Potassium citrate 282mg / Potassium bicarbonate 527mg modified-release granules sachets sugar free

Abstract Mechanosensitive TRPV4 channel plays a dominant role in maintaining [Ca 2+ ] i homeostasis and flow‐sensitive [Ca 2+ ] i signaling in the renal tubule. Polycystic kidney disease (PKD) manifests as progressive cyst growth due to cAMP‐dependent fluid secretion along with deficient mechanosensitivity and impaired TRPV4 activity. Here, we tested how regulation of renal TRPV4 function by dietary K + intake modulates the rate of cystogenesis and mechanosensitive [Ca 2+ ] i signaling in cystic cells of PCK453 rats, a homologous model of human autosomal recessive PKD (ARPKD). One month treatment with both high KCl (5% K + ) and KB/C (5% K + with bicarbonate/citrate) diets significantly increased TRPV4 levels when compared to control (0.9% K + ). High KCl diet caused an increased TRPV4‐dependent Ca 2+ influx, and partial restoration of mechanosensitivity in freshly isolated monolayers of cystic cells. Unexpectedly, high KB/C diet induced an opposite effect by reducing TRPV4 activity and worsening [Ca 2+ ] i homeostasis. Importantly, high KCl diet decreased cAMP, whereas high KB/C diet further increased cAMP levels in cystic cells (assessed as AQP2 distribution). At the systemic level, high KCl diet fed PCK453 rats had significantly lower kidney‐to‐bodyweight ratio and reduced cystic area. These beneficial effects were negated by a concomitant administration of an orally active TRPV4 antagonist, GSK2193874, resulting in greater kidney weight, accelerated cystogenesis, and augmented renal injury. High KB/C diet also exacerbated renal manifestations of ARPKD, consistent with deficient TRPV4 activity in cystic cells. Overall, we demonstrate that TRPV4 channel activity negatively regulates cAMP levels in cystic cells thus attenuating (high activity) or accelerating (low activity) ARPKD progression.

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Citrate, a tricarboxylic acid cycle intermediate, plays a central role in renal physiology by acting as both a urinary base equivalent and a potent inhibitor of calcium stone formation. Hypocitraturia, a common metabolic abnormality in calcium nephrolithiasis, is not a binary disorder but a continuum shaped by acid-base status, diet, potassium balance, proximal tubular handling, and systemic citrate status. We provide an update on the biology of citrate, renal regulation of its excretion, clinical pathophysiology, and treatment of hypocitraturia. Identical urinary citrate levels may have different implications depending on systemic acid-base status and urinary calcium excretion. Hypocitraturia prevalence is increasing, paralleling rises in metabolic syndrome, obesity, and dietary habit changes. Experimental models confirm that systemic or intracellular acidosis, potassium deficiency, and upregulation of renal transport and metabolism of citrate reduce urinary citrate, enhancing stone risk. Potassium citrate remains the cornerstone of therapy, increasing both urinary citrate and pH. However, its use requires caution in calcium phosphate stone formers and patients with chronic kidney disease. Citrate resistance, defined as inadequate urinary citrate response despite good potassium delivery, is a therapeutic challenge. Novel interventions including sodium-dicarboxylate cotransporter-1 (NaDC-1) inhibitors and citrate analogs such as hydroxycitrate may offer future alternatives. In conclusion, urinary citrate must be interpreted within physiological and clinical contexts. Recognizing hypocitraturia as a modifiable, non-binary risk factor allows for more precise risk stratification and individualized therapy in stone prevention, particularly when lithogenicity overlaps with acid-base and renal abnormalities.

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BACKGROUND: Renal tubular acidosis (RTA) refers to a group of kidney disorders characterized by defective acid excretion or bicarbonate reabsorption, leading to metabolic acidosis. This case series presents three cases of RTA with distinct etiologies and clinical manifestations. These cases emphasize the necessity of a comprehensive evaluation of RTA, considering both renal and systemic origins. CASE SUMMARY: The first case describes a female patient with osteopetrosis-related RTA, diagnosed with Guibaud-Vainsel syndrome, emphasizing the importance of genetic assessment. The second case delineates RTA secondary to focal segmental glomerulosclerosis, associating tubular dysfunction with glomerular pathology. In the first two cases whole exome sequencing confirmed genetic diagnosis. The third case illuminates RTA as a complication of Graves' disease, highlighting autoimmune implications. CONCLUSION: These cases underscore the interdisciplinary approach essential in RTA management. Understanding the diverse pathophysiology of RTA aids in tailored therapeutic strategies and improved patient outcomes.

Abstract licence: CC BY-NC

BACKGROUND: Pseudohypoaldosteronism type I (PHA1) is a rare genetic disorder characterized by renal or systemic resistance to aldosterone, resulting in hyponatremia, hyperkalemia, and metabolic acidosis. The autosomal recessive systemic form (PHA1B), caused by mutations in SCNN1A, SCNN1B, or SCNN1G, is particularly severe and typically manifests in the neonatal period. Among these, SCNN1B-related cases occur less frequently than SCNN1A-related cases. CASE PRESENTATION: We report a pair of dizygotic preterm twins (male and female) born at 35 + 5 weeks of gestation who presented at 8 days of age with poor feeding, weight loss, and severe jaundice. Both developed life-threatening hyperkalemia, hyponatremia, and metabolic acidosis, and these conditions were unresponsive to initial management including hydrocortisone. Laboratory findings showed markedly elevated plasma renin and aldosterone levels, with no evidence of congenital adrenal hyperplasia or other metabolic disorders. Whole-exome sequencing revealed compound heterozygous mutations in the SCNN1B gene: a splice-site variant (c.585+2T>C) inherited from the mother and a missense variant (c.1544T>C, p.Ile515Thr) from the father. Both mutations are novel and were confirmed by Sanger sequencing. Diagnosis of systemic PHA1B2 was established. Treatment with oral sodium chloride, sodium citrate, and potassium-binding resins led to gradual correction of electrolyte imbalance and clinical stabilization. CONCLUSION: These are the first reported Chinese cases of neonatal-onset PHA1B due to novel compound heterozygous SCNN1B mutations. This report broadens the mutational spectrum of SCNN1B and underscores the importance of early genetic testing in refractory neonatal electrolyte disturbances.

