Tubular Disorders Research Articles

Pediatric Tubular and Inherited Disorders in Asia

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.

Clinical features of pediatric renal glucosuria cases due to SLC5A2 gene variants

AbstractBackgroundFamilial renal glycosuria (FRG) is a rare renal tubular disorder characterized by a variable loss of glucose in the urine despite normal blood glucose levels, which is seen in a condition in which other tubular functions are preserved. In this study, the molecular and clinical characteristics of pediatric FRG cases due to SLC5A2 gene variants were defined.MethodsDemographic features, diagnostic tests, and molecular analyses of patients with a diagnosis of FRG cases due to SLC5A2 gene variants were retrospectively analyzed between 2016 and 2019.ResultsThe data of 16 patients who were clinically and genetically diagnosed with FRG in a 4‐year period were analyzed. Seven (44%) of the cases were female and 9 (56%) were male. The median age at diagnosis was 6 years old (2 months old to 17 years old). Neuromotor development was found to be appropriate for the age in each case. Systemic blood pressure was evaluated as normal. A homozygous pathogenic variant in the SLC5A2 gene was detected in 14 patients in the genetic examination. A heterozygous variant was detected in one patient. In the other patient, two different heterozygous pathological variants were found in the SLC5A2 gene.ConclusionsIt was revealed that growth and development were normal in children with glucosuria due to variations in the SCL5A2 gene. Renal function tests and urinary amino acid excretion were also within normal values. In our case series, the most common genetic variation in the SCL5A2 gene was the A219T (c.655G>A) variant.

Rickets due to renal tubular acidosis: A case report and our perspective

Renal tubular acidosis (RTA) is a diverse group of tubular disorders characterized by failure of urinary acidification in the presence of metabolic acidosis with variable electrolyte abnormalities. RTA can present with a variety of manifestations to the nephrologist, orthopedist, pediatrician, and endocrinologist. Short stature, rickets, renal stones, and failure to thrive are the presentations that the endocrinologist can encounter. Here, we present one such case of rickets caused by distal RTA with secondary proximal tubular dysfunction.

Bartter Syndrome: Perspectives of a Pediatric Nephrologist.

Bartter syndrome (BS) is one of the most well-known hereditary tubular disorders, characterized by hypokalemic, hypochloremic metabolic alkalosis, and polyuria/polydipsia. This disease usually presents before or during infancy, and adult nephrologists often inherit the patients from pediatric nephrologists since this is a life-long condition. Here, a few case scenarios will be presented to recount how they first got diagnosed and how their clinical courses were during childhood until adulthood, in addition to a brief review of the disease and its treatment.

Phenotypic and genotypic characteristics of children with Bartter syndrome.

Bartter syndrome (BS) is a group of autosomal-recessive tubular disorders and it is classified into five genetic subtypes. BS can also be classified by phenotype (antenatal, classic). Patients with mutations in the same gene can present different phenotypes. In the present study, target gene sequencing was performed to evaluate the genotype-phenotype relationship. Biochemical, clinical and renal ultrasonography results were collected at presentation and the last clinic visit. Genetic analyses were performed. The findings of patients with classical BS (cBS) and antenatal BS (aBS) at presentation and the last visit were compared. Our study included 21 patients (12 female, 57.1%) from 20 families with BS. The median age at diagnosis was 8 months and the median follow-up period was 39 months. The most frequent complaint was growth failure. We have found 18 different types of mutations in four genes, including nine in the CLCNKB gene, seven in the SLCA12A1 gene, one in the KCNJ1 gene and one in the BSND gene. In ten patients, nine different types of CLCNKB gene mutations were detected, five of them were novel. Seven different mutations in the SLC12A1 gene were detected in eight patients, five of them were novel. Compared to patients with aBS and cBS, prematurity was significantly higher in the group with aBS. Nephrocalcinosis was present in only one patient with cBS, all the ten hypercalciuric patients with aBS had nephrocalcinosis at the time of diagnosis and the last visit. The mean height standard deviation score (SDS) of patients with aBS were significantly lower than the cBS group at the time of presentation. The mean weight SDS at the time of presentation was worse in patients with aBS than in patients with cBS. The mean plasma potassium and chloride concentrations were significantly lower in the patients with cBS at the time of diagnosis. This investigation revealed the mutation characteristics and phenotype-genotype relationship of our patients and provided valuable data for genetic counseling.

