Distal Renal Tubular Acidosis Research Articles

Evaluation of urinary acidification in children: Clinical utility.

The kidney plays a fundamental role in acid-base homeostasis by reabsorbing the filtered bicarbonate and by generating new bicarbonate, to replace that consumed in the buffering of non-volatile acids, a process that leads to the acidification of urine and the excretion of ammonium (NH4 +). Therefore, urine pH (UpH) and urinary NH4 + (UNH4 +) are valuable parameters to assess urinary acidification. The adaptation of automated plasma NH4 + quantification methods to measure UNH4 + has proven to be an accurate and feasible technique, with diverse potential indications in clinical practice. Recently, reference values for spot urine NH4 +/creatinine ratio in children have been published. UpH and UNH4 +, aside from their classical application in the study of metabolic acidosis, have shown to be useful in the identification of incomplete distal renal tubular acidosis (dRTA), an acidification disorder, without overt metabolic acidosis, extensively described in adults, and barely known in children, in whom it has been found to be associated to hypocitraturia, congenital kidney abnormalities and growth impairment. In addition, a low UNH4 + in chronic kidney disease (CKD) is a risk factor for glomerular filtration decay and mortality in adults, even in the absence of overt metabolic acidosis. We here emphasize on the need of measuring UpH and UNH4 + in pediatric population, establishing reference values, as well as exploring their application in metabolic acidosis, CKD and disorders associated with incomplete dRTA, including growth retardation of unknown cause.

Lithiase urinaire de type IVa2 et pathologies associées : à propos de 3 cas

IntroductionUrinary lithiasis is a very common condition. The morpho-constitutional analysis of urinary stones is important for etiological diagnosis. It guides the explorations and the specific management. Type IVa2 stones are rare, have particular morphology and correspond to very targeted pathologies. We propose to report our cases of patients diagnosed with type IVa2 urinary lithiasis. MethodsOur retrospective work focused on three cases of patients with the morphological type of renal lithiasis IVa2, collected between 2008 and 2020 in the Medicine A Department of Charles Nicolle Hospital in Tunis. ResultsAll three patients were female; average age 37.6 years. The clinical symptomatology was identical marked by renal colic with recurrent episodes. The presence of a type IVa2 stone, isolated or associated with other components, guided the etiological investigation to look for a secondary or primary cause of distal renal tubular acidosis. We retained the diagnosis of a primary hyperparathyroidism in one case and a primary Gougerot-Sjögren's syndrome in the second case, and probable in the last case. ConclusionDetermination of urolithiasis nature (morphological and chemical), although carried out late, was of major interest to us and allowed us to make the diagnosis of distal tubular acidosis.

Particularités épidémiologiques, cliniques et évolutives de l’acidose tubulaire distale primitive chez l’enfant tunisien

IntroductionThe distal renal tubular acidosis of children is characterized by hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria and nephrocalcinosis. It is secondary to the inability of alpha intercalar cells of the distal tubule to acidify urine of genetic origin. ObjectiveTo analyse the epidemiological aspects of distal tubular acidosis in Tunisia and study its evolutionary profile. Patients and methodsWe conducted a retrospective descriptive study involving 44 patients followed at the paediatrics department of the Charles Nicolle Hospital in Tunis for 28 years (1991–2018). ResultsThe most common discovery circumstances were growth retardation (88.6%), dehydration (56.8%), ployuro-polydipsic syndrome (47.7%), vomiting (40.9%) and nephrocalcinosis (38.6%). Growth retardation was found in 52.3% of patients. Dehydration was diagnosed in 59.1% of patients on the first exam. Polyuria was constant with an average diuresis of 8 cc/kg/h. All patients had the complete form of distal renal tubular acidosis with an average alkaline reserve of 11.1 mmol/L. Nephocalcinosis was found in 77.3% associated with nepholithiasis in 22.7%. Twenty-four patients had sensorineural deafness, nine of whom had ATP6V1B1/2p13 mutation. The ATP6V0A4/7q33-34 mutation was present in two patients. We used a high alkaline treatment dose with an average maintenance dose of 8.17 mmol/kg/24 hours. In the long term, stunting persisted in 34% of patients. The mean of creatinine's clearance at the last evaluation was 89.38 mL/min/1.73 m2 SC with stage 2 of chronic kidney disease in 50% of patients. ConclusionDistal renal tubular acidosis has long been considered a benign pathology but is responsible for a progressive decline in GFD. Adequate metabolic control is needed to stabilize kidney function.

