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Background: Distal renal tubular acidosis (dRTA) is a condition characterized by the impaired ability to secrete hydrogen ions from the distal tubule. In pediatric patients, common clinical features of dRTA include excessive urine production (polyuria), frequent nighttime urination (nocturia), poor growth and weight gain (failure to thrive), difficulty with bowel movements (constipation), abnormal breathing, and the presence of kidney stones (nephrolithiasis). While urinary tract infections (UTIs) are frequently associated with dRTA, renal failure is uncommon and seldom reported in children. Case Presentation: A 10-year-old girl was referred for the evaluation due to a progressive loss of gross motor milestones over a period of 3 years. She also experienced an acute episode of paralysis and was found to have bilateral medullary nephrocalcinosis (right staghorn calculus) accompanied by moderate renal failure and a UTI. Her development in other areas was appropriate for her age. Importantly, there was a history suggestive of excessive urine production (polyuria), increased thirst (polydipsia), and frequent nighttime urination (nocturia). Physical examination revealed proximal myopathy, characterized by a waddling gait and a positive Gower's sign, as well as diminished reflexes and muscle tone in the lower limbs. Laboratory tests indicated the presence of sepsis (total leukocyte count – 26,660, CRP-174.29) and elevated renal parameters (serum creatinine – 4.27) along with active urinary abnormalities. Urine culture and sensitivity testing showed significant growth of Escherichia coli (>100,000 CFU). A computed tomography scan of the kidneys, ureters, and bladder revealed a staghorn calculus on the right side, as well as bilateral medullary nephrocalcinosis and swollen kidneys. The patient was diagnosed with dRTA based on several factors, including hypokalemic hyperchloremic metabolic acidosis with a normal anion gap, high urine pH, borderline hypercalciuria, presence of medullary nephrocalcinosis, and after ruling out other potential differential diagnoses. Following treatment for the UTI and sepsis, as well as standard treatment for dRTA, the child exhibited symptomatic improvement. Her creatinine levels returned to 0.8 mg/dL, and the septic markers declined to normal levels. To further investigate the cause of the initial decline in renal function in addition to the UTI, a renal biopsy was performed. Conclusion: This case report emphasizes the significance of including medullary nephrocalcinosis and renal tubular acidosis in the list of potential diagnoses for patients presenting with progressive gross motor developmental regression, acute flaccid paralysis, and proximal myopathy. Timely identification of these conditions can help avoid unnecessary and expensive investigations, while also facilitating prompt clinical recovery in affected children. Early diagnosis plays a crucial role in guiding appropriate management strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 20-month-old male diagnosed with bronchopneumonia and severe hypokalemia, ultimately identified as having distal renal tubular acidosis (dRTA) caused by ATP6V0A4 gene mutations. Topics discussed include the diagnostic process for metabolic acidosis and electrolyte imbalances, the role of genetic testing in confirming hereditary dRTA, and treatment outcomes following potassium citrate therapy.

Metabolic effects of high diet acid load (DAL) have been studied for years in adults, although only recently in children. Contemporary diets, especially those of Western societies, owe their acidogenic effect to high animal-origin protein content and low contribution of base-forming elements, such as fruits and vegetables. This imbalance, where dietary acid precursors exceed the body's buffering capacity, results in an acid-retaining state known by terms such as "eubicarbonatemic metabolic acidosis," "low-grade metabolic acidosis," "subclinical acidosis," or "acid stress". Its consequences have been linked to chronic systemic inflammation, contributing to various noncommunicable diseases traditionally considered more common in adulthood, but now have been recognized to originate at much earlier ages. In children, effects of high DAL are not limited to growth impairment caused by alterations of bone and muscle metabolism, but also represent a risk factor for conditions such as obesity, insulin resistance, diabetes, hypertension, urolithiasis, and chronic kidney disease (CKD). The possibility that high DAL may be a cause of chronic acid-retaining states in children with growth impairment should alert pediatricians and pediatric nephrologists, since its causes have been attributed traditionally to inborn errors of metabolism and renal pathologies such as CKD and renal tubular acidosis. The interplay between DAL, overall diet quality, and its cascading effects on children's health necessitates comprehensive nutritional assessments and interventions. This narrative review explores the clinical relevance of diet-induced acid retention in children and highlights the potential for prevention through dietary modifications, particularly by increasing fruit and vegetable intake alongside appropriate protein consumption. [ABSTRACT FROM AUTHOR]

Objectives Pseudohypoaldosteronism type 1A (PHA1A) is caused by haploinsufficiency of the mineralocorticoid receptor (MR). Heterozygous small insertions/deletions, transitions, and/or transversions within NR3C2 comprise the majority (85%-90%) of pathogenic copy number variants. Structural chromosomal abnormalities, contiguous gene deletion syndromes, and microdeletions are infrequent. We describe a neonate with PHA1A due to a novel NR3C2 microdeletion involving exons 1-2. Methods Literature review identified 39 individuals with PHA1A due to NR3C2 microdeletions. Transmission modality, variant description(s), testing method(s), exon(s) deleted, and affected functional domain(s) were characterized. Results In total, 40 individuals with NR3C2 microdeletions were described: 19 involved contiguous exons encoding a single MR domain; 21 involved contiguous exons encoding multiple MR domains. Transmission modality frequency was familial (65%), de novo (20%), or unknown (15%). Sequencing (Sanger or short-read next-generation) failed to detect microdeletions in 100% of tested individuals (n = 38). All were detected using deletion/duplication testing modalities. In 2 individuals, only microarray-based testing was performed; microdeletions were detected in both cases. Conclusion Initial testing for PHA1A should rely on sequencing to detect the most common genetic alterations. Deletion/duplication analysis should be performed when initial testing is nondiagnostic. Most NR3C2 microdeletions are parentally transmitted, thus highlighting the importance of familial genetic testing and counseling. [ABSTRACT FROM AUTHOR]