Primary Distal renal tubular acidosis: case series

Primary Distal renal tubular acidosis is an infrequent tubular disorder with complex pathophysiology that present with poor growth, skeletal changes and sometimes life-threatening hypokalemia. Here we present two siblings one girl and one boy with a consanguineous parents presented with polyuria, polydipsia, failure to thrive and skeletal deformity. Both cases showed non-anion gap metabolic acidosis with alkaline urine and the younger brother had periodic paralysis due to hypokalemia. After diagnosis and treatment they showed good response with alkali therapy.
 AKMMC J 2022; 13(1) : 56-59

A novel MAGED2 variant in a Chinese preterm newborn with transient antenatal Bartter\u2019s syndrome with 4\u2009years follow-up

BackgroundTransient antenatal Bartter’s syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation.Case presentationWe encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter’s syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter’s syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal.ConclusionsWe reported the first Chinese case of transient antenatal Bartter’s syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.

Assessing nephrology competence in general paediatrics-A survey of general paediatricians, paediatric nephrologists, residents, and program directors.

The objective of this study was to identify nephrology topics of lowest perceived competency and importance for general paediatricians. Surveys were distributed to general paediatricians, paediatric residents, paediatric residency program directors, and paediatric nephrologists. Perceived importance and competence were rated on a 5-point Likert scale. Means and 95% confidence intervals were calculated. Mean perceived competency from general paediatricians across all nephrology domains was 3.0, 95%CI (2.9 to 3.1) and mean importance was 3.2, 95%CI (3.1 to 3.3). Domains scoring below the means for competence and importance, respectively were kidney stones (2.5, 95%CI [2.2 to 2.7]) and 2.6, 95%CI [2.3 to 2.8]), acute kidney injury (2.5, 95%CI [2.2 to 2.8] and 2.4, 95%CI [2.1 to 2.8]), chronic kidney disease (1.9, 95%CI [1.7 to 2.2] and 2.1, 95%CI [1.8 to 2.4]), tubular disorders (1.8, 95%CI [1.6 to 2.0] and 2.0, 95%CI [1.8 to 2.3]), and kidney transplant (1.6, 95%CI [1.4 to 1.8] and 1.7, 95%CI [1.4 to 1.9]). Residents, program directors, and paediatric nephrologists agreed that stones, chronic kidney disease, tubular disorders, and transplant were of lower importance. However, acute kidney injury was the domain with the largest discrepancy in perceived importance between residents (4.4, 95%CI [4.2 to 4.6]), nephrologists (4.2, 95%CI [3.8 to 4.6]), and program directors (4.2, 95%CI [3.7 to 4.7]) compared to general paediatricians ([2.4, 95%CI [2.1 to 2.8]; P<0.05). Paediatricians did not believe acute kidney injury was important to their practice, despite expert opinion and evidence of long-term consequences. Educational interventions must address deficits in crucial domains of renal health in paediatrics.

Atypical histological abnormalities in an adult patient with nephronophthisis harboring NPHP1 deletion: a case report

BackgroundNephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13–14 years old), and adolescent type (approximately 19 years old). Here, we report a case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities.Case presentationA 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary β2-microglobulin was high (805 μg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP.ConclusionsNPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.

Tubulopathy meets Sherlock Holmes: biochemical fingerprinting of disorders of altered kidney tubular salt handling

Evolution moves in mysterious ways. Excretion of waste products by glomerular filtration made perfect sense when life evolved in the ocean. Yet, the associated loss of water and solutes became a problem when life moved onto land: a serious design change was needed and this occurred in the form of ever more powerful tubules that attached to the glomerulus. By reabsorbing typically more than 99% of the glomerular filtrate, the tubules not only minimise urinary losses, but, crucially, also maintain homeostasis: tubular reabsorption and secretion are adjusted so as to maintain an overall balance, in which urine volume and composition matches intake and environmental stressors. A whole orchestra of highly specialised tubular transport proteins is involved in this process and dysfunction of one or more of these results in the so-called kidney tubulopathies, characterised by specific patterns of clinical and biochemical abnormalities. In turn, recognition of these patterns helps establish a specific diagnosis and pinpoints the defective transport pathway. In this review, we will discuss these clinical and biochemical “fingerprints” of tubular disorders of salt-handling and how sodium handling affects volume homeostasis but also handling of other solutes.