Editorial Comment

In 1985, potassium citrate was approved by the FDA for kidney stone prevention in distal renal tubular acidosis with calcium stones, hypocitraturic calcium oxalate nephrolithiasis of any etiology and uric acid lithiasis with or without calcium stones. Potassium citrate is now widely used either alone or in combination with thiazide or thiazide analogue diuretics for the treatment of calcium nephrolithiasis.

Acute Hypokalemic Paralysis And Hashimoto's Thyroiditisa.

Acute hypokalemic paralysis (AHP) is a life-threatening emergency. It is exceptionally unusual for hypothyroidism to present with AHP. This association can be either primary or secondary through distal renal tubular acidosis. We report two cases who presented with acute quadriplegia. The succeeding investigations revealed severe hypokalemia and autoimmune hypothyroidism. The second case was found to have Sjogren's syndrome additionally. The underlying aetiology of hypokalemia in both cases was found to be dRTA. The combination of such conditions is reported sporadically. Here we also discuss the potential association of AHP with autoimmune conditions by proxy through dRTA.

Proximal Renal Tubular Acidosis and Fanconi Syndrome Associated with Tenofovir Disopyroxil Fumarat: The Importance of Arterial Blood Gas Analysis in Differrential Diagnosis of Severe Hypokalemia

Proksimal renal tübüler asidoz (pRTA) tek başına ya da Fanconi sendromu ile birlikte ortaya çıkabilir. İdiyopatik olabileceği gibi birçok ilaç ve hastalıkla da ilişkisi bildirilmiştir. 71 yaşında, kronik HBV enfeksiyonu nedeniyle tenofovir disoproksil fumarat (TDF) kullanımı olan kadın hasta, dirençli, semptomatik hipokalemi ile başvurdu. Venöz kan gazı analizi ile tanıya ulaşılamazken arter kan gazında görülen izole anyon açığı normal hipokalemik hiperkloremik metabolik asidoz ve biyokimyada hipomagnezemi, hipoürisemi, hipofosfatemi saptanması üzerine pRTA ve Fanconi sendromu düşünüldü. Diğer etiyolojik nedenlerin dışlanması ve öykünün uyumlu olması nedeniyle bu durum TDF kullanımına bağlandı ve TDF kesilerek tenofovir alfenamide (TAF) geçildiğinde klinik ve laboratuvar tam yanıt elde edildi. TDF ilişkili pRTA ve Fanconi sendromu ilacın kullanım süresinden bağımsız olarak ortaya çıkabilir ve TAF’a geçiş HBV enfeksiyonu tedavisini aksatmadan komplikasyonu ortadan kaldırabilir. Hipokalemi, hipomagnezemi ve hipofosfatemi gibi elektrolit bozuklukları, mikst asid baz bozukluğu olan ve etiyolojinin açıklanamadığı ya da klinik tablo ile uyumsuz venöz kan gazı analizi sonuçları elde edildiğinde, gözden kaçabilecek asid-baz bozuklukları ve anyon açıklığındaki farkları saptamak için arter kan gazı ile doğrulama ayırıcı tanıda yararlı olabilir.

Intradialysis Cardiac Arrest in a 40 year old Woman with Diabetic Nephropathy Precipitated by Hyperkalemia Induced by Type 4 Renal Tubular Acidosis.

