Salt, but not protein intake, is associated with accelerated disease progression in autosomal dominant polycystic kidney disease

Bart J Kramers,Iris W Koorevaar,Joost P.H Drenth,Johan W De Fijter,Antonio Gomes Neto,Dorien J.M Peters,Priya Vart,Jack F Wetzels,Robert Zietse,Ron T Gansevoort,Esther Meijer

doi:10.1016/j.kint.2020.04.053

Abstract

In autosomal dominant polycystic kidney disease (ADPKD), there are only scarce data on the effect of salt and protein intake on disease progression. Here we studied association of these dietary factors with the rate of disease progression in ADPKD and what the mediating factors are by analyzing an observational cohort of 589 patients with ADPKD. Salt and protein intake were estimated from 24-hour urine samples and the plasma copeptin concentration measured as a surrogate for vasopressin. The association of dietary intake with annual change in the estimated glomerular filtration rate (eGFR) and height adjusted total kidney volume (htTKV) growth was analyzed with mixed models. In case of significant associations, mediation analyses were performed to elucidate potential mechanisms. These patients (59% female) had a mean baseline age of 47, eGFR 64 mL/min/1.73m2 and the median htTKV was 880 mL. The mean estimated salt intake was 9.1 g/day and protein intake 84 g/day. During a median follow-up of 4.0 years, eGFR was assessed a median of six times and 24-hour urine was collected a median of five times. Salt intake was significantly associated with annual change in eGFR of-0.11 (95% confidence interval 0.20 --0.02] mL/min/1.73m2) per gram of salt, whereas protein intake was not (-0.00001 [-0.01 - 0.01] mL/min/1.73m2) per gram of protein). The effect of salt intake on eGFR slope was significantly mediated by plasma copeptin (crude analysis: 77% mediation, and, adjusted analysis: 45% mediation), but not by systolic blood pressure. Thus, higher salt, but not higher protein intake may be detrimental in ADPKD. The substantial mediation by plasma copeptin suggests that this effect is primarily a consequence of a salt-induced rise in vasopressin.

Highlights

I n chronic kidney disease (CKD), salt restriction is advocated to slow disease progression.[1]
The effect is significantly mediated by plasma copeptin level, suggesting that salt intake may have detrimental effects by increasing vasopressin
The association of salt intake with estimated glomerular filtration rate (eGFR) decline is in line with scarce earlier findings

Summary

Introduction

I n chronic kidney disease (CKD), salt restriction is advocated to slow disease progression.[1]. In a post hoc analysis of the HALT Progression of Polycystic Kidney Disease (HALT-PKD) study, a randomized controlled trial in 1044 patients with later-stage ADPKD, sodium excretion was associated with steeper estimated glomerular filtration rate (eGFR) decline in patients with later-stage ADPKD but not in patients with early-stage ADPKD.[5,6] It has been suggested that an association with eGFR decline may be caused by salt restriction potentiating the renal protective effects of RAAS blockade, similar to nonADPKD CKD.[6] An alternative explanation could be that salt intake leads to accelerated disease progression in ADPKD by stimulation of vasopressin secretion. In the subgroup of 200 patients with ADPKD, there were no significant differences in either substudy; the results were deemed inconclusive by the investigators, among others due to lack of power.[11,12] Given these scarce and inconclusive data, we aimed to investigate the relation between salt and protein intake and renal function decline in ADPKD. We aimed to study whether a potential association was mediated by vasopressin or by other potential mechanisms

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Conclusion