Ameliorative effect of taurine against diabetes and renal-associated disorders (Review).

To develop novel therapeutic methods for both diabetic and renal disorders, scientists had initially focused on elucidating the molecular mechanisms of taurine in established cell lines and mouse models. Although a large amount of data have been revealed, taurine has been confirmed to be the next step of novel promising therapeutic interventions against diabetic disorders. Taurine appears to ameliorate diabetes 1-related complications in various organs through its antioxidant, anti-inflammatory and anti-hormonal actions. In type 2 diabetes, taurine has been positively implicated in glucose homeostasis, exerting potent hypoglycemic, anti-obesity, hypotensive and hypolipidemic effects. Of particular interest is that taurine provides protection against renal dysfunction, including hypertension and proteinuria, specific glomerular and tubular disorders, acute and chronic renal conditions, and diabetic nephropathy. The ameliorative effects of taurine against renal disorders are based on its osmoregulatory properties, its association with signaling pathways and its association with the renin-angiotensin-aldosterone system (RAAS). Further clinical studies are required to ensure the importance of research findings.

MO032URINARY EXCRETION DISORDER IN 125 PATIENTS WITH GITELMAN SYNDROME

Abstract Background and Aims Long-term oral prescription of thiazide diuretics, which can block the sodium chloride co-transporter (NCC) of the distal tubule, has been recognized to affect the function of the proximal tubule. But the underlying mechanism is largely unknown. Gitelman syndrome (GS) is a recessively inherited salt-losing tubulopathy due to the loss-of-function mutation of NCC, which can be used as a good model to understand the pathophysiological mechanism of thiazide-related disorders. In this study, we summarized the clinical characteristics of proximal tubular function in the cohort of patients with GS, and explore the possible mechanisms of proximal tubular dysfunction secondary to distal tubular disorder. Method Patients who were diagnosed with GS (confirmed by gene sequencing) in our hospital from August 1, 2005 to December 31, 2019 were enrolled, as well as the selected gender- and age-matched healthy controls. For patients whose SLC12A3 gene was sequenced as a single heterozygous mutation, further whole exome sequencing was performed to clarify the gene mutation. Clinical data including demographic information, symptoms, and hematuria tests were collected. The hydrochlorothiazide test was performed to assess the function of NCC. Characteristics of calcium and phosphate metabolism and uric acid of patients were analyzed. Results A total of 125 patients with genetic diagnosed GS were enrolled, and 33 patients (26.4%) were with only a single heterozygous mutation. Twenty-five patients completed whole exome sequencing, and 9 patients (36%) were finally diagnosed with compound heterozygous mutations. Seven mutation sites were newly detected by whole exome sequencing, including 3 missense mutations, 1 splice-site point mutation and 3 intron mutations. Serum uric acid in GS patients was significantly higher than that in healthy controls (347.5±91.7 vs 309.9±85.3μmol/L; P&amp;lt;0.001). The proportions of men and women with hyperuricemia were 19.4% and 34.5%, respectively. Urinary fraction excretion of uric acid in the hyperuricemia group was significantly lower than that of patients with normal serum uric acid. Compared with healthy controls, GS patients had higher blood calcium level (2.41±0.17 vs 2.32±0.09mmol/L; P&amp;lt;0.001). However, urinary calcium, parathyroid hormone (26.79±14.21 vs 33.18±11.58μmol/L; P=0.005), and 25-hydroxyvitamin D (15.88±6.46 vs 19.56±6.06 nmol/L; P=0.001) were lower in GS patients. Lower blood magnesium level was associated with lower parathyroid hormone level. Conclusion In GS patients, low urinary calcium, high serum calcium and high serum uric acid levels were related with the compensation of proximal tubular function.