Purpose: We present a rare case of intra-dialytic cardiac arrest secondary to renal tubular acidosis precipitated by severe hyperkalemia. Renal tubular acidosis (RTA) type 4 results from defective distal tubular (DT) response to aldosterone and could lead to hyperkalemia and metabolic acidosis, conditions which in their severe forms, can precipitate cardiac arrest.
 Methodology: Here, we present the management of intra-dialysis cardiac arrest precipitated by severe hyperkalemia.
 Results: Patient was an 18 year old female, diabetic who had 3 episodes of intra-dialysis cardiac arrest requiring cardiac defibrillation. She was dyspneic, drowsy, pale, had flapping tremor and a tunneled internal jugular catheter insitu. Her pulse was 124/min, blood pressure was 166/98 mmHg and the third heart sounds was heard. Urinalysis showed 3 (+++) of protein. Arterial blood gases (ABGs) revealed hyperkalemia (7.0mmol/l), hypobicarbonatemia (12mmol/l), blood PH (7.2) and blood glucose (249mmol). Serum creatinine was 947umol/l and tall tented T waves were seen on electrocardiogram. 
 Unique contribution to theory, practice and policy: With a carefully prescribed dialysis, meal and drug regimen, intra-dialysis cardiac arrest can be prevented, and well managed when it occurs.

39-Year-Old Woman With Severe Weakness

39-Year-Old Woman With Severe Weakness

Nodular-like glomerular lesion after long-standing chronic renal infection in a patient with medullary sponge kidney and mild hyperglycemia

A 63-year-old Japanese woman was admitted to our institute for the evaluation of proteinuria. The patient was diagnosed with medullary sponge kidney, distal type renal tubular acidosis, and renal infection at the age of 37. Thereafter, the patient had repeated renal infections. Urinary proteinuria appeared at around the age of 61 and gradually increased up to 1.0 g daily. In the same period, glycated hemoglobin (HbA1c) increased to 7.0%. On kidney biopsy, light microscopy showed a nodular glomerular lesion and capsular drop. Linear staining for immunoglobulin G along the glomerular basement membrane was observed by immunofluorescence. Electron microscopy showed thickening of the glomerular basement membrane to a width of 800–900 nm. A class III glomerular lesion was diagnosed according to the Tervaert classification. This case indicates that mild but prolonged hyperglycemia for more than 10 years may also contribute to the formation of nodular lesions, although long-standing repeated chronic renal infection and chronic acidosis may have been a precipitating factor in the formation of diabetic nephropathy, including nodular glomerular lesions. This hypothesis is of interest because nodular lesions specific to diabetes are currently considered to be associated with long-term severe hyperglycemia. Learning points Nodular glomerular lesions in diabetes mellitus are thought to be associated with long-term severe hyperglycemia. This case shows that although mild, long-term hyperglycemia for more than 10 years may also contribute to the formation of nodular lesions and that repeated chronic kidney infections over the years and chronic acidosis may be facilitating factors in the formation of diabetic nephropathy, including nodular glomerular lesions. This case appears to be idiopathic nodular glomerulosclerosis of the medullary sponge kidney associated with chronic urinary tract infection.

Distal Renal Tubular Acidosis in Patients with Autoimmune Diseases-An Update on Pathogenesis, Clinical Presentation and Therapeutic Strategies.

Distal renal tubular acidosis (DRTA) has been reported in association with autoimmune diseases, such as Sjögren’s syndrome, systemic lupus erythematosus (SLE), autoimmune hepatitis, primary biliary cirrhosis, rheumatoid arthritis and autoimmune thyroiditis. Whether we talk about the complete or incomplete form of DRTA associated with autoimmune diseases, the real incidence is unknown because asymptomatic patients usually are not identified, and most of the reported cases are diagnosed due to severe symptoms secondary to hypokalemia, a frequent finding in these cases. The mechanisms involved in DRTA in patients with autoimmune diseases are far from being fully elucidated and most of the data has come from patients with Sjögren’s syndrome. This review will present different hypotheses raised to explain this association. Also, aiming for a better understanding of the association between autoimmune diseases and DRTA, our review summarizes data from 37 case reports published in the last five years. We will emphasize data regarding clinical presentation, biological alterations, treatment and outcome. A very important question is whether immunosuppressive therapy is helpful in DRTA associated with autoimmune diseases. Because the pathology is rather rare, treatment is not standardized, and reported results are often contradictory. Corticosteroids are frequently used, but multiple other immunosuppressive drugs have been proposed and will be approached in this review.

