Molecular cloning and characterization of the vasopressin-regulated urea transporter of rat kidney collecting ducts.

Absorption of urea in the renal inner medullary collecting duct (IMCD) contributes to hypertonicity in the medullary interstitium which, in turn, provides the osmotic driving force for water reabsorption. This mechanism is regulated by vasopressin via a cAMP-dependent pathway and activation of a specialized urea transporter located in the apical membrane. We report here the cloning of a novel urea transporter, designated UT1, from the rat inner medulla which is functionally and structurally distinct from the previously reported kidney urea transporter UT2. UT1 expressed in Xenopus oocytes mediated passive transport of urea that was inhibited by phloretin and urea analogs but, in contrast to UT2, was strongly stimulated by cAMP agonists. Sequence comparison revealed that the coding region of UT1 cDNA contains the entire 397 amino acid residue coding region of UT2 and an additional 1,596 basepair-stretch at the 5' end. This stretch encodes a novel 532 amino acid residue NH2-terminal domain that has 67% sequence identity with UT2. Thus, UT1 consists of two internally homologous portions that have most likely arisen by gene duplication. Studies of the rat genomic DNA further indicated that UT1 and UT2 are derived from a single gene by alternative splicing. Based on Northern analysis and in situ hybridization, UT1 is expressed exclusively in the IMCD, particularly in its terminal portion. Taken together, our data show that UT1 corresponds to the previously characterized vasopressin-regulated urea transporter in the apical membrane of the terminal IMCD which plays a critical role in renal water conservation

The urea transporter family (SLC14): physiological, pathological and structural aspects

Urea transporters (UTs) belonging to the solute carrier 14 (SLC14) family comprise two genes with a total of eight isoforms in mammals, UT-A1 to -A6 encoded by SLC14A2 and UT-B1 to -B2 encoded by SLC14A1. Recent efforts have been directed toward understanding the molecular and cellular mechanisms involved in the regulation of UTs using transgenic mouse models and heterologous expression systems, leading to important new insights. Urea uptake by UT-A1 and UT-A3 in the kidney inner medullary collecting duct and by UT-B1 in the descending vasa recta for the countercurrent exchange system are chiefly responsible for medullary urea accumulation in the urinary concentration process. Vasopressin, an antidiuretic hormone, regulates UT-A isoforms via the phosphorylation and trafficking of the glycosylated transporters to the plasma membrane that occurs to maintain equilibrium with the exocytosis and ubiquitin-proteasome degradation pathways. UT-B isoforms are also important in several cellular functions, including urea nitrogen salvaging in the colon, nitric oxide pathway modulation in the hippocampus, and the normal cardiac conduction system. In addition, genomic linkage studies have revealed potential additional roles for SLC14A1 and SLC14A2 in hypertension and bladder carcinogenesis. The precise role of UT-A2 and presence of the urea recycling pathway in normal kidney are issues to be further explored. This review provides an update of these advances and their implications for our current understanding of the SLC14 UTs

Prevalence of chronic kidney disease stages 3–5 in low- and middle-income countries in Asia: A systematic review and meta-analysis

Chronic kidney disease (CKD) is a major public health problem in low- and middle-income countries (LMICs). Although CKD prevalence has been rapidly increasing in LMICs, particularly in Asia, quantitative studies on the current epidemiology of CKD in this region are limited. This study aimed to identify the prevalence of CKD stages 3–5 in LMICs in Asia, by subregion, country economy classification, identification of CKD, traditional and non-traditional risk factors. A systematic review and meta-analysis of observational studies was conducted through a literature search of seven electronic databases and grey literature search published until November 2021. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the risk of bias of each study. A random-effects model was used to estimate pooled prevalence. The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42019120519). Of 4,548 potentially relevant records, 110 studies with moderate and high quality were included with 4,760,147 subjects. The average prevalence (95% CI) of CKD stages 3–5 in 14 LMICs in Asia was 11.2% (9.3–13.2%). The prevalence of CKD stages 3–5 was varied among subregions and country economic classification. CKD prevalence was 8.6% (7.2–10.2%) in east Asia, 12.0% (7.7–17.0%) in south-east Asia, 13.1% (8.7–18.2%) in western Asia, and 13.5% (9.5–18.0%) in south Asia. CKD prevalence was 9.8% (8.3–11.5%) in upper-middle-income countries and 13.8% (9.9–18.3%) in lower-middle-income countries. Prevalence of CKD stage 3–5 in LMICs in Asia is comparable to global prevalence. High level of heterogeneity was observed. Study of factors and interventions that lead to the delay of CKD progression is needed.</jats:p