The article focuses on the treatment of pediatric renal tubular acidosis (RTA) using the prolonged-release alkali formulation Sibnayal®, highlighting its effectiveness and tolerability in a clinical setting. It reports that while the efficacy is comparable to standard treatments, Sibnayal® is preferred by many patients, especially school-aged children, due to its ease of administration.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent. [ABSTRACT FROM AUTHOR]

We report on an infant with features of intermittent obstructive uropathy, acute kidney injury, hypertension and type 4 renal tubular acidosis (RTA) despite urethral catheterisation and fluid resuscitation. Radiological findings showed upper tract dilatation, likely bilateral vesicoureteric junction obstruction and bladder base thickening which was concerning for possible malignancy. Renal biopsy demonstrated eosinophilic infiltrate, suggestive of kidney involvement. Bladder biopsy was diagnostic for eosinophilic cystitis (EC) showing mature degranulating eosinophils. EC is a rare, easily treatable and important differential of bladder mass in children which may present with an atypical obstructive uropathy. This report adds to the limited literature of this condition within the paediatric population. EC should be considered early in children presenting with eosinophilia, urinary tract obstruction and kidney dysfunction, with uncertain aetiology. This case also highlights the need for detailed imaging, including visualisation of the bladder base, in cases of likely obstructive uropathy. [ABSTRACT FROM AUTHOR]

Isolated aldosterone synthase deficiency is a rare autosomal recessive disorder caused by pathogenic variants in CYP11B2, resulting in impaired aldosterone synthesis. We report on a neonate with isolated aldosterone synthase deficiency caused by a novel homozygous CYP11B2 variant Chr8: NM_000498.3: c.400G>A p.(Gly134Arg). The patient presented shortly after birth with severe signs of aldosterone deficiency. Interestingly, segregation analysis revealed that the patient's asymptomatic father was also homozygous for the CYP11B2 variant. Biochemical evaluation of the father indicated subclinical enzyme impairment, characterized by elevated aldosterone precursors. Apparently, this homozygous variant led to different clinical phenotypes in two affected relatives. In this manuscript we elaborate on the biochemical and genetic work-up performed and describe potential pitfalls in CYP11B2 sequencing due to its homology to CYP11B1.

Introduction: Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease’s spectrum. Methods: In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia. Results: Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+. Conclusion: Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity. Significance statement Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5–20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6–96.2%), and anti-Ro/SSA (36.4–84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature. [ABSTRACT FROM AUTHOR]

Isolated aldosterone synthase deficiency is a rare autosomal recessive disorder caused by pathogenic variants in CYP11B2, resulting in impaired aldosterone synthesis. We report on a neonate with isolated aldosterone synthase deficiency caused by a novel homozygous CYP11B2 variant Chr8:NM_000498.3:c.400G>A p.(Gly134Arg). The patient presented shortly after birth with severe signs of aldosterone deficiency. Interestingly, segregation analysis revealed that the patient's asymptomatic father was also homozygous for the CYP11B2 variant. Biochemical evaluation of the father indicated subclinical enzyme impairment, characterized by elevated aldosterone precursors. Apparently, this homozygous variant led to different clinical phenotypes in two affected relatives. In this manuscript we elaborate on the biochemical and genetic work-up performed and describe potential pitfalls in CYP11B2 sequencing due to its homology to CYP11B1. [ABSTRACT FROM AUTHOR]

Background: RMND1 is a nuclear gene needed for proper function of mitochondria. A pathogenic gene will cause multiple oxidative phosphorylation defects. A renal phenotype consisting of hyponatremia, hyperkalemia, and acidosis is frequently reported, previously considered to be due to aldosterone insensitivity. Methods: Clinical features and pathophysiology of three patients will be reported. DNA of these patients was subjected to exome screening. Results: In the first family, one pathogenic heterozygous and one highly probable heterozygous mutation were detected. In the second family, a homozygous pathogenic mutation was present. The electrolyte disbalance was not due to aldosterone insensitivity but to low plasma aldosterone concentration, a consequence of low plasma renin activity. This disbalance can be treated. In all three patients, the kidney function declined. In the first family, both children suffered from an unexplained arterial thrombosis with dire consequences. Conclusions: Hyporeninemic hypoaldosteronism is the mechanism causing the electrolyte disbalance reported in patients with RMND1 mutations, and can be treated. [ABSTRACT FROM AUTHOR]

Abstract Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug‐induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin‐related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose‐response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.

