE-CKD will also explore novel biomarkers, with the aim of illuminating mechanisms of progression, improving risk prediction and highlighting novel drug targets.
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Jun 1, 2024
Carolyn J Presley + 5
Open Access