Gitelman Syndrome in Post-Partum Pre-Eclampsia in Dr. Soetomo Hospital, Surabaya, Indonesia

Gitelman Syndrome (GS) is an autosomal recessive tubular kidney disorder. The disorder is rare with a prevalence estimated to be 1 in 40,000 individuals. We closely observed a 28-year-old female with complaints of stiffness and cramps on both hands and feet for 2 weeks and became worse in 3 days before admittance, nausea (+), vomiting (+), shortness of breath (+). Medical records showed that patient underwent post SC 32nd day because of severe pre-eclampsia + IUGR + Oligohydramnion. Physical examination showed GCS 456, blood pressure 140/80 mmHg, heart rate 96x/minute, respiration rate 24x/minute, temperature 37 oC. Laboratory results showed Hb 9.4 g/dl, MCV 86.8 fL, MCH 29.6 pg, MCHC 34.1 g/dL, WBC 7.83x103/uL, PLT 483x103/uL, potassium 2.8 mmol/L, sodium 138 mmol/L, chloride 95 mmol/L, calcium 8.3 mg/dL, magnesium 1.1 mg/dL, phosphate 3 mg/dL, BUN 8 mg/dL, serum creatinin 0.76 mg/dL, urinary calcium 488.4 mg/24 hours, urinary creatinine 488.4 mg/24 hours, proteinuria +1, and blood gas test suggested mixed metabolic alkalosis and respiratory acidosis. Gitelman Syndrome is characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The diagnosis of GS is generally relatively late because of its difficulty to be clinically categorized; therefore, a more comprehensive diagnosis approach is needed. The diagnosis of Gitelman Syndrome is based on clinical symptoms and laboratorial abnormalities and can be confirmed by genetic testing.

A Rare Case Report of Acquired Bartters With Positive Anti Scl70 Antibody

Introduction: Bartter syndrome autosomal recessive renal tubular disorders usualy presents in infant age group or antenatallyCase Description64 years housewife, a known case of hypothyroidism with in emergency with generalized weakness and hypotension. She had an small adrenal nodule work up which showed that it was non functional. On evaluation at time of stress (blood pressure 70/50) her serum cortisol was 300nmol/l and she was therefore started on hydrocortisone. Her records revealed hypokalemia for last 2 years. Workup of hypokalemia showed kaliuresis, metabolic alkalosis, hypercalciuria and excess chloride excretion in the urine, suggestive of bartter’s syndrome. But this needed further confirmation as bartter’s is rare in this age group and also the test was done at the time of stress. She was started on spironolactone and oral potassium supplementation. CECT head done for evaluation of postural dizziness showed chronic cortical venous thrombosis. On follow up ACTH stimulated cortisol was done which showed normal cortisol level so steroid was stopped. She was readmitted one month later with hypokalemia(K-1.8 meq/l) while being on same dosage of spironolactone and potassium. Workup of hypokalemia showed same feature of bartter’s syndrome. Considering the chain of events, a suggestion of bartter’s and response to steroid, a diagnosis of acquired autoimmune bartter’s syndrome along with hypothyroidism was made. An autoimmune work up showed anti SCL 70 positive2+(++). Patient responded to steroid, spironolactone, indomethacin and oral potassium supplementation. Discussion: Bartter’s syndrome can rarely happen in old age too. Seek for autoimmune cause once we suspect acquired bartter’s. To best of our knowledge previously only one case has been reported of acquired Bartter with systemic sclerosis. Patient may develop systemic sclerosis in future as anti SCL70 antibody is very specific for it. It is positive in less than 1 % of general population. Anti SCL70 antibody is rarely positive in Sjogrens syndrome. Our patient did not feature of sjogren or systemic sclerosis even after 4 years follow up

