Carboplatin-induced Renal Salt Wasting Syndrome in Paediatric Patients with Intracranial Germ Cell Tumours and Concomitant Diabetes Insipidus

We report the first case series of 14 children with intracranial germ cell tumour (iGCT) and concomitant central diabetes insipidus (DI), who developed hyponatremia secondary to renal salt wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum-based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatraemia can be asymptomatic until it is severe.

Differential diagnosis between syndrome of inappropriate antidiuretic hormone secretion and cerebral/renal salt wasting syndrome in children over 1 year: proposal for a simple algorithm

Hyponatremia, especially if acute and severe, can be a life-threatening condition. Several conditions can trigger hyponatremia. In this review, we will discuss two conditions that can determine euvolemic hyponatremia: the cerebral/renal salt wasting (CRSW) syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), including the two subtypes: reset osmostat (RO) and nephrogenic syndrome of inappropriate antidiuresis (NSIAD) and their differential diagnoses. Despite the passage of over 70 years since its first description, to date, the true etiopathogenesis of CRSW syndrome, a rare cause of hypovolemic/euvolemic hyponatremia, is almost unknown. SIADH, including RO and NSIAD, is sometimes difficult to differentiate from CRSW syndrome; in its differential diagnosis, the clinical approach based on the evaluation of the extracellular volume (ECV) was proven insufficient. We therefore suggest a simple diagnostic algorithm based on the assessment of the degree of hyponatremia, urinary osmolality, and the assessment of the fraction of urate excretion (FEUa) in conditions of hyponatremia and after serum sodium correction, to be applied in children over 1 year of life.

Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness

BackgroundThe transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na+,K+-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness.MethodsA candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants.ResultsWe identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents.ConclusionsBiallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.

Differentiating syndrome of inappropriate ADH, reset osmostat, cerebral/renal salt wasting using fractional urate excretion

ObjectivesClinical and laboratory data of reset osmostat (RO) and cerebral/renal salt wasting (C/RSW) mimic syndrome of inappropriate antidiuretic hormone (SIADH) and can pose diagnostic challenges because of significant overlapping between clinical and laboratory findings. Failure to correctly diagnose hyponatremia may result in increased mortality risk, longer hospital stay, and is cost-effective. We aim to illustrate clinical and laboratory similarities and difference among patients with hyponatremic disorders and discuss the diagnostic value of factional uprate excretion (FEurate) to differentiate SIADH from RO and C/RSW.Case presentationsWe report the use of FEurate in the evaluation of three patients with hyponatremia and elevated urine osmolality in the absence of edema or clinical evidence of dehydration to differentiate SIADH from RO and C/RSW.ConclusionsMeasurement of FEurate may offset in part the diagnostic confusion imparted by the diagnoses of SIADH, RO, and C/RSW.

Renal salt wasting syndrome in a patient with COVID-19; a case report and review of the literature

Introduction: Cerebral salt wasting or renal salt wasting (RSW) syndrome, may be more common than syndrome of inappropriate antidiuretic hormone secretion (SIADH) and may even occur in the absence of cerebral disease. We report a case of RSW in a Bangladeshi patient positive for COVID-19 without clinical cerebral disease. Case Presentation: A 53 years-old Bangladeshi patient presented with history of chest pain and acute MI. On examination, the patient was conscious, alert, vitally stable, chest with fine bilateral basal crepitation and heart with additional S3 sound and abdomen was lax with no organomegaly. There was no lower limbs oedema. His serum creatinine; 68 umol/L, urea; 3.4 mmol/L, K; 4.7 mmol/L, sodium; 135 mmol/L, uric acid; 141 mmol/L and phosphate was 1.3 mmol./L. Echocardiography (ECG) revealed anterior lateral wall STEMI. PCI was done for LAD. ECG revealed ejection fraction (EF) 10-15 %. Nasopharyngeal swab for COVID-19 was positive. Serum sodium decreased from 135 to 108 with signs of hypovolemia. Work up for hyponatremia revealed serum osmolality of 237 mOsm/kg, urine NA; 109 mmol/L, urine osmolality; 295 mOsm/kg, urine uric acid; 685 umol/L, and urine phosphate; 6.5 mmol/L. Additionally serum T3, T4, TSH and serum basal cortisol were normal. The patient received normal saline infusion and fludrocortisone and serum sodium increased to 134 mmol/L. Our patient had all the important clinical and laboratory characteristics of RSW in the absence of cerebral disease which include hyponatremia associated with hypovolemia, high urinary sodium excretion, increased fraction excretion of phosphate and persistent hypouricemia with increased fractional excretion of urate after correction of hyponatremia and with normal renal, adrenal and thyroid functions. Furthermore, there was a prompt response to saline replacement and fludrocortisone and steady improvement in serum sodium with negativity and improvement of COVID-19. Our diagnosis was RSW in the absence of cerebral disease and to our knowledge; this is the first case of RSW in a patient with COVID-19 in the literature. Conclusion: RSW should be considered in patients with COVID-19 with hyponatremia and absence of cerebral disease. We suggest changing cerebral salt wasting to the more appropriate term RSW.