Renal Tubular Acidosis in the Neonate.

See Bonus NeoBriefs videos and downloadable teaching slides Metabolic acidosis can manifest in the neonatal period and cause significant morbidity and mortality in neonates. Preterm infants are at an even higher risk of developing metabolic acidosis. If the acidosis results from a dysfunction of acid-base homeostasis by the renal system, the disorder is known as renal tubular acidosis (RTA). In this review, we will describe renal development and normal acid-base homeostasis by the renal system. We will also discuss the pathophysiology of the different types of RTA, laboratory findings to aid in diagnosis, and treatment considerations. Understanding RTA will help neonatal clinicians recognize and diagnose an infant affected by RTA and initiate treatment in a timely manner.

Kidney manifestations of pediatric Sjögren's syndrome.

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.

Pediatric Renal Rickets at a Tertiary Center.

We report clinical and etiological profile of 19 children (10 males) with renal rickets managed in the years 2021-2022. Median (IQR) age of presentation was 60 (18-96) months. The commonest cause was renal tubular acidosis (n=8). Genetic analysis revealed the diagnosis in 83% subjects (5 out of 6 tested).

Pattern of hereditary renal tubular disorders in Egyptian children.

BACKGROUND: Hereditary renal tubular disorders (HRTD) represent a group of genetic diseases characterized by disturbances in fluid, electrolyte, and acid-base homeostasis. There is a paucity of studies on pediatric HRTD in Egypt. In this study, we aimed to study the pattern, characteristics, and growth outcome of HRTD at an Egyptian medical center. METHODS: This study included children from one month to < 18-years of age with HRTD who were diagnosed and followed up at the Pediatric Nephrology Unit of Sohag University Hospital from January 2015 to December 2021. Data on patients` demographics, clinical features, growth profiles, and laboratory characteristics were collected. RESULTS: Fifty-eight children (57% males; 72% parental consanguinity; 60% positive family history) were diagnosed with seven HRTD types. The most commonly encountered disorders were distal renal tubular acidosis (distal renal tubular acidosis [RTA] 27 cases, 46.6%) and Bartter syndrome (16 cases 27.6%). Other identified disorders were Fanconi syndrome (6 cases with cystinosis), isolated proximal RTA (4 cases), nephrogenic diabetes insipidus (3 cases), and one case for each RTA type IV and Gitelman syndrome. The median age at diagnosis was 17 months with a variable diagnostic delay. The most common presenting features were failure to thrive (91.4%), developmental delay (79.3%), and dehydration episodes (72.4%). Most children showed marked improvement in growth parameters in response to appropriate management, except for cases with Fanconi syndrome. Last, only one case (with cystinosis) developed end-stage kidney disease. CONCLUSIONS: HRTD (most commonly distal RTA and Bartter syndrome) could be relatively common among Egyptian children, and the diagnosis seems challenging and often delayed.

Autosomal dominant distal renal tubular acidosis in two pediatric patients with mutations in the SLC4A1 gene. Can the maximum urinary pCO2 test be normal?

Primary distal renal tubular acidosis (dRTA) is a rare tubulopathy characterised by the presence of hyperchloremic metabolic acidosis. It is caused by the existence of a defect in the function of the H+ -ATPase located on the luminal side of the α-intercalated cells or the Cl - HCO3- (AE1) anion exchanger located on the basolateral side. Patients do not acidify the urine after acid overload (NH4Cl) or after stimulating H+ secretion by obtaining a high intratubular concentration of an anion such as chlorine (pH is measured) or HCO3- (urinary pCO2 is measured). We present a family with autosomal dominant dRTA produced by a heterozygous mutation in the SLC4A1 gene in which the two paediatric members showed a test of normal maximum urinary pCO2. Our hypothesis is that since the H + -ATPase is intact, at least initially, the stimulation induced by intratubular electronegativity to secrete H + could be effective, which would allow the maximum urinary pCO2 to be paradoxically normal, which could explain the onset, moderate presentation of symptoms and late diagnosis in patients with this mutation. This is the first documented case of a dominant dRTA in Mexico.

An Infant Case of Transient Distal Renal Tubular Acidosis and Fanconi Syndrome Caused by Rotavirus Gastroenteritis.