INTERCONNECTION BETWEEN TUBULAR RENAL DYSFUNCTION AND GENES POLYMORPHISM IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: Objective: to assess the relationship between NGAL concentration as an indicator of tubular disorders, and genetic markers of cardiovascular risk in hypertensive patients. Design and method: Materials and methods: 89 patients of working age with hypertension (mean age 48.32 ± 8.71) were examined, who were divided into 2 groups depending on serum NGAL. Group 1 - 20 patients with NGAL levels above reference values, Group 2 - 69 patients with NGAL levels in the range of normal values. For all patients, to evaluate tubular renal function, the concentration of NGAL in serum was determined by ELISA. All patients were examined for genotypes of AGT Thr174Met, GNB3 C825T, MTHFR C677T, MTRR Ile22Met, ApoE Cys130Arg, PRARA rs4253778. Results: Results: patients in the groups did not significantly differ in age, gender, risk factors, concomitant diseases and therapy, blood pressure and lipid profile. In group 1, the occurrence of AGT, MTHFR, and PRARA gene polymorphism was significantly higher in heterozygous form than in group 2 (p = 0.002, p &lt; 0.001, and p = 0.037, respectively). Patients in the groups did not significantly differ in occurrence of GNB3, MTRR, and ApoE gene polymorphism. Correlation analysis showed a direct relationship between the concentration of NGAL in the blood and the presence of AGT gene polymorphism (r = 0.38; p &lt; 0.05), GNB3 (r = 0.33; p &lt; 0.05), MTHFR (r = 0.35; p &lt; 0.05). The association of NGAL with the polymorphism of the GNB3, MTRR, and ApoE genes was not statistically significant. Conclusions: Conclusions: in patients of working age with hypertension, tubular dysfunction, assessed by the concentration of NGAL in the blood, is associated with the presence of AGT, MTHFR, PRARA gene polymorphism in a heterozygous form.

PECULIARITIES OF IONOREGULATORY RENAL FUNCTION OF RATS IN THE DYNAMICS OF EXPERIMENTAL DIABETES MELLITUS DEVELOPMENT WITH UNDERLYING PHARMACOLOGICAL BLOCADE OF RENIN-ANGIOTENSINALDOSTERONE SYSTEM

The aim of the study – to explore the role of the renin-angiotensin-aldosteronesystem (RAAS) in the disturbance of ionoregulatory renal function in alloxan-inducedexperimental diabetes mellitus (EDM).Material and methods. The experiments were carried out on 78 white non-linearmature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlyingpharmacological blockade of RAAS by administration of kaptopril. The study ofionoregulating function of the kidneys was provided by the clearance method under thecondition of water 2-hour diuresis.Results. Pharmacological blockade of RAAS in rats with alloxan-induced EDM causedan intensification of natriuresis at all stages of the experiment: increased urinaryconcentration of sodium ions, its excretion and clearance. On the 11th day of EDM, thesodium filtration charge increased with the development of hyponatremia, proximal anddistal sodium reabsorption standardized in volume of glomerular filtrate (GF) decreased,kaliuresis was suppressed, and sodium-free water clearance elevated. In case of 26-daylong EDM, the sodium filtration charge decreased, its absolute and relative reabsorption,the distal sodium reabsorption standardized by GF increased. Kaliuresis increased. In46-day long EDM, the sodium filtration charge decreased, and hyponatremia enhanced.Absolute and relative sodium reabsorption reduced due to both – proximal and distal.Kaliuresis augmented, the clearance of sodium-free water declined.Conclusions. The increase in urinary sodium loss during the 11-day EDM is stipulatedby glomerular hyperfiltration, causing a functional weakening of the tubulotubularbalance and relative dysfunction of the distal segment of the nephron, emphasizing therenoprotective effect of RAAS on ionoregulatory function of the kidneys. The decrease inthe total reabsorption potential of the tubular segment of the nephron in the dynamics ofEDM development reflects on the proximal tubules, and preserved tubulotubular balancecertifies functional intactness of the distal tubules in 26-day long EDM. RAAS pathologicalactivation and attenuation of the renal blood flow autoregulation by tubuloglomerularfeedback may serve as an initiating factor in the development of tubular disorders in 26-day long alloxan diabetes with following progression in 46-day long EDM.