Gordon's syndrome, also known as pseudohypoaldosteronism type II and familial hyperkalaemic hypertension, is a rare inherited condition characterised by familial hyperkalaemia, normal anion gap hyperchloraemic metabolic acidosis, low renin with normal glomerular filtration rate and hypertension. The outcome of 11 pregnancies in 3 women with Gordon's syndrome is presented and combined with 13 pregnancies in 7 women previously described. Pregnancy in women with Gordon's syndrome appears to be associated with a significant risk of adverse pregnancy outcomes, particularly where there is maternal hypertension preconception. No pregnancy registry exists for Gordon's syndrome. The available data is limited to case reports and small case series and may be affected by bias. A pregnancy registry would be valuable to assist in preconception counselling and management during pregnancy. The goal of this study was to summarise the available cases describing pregnancy outcomes with maternal Gordon's syndrome. [ABSTRACT FROM AUTHOR]

A 21-year-old euthyroid gentleman born to nonconsanguineous parents was diagnosed with bipolar affective disorder. He presented 4 years later with hypokalemic quadriparesis. On evaluation, he was found to have features of both proximal and distal renal tubular acidosis. Ophthalmologic examination by slit lamp confirmed the presence of the Kayser--Fleischer ring. The diagnosis of Wilson's disease was established with serum ceruloplasmin levels and 24-h urinary copper levels. Here is a rare clinical presentation of Wilson's disease in the form of hypokalemic muscle paralysis due to proximal renal tubular acidosis with distal tubule involvement. The diagnosis was delayed due to the initial presentation with psychiatric symptoms. [ABSTRACT FROM AUTHOR]

Abstract A 13‐year‐old spayed female Schnauzer dog with chronic kidney disease (CKD; International Renal Interest Society stage 2, non‐proteinuric, normotensive), diabetes mellitus, hypercortisolism and myxomatous mitral valve degeneration (American College of Veterinary Internal Medicine stage B2) presented with electrolyte imbalance that had progressed to hyperkalaemia and hyponatremia, with a sodium to potassium (Na:K) ratio of 19.6. Cortisol levels after the adrenocorticotropic hormone stimulation test were within the therapeutic range, but aldosterone levels were below the reference range; hence, isolated hypoaldosteronism was diagnosed. After administration of deoxycorticosterone pivalate (DOCP), the electrolyte imbalance improved with a Na:K ratio of 27.7. This is the first report of the management of isolated hypoaldosteronism and hypercortisolism using trilostane and DOCP in a dog. This case highlights the importance of recognizing isolated hypoaldosteronism after long‐term treatment with trilostane in a canine patient with CKD.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disease caused by activating mutations in the arginine vasopressin (AVP) receptor-2 (AVPR2) gene. Affected patients excrete concentrated urine despite very low levels of AVP, and consequently develop euvolemic hyponatremia. Due to its low frequency, patients may be misdiagnosed and treated incorrectly. We report two related male infants with NSIAD that was initially confused with hyporeninemic hypoaldosteronism (HH). First, a 2-month-old male presented with hyponatremia, low plasma osmolality, relatively high urine osmolality, and low plasma renin-aldosterone levels. These clinical and laboratory findings were compatible with syndrome of inappropriate antidiuretic hormone (ADH) secretion without apparent cause. Consequently, fludrocortisone was initiated with a presumptive diagnosis of HH. While correcting hyponatremia, fludrocortisone treatment led to hypertension and was discontinued promptly. The second patient, aged one year, was admitted with a history of oligohydramnios, had been hospitalized four times due to hyponatremia since birth, and had a diagnosis of epilepsy. Similarly, the second infant had clinical and laboratory findings compatible with syndrome of inappropriate ADH secretion with no apparent cause. Fluid restriction normalized his serum sodium despite the plasma AVP level being undetectable. In both infants, AVPR2 gene analysis revealed a known mutation (c.409C>T; p.R137C) and confirmed the diagnosis of NSIAD. In conclusion, NSIAD should be considered in all patients with unexplained euvolemic hyponatremia despite high urine osmolality. If NSAID is not considered, the plasma reninaldosterone profile can be confused with HH, especially in infants. [ABSTRACT FROM AUTHOR]

