Competing-Risk Analysis of Death and End Stage Kidney Disease by Hyperkalaemia Status in Non-Dialysis Chronic Kidney Disease Patients Receiving Stable Nephrology Care.

Michele Provenzano,Hiddo Heerspink,Felice Nappi,Carmela Iodice,Domenico Russo,Carlo Garofalo,Toni De Stefano,Paolo Chiodini,Giuseppe Conte,Silvio Borrelli,Luca De Nicola,Roberto Minutolo,Vincenzo Bellizzi

doi:10.3390/jcm7120499

Abstract

Hyperkalaemia burden in non-dialysis chronic kidney disease (CKD) under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalaemia (serum potassium, sK ≥ 5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of end stage kidney disease (ESKD) and death after visit 2. Age was 65 ± 15 years, eGFR 35 ± 17 mL/min/1.73 m2, proteinuria 0.40 (0.14–1.21) g/24 h. In the two visits sK was 4.8 ± 0.6 and levels ≥6 mEq/L were observed in 4%. Hyperkalaemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis (sub-hazard ratio-sHR, 95% Confidence Interval-CI) evidenced that new onset (sHR 1.34, 95% CI 1.05–1.72) and persistent (sHR 1.27, 95% CI 1.02–1.58) hyperkalaemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalaemia status is common (37%) and predicts per se higher ESKD risk but not mortality.

Highlights

Chronic hyperkalaemia is common in non-dialysis chronic kidney disease (ND-CKD)
A vicious circle may ensue with hyperkalaemia onset and dependent non-use or withdrawal of RASI leading to end-stage kidney disease (ESKD)
Novel K binders have been developed to treat chronic hyperkalaemia and improve effectiveness of RASI therapy [21,22]; knowing the hyperkalaemia burden in renal clinics, where these new drugs will be largely used, becomes a preliminary but essential step. To fill this important gap of knowledge, we studied a large prospective cohort of ND-CKD patients under stable nephrology care to verify in outpatient CKD clinics (I) the prevalence of hyperkalaemia at referral and after 12 months, (II) the hyperkalaemia-related risk of ESKD and all-cause death in the subsequent period of follow up

Summary

Introduction

Chronic hyperkalaemia is common in non-dialysis chronic kidney disease (ND-CKD). Recent observational studies have reported a greater prevalence of high serum potassium (sK) in this population than in general population; the reported rates have been extremely variable—from 1% to 50%—being mainly dependent on GFR and comorbidities of included patients, as on the number of sK measurements [1,2,3,4,5,6,7]. While in unselected population hyperkalaemia poses a risk excess of mortality for even moderate increases of sK (≥5.0 mEq/L) [7,8,9,10,11,12,13], the association between hyperkalaemia and progression to end-stage kidney disease (ESKD) remains controversial [1,4,10,13,14,15] Gaining insights into this association is essential because a main determinant of hyperkalaemia is the prescription of inhibitors of renin-angiotensin-system (RASI) [16,17], that are the first-choice antihypertensive agents in CKD due to the nephroprotective efficacy [18]. Increased awareness of this phenomenon and adequate management of hyperkalaemia through dietary and/or pharmacological intervention may interrupt this circle [20,21,22]

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