Renal Effects of Metabolic Acidosis in the Normal Rat

doi:10.1159/000189109

Cited by 11 publications

(2 citation statements)

References 14 publications

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“…Alterations in dietary fixed acid loads can alter ammonia excretion, but changes in ammonia excretion in mice with AR deletion cannot be attributed to this mechanism as KS-AR-KO did not alter food intake. Most changes that occur in ammonia metabolism, such as occurs with metabolic acidosis or hypokalemia, result in changes in kidney and proximal tubule size that parallel ammonia excretion (59)(60)(61). However, male mice with renal AR deletion have increased ammonia excretion but decreased total kidney and proximal tubule size, indicating that the effect on ammonia excretion is not a nonspecific response to changes in renal mass.…”

Section: Discussionmentioning

confidence: 99%

Role of the renal androgen receptor in sex differences in ammonia metabolism

Harris

Castro

Lee

et al. 2021

American Journal of Physiology-Renal Physiology

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Background: There are sex differences in renal ammonia metabolism and structure, many of which are mediated by testosterone. This study's goal was to determine the role of renal expression of testosterone's canonical receptor, androgen receptor (AR), in these sexual dimorphisms. Methods: We studied mice with kidney-specific AR deletion (KS-AR-KO) generated using Cre/loxP techniques; control mice were Cre-negative littermates (WT). Results: In male, but not female, mice, KS-AR-KO increased ammonia excretion, which eliminated sex differences. Although renal structural size typically parallel ammonia excretion, KS-AR-KO decreased kidney size, cortical proximal tubule volume density and cortical proximal tubule cell height in males; neither were altered in females and collecting duct volume density was unaltered in both sexes. Analysis of key protein involved in ammonia handling showed in male mice that KS-AR-KO increased both PEPCK and NKCC2 expression, and decreased NHE3 and NBCe1-A expression. In female mice, KS-AR-KO did not alter these parameters. These effects occurred even though KS-AR-KO did not alter plasma testosterone, food intake or serum Na+, K+, or HCO3- significantly in either sex. Conclusions: AR-dependent signaling pathways in male, but not female, kidney regulate PEPCK and NKCC2 expression and lead to the sexual differences in ammonia excretion. Opposing effects on NHE-3 and NBCe1-A expression likely limit the magnitude of ammonia excretion changes. Since AR is not present in the TAL, the effect of KS-AR-KO on NKCC2 expression is indirect. Finally, AR mediates the greater kidney size and PT volume density in male than in female mice.

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Section: Discussionmentioning

confidence: 99%

Role of the renal androgen receptor in sex differences in ammonia metabolism

Harris

Castro

Lee

et al. 2021

American Journal of Physiology-Renal Physiology

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“…A previous study has shown that acidosis causes proteinuria because of renal tubular loss [21]. However, it has been speculated that acidosis increases glomerular proteinuria by changing the charge of the proteins or glomerular basement to allow excessive protein filtrated [7].…”

Section: Discussionmentioning

confidence: 99%

Activation of Intrarenal Renin-Angiotensin System during Metabolic Acidosis

Chen

Tsai

et al. 2011

Am J Nephrol

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Background: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role and the change of the intrarenal renin-angiotensin system (RAS) during metabolic acidosis are uncertain, and whether acidosis can evoke inflammation remains unclear. Methods: Male Sprague-Dawley rats were fed with water containing 0.14 M NH₄Cl to induce metabolic acidosis for 1 and 8 weeks, respectively. They were compared with animals fed with deionized water (control) and equimolar sodium chloride water (NaCl). Gene expression analysis of RAS components included renin, renin/prorenin receptor, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 and 2 receptors (AT1R and AT2R). Histological examination was also performed to detect morphological change. Results: Acidosis was found in 1-week NH₄Cl-treated rats but not in the 8-week group. More than twofold proteinuria and a significant decline of glomerular filtration rate (GFR) were observed in acid-loaded rats. Compared to the control and NaCl groups, angiotensinogen, ACE, AT1R and AT2R were significantly increased in the 1-week acidosis group (all p < 0.05). Sustained increase of AT1R expression was found as NH₄Cl was continued for 8 weeks. There was no significant change in transforming growth factor-β and nuclear factor-ĸB. The architecture of tubular epithelial cells was affected during our experiment. Conclusion: Metabolic acidosis induced proteinuria and decline of GFR in association with activation of intrarenal RAS.

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Pore size and charge selectivity of the glomerular membrane at the time of diagnosis of diabetes

Holmquist¹,

Sjöblad²,

Torffvit

2004

Pediatr Nephrol

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The urinary albumin excretion rate is increased at the time of diagnosis of diabetes. We investigated whether this is caused by change in pore size or charge selectivity in the glomerular basement membrane. Urine excretion of immunoglobulins (IgG2, IgG4), glycosaminoglycans (GAG), and albumin was analyzed during the first 20 days after diagnosis of diabetes in children aged 4-15 years; 36 diabetic and 24 age-matched apparently healthy children were included. The excretion of albumin was significantly increased on day 1 in the diabetic children. Between day 1 and 20 the excretion of IgG2 and IgG4 decreased significantly from normal to a level below normal. GAG excretion was not affected. The GAG/creatinine index (GAGCI) was normal. IgG2CI was significantly below normal on days 4-20. IgG4CI was below normal on days 2-20. The albumin creatinine index decreased significantly from day 1 to normal levels on day 4-20. A charge selectivity index, expressed as the ratio between the neutrally charged IgG2 and the negatively charged IgG4, was significantly below the normal level on days 16 and 20. In conclusion, an increased albumin excretion rate in urine did not seem to be caused by a change in charge selectivity. Other explanations such as change in the small pore radius or tubular reabsorption are suggested.

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Renal Effects of Metabolic Acidosis in the Normal Rat

Cited by 11 publications

References 14 publications

Role of the renal androgen receptor in sex differences in ammonia metabolism

Role of the renal androgen receptor in sex differences in ammonia metabolism

Activation of Intrarenal Renin-Angiotensin System during Metabolic Acidosis

Pore size and charge selectivity of the glomerular membrane at the time of diagnosis of diabetes

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