Down syndrome is the most common chromosomal abnormality diagnosed in newborn babies. Infants with Down syndrome have characteristic dysmorphic features and can have neuropsychiatric disorders, cardiovascular diseases, gastrointestinal abnormalities, eye problems, hearing loss, endocrine and hematologic disorders, and many other health issues. We present the case of a newborn with Down syndrome. The infant was a female, born at term through c-section. She was diagnosed before birth with a complex congenital malformation. In the first few days of life, the newborn was stable. In her 10th day of life, she started to show respiratory distress, persistent respiratory acidosis, and persistent severe hyponatremia, and required intubation and mechanical ventilation. Due to her rapid deterioration our team decided to do a screening for metabolic disorders. The screening was positive for heterozygous Duarte variant galactosemia. Further testing on possible metabolic and endocrinologic issues that can be associated with Down syndrome was performed, leading to hypoaldosteronism and hypothyroidism diagnoses. The case was challenging for our team because the infant also had multiple metabolic and hormonal deficiencies. Newborns with Down syndrome often require a multidisciplinary team, as besides congenital cardiac malformations they can have metabolic and hormonal deficiencies that can negatively impact their short- and long-term prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Liddle syndrome is an autosomal dominantly inherited disorder usually arising from single mutations of the genes that encode for the alpha, beta and gamma epithelial sodium channel (ENaC) subunits. This leads to refractory hypertension, hypokalaemia, metabolic alkalosis, hyporeninaemia and hypoaldosteronism, through over-activation of the ENaC. Case presentation: We describe a 5-day old neonate who presented with severe hypernatraemic dehydration requiring admission to Steve Biko Academic Hospital in South Africa in 2012. Further evaluation revealed features in keeping with Liddle syndrome. Two compound heterozygous mutations located at different subunits encoding the ENaC were detected following genetic sequencing done in 2020. The severe clinical phenotype observed here could be attributed to the synergistic effect of these known pathological mutations, but may also indicate that one of the other variants detected has hitherto undocumented pathological effects. Management and outcome: This child's treatment course was complicated by poor adherence to therapy, requiring numerous admissions over the years. Adequate blood pressure control was achieved only after the addition of amiloride at the end of 2018, which raised the suspicion of an ENaC abnormality. Conclusion: To our knowledge, this is the first Liddle syndrome case where a combined effect from mutations resulted in severe disease. This highlights the importance of early recognition and management of this highly treatable genetic disease to prevent the grave sequelae associated with long-standing hypertension. Whole exome sequencing may assist in the detection of known mutations, but may also unveil new potentially pathological variants. What this study adds: This study highlights the importance of developing a high index of suspicion of tubulopathy such as Liddle syndrome for any child presenting with persistent hypertension associated with hypokalaemic metabolic alkalosis. [ABSTRACT FROM AUTHOR]

Background: Endocrine causes of hypertension constitute a very small percentage of patients with secondary hypertension. Apparent mineralocorticoid excess (AME) is a rare genetic form of young-onset secondary hypertension. Clinical Description: We present a case of a 16-year-old boy who was diagnosed with hypertension at 5 years of age, had recurrent episodes of hypokalemic paralysis, and deranged renal function for 1 year. Hypertension was uncontrollable with multiple antihypertensive agents until an aldosterone antagonist (spironolactone) was added. Clinical history and evaluation could not identify any secondary causes of hypertension. There was no significant family history. Growth and puberty were age-appropriate. Management and Outcome: Endocrine workup was planned considering hypokalemia and metabolic alkalosis. This demonstrated hyporeninemic hypoaldosteronism and raised the possibility of AME and Liddle syndrome. Clinical exome sequencing revealed a probable diagnosis of AME due to a novel homozygous variant (c.911A>G) in HSD11B2 gene. Sanger sequencing confirmed heterozygosity of the same variant in both parents. Conclusion: A novel homozygous variant was found in HSD11B2 gene in a subject with early-onset hypertension associated with hypokalemic metabolic alkalosis, establishing the diagnosis of AME. The use of an algorithmic approach and individualized planning of genetic studies can help in early diagnosis. This helps clinicians to select the appropriate antihypertensive drug, attain good control, and prevent the development of end-organ damage. A high index of suspicion should be kept for AME and other hyporeninemic hypoaldosteronism conditions in the case of early-onset hypertension.

A 13‐year‐old spayed female Schnauzer dog with chronic kidney disease (CKD; International Renal Interest Society stage 2, non‐proteinuric, normotensive), diabetes mellitus, hypercortisolism and myxomatous mitral valve degeneration (American College of Veterinary Internal Medicine stage B2) presented with electrolyte imbalance that had progressed to hyperkalaemia and hyponatremia, with a sodium to potassium (Na:K) ratio of 19.6. Cortisol levels after the adrenocorticotropic hormone stimulation test were within the therapeutic range, but aldosterone levels were below the reference range; hence, isolated hypoaldosteronism was diagnosed. After administration of deoxycorticosterone pivalate (DOCP), the electrolyte imbalance improved with a Na:K ratio of 27.7. This is the first report of the management of isolated hypoaldosteronism and hypercortisolism using trilostane and DOCP in a dog. This case highlights the importance of recognizing isolated hypoaldosteronism after long‐term treatment with trilostane in a canine patient with CKD. [ABSTRACT FROM AUTHOR]

Introduction: Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors. Methods: Retrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated. Results: Patients had a median age of 77 [65 - 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors. Conclusions: Hypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting. [ABSTRACT FROM AUTHOR]

IntroductionHypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors.MethodsRetrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated.ResultsPatients had a median age of 77 [65 – 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors.ConclusionsHypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting.

