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Vitamin D3 is clinically used for the treatment of vitamin D3 deficiency or osteoporosis, partially because of its role in regulating phosphate (Pi) and calcium (Ca2+) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in Pi homeostasis; however, the role of vitamin D3 in hypophosphatemia has never been investigated. We administered vehicle or vitamin D3 to wild-type (WT) mice or hypophosphatemic Npt2a−/− mice. In contrast to WT mice, vitamin D3 treatment increased plasma Pi levels in Npt2a−/− mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca2+ was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary Pi and Ca2+/creatinine ratios, in Npt2a−/− mice, Pi/creatinine was unchanged and Ca2+/creatinine drastically decreased, coinciding with the highest kidney Ca2+ content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a−/− mice, vitamin D3 treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a−/− only, the latter might facilitate the increase in plasma Pi in Npt2a−/− mice. Npt2a might function as regulator between renal Ca2+ excretion and reabsorption in response to vitamin D3. [ABSTRACT FROM AUTHOR]

The article explores the potential relationship between uric acid and the progression of polycystic kidney disease (PKD). Previous research has shown that high levels of uric acid can worsen the outcomes of PKD, but the mechanism behind this is not fully understood. The article suggests that further research is needed to investigate the interplay between uric acid metabolism and other signaling mechanisms, as well as the role of specific genes and transporters. The study was supported by grants from the National Institutes of Health and the Ben J. Lipps Research Fellowship Program, and the authors declare no conflicts of interest. [Extracted from the article]

High K+ supplementation is correlated with a lower risk of the composite of death, major cardiovascular events, and ameliorated blood pressure, but the exact mechanisms have not been established. Inwardly rectifying K+ (Kir) channels expressed in the basolateral membrane of the distal nephron play an essential role in maintaining electrolyte homeostasis. Mutations in this channel family have been shown to result in strong disturbances in electrolyte homeostasis, among other symptoms. Kir7.1 is a member of the ATP-regulated subfamily of Kir channels. However, its role in renal ion transport and its effect on blood pressure have yet to be established. Our results indicate the localization of Kir7.1 to the basolateral membrane of aldosterone-sensitive distal nephron cells. To examine the physiological implications of Kir7.1, we generated a knockout of Kir7.1 (Kcnj13) in Dahl salt-sensitive (SS) rats and deployed chronic infusion of a specific Kir7.1 inhibitor, ML418, in the wild-type Dahl SS strain. Knockout of Kcnj13 (Kcnj13-/-) resulted in embryonic lethality. Heterozygous Kcnj13þ/- rats revealed an increase in K+ excretion on a normal-salt diet but did not exhibit a difference in blood pressure development or plasma electrolytes after 3 wk of a high-salt diet. Wild-type Dahl SS rats exhibited increased renal Kir7.1 expression when dietary K+ was increased. K+ supplementation also demonstrated that Kcnj13þ/- rats excreted more K+ on normal salt. The development of hypertension was not different when rats were challenged with high salt for 3 wk, although Kcnj13þ/- rats excrete less Na+. Interestingly, chronic infusion of ML418 significantly increased Na+ and Cl- excretion after 14 days of high salt but did not alter salt-induced hypertension development. Here, we found that reduction of Kir7.1 function, either through genetic ablation or pharmacological inhibition, can influence renal electrolyte excretion but not to a sufficient degree to impact the development of SS hypertension. [ABSTRACT FROM AUTHOR]

Recently, research has redirected its interests in uric acid (UA) from gout, an inflammatory disease in joints, to groups of closely interrelated pathologies associated with cardiovascular and kidney dysfunction. Many epidemiological, clinical, and experimental studies have shown that UA may play a role in the pathophysiology of the cardiorenal syndrome continuum; however, it is still unclear if it is a risk factor or a causal role. Hyperuricemia has been well studied in the past two decades, revealing mechanistic insights into UA homeostasis. Likewise, some epidemiological and experimental evidence suggests that hypouricemia can lead to cardiorenal pathologies. The goal of this review is to highlight why studying both hyperuricemia and hypouricemia is warranted as well as to summarize the relevance of UA to kidney function [ABSTRACT FROM AUTHOR]

High K + supplementation is correlated with a lower risk of the composite of death, major cardiovascular events, and ameliorated blood pressure, but the exact mechanisms have not been established. Inwardly rectifying K + (K ir ) channels expressed in the basolateral membrane of the distal nephron play an essential role in maintaining electrolyte homeostasis. Mutations in this channel family have been shown to result in strong disturbances in electrolyte homeostasis, among other symptoms. K ir 7.1 is a member of the ATP-regulated subfamily of K ir channels. However, its role in renal ion transport and its effect on blood pressure have yet to be established. Our results indicate the localization of K ir 7.1 to the basolateral membrane of aldosterone-sensitive distal nephron cells. To examine the physiological implications of K ir 7.1, we generated a knockout of K ir 7.1 ( Kcnj13 ) in Dahl salt-sensitive (SS) rats and deployed chronic infusion of a specific K ir 7.1 inhibitor, ML418, in the wild-type Dahl SS strain. Knockout of Kcnj13 ( Kcnj13 -/- ) resulted in embryonic lethality. Heterozygous Kcnj13 +/- rats revealed an increase in K + excretion on a normal-salt diet but did not exhibit a difference in blood pressure development or plasma electrolytes after 3 wk of a high-salt diet. Wild-type Dahl SS rats exhibited increased renal K ir 7.1 expression when dietary K + was increased. K + supplementation also demonstrated that Kcnj13 +/- rats excreted more K + on normal salt. The development of hypertension was not different when rats were challenged with high salt for 3 wk, although Kcnj13 +/- rats excrete less Na + . Interestingly, chronic infusion of ML418 significantly increased Na + and Cl - excretion after 14 days of high salt but did not alter salt-induced hypertension development. Here, we found that reduction of K ir 7.1 function, either through genetic ablation or pharmacological inhibition, can influence renal electrolyte excretion but not to a sufficient degree to impact the development of SS hypertension. NEW & NOTEWORTHY To investigate the role of the K ir 7.1 channel in salt-sensitive hypertension, its function was examined using complementary genetic and pharmacological approaches. The results revealed that although reducing K ir 7.1 expression had some impact on maintaining K + and Na + balance, it did not lead to a significant change in the development or magnitude of salt-induced hypertension. Hence, it is probable that K ir 7.1 works in conjunction with other basolateral K + channels to fine-tune membrane potential.