Abstract P3026: Impact of Dietary Electrolytes on Post-Nephrectomy Blood Pressure, Proteinuria and Renal Function

Abstract

When chronic kidney disease progresses to end stage renal disease, the optimal treatment is living kidney donation (LKD). A 10 yr prospective study of 1214 donors (PMID 27006347), reported that LKD increased risk of hypertension (HTN), by 3.64-fold, as well as HTN induced albuminuria. Our objective was to test whether a DASH-style diet (DD: 0.74% NaCl, 3%K with 1% each: Cl - , citrate, HCO 3 - ) would blunt hypertension and albuminuria following UNX vs. a western style diet (WD: 2% NaCl, 1%KCl). Uninephrectomized (UNX) male SD rats (n=5/group) preequilibrated on diets were analyzed 12-14 wks post-UNX. Systolic BP (SBP, mmHg) was similar pre-UNX in DD (126 ± 8) and WD (132 ± 8); SBP increased post-UNX by 7 ± 2 (DD) and 21 ± 5 (WD) mmHg, p=0.04. Urine injury markers (albumin, angiotensinogen, KIM-1 and plasminogen) increased in both DD and WD (all p<0.01). Kidney weight increased similarly from 1.5 ± 2 (pre-UNX) to 2.3 ± 0.2 g (post-UNX) in pooled DD, WD. By IHC, glomeruli diameters increased 1.6-fold pre-vs. post-UNX. Transporter profiles were generated from both pre-and post-UNX kidneys. Pre-UNX, DD (vs. WD) exhibited lower abundance of proximal tubule (PT) NHE3, NaPi2 and NHERF1, and higher abundance of NKA α1, NCC, NCCp, claudin 7, SPAK, ENaC subunits and AQP2 (all p < 0.01). Post-UNX (vs. pre-UNX) abundance, normalized to equivalent protein, exhibited lower claudin2, megalin, AQP1 and AQP2 in both DD and WD (all p < 0.01), and, specifically to DD post-UNX: 1.4-fold increases in NCCp, SPAKp and 0.7-fold decreases in cleaved α and γ ENaC (all p<0.05). By IHC, NHE3 localized within the apical microvilli in DD and WD pre- and post-UNX. Lithium clearance (CLi, ml/min/Kg BW) increased post-UNX in DD (p=0.006) not WD; post UNX CLi was higher in DD (0.075 ± 0.013) vs WD (0.042 ± 0.009), p=0.036. In conclusion, the phenotype of HTN and proteinuria observed following LKD in humans is evident in this pilot SD rat study. Compared to the 2% NaCl/1% KCl “Western style” diet, the 3% K + and alkali rich “DASH style diet” lowered baseline PT transporter levels, increased CLi (indicator of flow out of PT), elevated distal Na + transporters (likely due to flow from PT) and blunted the rise in BP post-UNX. The findings suggest that DASH style dietary electrolytes may improve outcomes following LKD.