We report an infant case of transient distal renal tubular acidosis and Fanconi syndrome caused by rotavirus gastroenteritis. A 10-month-old boy was admitted to the hospital because of frequent vomiting, lack of vitality, and dehydration. He was diagnosed with rotavirus gastroenteritis on account of his positive stool rotavirus antigen test. Although he presented with acidemia and severe mixed metabolic acidosis, he also had a urine pH of 6.0, indicating impaired urinary acidification. Therefore, he was diagnosed with distal renal tubular acidosis. On the third day of hospitalization, a relatively low %tubular reabsorption of phosphate level with hypophosphatemia, increased fractional excretion of uric acid with hypouricemia, and high urinary ß2-microglobulin levels were observed. Moreover, he was diagnosed with Fanconi syndrome on account of multiple proximal tubular dysfunctions. After remission of rotavirus gastroenteritis, the signs of renal tubular dysfunction improved. This was a case of rotavirus gastroenteritis-caused transient distal renal tubular acidosis and Fanconi syndrome. Severe metabolic acidosis resulted from anion-gap metabolic acidosis due to acute kidney injury by rotavirus gastroenteritis and normal anion-gap acidosis due to renal tubular acidosis. When renal tubular acidosis is associated with a disease that causes anion-gap metabolic acidosis, mixed metabolic acidosis occurs and becomes exacerbated. Furthermore, it is important to consider the complications of renal tubular acidosis in the case of severe metabolic acidosis.

Renal tubular acidosis without interstitial nephritis in Sjögren's syndrome: a case report and review of the literature.

BACKGROUND: Renal tubular acidosis is the principal clinical feature associated with tubulointerstitial nephritis in patients with primary Sjögren's syndrome. Renal tubular dysfunction due to interstitial nephritis has been considered the underlying pathophysiology connecting renal tubular acidosis and primary Sjögren's syndrome. However, the detailed mechanisms underlying the pathophysiology of renal tubular acidosis in primary Sjögren's syndrome is not fully understood. CASE PRESENTATION: A 30-year-old woman was admitted with complaints of weakness in the extremities. The patient was hospitalized thirteen years earlier for similar issues and was diagnosed with hypokalemic paralysis due to distal renal tubular acidosis with primary Sjögren's syndrome. This diagnosis was based on a positive Schirmer's test. Besides, anti-Sjögren's syndrome-related antigen A was also detected. Laboratory tests indicated distal RTA; however, a renal biopsy showed no obvious interstitial nephritis. Laboratory tests conducted during the second admission indicated distal renal tubular acidosis. Therefore, a renal biopsy was performed again, which revealed interstitial nephritis. Histological analysis of acid-base transporters revealed the absence of vacuolar type H+-ATPases in the collecting duct. The vacuolar type H+-ATPase was also absent in the past renal biopsy, suggesting that the alteration in acid-base transporters is independent of interstitial nephritis. CONCLUSIONS: This case study demonstrates that vacuolar-type H+-ATPases are associated with distal renal tubular acidosis, and distal renal tubular acidosis precedes interstitial nephritis in patients with primary Sjögren's syndrome.

Acidosis tubular renal distal autosómica dominante en dos pacientes pediátricos con mutaciones en el gen SLC4A1. ¿La prueba de la pCO2 urinaria máxima puede ser normal? / Autosomal dominant distal renal tubular acidosis in two pediatric patients with mutations in the SLC4A1 gene. Can the maximum urinary pCO2 test be normal?

La acidosis tubular renal distal (ATRd) primaria es una tubulopatía poco frecuente caracterizada por la presencia de acidosis metabólica hiperclorémica. Está generada por la existencia de un defecto en la función de la H+-ATPasa situada en el lado luminal de las células α-intercaladas o del intercambiador de aniones Cl−-HCO3− (AE1) ubicado en el lado basolateral. Los pacientes no acidifican la orina tras una sobrecarga ácida (NH4Cl) o tras estimular la secreción de H+ mediante la obtención de una elevada concentración intratubular de un anión como cloro (se mide el pH) o HCO3− (se mide la pCO2 urinaria). Se presenta una familia con ATRd autosómica dominante producida por una mutación heterocigota en el gen SLC4A1 en la que los 2 miembros en edad pediátrica mostraron una prueba de la pCO2 urinaria máxima normal. Nuestra hipótesis es que al estar intacta, al menos inicialmente, la H+-ATPasa, podría ser efectivo el estímulo inducido por la electronegatividad intratubular para secretar H+ lo que permitiría que la pCO2 urinaria máxima fuera paradójicamente normal, lo que pudiera explicar el inicio tardío, la presentación moderada de los síntomas y el diagnóstico en edades más avanzadas, en los pacientes con dicha mutación. Este es el primer caso documentado de una ATRd dominante en México. (AU)

