Molecular Pathophysiology of Acid-Base Disorders

Wagner, Carsten A.; Silva, Pedro Henrique Imenez; Bourgeois, Soline

doi:10.1016/j.semnephrol.2019.04.004

Cited by 38 publications

(38 citation statements)

References 132 publications

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“…[ 37 ] The latter effect reduces the enzymatic generation of bicarbonate ions luminally available to bind sodium ions, blunting the reabsorption of sodium ions and nephric capacity to augment effective arterial blood volume. [ 49 ] The former effect promotes acidification of the neural interstitial milieu, enhancing the presynaptic and axon terminal vesicular uptake of the divalent cation zinc, co-released with glutamate. [ 50 ] Sulfamethoxazole-mediated neural interstitial acidification and enhanced release of glutamate may enhance the release of vasopressin by the hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

Trimethoprim-sulfamethoxazole-induced hyponatremia in an elderly lady with Achromobacter xylosoxidans pneumonia

Ghali

Kim

2020

Medicine

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Rationale: Hyponatremia occurs frequently in the hospital setting and may be attributable to a host of etiologies. Drugs are frequently implicated. Trimethoprim-sulfamethoxazole (TMP/SMX) represents a well-recognized pharmacologic precipitant of drug-induced hyponatremia, with several reports extant in the retrievable literature. Nephrologists thus debate the mechanisms giving rise to TMP/SMX-induced hyponatremia and the precise mechanism by which treatment with TMP/SMX generates reductions of serum sodium concentration remain controversial. The agent has a well-known effect of antagonizing the effects of aldosterone upon the distal nephron. Renal salt wasting and the syndrome of inappropriate antidiuretic hormone secretion represent implicated mechanistic intermediaries in TMP/SMX-induced hyponatremia. Patient concerns: The patient endorsed no explicit concerns. Diagnoses: We describe the case of an 83-year-old female clinically diagnosed with pneumonia found to have an initial serum sodium in the range of 130 to 134 mEq/L consistent with mild hyponatremia upon admission. Sputum cultures grew Achromobacter xylosoxidans susceptible to TMP/SMX. The patient's serum sodium concentration precipitously decline following institution of treatment with TMP/SMX to 112 to 114 mEq/L during the course of 5 days. Interventions: Severe hyponatremia proved recalcitrant to initial therapy with supplemental salt tabs and standard doses of the vasopressin receptor antagonist tolvaptan. Outcomes: Escalating doses of tolvaptan increased the patient's sodium to 120 to 124 mEq/L. The patient was transferred to another hospital for further management. During her stay, the patient did not exhibit frank or obvious clinical features consistent with hyponatremia nor readily appreciable evidence of volume depletion. Lessons: TMP/SMX represents a frequent, though underreported cause of hyponatremia in the hospital setting several authors believe natriuresis may represent the most common mechanism underlying TMP/SMX-induced hyponatremia. Evidence implicating natriuresis to be mechanistic in TMP/SMX-induced hyponatremia include clinically appreciable hypovolemia and resolution of hyponatremia with oral or intravenous salt repletion. Salt repletion failed to monotherapeutically enhance our patient's hyponatremiadisfavoring renal salt wasting as originately mechanistic. Contemporaneous refractoriness of serum sodium to fluid restriction nor standard doses of tolvaptan confounded our initial attempts to mechanistically attribute the patient's hyponatremia to a specific cause. Clinical euvolemia and rapid response of hyponatremia to exceptionally high doses of tolvaptan strongly favors syndrome of inappropriate antidiuretic hormone to represent the chief mechanism by which TMP/SMX exacerbates hyponatremia.

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Section: Discussionmentioning

confidence: 99%

Trimethoprim-sulfamethoxazole-induced hyponatremia in an elderly lady with Achromobacter xylosoxidans pneumonia

Ghali

Kim

2020

Medicine

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“…It plays an important role in acid-base transport and salt reabsorption in the proximal convoluted tubule, where interplay among CA2, pendrin and cotransporter NCC was highlighted [34]. Moreover, mutations of CA2 gene per se cause mixed renal tubular acidosis, with osteopetrosis and mental retardation [35]. In addition, a very recent paper suggests that the use of Acetazolamide, a carbonic-anhydrase inhibitor, in combination with standard therapy in children with BS may counteract the metabolic alkalosis [36].…”

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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“…The kidneys play a key role in the regulation of the acid-base balance by reabsorption of filtered bicarbonate, regeneration of bicarbonate via ammoniagenesis, and acid excretion [28]. While some of the pathogenic mechanisms of chronic MA in KTRs are similar to those in CKD patients, others seem to be specific to KTx.…”

Section: Causes Of Ma After Ktxmentioning

confidence: 99%

Causes and Consequences of Metabolic Acidosis in Patients after Kidney Transplantation

Ritter

Mohebbi

2020

Kidney Blood Press Res

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Background: Metabolic acidosis (MA) is a common complication in kidney transplantation (KTx). It is more prevalent in KTx than in CKD, and it occurs at higher glomerular filtration rates. The pathophysiologic understanding of MA in KTx and its clinical impact has been highlighted by few recent studies. However, no guidelines exist yet for the treatment of MA after KTx. Summary: MA in KTx seems to share pathophysiologic mechanisms with CKD, such as impaired ammoniagenesis. Additional kidney transplant-specific factors seem to alter not only the prevalence but also the phenotype of MA, which typically shows features of renal tubular acidosis. There is evidence that calcineurin inhibitors, immunological factors, process of donation, donor characteristics, and diet may contribute to MA occurrence. According to several mainly observational studies, MA seems to play a role in disturbed bone metabolism, cardiovascular morbidity, declining graft function, and mortality. A better understanding of the pathophysiology and evidence from randomized controlled trials, in particular, are needed to clarify the role of MA and the potential benefit of alkali treatment in KTx. Alkali therapy might not only be beneficial but also cost effective and safe. Key Messages: MA seems to be associated with several negative outcomes in KTx. A deeper understanding of the pathophysiology and clinical consequences of MA in KTx is crucial. Clinical trials will have to determine the potential benefits of alkali therapy.

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Molecular Pathophysiology of Acid-Base Disorders

Cited by 38 publications

References 132 publications

Trimethoprim-sulfamethoxazole-induced hyponatremia in an elderly lady with Achromobacter xylosoxidans pneumonia

Trimethoprim-sulfamethoxazole-induced hyponatremia in an elderly lady with Achromobacter xylosoxidans pneumonia

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

Causes and Consequences of Metabolic Acidosis in Patients after Kidney Transplantation

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