Down syndrome is the most common chromosomal abnormality diagnosed in newborn babies. Infants with Down syndrome have characteristic dysmorphic features and can have neuropsychiatric disorders, cardiovascular diseases, gastrointestinal abnormalities, eye problems, hearing loss, endocrine and hematologic disorders, and many other health issues. We present the case of a newborn with Down syndrome. The infant was a female, born at term through c-section. She was diagnosed before birth with a complex congenital malformation. In the first few days of life, the newborn was stable. In her 10th day of life, she started to show respiratory distress, persistent respiratory acidosis, and persistent severe hyponatremia, and required intubation and mechanical ventilation. Due to her rapid deterioration our team decided to do a screening for metabolic disorders. The screening was positive for heterozygous Duarte variant galactosemia. Further testing on possible metabolic and endocrinologic issues that can be associated with Down syndrome was performed, leading to hypoaldosteronism and hypothyroidism diagnoses. The case was challenging for our team because the infant also had multiple metabolic and hormonal deficiencies. Newborns with Down syndrome often require a multidisciplinary team, as besides congenital cardiac malformations they can have metabolic and hormonal deficiencies that can negatively impact their short- and long-term prognosis.

The premature ventricular contractions (PVCs) have usually good prognosis in patients without structural heart disease. In case of left ventricular ejection fraction depression or symptoms, antiarrhythmic drugs or cardiac ablations could be an option for management. We present a case of a patient with high burden of PVC admitted for cardiac ablation. Preoperative assessment revealed hyperkalemia and metabolic acidosis which ended up with type‐4 renal tubular acidosis (RTA). Its rare cause and management may draw attention to the possibility of type ‐4 RTA as the cause of the PVC, and hyperkalemia. [ABSTRACT FROM AUTHOR]

The article focuses on a Japanese girl with aldosterone synthase deficiency (ASD), a rare autosomal recessive disorder causing severe dehydration, salt wasting, and failure to thrive in infancy due to CYP11B2 gene variants. Topics discussed include the patient's clinical presentation, genetic analysis revealing compound heterozygous variants, successful fludrocortisone therapy, and the overall good prognosis of ASD with decreasing treatment needs in adulthood.

Background: The biochemical hallmarks of transient pseudo-hypoaldosteronism associated with a pyelonephritis include hyponatremia, hyperkalemia, and acidosis. We tested if the kidney-urinary tract ultrasound helps in predicting the diagnosis of overt pseudo-hypoaldosteronism in infants with a pyelonephritis. Cases presentation: Between 2013 and 2020, we managed 71 previously healthy infants 4 weeks to 24 months of age with a pyelonephritis (42 males and 29 females) and made the biochemical diagnosis of pseudo-hypoaldosteronism in 17 (24%). Infants with and without pseudo-hypoaldosteronism did not significantly differ with respect to the prevalence of kidney-urinary tract ultrasound abnormalities, graded by means of the UTD classification system of urinary tract abnormalities. Conclusions: Kidney-urinary tract ultrasound is almost routinely obtained in children with a febrile urinary tract infection. Our experience does not support the hypothesis that ultrasound might be relevant for the diagnosis of overt transient pseudo-hypoaldosteronism in babies affected by a urinary tract infection. Our data confirm the assumption that negative studies may be important for advancing clinical practice. [ABSTRACT FROM AUTHOR]

Background and Objective: The registries and guidelines for kidney diseases in children mostly do not include the Asian population and hence, its applicability is questionable. As a first step to address this question, the tubular and inherited disease working group of the Asian Pediatric Nephrology Association aimed to assess the current situation of pediatric tubular and inherited disorders in Asia. Methods: Our group conducted an online survey among the members of AsPNA from September to October 2020. Data collected included demographics, number of patients each physician cares for per year, methods of diagnosis, and access to genetic tests. Descriptive analysis was performed. Results: A total of 299 pediatric nephrologists from 21 countries in Asia participated. Distal renal tubular acidosis, Bartter syndrome, autosomal dominant polycystic kidney disease, autosomal recessive kidney disease, and Alport syndrome were the commonly reported diseases. Around 70% employed clinical history, radiologic imaging, and biochemical tests for diagnosis. More than half (55.4%) of the institutions have access to genetic testing. For future collaborative projects, 88% expressed interest to participate. Conclusions: The results highlight the diversity of disease prevalence, diagnostic practices, capability, and access to genetic tests across Asia. The data gathered from this preliminary survey can be used to address knowledge gaps, and improve management and outcomes. [ABSTRACT FROM AUTHOR]

Background: Aldosterone synthase deficiency (ASD) caused by mutations in the CYP11B2 gene is characterized by isolated mineralocorticoid deficiency. Data are scarce regarding clinical and biochemical outcomes of the disease in the follow-up. Objective: Assessment of the growth and steroid profiles of patients with ASD at the time of diagnosis and after discontinuation of treatment. Design and method: Children with clinical diagnosis of ASD were included in a multicenter study. Growth and treatment characteristics were recorded. Plasma adrenal steroids were measured using liquid chromatography-mass spectrometry. Genetic diagnosis was confirmed by CYP11B2 gene sequencing and in silico analyses. Results: Sixteen patients from 12 families were included (8 females; median age at presentation: 3.1 months, range: 0.4 to 8.1). The most common symptom was poor weight gain (56.3%). Median age of onset of fludrocortisone treatment was 3.6 months (range: 0.9 to 8.3). Catch-up growth was achieved at median 2 months (range: 0.5 to 14.5) after treatment. Fludrocortisone could be stopped in 5 patients at a median age of 6.0 years (range: 2.2 to 7.6). Plasma steroid profiles revealed reduced aldosterone synthase activity both at diagnosis and after discontinuation of treatment compared to age-matched controls. We identified 6 novel (p.Y195H, c.1200 + 1G > A, p.F130L, p.E198del, c.1122-18G > A, p.I339_E343del) and 4 previously described CYP11B2 variants. The most common variant (40%) was p.T185I. Conclusions: Fludrocortisone treatment is associated with a rapid catch-up growth and control of electrolyte imbalances in ASD. Decreased mineralocorticoid requirement over time can be explained by the development of physiological adaptation mechanisms rather than improved aldosterone synthase activity. As complete biochemical remission cannot be achieved, a long-term surveillance of these patients is required. [ABSTRACT FROM AUTHOR]