Primary distal renal tubular acidosis (dRTA) is a rare tubulopathy characterized by the presence of hyperchloremic metabolic acidosis. It is caused by the existence of a defect in the function of the H+-ATPase located on the luminal side of the α-intercalated cells or the Cl− HCO3− (AE1) anion exchanger located on the basolateral side. Patients do not acidify the urine after acid overload (NH4Cl) or after stimulating H+ secretion by obtaining a high intratubular concentration of an anion such as chlorine (pH is measured) or HCO3− (urinary pCO2 is measured). We present a family with autosomal dominant dRTA produced by a heterozygous mutation in the SLC4A1 gene in which the two pediatric members showed a test of normal maximum urinary pCO2. Our hypothesis is that since the H+-ATPase is intact, at least initially, the stimulation induced by intratubular electronegativity to secrete H+ could be effective, which would allow the maximum urinary pCO2 to be paradoxically normal, which could explain the onset, moderate presentation of symptoms and late diagnosis in patients with this mutation. This is the first documented case of a dominant dRTA in Mexico. (AU)

A report of three cases of patients with tubulointerstitial nephritis with IgM-positive plasma cells, treatment, and serum-IgM as a sensitive marker for relapse.

BACKGROUND: Tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) is a newer disease about which there are many unclear points. Glucocorticoid therapy is effective in many cases of IgMPC-TIN; however, relapse during glucocorticoid tapering has been reported. Relapse and its treatment are poorly defined. CASE PRESENTATION: Case 1 was a 61-year-old man with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. He was diagnosed with IgMPC-TIN accompanied by Fanconi syndrome and distal renal tubular acidosis (d-RTA). Prednisolone (PSL; 30 mg daily, 0.45 mg/kg/day) treatment was highly effective, and PSL was gradually tapered and discontinued after 1 year. However, 1 month after PSL discontinuation, therapeutic markers were elevated. Therefore, PSL (10 mg daily, 0.15 mg/kg/day) was administered, and the markers indicated improvement. Case 2 was a 43-year-old woman referred for renal dysfunction and proteinuria. Laboratory data revealed that she had primary biliary cholangitis (PBC), d-RTA, and Fanconi syndrome. A renal biopsy showed accumulation of IgM-positive plasma cells in the tubulointerstitium without any glomerular changes. A diagnosis of IgMPC-TIN was made and the patient was started on PSL (35 mg daily, 0.6 mg/kg/day). Therapeutic markers decreased immediately and PSL was discontinued after 1 year. Three months later, the proteinuria and Fanconi syndrome worsened. PSL treatment was restarted (20 mg daily, 0.35 mg/kg/day) and markers indicated improvement. Case 3 was a 45-year-old woman with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. The patient had PBC, Sjögren syndrome, d-RTA, and Fanconi syndrome, and the diagnosis of IgMPC-TIN was made. The patient was started on PSL (30 mg daily, 0.4 mg/kg/day) and disease markers decreased immediately. However, when PSL was tapered to 15 mg daily (0.2 mg/kg/day), the patient's serum IgM levels increased; therefore, we maintained the PSL at 15 mg daily (0.2 mg/kg/day). CONCLUSION: We report three cases of relapsed IgMPC-TIN associated with reduction or discontinuation of glucocorticoid therapy. In these cases, elevation of serum IgM preceded that of other markers such as urinary ß2-microglobulin, proteinuria, and glycosuria. We recommend monitoring serum IgM levels while tapering glucocorticoids; a maintenance dose of glucocorticoid should be considered if relapse is suspected or anticipated.

Severe Hypokalemia Complicated by Acute Myopathy: Initial Manifestation of Primary Sjögren's Syndrome-Associated Renal Tubular Acidosis.

