Mechanism of Hyperkalemia-Induced Metabolic Acidosis

Harris, Autumn N.; Grimm, P. Richard; Lee, Hyun‐Wook; Delpire, Eric; Fang, Liangjuan; Verlander, Jill W.; Welling, Paul A.; Weiner, I. David

doi:10.1681/asn.2017111163

Cited by 74 publications

(63 citation statements)

References 78 publications

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“…These patients have hyperkalemia, metabolic acidosis and impaired ammonia excretion, and correcting the hyperkalemia corrects the acidosis and normalizes ammonia excretion (68) . Moreover, the relationship between plasma K + and urinary ammonia excretion (68) in patients with isolated hypoaldosteronism is nearly identical to that observed in mice (58) .…”

Section: Type IV Renal Tubular Acidosis (Rta)supporting

confidence: 66%

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Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance

Weiner

Verlander

2019

Seminars in Nephrology

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Ammonia metabolism has a critical role both in acid-base homeostasis and in other cellular functions. Kidneys have a central role in bicarbonate generation, which occurs through the process of net acid excretion; ammonia metabolism is the quantitatively greatest component of net acid excretion, both under basal conditions and in response to acid-base disturbances. Several recent studies have substantially advanced our understanding of the molecular mechanisms and regulation of ammonia metabolism. First, the previous paradigm that ammonia transport could be explained by passive NH 3 diffusion and NH 4 + trapping has been advanced by the recognition that specific transport of NH 3 and of NH 4 + by specific membrane proteins is critical to ammonia transport. Second, significant advances have been made in the understanding of the regulation of ammonia metabolism. Novel studies show that hyperkalemia directly inhibits ammonia metabolism, thereby leading to the metabolic acidosis present in Type IV RTA. Other studies show that the proximal tubule protein, NBCe1, and specifically the A variant, NBCe1-A, have a major role regulating renal ammonia metabolism. Thirdly, there are important sex differences in ammonia metabolism that involve structural and functional differences in the kidney. In this review we discuss these important aspects of the emerging features of ammonia metabolism and transport.

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Section: Type IV Renal Tubular Acidosis (Rta)supporting

confidence: 66%

“…DCT-CA-SPAK mice spontaneously develop hyperkalemia in association with metabolic acidosis and suppressed ammonia excretion (58) . The renal acid-base disorder was specific to ammonia excretion; titratable acid excretion was unchanged.…”

Section: Type IV Renal Tubular Acidosis (Rta)mentioning

confidence: 99%

Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance

Weiner

Verlander

2019

Seminars in Nephrology

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“…An additional set of renal pathologies follows the integration of acid/base and salt/water handling by the nephron. For example, states and conditions of increased sodium reabsorption by the proximal tubule (e.g., volume contraction) or collecting duct (e.g., hyperactivity of the epithelial Na + channel ENaC in Liddle’s syndrome) result in MAlk (see Metabolic Alkalosis) while hyperkalemia can cause MAc [260] .…”

Section: Applications By Organ Systemmentioning

confidence: 99%

The therapeutic importance of acid-base balance

Quade

Parker

Occhipinti

2021

Biochemical Pharmacology

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Baking soda and vinegar have been used as home remedies for generations and today we are only a mouse-click away from claims that baking soda, lemon juice, and apple cider vinegar are miracles cures for everything from cancer to COVID-19. Despite these specious claims, the therapeutic value of controlling acid-base balance is indisputable and is the basis of Food and Drug Administration-approved treatments for constipation, epilepsy, metabolic acidosis, and peptic ulcers. In this narrative review, we present evidence in support of the current and potential therapeutic value of countering local and systemic acid-base imbalances, several of which do in fact involve the administration of baking soda (sodium bicarbonate). Furthermore, we discuss the side effects of pharmaceuticals on acid-base balance as well as the influence of acid-base status on pharmacokinetic properties of drugs. Our review considers all major organs systems as well as information relevant to several clinical specialties such as anesthesiology, infectious disease, oncology, dentistry, and surgery.

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“…VATB1 represents the kidney isoform of the vacuolar-type ATPases [40] and is localized to the distal nephron [41]. It is involved in the intracellular pH regulation, by actively secreting protons into urine and heterozygous mutations have recently been reported in patients with some forms of renal tubular acidosis [42].…”

Section: Discussionmentioning

confidence: 99%

Urinary Extracellular Vesicles and Salt-Losing Tubulopathies: A Proteomic Approach

et al. 2020

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Renal tubular cells release urinary extracellular vesicles (uEV) that are considered a promising source of molecular markers for renal dysfunction and injury. We investigated uEV proteomes of patients with hereditary salt-losing tubulopathies (SLTs), focusing on those caused by Gitelman and Bartter (BS) syndromes, to provide potential markers for differential diagnosis. Second morning urine was collected from patients with genetically proven SLTs and uEV were isolated by the ultracentrifugation-based protocol. The uEV proteome was run through a diagonal bidimensional electrophoresis (16BAC/SDS-PAGE), to improve hydrophobic protein resolution. Sixteen differential spots from the proteome of two variants (BS2 and BS3) were analysed by nLC-ESI-MS/MS after in-gel tryptic digestion. A total of 167 protein species were identified from 7 BS2 spots and 9 BS3 spot. Most of these proteins were membrane-associated proteins, in particular transmembrane proteins, and were related to typical renal functions. The differential content of some uEV was then validated by immunoblotting. Our work suggests that uEV proteomics represents a promising strategy for the identification of differential SLT proteins. This could play a role in understanding the pathophysiological disease mechanisms and may support the recognition of different syndromes.

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Mechanism of Hyperkalemia-Induced Metabolic Acidosis

Cited by 74 publications

References 78 publications

Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance

Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance

The therapeutic importance of acid-base balance

Urinary Extracellular Vesicles and Salt-Losing Tubulopathies: A Proteomic Approach

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