Mechanistic insights into the primary and secondary alterations of renal ion and water transport in the distal nephron.

The kidneys, by equilibrating the outputs to the inputs, are essential for maintaining the constant volume, pH, and electrolyte composition of the internal milieu. Inability to do so, either because of internal kidney dysfunction (primary alteration) or because of some external factors (secondary alteration), leads to pathologies of varying severity, leading to modification of these parameters and affecting the functions of other organs. Alterations of the functions of the collecting duct (CD), the most distal part of the nephron, have been extensively studied and have led to a better diagnosis, better management of the related diseases, and the development of therapeutic tools. Thus, dysfunctions of principal cell-specific transporters such as ENaC or AQP2 or its receptors (mineralocorticoid or vasopressin receptors) caused by mutations or by compounds present in the environment (lithium, antibiotics, etc.) have been demonstrated in a variety of syndromes (Liddle, pseudohypoaldosteronism type-1, diabetes insipidus, etc.) affecting salt, potassium, and water balance. In parallel, studies on specific transporters (H+ -ATPase, anion exchanger 1) in intercalated cells have revealed the mechanisms of related tubulopathies like distal renal distal tubular acidosis or Sjögren syndrome. In this review, we will recapitulate the mechanisms of most of the primary and secondary alteration of the ion transport system of the CD to provide a better understanding of these diseases and highlight how a targeted perturbation may affect many different pathways due to the strong crosstalk and entanglements between the different actors (transporters, cell types).

Systematic assessment of monogenic etiology in adult-onset kidney stone formers undergoing urological intervention-evidence for genetic pretest probability.

Kidney stone disease (KSD) is a prevalent condition associated with high morbidity, frequent recurrence, and progression to chronic kidney disease (CKD). The etiology is multifactorial, depending on environmental and genetic factors. Although monogenic KSD is frequent in children, unbiased prevalence data of heritable forms in adults is scarce. Within 2 years of recruitment, all patients hospitalized for urological kidney stone intervention at our center were consecutively enrolled for targeted next generation sequencing (tNGS). Additionally, clinical and metabolic assessments were performed for genotype-phenotype analyses. The cohort comprised 155 (66%) males and 81 (34%) females, with a mean age at first stone of 47 years (4-86). The diagnostic yield of tNGS was 6.8% (16/236), with cystinuria (SLC3A1, SLC7A9), distal renal tubular acidosis (SLC4A1), and renal phosphate wasting (SLC34A1, SLC9A3R1) as underlying hereditary disorders. While metabolic syndrome traits were associated with late-onset KSD, hereditary KSD was associated with increased disease severity in terms of early-onset, frequent recurrence, mildly impaired kidney function, and common bilateral affection. By employing systematic genetic analysis to a less biased cohort of common adult kidney stone formers, we demonstrate its diagnostic value for establishing the underlying disorder in a distinct proportion. Factors determining pretest probability include age at first stone (<40 years), frequent recurrence, mild CKD, and bilateral KSD.

