Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease

Abstract

The CRISP study of polycystic kidney disease (PKD) found that urinary sodium excretion associated with the rate of total kidney volume increase. Whether sodium restriction slows the progression of Autosomal Dominant PKD (ADPKD) is not known. To evaluate this we conducted a post-hoc analysis of the HALT-PKD clinical trials of renin-angiotensin blockade in patients with ADPKD. Linear mixed models examined whether dietary sodium affected rates of total kidney volume or change in estimated glomerular filtration rate (eGFR) in patients with an eGFR over 60 ml/min/1.73 m2 (Study A) or the risk for a composite endpoint of 50% reduction in eGFR, end-stage renal disease or death or the rate of eGFR decline in patients with an eGFR 25-60 ml/min/1.73 m2 (Study B) all in patients initiated on an under100 mEq sodium diet. During the trial urinary sodium excretion significantly declined by an average of 0.25 and 0.41 mEq/24 hour per month in studies A and B, respectively. In Study A, averaged and time varying urinary sodium excretions were significantly associated with kidney growth (0.43%/year and 0.09%/year, respectively, for each 18 mEq urinary sodium excretion). Averaged urinary sodium excretion was not significantly associated with faster eGFR decline (−0.07 ml/min/1.73m2/year for each 18 mEq urinary sodium excretion). In Study B, the averaged but not time-varying urinary sodium excretion significantly associated with increased risk for the composite endpoint (hazard ratio 1.08 for each 18 mEq urinary sodium excretion) and a significantly faster eGFR decline (−0.09 ml/min/1.73m2/year for each mEq 18 mEq urinary sodium excretion). Thus, sodium restriction is beneficial in the management of ADPKD.

Age- and height-adjusted total kidney volume growth rate in autosomal dominant polycystic kidney diseases

“…Renal and extrarenal phenotypes of ADPKD are heterogeneous due to the varieties of PKD mutation types [13, 15, 16], modifying genetic factors [17], gender differences [18] and environmental factors [19]. Genetic, imaging, clinical, laboratory, and environmental predictors are factors that are related to determining ADPKD disease severity [20].…”

International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people

“…The dietary salt intake of the general population of infants, toddlers and older children on a Western diet far exceeds the recommended amounts 94 . In adults with CKD, high salt intake is associated with higher blood pressure, proteinuria and progression to ESRD [95][96][97][98] . Higher sodium intake also blunts the antihypertensive and antiproteinuric effects of RAAS blockade 99,100 .…”

“…Higher sodium intake also blunts the antihypertensive and antiproteinuric effects of RAAS blockade 99,100 . In patients with ADPKD, urinary sodium excretion correlates with kidney growth 98,101 . Moreover, in patients with later-stage ADPKD, higher urinary sodium levels (a surrogate for sodium intake) increased the risk of a composite end point of a 50% reduction in eGFR, ESRD or death 98 .…”

“…In patients with ADPKD, urinary sodium excretion correlates with kidney growth 98,101 . Moreover, in patients with later-stage ADPKD, higher urinary sodium levels (a surrogate for sodium intake) increased the risk of a composite end point of a 50% reduction in eGFR, ESRD or death 98 . Few interventional trials exist, but restricting salt intake lowers blood pressure and proteinuria in adults with ADPKD or CKD 102,103 .…”

Polycystic Kidney Disease and the Vasopressin Pathway

“…In a recent post hoc analysis of the HALT-PKD clinical trials, dietary sodium -measured as averaged sodium excretion -showed to be associated with the rate of TKV increase but not with the rate of eGFR decline in ADPKD patients with an eGFR over 60 mL/min/1.73 m 2 . In patients with an eGFR 25-60 mL/min/1.73 m 2 averaged sodium excretion was associated with reaching a composite end point of 50% reduction of eGFR, end-stage renal disease (ESRD) or death, and with a faster rate of eGFR decline [36] . Markers of vasopressin were not studied in the HALT-PKD trials.…”