The steroid hormone aldosterone, produced by the zona glomerulosa (zG) of the adrenal gland, is a master regulator of plasma electrolytes and blood pressure. While aldosterone control by the renin-angiotensin system is well understood, other key regulatory factors have remained elusive. Here, we replicated a prior association between a non-coding variant in WNT2B and an increased risk of primary aldosteronism, a prevalent and debilitating disease caused by excessive aldosterone production. We further show that in both mice and humans, WNT2B is expressed in the mesenchymal capsule surrounding the adrenal cortex, in close proximity to the zG. Global loss of Wnt2b in the mouse results in a dysmorphic and hypocellular zG, with impaired aldosterone production. Similarly, humans harboring WNT2B loss-of-function mutations develop a novel form of Familial Hyperreninemic Hypoaldosteronism, designated here as Type 4. Additionally, we demonstrate that WNT2B signals by activating the non-canonical Wnt/planar cell polarity pathway. Our findings identify WNT2B as a key regulator of zG function and aldosterone production with important clinical implications.

Systemic pseudohypoaldosteronism (PHA) is a rare, salt-wasting syndrome that is caused by inactivating variants in genes encoding epithelial sodium channel subunits. Hyponatremia, hyperkalemia, metabolic acidosis, increased aldosterone and renin levels are expected findings in PHA. Clinical management is challenging due to high dose oral replacement therapy. Furthermore, patients with systemic PHA require life-long therapy. Here we report a patient with systemic PHA due to SCNN1B variant whose hyponatremia and hyperkalemia was detected at the 24th hour of life. Hyperkalemia did not improve with conventional treatments and dialysis was required. He also developed myocarditis and hypertension in follow-up. Challenges for diagnosis and treatment in this patient are discussed herein. In addition, published evidence concerning common features of patients with SCNN1B variant are reviewed. [ABSTRACT FROM AUTHOR]

Dehydration with hyponatremia can occur from a variety of causes and can be potentially fatal to infants. Pseudohypoaldosteronism type 1 (PHA1) is a rare disease that can cause severe dehydration along with hyponatremia and hyperkalemia because of renal tubular unresponsiveness to mineralocorticoids. Autosomal dominant PHA1 (ADPHA1, OMIM #177735) is caused by inactivating mutations in the NR3C2 gene, which encodes the mineralocorticoid receptor, and it can lead to renal salt-wasting, dehydration, and failure to thrive during infancy. Here, we report a case of a 20-day-old female neonate who presented as severe dehydration with hyponatremia and polyuria. We suspected that her diagnosis might be PHA1 based on markedly elevated plasma renin activity and serum aldosterone levels. For the genetic diagnosis of PHA1, we performed targeted exome sequencing of all causative genes of PHA1, but the result was negative. We confirmed by chromosomal microarray that a novel heterozygous microdeletion was found in the 4q31.23 region spanning exons 7–9 of the NR3C2 gene, and the patient was diagnosed with ADPHA1. In conclusion, our patient is a case of ADPHA1 that developed into a salt-wasting crisis in the neonatal period due to a microdeletion of the 4q31.23 region inherited from her father. [ABSTRACT FROM AUTHOR]

Hyperkalaemia is a common biochemical finding that can allude to preanalytical or truly pathological causes. Here, we present a case of a 41-year-old female patient who has regularly presented with incidences of isolated hyperkalaemia since 2012, with otherwise normal renal function and no other associated symptoms. Investigations into the patient's family history revealed similar biochemical findings in her brother and eldest son. Familial causes of hyperkalaemia were investigated and an eventual diagnosis of pseudo-hypoaldosteronism type 2C was established. This is a rare congenital renal tubular disorder – also known as Gordon syndrome – that can cause a characteristic triad of symptoms that include hyperkalaemia, metabolic acidosis and hypertension. The presence and severity of each of these symptoms is dependent upon the disease-causing mutation that occurs in WNK4, WNK1, CUL3 or KLHL3 genes. These mutations alter the regulation of sodium/chloride co-transporter (NCC) expression on the luminal membrane of the principal cells of the distal convoluted tubule, disrupting normal homeostatic regulation of electrolyte reabsorption and excretion. The resolution for treating this condition is the administration of a thiazide diuretic, which directly counteracts the effects of NCC co-transporter overexpression and consequently aims to resolve the symptoms that arise as a result of this aberrant signalling. The case described here uniquely presents an extremely rare pathogenic variant in the conserved acidic motif of WNK1 resulting in a clear electrolyte phenotype with no hypertension. [ABSTRACT FROM AUTHOR]

