The pathophysiology of distal renal tubular acidosis

Abstract

The kidneys have a central role in the control of acid-base homeostasis owing to bicarbonate reabsorption and production of ammonia and ammonium in the proximal tubule and active acid secretion along the collecting duct. Impaired acid excretion by the collecting duct system causes distal renal tubular acidosis (dRTA), which is characterized by the failure to acidify urine below pH 5.5. This defect originates from reduced function of acid-secretory type A intercalated cells. Inherited forms of dRTA are caused by variants in SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, WDR72 and likely in other genes that are yet to be discovered. Inheritance of dRTA follows autosomal dominant and recessive patterns. Acquired forms of dRTA are caused by various types of autoimmune diseases or adverse effects of some drugs.Incomplete dRTA is frequently found in patients with and without kidney stone disease.These patients fail to appropriately acidify their urine when challenged, suggesting that incomplete dRTA may represent an intermediate state in the spectrum of the ability to excrete acids. Unrecognized or insufficiently treated dRTA can cause rickets and failure to thrive in children, osteomalacia in adults, nephrolithiasis and nephrocalcinosis. Electrolyte disorders are also often present and poorly controlled dRTA can increase the risk of developing chronic kidney disease. GlossaryEndolymph: Potassium rich fluid filling the cochlear duct and membranous labyrinth of the inner ear, secreted by the stria vascularis.Ovalocytosis: red blood cell deformity with oval-shaped red blood cells, also called elliptcytosis, that are mostly caused by defects in the cytoskeleton. In the case of SAO, the anchoring of the cytoskeleton to the membrane is reduced due to the absence of the AE1 containing protein complex.Sjögren overlap syndrome. Overlap of autoimmune disorders with anti-SSA(Ro) positive antibodies that may include features of Sjögren, SLE, myositis, scleroderma, vasculitis and rheumatoid arthritis.

Natural Metal Polyphenol Nanozyme: Free Radical Scavenging and Antioxidation for the Treatment of Acute Kidney Injury

“…In comparison, these injuries were markedly attenuated by RosA-Mn NPs treatment, confirming the potential ability of RosA-Mn NPs to protect against renal damage (Figure h). Excessive apoptosis of renal tubular epithelial cells and subsequent impairment of tubular repair have been reported to contribute to tubulointerstitial injury . Renal tubular cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).…”

“…Excessive apoptosis of renal tubular epithelial cells and subsequent impairment of tubular repair have been reported to contribute to tubulointerstitial injury. 35 Renal tubular cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The fluorescence images and their quantification showed that the proportion of TUNEL positive cells in the CDDP-treated kidney tissue of AKI mice was much higher than that in the kidneys of mice treated with RosA-Mn NPs (see Figures 4h and 4f).…”

The B1 H+-ATPase (Atp6v1b1) Subunit in Non–Type A Intercalated Cells is Required for Driving Pendrin Activity and the Renal Defense Against Alkalosis

“…H 1 -ATPase Activity is Decreased at the Basolateral Side of Non-Type A ICs Despite an Increased Basolateral Accumulation of the B2 Subunit The absence of the B1 subunit in type A ICs is partly compensated by enhanced abundance of the B2 isoform, which however fails to support stimulation of H 1 -ATPase activity by acidosis or angiotensin II. 22,23,25,26 Immunohistochemistry on kidneys from alkali-loaded mice showed diffuse staining for the B2 subunit toward the basolateral membrane of pendrin-positive ICs in Atp6v1b1 1/1 and a stronger and more pronounced basolateral B2 staining in pendrin-positive ICs in Atp6v1b1 2/2 mice (Figure 4, A and B, and Supplemental Table 6). Thus, we assessed whether basolateral H 1 -ATPase activity, necessary for proton reabsorption and bicarbonate secretion by non-type A IC, is affected by Atp6v1b1 gene deletion.…”

“…17,20,21 Mutations in the gene encoding the B1 subunit (ATP6V1B1) cause distal renal tubular acidosis (dRTA) in man, characterized by the inability of the distal nephron to appropriately acidify the urine. 19,22 A mouse model deficient for the Atp6v1b1 gene showed impaired H 1 secretion by type A ICs in the CD. 23,24 Moreover, in the absence of the B1 subunit, the B2 subunit is upregulated in type A ICs and assumes a more apical localization.…”

Urinary Tract Infections: Renal Intercalated Cells Protect against Pathogens

“…As host defense mechanisms in the bladder are evaded, UPEC can reach the collecting duct (CD). The CD contains a salt-and-pepper, highly plastic epithelium 8 that is composed of two major cell types: intercalated cells (ICs) and principal cells (PCs) (Figure 1). Aquaporin-2-expressing cells serve as precursors for PCs, and IC subtypes and their differentiation is regulated by forkhead box protein I1 (Foxi1) transcription factor and JAG1 and NOTCH1/2 signaling.…”