High Dietary K Intake Inhibits Proximal Tubule Transport and Reduces GFR

Abstract

The kidneys respond to increased dietary K+ intake by excreting more K+ in the urine to maintain K+ balance. A key event underlying this regulation is increased secretion of K+ by distal nephron segments including the late DCT (DCT2), and the connecting tubule (CNT). It has been suggested that more proximal nephron segments may contribute to this process by reducing Na+ reabsorption, thus augmenting distal Na+ delivery. There is, however, little information on the magnitude of these proximal adjustments and their impact on distal Na+ flow. To address this issue, we used micropuncture to quantify the modulation of Na+ and K+ transport by proximal tubule (PT) in response to elevation of K+ intake in the rat. The impact of chronic dietary K+ loading on PT function was measured using free-flow micropuncture, along with measurements of overall kidney function, including urine volume (UV), glomerular filtration rate (GFR), and absolute (ENa, EK) and fractional (FENa, FEK) Na+ and K+ excretion. The difference between CK (Control-K 1% KCl) and HK CK (high-K 5% KCl, 7 days) treated rats were compared. HK intake significantly reduced GFR by 29%, increased UV by 77%, and increased EK by 202%. HK did not change ENa (0.84 vs. 0.76μ Eq/min/100gBW) but significantly increased FENa (1.40 vs. 0.64%), indicating that fractional Na+ absorption is reduced by HK. To assess PT function, we measured the ratio of FITC-Inulin (as a volume maker), Na+ and K+concentrations in the tubular fluid and plasma (TF/P) and normalized the [Na] TF/P and [K] TF/P by Inulin TF/P (In TF/P). Tubular fluid was collected at the 20%, 60% and 80% of the length of PTs. In TF/P increased along the tubule in both CK and HK treated rats. In TF/P was 1.04, 2.79 and 3.83 in CK and was 0.98, 1.78 and 2.16 in HK at the position of 20%, 60% and 80% of the PT respectively, indicating that volume is absorbed along the tubule. In TF/P was lower in HK in all positions and was significantly reduced at the end (80%) of the PT, indicating that fluid absorption is reduced by HK. In addition, the fractional delivery of Na+, TF/P Na+/In ratio, decreases along the tubule, quantifying PT Na+ reabsorption. We find that in comparison with CK, HK increased this ratio. It was 0.91, 0.49, and 0.34 in CK and was 1.22, 0.74, and 0.63 in HK respectively, documenting that HK reduced PT Na+ absorption. This effect offsets the reduction in filtered load of Na+ and predicts a 33% increase in Na+ delivered out of the PT. Micropuncture data also show that K+ concentrations in the tubular fluid (TF) are significantly increased by HK in all positions of the PT compared with the CK; at the 80% point of PT, TF K+ was 4.7mM in CK and was 6.1 mM in HK. Our results demonstrate that with increased dietary K+ intake, there is reduction of GFR and additional reduction in fractional PT transport. The net effect may facilitate K+ excretion and help balance Na+ excretion by shifting Na+reabsorption to K-secreting segments of the nephron. NIH NIDDK R01 DK117650 (Tong Wang); RO1-DK-29857 (Alan M. Weinstein); and R01-DK111380 (Lawrence Palmer) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.