Background: Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. Methods: A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. Results: A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240–1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. Conclusion: Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency. [ABSTRACT FROM AUTHOR]

Abstract Background X-linked Adrenal Hypoplasia Congenita (AHC) is a rare cause of primary adrenal insufficiency due to mutations in the NR0B1 gene, causing a loss of function of the nuclear receptor protein DAX-1. Adrenal insufficiency usually appears in the first 2 months of life, but can sometimes emerge during childhood. Hypogonadotropic Hypogonadism is often associated later in life and patients may develop azoospermia. We describe an unusual onset of AHC started with isolated hypoaldosteronism as first and only sign of the disease. Case presentation A 18-days-old newborn presented with failure to thrive and feeding difficulties. Blood tests showed severe hyponatremia, hyperkalemia and hypochloremia. Renin was found over the measurable range and aldosterone was low whereas cortisol level was normal with a slightly increased ACTH. In the suspicion of Primary Hypoaldosteronism, correction of plasmatic electrolytes and replacement therapy with Fludrocortisone were promptly started. The subsequent evidence of low plasmatic and urinary cortisol and increased ACTH required the start of Hydrocortisone replacement therapy and it defined a clinical picture of adrenal insufficiency. Genetic analysis demonstrated a novel mutation in the DAX-1 gene leading to the diagnosis of AHC. Conclusions AHC onset may involve the aldosterone production itself, miming an isolated defect of aldosterone synthesis. NR0B1/DAX-1 mutations should be considered in male infants presenting with isolated hypoaldosteronism as first sign of adrenal insufficiency.

Corticosterone methyloxidase deficiency type 2 is an autosomal recessive disorder presenting with salt loss and failure to thrive in early childhood and is caused by inactivating mutations of the CYP11B2 gene. Herein, we describe four Turkish patients from two families who had clinical and hormonal features compatible with corticosterone methyloxidase deficiency and all had inherited novel CYP11B2 variants. All of the patients presented with vomiting, failure to thrive and severe dehydration, except one patient with only failure to thrive. Biochemical studies showed hyponatremia, hyperkalemia and acidosis. All patients had normal cortisol response to adrenocorticotropic hormone stimulation test and had elevated plasma renin activity with low aldosterone levels. Three patients from the same family were found to harbor a novel homozygous variant c.1175T>C (p.Leu392Pro) and a known homozygous variant c.788T>A (p.Ile263Asn) in the CYP11B2 gene. The fourth patient had a novel homozygous variant c.666_667delCT (p.Phe223ProfsTer35) in the CYP11B2 gene which caused a frame shift, forming a stop codon. Corticosterone methyloxidase deficiency should be considered as a differential diagnosis in patients presenting with hyponatremia, hyperkalemia and growth retardation, and it should not be forgotten that this condition is life-threatening if untreated. Genetic analyses are helpful in diagnosis of the patients and their relatives. Family screening is important for an early diagnosis and treatment. In our cases, previously unreported novel variants were identified which are likely to be associated with the disease. [ABSTRACT FROM AUTHOR]

Potassium is the main intracellular cation, its asymmetric distribution between intra and extracellular space relies mainly on the activity of the Na+/K+ ATPase pump. Any variation in potassium levels may alter the functionality of excitable tissues, underlining the importance of these precise regulatory processes. In this article we review the mechanisms responsible for the regulation of potassium balance with particular emphasis on the renal regulation of potassium excretion. This is followed by a brief discussion of the classification, pathophysiology and diagnostic approach of the most common tubulopathies. The internal balance of potassium refers to the regulation of the intra/extracellular distribution of this cation, avoiding short term fluctuations in potassium concentration induced by variations in dietary potassium content. Internal balance is regulated by insulin and catecholamines acting through specific intracellular signaling mechanisms. The external balance of potassium are the predominantly renal mechanisms that adjust potassium excretion to match the potassium dietary intake. The excretion of potassium by the kidney results from the balance between potassium reabsorption in the proximal nephron and the complex potassium secretory mechanisms of the distal nephron. Among the principal regulating factors of potassium secretion in the distal nephron are the delivery of sodium and water and aldosterone. Mineralocorticoid activity is regulated intracellularly by WNK proteins. The electrolyte and acid-base profile as well as the presence of hypo or hyperkalemia are the cornerstones for the diagnostic approach of hereditary or acquired tubulopathies. Knowledge of the homeostatic mechanisms that regulate potassium balance are a guide for the clinician to the correct diagnosis and therapy of the most common disorders of potassium excretion. [ABSTRACT FROM AUTHOR]

