Activation of Intrarenal Renin-Angiotensin System during Metabolic Acidosis

Ng, Hwee-Yeong; Chen, Hung‐Chun; Tsai, Yan-Chr; Yang, Yu-Kun; Lee, Chien-Te

doi:10.1159/000328742

Cited by 50 publications

(37 citation statements)

References 51 publications

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“…These include tubulointerstitial fibrosis (19-21), bone demineralization (22), protein catabolism and sarcopenia (23), inflammation (24), stimulation of the reninangiotensin system (25) and adrenocortiocotrophic hormone (26), and resistance to growth hormone and IGF (27). However, including some of these factors in the Cox models did not attenuate the association between low bicarbonate and mortality.…”

Section: Discussionmentioning

confidence: 99%

Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study

Raphael¹,

Murphy²,

Shlipak³

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Low serum bicarbonate associates with mortality in CKD. This study investigated the associations of bicarbonate and acid-base status with mortality in healthy older individuals.Design, setting, participants, & measurements We analyzed data from the Health, Aging, and Body Composition Study, a prospective study of well functioning black and white adults ages 70-79 years old from 1997. Participants with arterialized venous blood gas measurements (n=2287) were grouped into ,23.0 mEq/L (low), 23.0-27.9 mEq/L (reference group), and $28.0 mEq/L (high) bicarbonate categories and according to acid-base status. Survival data were collected through February of 2014. Mortality hazard ratios (HRs; 95% confidence intervals [95% CIs]) in the low and high bicarbonate groups compared with the reference group were determined using Cox models adjusted for demographics, eGFR, albuminuria, chronic obstructive pulmonary disease, smoking, and systemic pH. Similarly adjusted Cox models were performed according to acid-base status.Results The mean age was 76 years, 51% were women, and 38% were black. Mean pH was 7.41, mean bicarbonate was 25.1 mEq/L, 11% had low bicarbonate, and 10% had high bicarbonate. Mean eGFR was 82.1 ml/min per 1.73 m 2 , and 12% had CKD. Over a mean follow-up of 10.3 years, 1326 (58%) participants died. Compared with the reference group, the mortality HRs were 1.24 (95% CI, 1.02 to 1.49) in the low bicarbonate and 1.03 (95% CI, 0.84 to 1.26) in the high bicarbonate categories. Compared with the normal acid-base group, the mortality HRs were 1.17 (95% CI, 0.94 to 1.47) for metabolic acidosis, 1.21 (95% CI, 1.01 to 1.46) for respiratory alkalosis, and 1.35 (95% CI, 1.08 to 1.69) for metabolic alkalosis categories. Respiratory acidosis did not associate with mortality.Conclusions In generally healthy older individuals, low serum bicarbonate associated with higher mortality independent of systemic pH and potential confounders. This association seemed to be present regardless of whether the cause of low bicarbonate was metabolic acidosis or respiratory alkalosis. Metabolic alkalosis also associated with higher mortality.

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Section: Discussionmentioning

confidence: 99%

Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study

Raphael¹,

Murphy²,

Shlipak³

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…Aldosterone released in excess could mediate a decline in GFR via its hemodynamic effects and profibrotic actions. 42,43 Additionally, metabolic acidosis can impair GFR and other renal function through its diuretic and natriuretic effects. 44 Finally, in view of the novelty of our findings and the absence of empirical evidence of renal function impairment in areas where C citratus is widely consumed, further human study is recommended.…”

Section: Discussionmentioning

confidence: 99%

Effect of Lemongrass Tea Consumption on Estimated Glomerular Filtration Rate and Creatinine Clearance Rate

Ekpenyong

Daniel

Antai

2015

Journal of Renal Nutrition

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“…9,10 Possible mechanisms for the deleterious effect of acidosis on GFR may be the inadvertent pro-fibrotic effects of inducing regulatory mechanisms in the kidney, such as increased renal ammonium production, endothelin-A receptor activation and prolonged activation of the renin-angiotensin system. [11][12][13] A systematic review of six randomised controlled trials which administered oral sodium bicarbonate to pre-dialysis CKD patients, versus standard of care treatment or placebo, demonstrated a net improvement in GFR with alkali therapy, as well as reduced initiation of renal replacement and no safety concerns in the longer term. 14 Hence, this appears to be a safe and inexpensive therapy to delay progression of CKD.…”

Section: Sodium Bicarbonatementioning

confidence: 99%

Drug therapies to delay the progression of chronic kidney disease

2015

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Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and to the economy of managing the later stages of CKD have prompted efforts to develop interventions to delay the development and progression of this syndrome. In this article, we review established and novel agents that may aid in delaying the progression of CKD and improve patient outcomes. KEYWORDS: Chronic kidney disease, progression, drug therapy IntroductionChronic kidney disease (CKD), as defined by proteinuria or a reduced glomerular filtration rate (GFR) below 90 mL/min/1.73 m 2 persisting for greater than 3 months, is reported to affect 13% of US adults.1 There is a significantly higher prevalence in the elderly and those with hypertension or diabetes, and with these comorbidities increasing in prevalence and the population ageing, CKD is projected to affect up to 16% of adults by 2030.2,3 Even in its early stages, CKD is associated with accelerated cardiovascular disease and increased mortality, with an exponential increase in attributable risk as GFR declines to end-stage kidney disease (ESKD). 4,5 The mortality rate in ESKD patients maintained on dialysis is striking, with a life expectancy less than one-third that of their counterparts without ESKD, and a 5-year survival rate on dialysis of only 40%. 6 There is also a substantial healthcare cost associated with provision of ESKD care, currently estimated at $33 billion annually in the US, ABSTRACT equating to 6.3% of the Medicare Budget. 6 Hence, there may be significant healthcare and economic benefits to be garnered from halting or delaying CKD progression. In this article, we discuss recent evidence for established and emerging therapies that may alter the progression of CKD. Non disease-specific drug therapies Sodium bicarbonateCKD is associated with a metabolic acidosis, particularly at lower levels of GFR <25 mL/min/1.73 m 2 , which is predominantly attributed to reduced hydrogen ion excretion as titratable acids or ammonium in the urine. Chronic metabolic acidosis exacerbates CKD-related mineral bone disease, leads to muscle atrophy, and is associated with other complications such as abnormal albumin synthesis, thyroid dysfunction and insulin resistance. 7,8 Observational data demonstrate a strong risk of progression of CKD in those with a lower serum bicarbonate level, as well as an increased mortality risk. 9,10 Possible mechanisms for the deleterious effect of acidosis on GFR may be the inadvertent pro-fibrotic effects of inducing regulatory mechanisms in the kidney, such as increased renal ammonium production, endothelin-A receptor activation and pr...

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Activation of Intrarenal Renin-Angiotensin System during Metabolic Acidosis

Cited by 50 publications

References 51 publications

Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study

Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study

Effect of Lemongrass Tea Consumption on Estimated Glomerular Filtration Rate and Creatinine Clearance Rate

Drug therapies to delay the progression of chronic kidney disease

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