Gitelman syndrome, a rare cause of refractory hypokalemia. A case repor

Introduction: Gitelman syndrome is a rare hereditary primary renal tubular disorder, with a prevalence of approximately 1 to 10 cases per 40 000 people. It does not have specific symptoms, so its diagnosis depends on high clinical suspicion by the treating physical and a sequential approach to hypokalemia, especially in young patients. Thus, a diagnostic algorithm is proposed at the end of this report. Case presentation: A 23-year-old woman with a history of hospitalization due to hypokalemia presented to the emergency service with intermittent cramping in her lower limbs, which was exacerbated by gastrointestinal symptoms. Laboratory tests reported the following findings: metabolic alkalosis, elevated levels of potassium, magnesium, chloride and sodium in urine, and reduced levels of calcium in urine. Thus, potassium supplementation and eplerenone administration were started, obtaining the complete resolution of symptoms. At her last follow-up appointment, the patient was asymptomatic, and her serum electrolyte levels were normal. In addition, during her hospital stay and due to the high suspicion of Gitelman syndrome, a genetic study was performed, which reported a mutation of the SCL12A3 gene, confirming the diagnosis. Conclusion: The sequential approach to a patient with recurrent hypokalemia is very important to reach an accurate diagnosis among a wide range of differential diagnoses.

Gitelman syndrome and ectopic calcification in the retina and joints.

Gitelman syndrome is a rare inherited renal tubular disorder with features that resemble thiazide use, including a hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria and a low or normal blood pressure, hyperreninemia and hyperaldosteronism. Treatment is primarily correction of the potassium and magnesium levels. The diagnosis is confirmed with genetic testing but Gitelman syndrome is often not suspected. However, the association with ectopic calcification in the retina, blood vessels and chondrocalcinosis in the joints is a useful pointer to this diagnosis. Bilateral symmetrical whitish deposits of calcium pyrophosphate are visible superotemporally on ophthalmoscopy and retinal photography but are actually located beneath the retina in the sclerochoroid. Optical coherence tomography is even more sensitive for their detection. These deposits increase in size with time, but the rate of progression slows with long-term correction of the hypomagnesemia. Calcification may be complicated by atrophy of the overlying retina and visual loss. The deposits often correlate with ectopic calcification in the aorta and coronary and cerebral vessels. Chondrocalcinosis occurs in the large joints such as the knees. Ectopic calcification in Gitelman syndrome indicates the need for more aggressive management of Mg levels. Calcification is much less common in Bartter syndrome, which itself is rarer and associated less often with hypomagnesemia.

Transient generalized proximal tubular dysfunction in an infant with a urinary tract infection: the effect of maternal infliximab therapy?

Abstract Objectives Urinary tract infections (UTIs) are common in childhood. Distal tubular dysfunction during a UTI is relatively common, but proximal tubular involvement is a unique feature in humans. Case presentation We present the first case of transient generalized proximal tubular dysfunction (renal Fanconi syndrome) in an infant with an UTI. During pregnancy, his mother was treated for Crohn’s disease with infliximab (last dose at 28 weeks of gestation). He presented at the age of six weeks with a reduced intake, and was found to have amino-aciduria, glucosuria, and urinary loss of potassium, bicarbonate and low-molecular-weight proteins. Within a few weeks after antibiotic treatment for the UTI, no proximal tubular disorder remained and the boy is doing well. Conclusions We hypothesize that the inflammatory response caused by the UTI was more profoundly present due to the maternal infliximab therapy, and thereby included not only the distal but also the proximal tubules.

Néphrocalcinose de l’enfant

Nephrocalcinosis is defined by calcium phosphate or calcium oxalate deposits in the kidney parenchyma, particularly in tubular epithelial cells and interstitial tissue. It should be differentiated from urolithiasis where calcium salts deposits are located in the kidney and urinary tract. The epidemiology of nephrocalcinosis in children is unknown but the condition is not so rare, with an increased incidence in preterm infants. Often detected as an incidental finding, nephrocalcinosis may be classified according to the radiological type: medullary, cortical or diffuse. Nephrocalcinosis in children can be caused by a variety of etiology. The most common causes concern medullary nephrocalcinosis and include hereditary tubular disorders, in particular distal renal tubular acidosis and Dent disease, metabolic disorders such as idiopathic hypercalciuria and hyperoxaluria, and iatrogenic causes such as vitamin D intoxication. In the newborn, the main cause is hypercalciuria of the premature baby, whose multifactorial origin is largely iatrogenic. Primary hyperoxaluria which can lead to early onset nephrocalcinosis and usually to chronic kidney disease should always be considered and further investigated. In order to provide a specific diagnosis, it is essential to take into account the family history, the clinical context and complete laboratory data. Early initiation of an appropriate etiological treatment is recommended and may prevent or delay the progression to chronic kidney disease in some cases.