Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression

Abstract

ID. Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression. Am J Physiol Renal Physiol 293: F1238-F1247, 2007. First published July 25, 2007; doi:10.1152/ajprenal.00151.2007.-Kidneys can maintain acid-base homeostasis, despite reduced renal mass, through adaptive changes in net acid excretion, of which ammonia excretion is the predominant component. The present study examines whether these adaptations are associated with changes in the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). We used normal Sprague-Dawley rats and a 5/6 ablation-infarction model of reduced renal mass; control rats underwent sham operation. After 1 wk, glomerular filtration rate, assessed as creatinine clearance, was decreased, serum bicarbonate was slightly increased, and Na ϩ and K ϩ were unchanged. Total urinary ammonia excretion was unchanged, but urinary ammonia adjusted for creatinine clearance, an index of per nephron ammonia metabolism, increased significantly. Although reduced renal mass did not alter total Rhcg protein expression, both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated hypertrophy of both intercalated cells and principal cells in the cortical and outer medullary collecting duct that was associated with increased apical and basolateral Rhcg polarization. Rhbg expression, analyzed using immunoblot analysis, immunohistochemistry, and measurement of cell-specific expression, was unchanged. We conclude that altered subcellular localization of Rhcg contributes to adaptive changes in single-nephron ammonia metabolism and maintenance of acid-base homeostasis in response to reduced renal mass. intercalated cell; principal cell; cortical collecting duct; outer medullary collecting duct REDUCED RENAL MASS IS ASSOCIATED with maintenance of fluid and electrolyte homeostasis until very substantial changes in glomerular filtration rate develop. For many components of fluid and electrolyte homeostasis, such as H 2 O, Na ϩ , and phosphate, homeostasis involves decreased tubular reabsorption that increases fractional excretion until there are appropriate rates of renal excretion. However, acid-base homeostasis requires fundamentally different mechanisms. Renal ammonia excretion, the predominant component of renal net acid excretion (10, 18, 42), does not depend on glomerular filtration of ammonia (37, 39). Instead, ammonia metabolism involves coordinated intrarenal ammonia production and epithelial segment transport (10,18,28). Thus maintenance of normal ammonia excretion in the presence of decreased nephron number associated with reduced renal mass requires adaptive changes in individual renal epithelial segment ammonia metabolism.Recent evidence suggests that the nonerythroid ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg), are important for renal ammonia metabolism. Rhbg and Rhcg transport ammonia (2,36,60) and are expressed in the distal ...

Renal ammonia excretion in response to hypokalemia: effect of collecting duct-specific Rh C glycoprotein deletion

“…Immunolocalization was accomplished using immunoperoxidase procedures described previously (14,15,17). Briefly, sections were dewaxed in ethanol, rehydrated, and then rinsed in PBS.…”

“…Evidence supporting a critical role for Rhcg in renal ammonia transport includes findings that 1) Rhcg transports NH 3 (reviewed in Ref. 32); 2) changes in Rhcg expression parallel ammonia excretion in multiple conditions, including metabolic acidosis and reduced renal mass (15,17,21,22); 3) Rhcg gene deletion impairs both basal and acidosis-stimulated renal ammonia excretion (3, 17, 18); and 4) Rhcg deletion decreases apical NH 3 permeability in isolated, perfused collecting ducts (3).Hypokalemia is a common clinical condition and typically gives rise to increased renal ammonia excretion (23, 26). However, in contrast to both metabolic acidosis and reduced renal mass, conditions in which increased single-nephron ammonia excretion facilitates normal acid-base homeostasis, the increased renal ammonia excretion in hypokalemia is not adaptive in terms of acid-base homeostasis; in many species, including both rats and humans, hypokalemia can cause development of an acid-base disorder, namely, metabolic alkalosis (6, 11, 13).…”

“…Evidence supporting a critical role for Rhcg in renal ammonia transport includes findings that 1) Rhcg transports NH 3 (reviewed in Ref. 32); 2) changes in Rhcg expression parallel ammonia excretion in multiple conditions, including metabolic acidosis and reduced renal mass (15,17,21,22); 3) Rhcg gene deletion impairs both basal and acidosis-stimulated renal ammonia excretion (3, 17, 18); and 4) Rhcg deletion decreases apical NH 3 permeability in isolated, perfused collecting ducts (3).…”

Expression of the ammonia transporter family member, Rh B Glycoprotein, in the human kidney

“…In particular, the nonerythroid glycoproteins, Rh B Glycoprotein and Rh C Glycoprotein, are ammonia-specific transporters (6,17,37,38) expressed in the distal convoluted tubule (DCT), connecting segment (CNT), and the collecting duct (7,26,31). In animal models, multiple conditions with altered renal ammonia transport have parallel changes in Rhbg and Rhcg expression (11,12,16,22,27). Definitive evidence for the functional significance of Rhbg and Rhcg expression was shown in studies in which genetic deletion of either Rhbg or Rhcg altered basal ammonia metabolism and impaired ammonia excretion in response to an acid load (3,4,19,20).…”

High Weight Differences between Donor and Recipient Affect Early Kidney Graft Function—A Role for Enhanced IL-6 Signaling

“…In order to meet the metabolic demands, glomerular hyperfiltration and hypertension are thought to begin (10), a process which is also observed after surgical reduction of renal mass (11). Glomerular hypertension then results in mechanical damage to the capillary wall and increased filtration of proteins to tubular lumen (12).…”