Renal Acidification in Elderly Subjects

Agarwal, Brajesh N.; Cabebe, Franklin G.

doi:10.1159/000182004

Cited by 89 publications

(32 citation statements)

References 10 publications

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“…In contrast to prior human reports that described either a tendency to (4,5,17) or a significant increase in [K] p during AMA (2,13), we found no appreciable change in [K] p . The major methodologic differences between these and the present study are the use of demonstrably arterialized plasma (versus venous serum or plasma) and the wider range of plasma bicarbonate values achieved in the present study.…”

Section: Discussioncontrasting

confidence: 99%

“…In human studies reporting venous plasma or serum (2,4,5,17) potassium values after a small acute NH 4 Cl load, a tendency to elevated values was observed, with statistical significance in only one study (2), but interpretation was precluded by high variance and modest degrees of acidosis. Importantly, no arterial or arterialized plasma or serum potassium values have been reported in normal human subjects with experimentally induced AMA of any cause.…”

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confidence: 94%

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Acute Metabolic Acidosis

Wiederseiner

Muser²,

Lutz

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Despite the high incidence of acute metabolic acidosis, there are no reliable human data to enable physicians to accurately diagnose this disorder. In addition, there is uncertainty about the direction and magnitude of plasma potassium changes in acute metabolic acidosis. The systemic and renal acid-base, electrolyte, and endocrine response to acute acid loads (imposed by three timed NH 4 Cl infusions into the duodenum, 0.9 mmol of NH 4 Cl per kg of body weight over 30 min each) was characterized in six healthy male subjects in whom a metabolic steady-state had been established. Arterialized blood CO 2 tension decreased by 0.85 mmHg per mmol/L decrease in plasma bicarbonate concentration and blood hydrogen ion concentration increased by 0.45 nmol/L per mmol/L decrease in plasma bicarbonate concentration. Plasma potassium did not change significantly (ϩ0.02 Ϯ 0.02 mmol/L per mmol decrease in plasma bicarbonate concentration). Plasma insulin increased and plasma glucagon levels decreased in acute metabolic acidosis, while catecholamines and aldosterone were not affected significantly. These data provide the first diagnostic criteria for the diagnosis of acute metabolic acidosis in humans. The finding of a hyperinsulinemic response in acute metabolic acidosis suggests that an insulin response counterregulates any acidemia-induced cellular potassium efflux, resulting in stable plasma potassium concentrations.

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Section: Discussioncontrasting

confidence: 99%

mentioning

confidence: 94%

Acute Metabolic Acidosis

Wiederseiner

Muser²,

Lutz

et al. 2004

Journal of the American Society of Nephrology

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“…Obesity, a common finding in patients with type 2 diabetes, is also associated with lower urine pH (10,11). To date, the role of other confounding factors, such as impaired renal function (12), age (13), ethnicity (14), and dietary factors, that also known to influence urine pH have not been investigated in this population (3,4,7). To understand better the metabolic factors that lead to an unduly acidic urine and thus increase the risk for UA stones in individuals with type 2 diabetes, we conducted a metabolic study under a controlled dietary environment while controlling other variables that are known to influence urinary pH.…”

mentioning

confidence: 99%

Metabolic Basis for Low Urine pH in Type 2 Diabetes

Maalouf

Cameron

Moe³

et al. 2010

Clinical Journal of the American Society of Nephrology

130

113

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Background and objectives: Type 2 diabetes is associated with excessively low urine pH, which increases the risk for uric acid nephrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes.Design, setting, participants, & measurements: Nine non-stone-forming patients who had type 2 diabetes and low urine pH and 16 age-and body mass index-matched non-stone-forming volunteers without type 2 diabetes were maintained on a constant metabolic diet for 7 days, and 24-hour urine was collected on the last 2 days of the diet.Results: Urine dietary markers (potassium, sulfate, phosphorus, and urea nitrogen) were not different between the two groups. Patients with type 2 diabetes exhibited a significantly lower 24-hour urine pH (5.45 ؎ 0.27 versus 5.90 ؎ 0.42; P < 0.01) and higher net acid excretion (NAE; 57 ؎ 12 versus 38 ؎ 18 mEq/d; P < 0.01) compared with control subjects. The proportion of NAE excreted as ammonium (NH 4 ؉ /NAE) was significantly lower in patients with type 2 diabetes than in control subjects

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“…56 Indeed, the capacity to excrete acid in the urine becomes diminished with age due to a reduction in ammonium production independent of a decreased GFR. 57 Another example is diabetes mellitus. Prior studies have elucidated that rodent models of streptozotocininduced diabetes demonstrate nephropathy affecting both the proximal and distal tubular segments, and are characterized by the early inhibition of autophagy.…”

Section: Discussionmentioning

confidence: 99%

Autophagic Clearance of Mitochondria in the Kidney Copes with Metabolic Acidosis

Namba¹,

Takabatake²,

Kimura

et al. 2014

Journal of the American Society of Nephrology

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Metabolic acidosis, a common complication of CKD, causes mitochondrial stress by undefined mechanisms. Selective autophagy of impaired mitochondria, called mitophagy, contributes toward maintaining cellular homeostasis in various settings. We hypothesized that mitophagy is involved in proximal tubular cell adaptations to chronic metabolic acidosis. In transgenic mice expressing green fluorescent proteintagged microtubule-associated protein 1 light chain 3 (GFP-LC3), NH 4 Cl loading increased the number of GFP puncta exclusively in the proximal tubule. In vitro, culture in acidic medium produced similar results in proximal tubular cell lines stably expressing GFP-LC3 and facilitated the degradation of SQSTM1/p62 in wild-type cells, indicating enhanced autophagic flux. Upon acid loading, proximal tubule-specific autophagydeficient (Atg5-deficient) mice displayed significantly reduced ammonium production and severe metabolic acidosis compared with wild-type mice. In vitro and in vivo, acid loading caused Atg5-deficient proximal tubular cells to exhibit reduced mitochondrial respiratory chain activity, reduced mitochondrial membrane potential, and fragmented morphology with marked swelling in mitochondria. GFP-LC3-tagged autophagosomes colocalized with ubiquitinated mitochondria in proximal tubular cells cultured in acidic medium, suggesting that metabolic acidosis induces mitophagy. Furthermore, restoration of Atg5-intact nuclei in Atg5-deficient proximal tubular cells increased mitochondrial membrane potential and ammoniagenesis. In conclusion, metabolic acidosis induces autophagy in proximal tubular cells, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. Our results provide a rationale for the beneficial effect of alkali supplementation in CKD, a condition in which autophagy may be reduced, and suggest a new therapeutic option for acidosis by modulating autophagy.

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Renal Acidification in Elderly Subjects

Cited by 89 publications

References 10 publications

Acute Metabolic Acidosis

Acute Metabolic Acidosis

Metabolic Basis for Low Urine pH in Type 2 Diabetes

Autophagic Clearance of Mitochondria in the Kidney Copes with Metabolic Acidosis

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