Background: Secondary pseudohypoaldosteronism (PHA) is a rare, transient condition caused by renal tubular resistance to aldosterone, most commonly associated with urinary tract infection (UTI) and/or congenital anomalies of the kidney and urinary tract (CAKUT). It mimics primary adrenal disorders, presenting with life-threatening electrolyte disturbances in early infancy. Case Presentation: We report a male infant admitted twice within the first four months of life with severe dehydration, hyponatremia, hyperkalemia, metabolic acidosis, and acute kidney injury (AKI). Urine cultures grew Klebsiella pneumoniae and later Escherichia coli. Imaging studies demonstrated obstructive CAKUT, including posterior urethral valves, bilateral megaureters, hydronephrosis, and bladder diverticulosis. Congenital adrenal hyperplasia was excluded. Further evaluation showed markedly elevated plasma renin and aldosterone levels, confirming secondary PHA. The patient was successfully treated with intravenous fluids, electrolyte correction, and antibiotic therapy. Subsequently, oral sodium chloride and bicarbonate supplementation were added. Stepwise surgical correction of the urinary tract anomalies was initiated. Conclusions: Secondary PHA should be considered in infants presenting with failure to thrive, dehydration, hyponatremia, and hyperkalemia, particularly in the presence of UTI or CAKUT. Early recognition and differentiation from primary adrenal disorders are essential to prevent life-threatening complications. Prompt correction of electrolyte imbalance and management of the underlying urinary tract pathology are crucial for favorable outcomes.

Recent clinical trials have shown that distal nephron-acting diuretics are effective in managing fluid retention and salt-sensitive hypertension in people with chronic kidney disease (CKD). However, their use may be complicated by diuretic-induced hyponatremia. This study aimed to characterize the metabolomic effects of distal diuretics in people with CKD, including those who develop hyponatremia. Therefore, we analyzed plasma and 24-hour urine samples from a previously completed randomized controlled trial including individuals with CKD (mean eGFR 39 ± 13 ml/min/1.73 m[2]) treated with amiloride/hydrochlorothiazide (5 mg/50 mg daily) for two weeks. The study included 26 participants in whom we analyzed a set of targeted metabolites. Global untargeted metabolomics was performed in a subcohort of 12 participants including 4 patients who developed hyponatremia (plasma sodium <136 mmol/L) and 8 diuretic-treated controls with stable sodium levels. Distal diuretic therapy decreased plasma glutamine levels and the excretion of several tricarboxylic acid (TCA) cycle-related metabolites. Furthermore, distal diuretics significantly increased urinary ammonium excretion in the absence of hypokalemia or metabolic acidosis. Untargeted metabolomic analysis revealed 988 unique metabolites in the urine. Among those with hyponatremia, we observed a metabolomic signature of oxidative stress, likely due to altered glutamine and carnitine metabolism. These findings suggest that distal diuretics not only act locally in the distal convoluted tubule but also influence proximal tubular metabolism. In conclusion, our results highlight that distal diuretics induce significant metabolic changes in CKD, with urine metabolomics offering valuable insights into the physiological pathways and mechanisms underlying both therapeutic effects and adverse responses.

Periodic paralyses (PPs) are rare skeletal muscle ion channelopathies caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. PPs can be divided into primary periodic paralyses (PPPs) and secondary PPs by the aetiology. Secondary PPs are common in hyperthyroidism, primary aldosteronism, renal tubular acidosis, or be related to other causes such as medication intake or potassium loss from the digestive or renal systems. Both conditions are characterized by episodic flaccid muscle weakness.

Acid-base homeostasis is maintained by renal and respiratory systems. The inability of the renal tubules to excrete acids or retain bicarbonate in adequate amounts leads to renal tubular acidosis (RTA). These disorders are characterised by the presence of normal anion gap metabolic acidosis with hyperchloremia. Both distal RTA (type 1) and proximal RTA (type 2) can occur due to a primary/inherited defect in the renal tubule or may arise due to some secondary/acquired causes. Urinary acidification defect defines type 1 RTA, while type 2 RTA is characterised by defective bicarbonate handling in the proximal tubule. Type 3 RTA includes features of both type 1 and type 2 RTA, whereas type 4 RTA is characterised by the presence of hyperkalaemia with normal anion gap metabolic acidosis. In this review article, we describe the various types of RTA and its pathophysiology along with a systematic and practical approach to a suspected case of RTA and its management.