DEMOGRAPHIC AND CLINICAL PROFILE OF HYPOKALEMIC PARALYSIS IN PATIENTS OF TERTIARY CARE HOSPITAL IN SOUTH INDIA

Introduction: Hypokalemic paralysis is an important reversible cause of acute accid paralysis. Severe hypokalemia if not managed appropriately can lead to cardiac arrhythmia, respiratory failure and cardiac arrest. Therefore, this study was conducted with the objective of nding the causes of hypokalemic paralysis in the study population. A cross sectional study was done from January 2019 to January 2021 inMaterials and Methods: the patients admitted in the Department of Nephrology, Thanjavur Medical College, Tamil Nadu. Systematic random sampling method was followed and every fth patient admitted with documented serum potassium levels of &lt;3.5mEq/L and acute onset of accid weakness was included in the study till a minimum sample size of 50 was reached. Most of the study participants, 16 (32%) had dRTA (distal renal tubularResults: acidosis) followed by SPP (sporadic periodic paralysi) in 14 (28%). Gitelman syndrome (GS) was found in 9 (18%), Bartter syndrome (BS) in 4 (8%), thyrotoxic periodic paralysis (TPP) in 4 (8%) and proximal renal tubular acidosis (pRTA) in 3 (6%) participants. Renal loss ofConclusion: potassium (distal renal tubular acidosis) was the most common cause for hypokalemic paralysis. Early recognition as well as prompt treatment of hypokalemic paralysis will reduce the morbidity and mortality.

Distal renal tubular acidosis presenting with an acute hypokalemic paralysis in an older child with severe vesicoureteral reflux and syringomyelia: a case report

BackgroundDistal renal tubular acidosis (dRTA) is the most common type of renal tubular acidosis (RTA) in children. Pediatric dRTA is usually genetic and rarely occurs due to acquired issues such as obstructive uropathies, recurrent urinary tract infections (UTIs), and chronic kidney disease (CKD). Although persistent hypokalemia frequently occurs with dRTA, acute hypokalemic paralysis is not frequently reported, especially in older children.Case presentationAn eight-year-old girl presented with an acute first episode of paralysis. A physical examination revealed normal vital signs, short stature consistent with her genetic potential, and decreased muscle strength of her upper and lower extremities. Preexisting conditions included stage 4 CKD due to recurrent UTIs, severe vesicoureteral reflux and bilateral hydronephrosis, neurogenic bladder, and multisegment thoracic syringomyelia. Her laboratory work-up revealed hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap. She also had a urine osmolal gap of 1.9 mOsmol/kg with a high urine pH. Intravenous potassium replacement resulted in a complete resolution of her paralysis. She was diagnosed with dRTA and discharged with oral bicarbonate and slow-release potassium supplementation.ConclusionsThis case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.

Hereditary fructose intolerance: A comprehensive review.

Hereditary fructose intolerance (HFI) is a rare autosomal recessive inherited disorder that occurs due to the mutation of enzyme aldolase B located on chromosome 9q22.3. A fructose load leads to the rapid accumulation of fructose 1-phosphate and manifests with its downstream effects. Most commonly children are affected with gastrointestinal symptoms, feeding issues, aversion to sweets and hypoglycemia. Liver manifestations include an asymptomatic increase of transaminases, steatohepatitis and rarely liver failure. Renal involvement usually occurs in the form of proximal renal tubular acidosis and may lead to chronic renal insufficiency. For confirmation, a genetic test is favored over the measurement of aldolase B activity in the liver biopsy specimen. The crux of HFI management lies in the absolute avoidance of foods containing fructose, sucrose, and sorbitol (FSS). There are many dilemmas regarding tolerance, dietary restriction and occurrence of steatohepatitis. Patients with HFI who adhere strictly to FSS free diet have an excellent prognosis with a normal lifespan. This review attempts to increase awareness and provide a comprehensive review of this rare but treatable disorder.

