Molecular Mechanisms and Regulation of Urinary Acidification

Kurtz, Ira

doi:10.1002/cphy.c140021

Cited by 26 publications

(21 citation statements)

References 833 publications

(1,049 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The basolateral localization of MEIK-NBCn2 in the mTAL parallels that of NBCn1. 24,30 Because NBCn1 contributes to NH 4 + reabsorption in the mTAL, MEIK-NBCn2 likely does the same.…”

Section: Discussionmentioning

confidence: 99%

“…For well over a half century, the consensus has been that this HCO 3 2 traffic-about 80% of which normally occurs in the proximal tubule (PT)-is coupled exclusively with the secretion of H + into the tubule lumen. [1][2][3][4] As shown in Figure 1, this H + secretion is because of the action of the apical Na + /H + exchanger NHE3 (Slc9a3) and vacuolar-type H + pump. Under normal conditions, the vast majority of the H + secreted into the PT lumen follows pathway 1 in Figure 1, converting filtered HCO 3 2 to CO 2 and H 2 O, a reaction catalyzed by carbonic anhydrase 4.…”

mentioning

confidence: 97%

“…A tiny fraction of the secreted H + follows pathways 2 and 3 in Figure 1 to titrate buffers other than HCO 3 2 . In pathway 2, glutamine generates NH 3 , which enters the lumen and combines secreted H + to form NH 4 + , which ultimately appears in the urine. The glutamine metabolism also generates "new HCO 3 2 ," which appears in the blood.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Na+/HCO3 – Cotransporter NBCn2 Mediates HCO3 − Reclamation in the Apical Membrane of Renal Proximal Tubules

Guo

Liu

et al. 2017

JASN

View full text Add to dashboard Cite

The kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO filtered in glomeruli and by secreting additional H to titrate luminal buffers. For proximal tubules, which are responsible for about 80% of this activity, it is believed that HCO reclamation depends solely on H secretion, mediated by the apical Na/H exchanger NHE and the vacuolar proton pump. However, and the proton pump cannot account for all HCO reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na/HCO cotransporter NBCn2, the amino termini of which start with the amino acids MCDL (MCDL-NBCn2) and MEIK (MEIK-NBCn2). Western blot analysis and immunocytochemistry revealed that MEIK-NBCn2 predominantly localizes at the basolateral membrane of medullary thick ascending limbs in the rat kidney, whereas MCDL-NBCn2 localizes at the apical membrane of proximal tubules. Notably, NHCl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE Conversely, NaHCO-induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO reclamation: the conventional indirect pathway, in which NHE and the proton pump secrete H to titrate luminal HCO, and the novel direct pathway, in which NBCn2 removes HCO from the lumen. The reciprocal regulation of NBCn2 and NHE under different physiologic conditions is consistent with our mathematical simulations, which suggest that HCO uptake and H secretion have reciprocal efficiencies for HCO reclamation versus titration of luminal buffers.

show abstract

“…The basolateral localization of MEIK-NBCn2 in the mTAL parallels that of NBCn1. 24,30 Because NBCn1 contributes to NH 4 + reabsorption in the mTAL, MEIK-NBCn2 likely does the same.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

See 1 more Smart Citation

Na+/HCO3 – Cotransporter NBCn2 Mediates HCO3 − Reclamation in the Apical Membrane of Renal Proximal Tubules

Guo

Liu

et al. 2017

JASN

View full text Add to dashboard Cite

show abstract

“…One of the main functions of the kidney is to keep the systemic acid-base chemistry constant. The kidney has evolved so that it can regulate blood acidity by means of three key functions: (1) by reabsorbing the HCO3 − filtered through the glomeruli to prevent its excretion in the urine; (2) by generating a sufficient quantity of new HCO3 − to compensate for the loss of HCO3 − due to dietary metabolic H+ loads and loss of HCO3 − in the urea cycle; and (3) by excreting HCO3 − (or metabolizable organic anions) following a systemic base load [40]. For the kidney to be able to perform these functions, various types of cell throughout the nephron have to respond to changes in acid-base chemistry by modulating specific ion transport and/or metabolic processes in a coordinated fashion, such that the urine and renal vein chemistry is adjusted appropriately.…”

Section: Regulation Of Urinary Acidificationmentioning

confidence: 99%

Understanding the Pathophysiology of Nephrocalcinosis

Priante¹,

Ceol²,

Terrin³

et al. 2017

Updates and Advances in Nephrolithiasis - Pathophysiology, Genetics, and Treatment Modalities

View full text Add to dashboard Cite

Many in vitro and in vivo studies on the mechanisms underlying calcium nephrolithiasis have provided evidence of a frequently associated condition, i.e., a microscopic renal crystal deposition that can occur within the tubular lumen (intratubular nephrocalcinosis) or in the interstitium (interstitial nephrocalcinosis). Medullary nephrocalcinosis is the typical pattern seen in 98% of cases of human nephrocalcinosis, with calcification clustering around each renal pyramid. It is common in patients with metabolic conditions that predispose them to renal calcium stones. Cortical nephrocalcinosis is rare and usually results from severe destructive disease of the cortex. It has been described in chronic glomerulonephritis, but often in association with another factor, such as an increased calcium ingestion, acute cortical necrosis, chronic pyelonephritis or trauma. The most accredited hypothesis to explain the onset of interstitial nephrocalcinosis is purely physicochemical, relating to spontaneous Ca 2 PO 4 crystallization in the interstitium due to oversaturation of Ca 2 PO 4 salts in this milieu. The theory that nephrocalcinosis is a process driven by osteogenic cells was first proposed by our group. We review nephrocalcinosis in terms of its definition, genetic associations, and putative mechanisms, pointing out how much evidence in the literature suggests that it may have some features in common with, and pathogenic links to vascular calcification.

show abstract

“…[1] Kidneys perform a large number of important functions such as controlling body fluids volume and composition, as well as removal of metabolic wastes from body. [2,3] Renal cell carcinoma also called renal adenocarcinoma or kidney cancer, it is a disease in which malignant cells are found in the lining of tubules in the kidney. It is the eighth most common malignancy which affect adults, and accounts for 3% to 4% of new cancer cases arising in U.S and is the 7 th most common cancer in men and 9 th most common cancer in women.…”

Section: Introductionmentioning

confidence: 99%