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ABSTRACT Hyperchloremic metabolic acidosis is an underreported but common metabolic complication following therapeutic plasma exchange (TPE) with an albumin‐saline solution, particularly when multiple TPE sessions are performed within a limited period. The risk of hyperchloremic metabolic acidosis may be the highest in patients with chronic kidney disease because of their limited acid excretion capacity. We prospectively collected data from all patients who received TPE at Amsterdam UMC between February 2023 and March 2025. We collected data on demographics, TPE‐related parameters, and blood electrolyte concentrations. We investigated the effect of TPE on plasma sodium, chloride, and bicarbonate concentrations, the occurrence of adverse events, and the modulating role of kidney function. Data from 64 patients with 320 TPE sessions were included in the analysis. The mean age was 50 years, 55% of the patients were male and the mean eGFR was 35 mL/min/1.73 m 2 . The effect of a single TPE on plasma electrolyte concentration was independent of kidney function. However, after multiple TPE sessions, a lower eGFR was associated with a greater increase in plasma chloride concentration ( p < 0.001) and a larger decrease in plasma bicarbonate concentration ( p < 0.001) despite oral bicarbonate supplementation and a lower baseline plasma bicarbonate concentration. Patients with a lower eGFR were more likely to experience adverse events during a TPE session ( p = 0.004). Chronic kidney disease is a risk factor for developing hyperchloremic metabolic acidosis and adverse events during an intensive TPE cycle.

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Introduction: Hypokalemic periodic paralysis (HPP) is a severe yet reversible neuromuscular condition precipitated by profound hypokalemia. Autoimmune disorders can exacerbate renal potassium loss resulting in abrupt muscle weakness. Primary Sjögren's syndrome (pSS), an autoimmune disease characterized by exocrine gland insufficiency, can lead to renal tubular dysfunction and episodes of HPP when distal acidification is compromised. Case presentation: A 40-year-old woman was admitted with rapidly progressive, painless quadriplegia for over 2 days. Laboratory tests revealed critical hypokalemia (1.4 mEq/L), metabolic acidosis, and alkaline urine pH, which was consistent with type 1 distal renal tubular acidosis (dRTA). Serologic studies confirmed pSS. Corrective measures included intravenous potassium chloride and sodium bicarbonate along with immunomodulation with intravenous methylprednisolone, followed by oral prednisolone. Discussion: The patient's presentation illustrates how autoimmune-mediated renal tubular dysfunction can precipitate HPP. Failure of distal acid excretion impairs potassium handling, amplifying the risk of potentially life-threatening neuromuscular collapse. Stabilization requires meticulous electrolyte repletion and treatment of the underlying autoimmunity. Restoration of serum potassium levels, acid-base balance, and targeted immunosuppression resulted in rapid clinical improvement. Conclusion: An accurate diagnosis of HPP secondary to dRTA and Sjögren's syndrome requires high clinical suspicion. Prompt recognition and intervention, including immunotherapy and balanced electrolyte replacement, can prevent profound neuromuscular complications and improve patient outcome.

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There is a widespread belief that organic sodium salts included in intravenous solutions serve as bicarbonate precursors, and that this mechanism explains their effects on plasma pH. We aimed to explain why the effect of organic anions, such as citrate, acetate, gluconate, and lactate on the acid-base balance is independent of bicarbonate generation. For this purpose, we mainly focused on regional citrate anticoagulation (RCA). The sodium load provided with these buffers and its contribution to the plasma strong ion difference is a more suitable model for explaining and predicting their alkalinizing effect. Moreover, the bicarbonate generated from the metabolization of these buffers via the Krebs cycle results from CO2 dissolution in water, and thus yields bicarbonate together with a proton (H+). As such, metabolization of these buffers does not cause alkalosis per se.

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Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse event with unclear mechanisms and limited treatment alternatives. This study aimed to investigate the efficacy of two alkalizing agents, a mixture of potassium citrate and sodium citrate (K/Na citrate) or sodium bicarbonate (NaHCO3), in preventing and treating paclitaxel (PTX)-induced mechanical allodynia in rodents. The results from rodent models demonstrated that repeated prophylactic administration of K/Na citrate or NaHCO3 could inhibit the development of PTX-induced mechanical allodynia. Moreover, K/Na citrate was effective in preventing the PTX-induced exacerbation of mechanical allodynia, even when treatment was initiated immediately after the onset of allodynia. K/Na citrate also reduced the levels of the plasma complement component anaphylatoxin C3a in a PTX-induced CIPN rat model. Complement activation, resulting in the production of C3a, has been implicated in the pathogenesis of this model. Additionally, pretreatment with Na citrate significantly prevented the reduction in neurite outgrowth caused by PTX. Furthermore, K/Na citrate inhibited spontaneous and mechanical stimuli-induced firing in spinal dorsal horn neurons. These findings indicate that K/Na citrate may regulate the development of PTX-induced mechanical allodynia by modulating complement activation and providing neuroprotection against PTX-induced peripheral nerve injury. This study implies that alkalization could help prevent PTX-induced peripheral neuropathy and mitigate its exacerbation.

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