Sjogren- Larsson Syndrome with Type-1 Distal Renal Tubular Acidosis in Siblings

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive lipid metabolic disorder caused because of the defect in fatty alcohol oxidation resulting from fatty aldehyde dehydrogenase (FALDH3A2) deficiency. Sjogren-Larsson syndrome is constituted by the trio of generalised spastic paralysis, intellectual impairment, &amp; ichthyosis. The inability of hydrogen ions secretion from the distal tubule characterises dRTA (distal (Type 1) renal tubular acidosis). The dRTA aetiology is diverse, but it can be acquired or inherited. We report siblings who presented with congenital ichthyotic hyperkeratosis, spastic diplegia and severe learning disabilities, which were suggestive of SLS. Distal renal tubular acidosis diagnosis was done on the basis of severe serum hypokalaemia, urine electrolytes showing high potassium levels, metabolic acidosis with a positive anion gap, high pH of urine, Urinary &amp; Blood PCO2 difference (UB PCO2) on the lower side, (FeHCO3%) showing mild bicarbonaturia (&lt;5%), medullary nephrocalcinosis, Hypercalciuria as well as the omission of other differential diagnosis. Management in SLS was supportive. The child demonstrated symptomatic improvement after starting standard therapy for SLS &amp; distal renal tubular acidosis. To conclude, distal renal tubular acidosis ailment in children can be controlled with a good long-term prognosis, but precise diagnosis as well as management are critical. Early detection can assist the physician in implementing appropriate supportive care as well as possible curative gene therapy. Keywords: Ichthyosis, spastic diplegia, Intellectual disability, Distal Renal Tubular Acidosis, Hypokalaemia

Genotype-phenotype analysis and prognosis in children with primary distal renal tubular acidosis

Objective: The purpose of this study was to investigate the relationship between genotypes and clinical phenotypes of primary distal renal tubular acidosis (dRTA) in children. Methods: Clinical information, genetic testing information and follow-up data (until March 2021) of children with dRTA from Children's Hospital of Chongqing Medical University (from January 2010 to December 2020) were analyzed retrospectively. According to different pathogenic genes, patients were divided into SLC4A1 gene and ATP6V0A4+ATP6V1B1 gene groups. Age at onset, clinical manifestations and laboratory findings were compared. Self-comparisons of height standard deviation score (HtSDS), weight standard deviation score (WtSDS), blood pH and serum potassium before and after treatment were tested. T-test, Fisher's exact test and rank sum test were used to analyze among groups. Results: Among 27 children with dRTA (16 boys and 11 girls), the age of onset was 33.4 (10.0, 36.0) months.There were 22 patients (81%) with SLC4A1 gene variation, 3 patients (11%) with ATP6V1B1 gene variation and 2 patients (8%) with ATP6V0A4 gene variation. Totally 22 patients (81%) with renal calcium deposition, 19 patients (70%) hypokalemia, 18 patients (67%) short stature, 16 patients (59%) malnutrition, 16 patients (59%) rickets, and 15 patients (56%) polydipsia and polyuria. Noteworthily, the genotyping results indicated that the age at onset in SLC4A1 gene group was older than that in ATP6V0A4+ATP6V1B1 gene group, with a statistically significant difference (27.3 (12.0, 36.0) vs. 8.2 (2.5, 15.0) months, H=6.33, P=0.012). However, there were no significant differences in clinical manifestations or laboratory test results (all P>0.05). Furthermore, the course of disease was 3.9 (1.3, 6.0) years and the follow-up period was 3.1 (1.0, 4.5) years in 27 patients. In addition, there were no significant differences in recovery rate of clinical manifestations and last laboratory findings between SLC4A1 gene group and ATP6V0A4+ATP6V1B1 gene group (all P>0.05). HtSDS and WtSDS of those patients significantly increased after treatment (-3.2±1.9 vs. -2.1±1.1, -2.5±1.5 vs. 0±1.9, t=-2.94, -5.44, both P<0.01). Serum K+ and blood pH were restored eventually ((3.2±0.5) vs. (4.0±0.5) mmol/L, 7.27±0.07 vs. 7.37±0.07, t=-4.92, -5.25, both P<0.01). Totally 14 patients had normalized serum potassium, 12 patients had normalized blood pH, but only 4 patients had normalized serum bicarbonate concentration and normal base excess. Conclusions: The age of onset of patients who had SLC4A1 gene mutation was older than that of patients with ATP6V0A4 gene and ATP6V1B1 gene mutations. However, there was no obvious correlation between the condition and prognosis of the dRTA patients and pathogenic genes. Early diagnosis, early treatment, regular follow-up and timely adjustment of the dosage of medication can significantly improve the prognosis of dRTA in children. Serum bicarbonate concentration and actual base excess might not be the necessory indicators to assess clinical recovery.