Context: Isolated congenital hypoaldosteronism presents in early infancy with symptoms including vomiting, severe dehydration, salt wasting, and failure to thrive. The main causes of this rare autosomal recessive disorder is pathogenic variants of the CYP11B2 gene leading to aldosterone synthase deficiency.Objective: To investigate the presence of CYP11B2 pathogenic variants in a cohort of patients with a clinical, biochemical, and hormonal profile suggestive of aldosterone synthase deficiency.Design: Clinical and molecular study.Setting: Tertiary academic Children's Hospital, Center for Rare Pediatric Endocrine Diseases.Patients and Methods: Sixty-two patients (56 unrelated patients and 6 siblings), with hypoaldosteronism and their parents, underwent CYP11B2 gene sequencing after its selective amplification against the highly homologous CYP11B1 gene. In silico analysis of the identified novel variants was carried out to evaluate protein stability and potential pathogenicity.Results: CYP11B2 gene sequencing revealed that 62 patients carried a total of 12 different pathogenic CYP11B2 gene variants, 6 of which are novel. Importantly, 96% of the 56 patients carried the previously reported p.T185I variant either in homozygosity or in compound heterozygosity with another variant. The 6 novel variants detected were: p.M1I, p.V129M, p.R141Q, p.A165T, p.R448C, and the donor splice site variant of intron 8, c.1398 + 1G > A.Conclusion: Molecular diagnosis was achieved in 62 patients with aldosterone synthase deficiency, the largest cohort thus far reported. Six novel genetic variants were identified as possibly pathogenic, extending the spectrum of reported molecular defects of the CYP11B2 gene. [ABSTRACT FROM AUTHOR]

Introduction: Calcineurin inhibitors (CNIs) are widely used in transplantation. Although CNI-related hyperkalemia is common (10%-60.6%), the underlying pathogenetic mechanism is not well-elucidated and may lead to dose adjustment or treatment withdrawal., Objective: The aim of this study is to describe CNI-related hyperkalemia due to hyporeninemic hypoaldosteronism in pediatric transplant recipients who were successfully treated with fludrocortisone., Method: In a total of 55 hematopoietic stem cell (HSCT) and 35 kidney transplant recipients followed according to institutional immunosuppression protocols, recipients diagnosed with CNI-related hyperkalemia were reviewed. Recipients who were receiving intravenous fluid, potassium, or were diagnosed with hemolysis, acute graft rejection, or had an eGFR < 30 mL/min/1.73m 2 , were excluded. A detailed analysis of clinical history as well as biochemical studies was carried out to reveal possible pathophysiology., Results: Three pediatric transplant recipients (one HSCT, two kidney transplantation) with findings of hyperkalemia, hyponatremia, and a mild elevation in blood urea nitrogen while on CNIs were recruited. Urinary potassium excretion was diminished while sodium excretion was increased. Plasma aldosterone levels were low, and renin was not increased in response. Primary adrenal insufficiency was ruled out, and hyporeninemic hypoaldosteronism was diagnosed. CNI-related hyperkalemia was detected earlier in case 1, who had HSCT (22 days), than in the second and third cases, who had kidney transplantation (24 and 30 months post-transplantation, respectively). The discrepancy was hypothesized to be explained by higher overall CNI dose due to higher serum target CNI used in HSCT than kidney transplantation. Electrolyte imbalance was reversed upon administration of physiologic dose fludrocortisone (0.05 mg, daily), while fludrocortisone was ceased after CNI withdrawal in case 1, which is additional evidence for the etiological association of CNIs and hyporeninemic hypoaldosteronism., Conclusion: Our three cases strengthen the premise that CNI-related hyperkalemia may be due to hyporeninemic hypoaldosteronism, and the timing and severity may be related to CNI dose. Fludrocortisone is a safe and effective treatment in CNI-related hyperkalemia, providing maintenance of CNIs, which are one of the essential therapeutic agents for pediatric transplantation., (© 2024 Wiley Periodicals LLC.)

Arthrogryposis-renal dysfunction-cholestasis (ARC) is a rare multisystem disorder caused by mutations in the VPS33B gene, which in turn lead to a premature truncation of the gene product. This autosomal recessive disease has variations in phenotype. We report an infant girl who had severe presentation in the form of dysmorphic features, abnormal hearing assessment and refractory electrolytes disturbances. She was a product of consanguineous marriage with family history of similar presentation. The child passed away at age of 6 months due to aspiration pneumonia. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to assess genotype–phenotype correlations with long-term prognosis in children with distal kidney tubular acidosis (dKTA). The kidney function of children with dKTA could be impaired in the long-term. Methods: Thirty-one children with dKTA from 23 families were included in the present study. Demographic features, growth parameters, clinical manifestations, follow-up results, and genetic analysis results of the patients were recorded. Results: Eighteen children (58.1%) were male. The median age at diagnosis was 3 months. The median follow-up period was 77 months and the longest was 23.5 years. Eight (28.8%) patients had chronic kidney disease (CKD) stage 2 or 3. Three patients aged 24, 23, and 19 years had CKD stage 3 with an estimated glomerular filtration rate of 54, 57, and 48 mL/min/1.73 m2, respectively. Thirteen patients had mutations in the ATP6V0A4 gene, eight had mutations in the ATP6V1B1 gene, and three had mutations in the SLC4A1 gene. There was no significant correlation between molecular diagnosis and CKD. Growth retardation with a height below a standard deviation (SD) score of − 2 was found in 14 patients (45.1%) at the time of diagnosis. The mean height SD score at the last visit was significantly higher in patients who had adequate metabolic control at > 75% of all visits as compared with that in patients who did not. Conclusion: Patients with dKTA usually have a good clinical prognosis in childhood with appropriate treatment; however, dRTA is characterized by deterioration of kidney function in adulthood, particularly after puberty. [ABSTRACT FROM AUTHOR]