Thymomas are well-established disruptors of central immune tolerance, yet their capacity to drive systemic autoimmunity via a single autoantigen remains incompletely characterized. We report a 59-year-old male who, following resection of a Masaoka stage IIb type B2 thymoma, developed sequential neurological, endocrine, and renal manifestations over 18 months. Clinical evaluation confirmed stiff-person syndrome (SPS) with axial muscle hypermetabolism on PET-CT, latent autoimmune diabetes (HbA1c 11%), subclinical hypothyroidism (TSH 15.28 μIU/mL), and distal renal tubular acidosis (dRTA) evidenced by severe hypokalemia (K[+] 2.4 mmol/L) and inappropriately alkaline urine (pH 7.5). All three syndromes were associated with persistently high-titer glutamic acid decarboxylase 65 (GAD65) autoantibodies (>500 nmol/L in serum). Epitope mapping identified molecular mimicry between the GAD65 peptide [2][60]PEVKEK[2][65] and homologous sequences in renal H[+]-ATPase and thyroid peroxidase, providing a mechanistic basis for multi-organ cross-reactivity. Treatment with intravenous immunoglobulin (IVIG) led to a 53.6% reduction in serum and an 80% decline in cerebrospinal fluid GAD65 antibody levels, paralleling clinical improvement. This case illustrates how thymoma-induced loss of tolerance to GAD65 can trigger widespread autoimmune injury through conformational epitope spreading, positioning GAD65 as a paraneoplastic pan-autoantigen. High-titer GAD65 antibodies may serve as a biomarker for systemic involvement, supporting early multidisciplinary surveillance in thymoma patients.

Inherited distal renal tubular acidosis (dRTA) is a rare but clinically significant disorder of renal acid-base regulation that frequently presents in infancy or early childhood. Among the genetic causes of autosomal recessive dRTA, mutations in the ATP6V1B1 gene are particularly important due to their association with early-onset disease and sensorineural hearing loss. Failure to recognize and treat this condition promptly can result in growth retardation, bone disease, nephrocalcinosis, chronic kidney disease, and permanent auditory impairment. This article presents a comprehensive review of the pediatric literature concerning dRTA. We focus on the pathophysiology, pediatric presentation, renal and audiological outcomes, genetic architecture, and management implications of ATP6V1B1-associated dRTA in children. We highlight evolving genotype-phenotype correlations, the emerging recognition of autosomal recessive disease mechanisms, and the importance of early diagnosis and long-term multidisciplinary follow-up.

Distal renal tubular acidosis (dRTA) can result from mutations in the SLC4A1 gene, which encodes the anion exchanger 1, a protein essential for bicarbonate-chloride exchange in the distal nephron. Anion exchanger 1 dysfunction disrupts acid-base homeostasis, leading to the development of non-anion gap metabolic acidosis. Transient, pregnancy-related presentations of dRTA are rare and remain poorly characterized. We report the case of a 35-year-old woman who, at 25 weeks of gestation, was found to have severe hypokalemia, normal anion gap metabolic acidosis, and a positive urinary anion gap, consistent with dRTA. After the delivery of a healthy, full-term newborn, her electrolyte abnormalities resolved spontaneously. Genetic testing revealed a pathogenic SLC4A1 mutation, confirming autosomal dominant dRTA. This case highlights a rare, transient form of genetically confirmed dRTA unmasked during pregnancy. It emphasizes the importance of evaluating persistent hypokalemia during pregnancy and considering genetic testing, even in asymptomatic individuals. Early recognition can guide appropriate management and genetic counseling for both patients and their offspring.

X-linked hypophosphatemia (XLH), a rare genetic disorder caused by PHEX mutations, leads to fibroblast growth factor 23-mediated phosphate wasting, hypophosphatemia, and impaired bone mineralization. We report a 28-year-old woman with XLH carrying a heterozygous PHEX c.1080-1G>A splice-site mutation and a CLDN16 c.165_166delinsC mutation. Diagnosed at 18 months of age, she received long-term phosphate and active vitamin D metabolites, which resulted in secondary hyperparathyroidism, vertebral fractures, and medullary nephrocalcinosis requiring subtotal parathyroidectomy. Although CLDN16 mutation carriers are usually asymptomatic, coexistence of XLH and prolonged phosphate therapy may exacerbate renal magnesium and calcium handling defects, potentially contributing to nephrocalcinosis. Burosumab was initiated for ongoing complications. Before surgery, she was wheelchair dependent due to severe diffuse bone pain. Postoperatively, pain improved and she regained independent ambulation, which further improved after burosumab initiation. Laboratory findings showed partial but sustained improvements in serum phosphate, alkaline phosphatase, and parathyroid hormone levels. Incomplete biochemical normalization may reflect renal tubular acidosis and medullary calcinosis. This case suggests long-term phosphate therapy can adversely affect parathyroid glands and may exacerbate nephrocalcinosis in the presence of tubular vulnerabilities. It supports burosumab as an effective therapeutic option in patients with coexisting renal tubular disorders.