DISTAL RENAL TUBULAR ACIDOSIS WITH SEVERE HYPOKALEMIA – A CASE REPORT

Background: Renal tubular acidosis is a group of transport defects secondary to either reduced distal secretion of hydrogen ion or decreased proximal tubular reabsorption of bicarbonate or both, resulting in impaired acidication of urine with persistent hyperchloremic metabolic acidosis. Our case is that of a 5-year-old female child presenting with failure to thrive and weakness.Clinical description and Investigations: Physical examination revealed skeletal deformities with enamel defects. Subsequent blood tests and arterial blood gas analysis revealed hyperchloremic metabolic acidosis with hypokalemia. Urine analysis revealed a positive urinary anion gap with hypercalciuria and hypocitraturia. Imaging studies revealed skeletal changes secondary to rickets and USG whole abdomen showed bilateral kidney nephrocalcinosis. Oral ammonium chloride loading was given and blood and urine pH were monitored every hour for the next 6 hours but the urine pH failed to fall below 5.3 which led us to a diagnosis of distal renal tubular acidosis. Bicarbonate and potassium citrate supplementation was given alongTreatment: with vitamin D and calcium to this child. Timely diagnosis and initiation of appropriate supplementation can help in improving theConclusion: quality of life of these patients.

Genetic and clinical profile of patients with hypophosphatemic rickets

Nutritional vitamin D deficiency is the most frequent cause of rickets followed by genetic causes, that include entities like classic hypophosphatemic rickets (FGF23 related), Dent disease, Fanconi syndrome, renal tubular acidosis, and vitamin D dependent rickets. Hypophosphatemia is a feature in all these forms. The diagnosis relies on a combination of clinical, biochemical and radiological features, but genetic testing is required to confirm the diagnosis. We screened 66 patients with hypophosphatemic rickets referred to this center between May 2015 and July 2019 using whole exome sequencing (WES) in addition to the measurement of their intact serum fibroblast growth factor 23 (FGF23) levels. WES revealed 36 pathogenic and 28 likely pathogenic variants in 16 different genes (PHEX, FGF23, DMP1, ENPP1, CLCN5, CTNS, SLC2A2, GATM, SLC34A1, EHHADH, SLC4A1, ATP6V1B1, ATP6V0A4, CYP27B1, VDR and FGFR1) in 63 patients which helped differentiate between the various forms of hypophosphatemic rickets. Intact serum FGF23 levels were significantly higher in patients with variations in PHEX, FGF23, DMP1 or ENPP1 genes. The major genetic causes of rickets were classic hypophosphatemic rickets with elevated FGF23 levels, distal renal tubular acidosis, and vitamin D dependent rickets. Based on the present results, we propose a customized gene panel for targeted exome sequencing, which will be useful for confirming the diagnosis in most patients with hypophosphatemic rickets.

Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy.

Novel immunotherapy drugs have changed the landscape of cancer medicine. Immune checkpoint inhibitors and chimeric antigen receptor T cells are being used and investigated in almost all types of cancers. Immune-related adverse events have been associated with immunotherapies. AKI has been the most commonly associated kidney adverse event. In this review, we showcase the several associated electrolyte disorders seen with immunotherapy. Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common. Endocrine causes of hyponatremia are rare. Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis. Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations, including immune checkpoint inhibitor-induced parathyroid hormone-related peptide production, sarcoid-like granulomas, and hyperprogression of the disease. Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor-induced tumor lysis syndrome. Chimeric antigen receptor T cell therapy-associated electrolyte disorders are also common. This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur. Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.