BACKGROUND Severe hypokalemia, which often causes life-threatening malignant arrhythmias, is usually first diagnosed in the Emergency Department (ED). It is important to note that hypokalemia is often closely and complexly related to renal tubular acidosis (RTA) associated with autoimmune diseases such as Sjögren's syndrome (SS), especially in females with acute myopathy or acute liver injury (ALI). Severe hypokalemia can directly cause muscle injury, which can lead to hyper-creatine kinaseemia (HCK) and ALI, while SS can also directly cause hypokalemia, HCK, and even ALI and renal tubular/interstitial injury. Therefore, by reporting a rare case of SS-associated RTA (SS-RTA), we systematically reviewed the relationship between SS-RTA and severe hypokalemia, which may be beneficial to increase attention on this topic. CASE REPORT A 35-year-old female patient who presented to the ED primarily for limb weakness symptoms was initially diagnosed with severe hypokalemia, acute myopathy, and ALI. She was eventually diagnosed with primary SS (pSS) and SS-RTA, although she did not present with the typical dry mouth, dry eyes, and other clinical manifestations of SS. CONCLUSIONS Severe hypokalemia is a serious life-threatening emergency, and although the differential diagnosis is very broad, we should be aware of RTA associated with autoimmune diseases such as SS in female patients, especially when combined with clinical manifestations such as acute myopathy and ALI that cannot be explained by other causes. Simultaneously, we hope to be able to guide emergency physicians encountering similar patients to complete the diagnostic and therapeutic process.

Distal renal tubular acidosis in a patient with Hashimoto's thyroiditis: a case report.

Renal tubular acidosis (RTA) is a rare disorder that can be inherited or acquired, and results in an inability of the kidneys to maintain normal acid-base balance. We present a case of recurrent, severe hypokalaemia and rhabdomyolysis in a young woman who had an associated normal anion gap metabolic acidosis and was subsequently diagnosed with distal RTA associated with Hashimoto's thyroiditis. Distal RTA associated with Hashimoto's thyroiditis is rare and probably develops because of autoimmune-mediated mechanisms, causing an inability of the H+-ATPase pump in alpha-intercalated cells of the cortical collecting duct to secrete H+, with subsequent failure of urinary acidification. In this case, this hypothesis was supported by the exclusion of common genetic mutations associated with distal RTA. We illustrate that utilizing a systematic, physiology-based approach for challenging electrolyte and acid-base disorders enables identification of the root cause and underlying disease mechanisms.

Medullary Spongy Kidney in a Middle-aged Woman with Primary Biliary Cirrhosis, Sjogren's Syndrome and Type 1 Renal Tubular Acidosis.

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Transient distal renal tubular acidosis with nephrogenic diabetes insipidus after general anaesthesia in a dog.

A 3-year-old, 3.5 kg, female spayed Pomeranian was referred due to persistent vomiting, anorexia, polyuria and polydipsia, 7 days after receiving general anaesthetic for a medial patellar luxation correction. Physical examination revealed lethargy, tachypnoea and 7% dehydration. Complete blood count and serum chemistry results were unremarkable, and venous blood gas analysis revealed hypokalaemia and hyperchloraemic metabolic acidosis with a normal anion gap. Urinalysis revealed a urine specific gravity (USG) of 1.005, pH of 7.0 and proteinuria, and the bacterial culture was negative. Based on these results, the dog was diagnosed with distal renal tubular acidosis, and potassium citrate was prescribed to correct metabolic acidosis. In addition, concurrent diabetes insipidus (DI) was suspected because the dog showed persistent polyuria, polydipsia and a USG below 1.006 despite dehydration. After 3 days of initial treatment, acidosis was corrected, and vomiting resolved. Desmopressin acetate and hydrochlorothiazide were also prescribed for DI, but the USG was not normalized. Based on the insignificant therapeutic response, nephrogenic DI was highly suspected. DI was resolved after 24 days. This case report describes the concomitant presence of RTA and DI in a dog after general anaesthesia.

Hearing Loss Related to Gene Mutations in Distal Renal Tubular Acidosis.

INTRODUCTION: Distal renal tubular acidosis (dRTA) is a disease that may develop either primarily or secondarily, resulting from urinary acidification defects in distal tubules. Hearing loss may accompany primary forms of dRTA. This study aims to determine the characteristics of hearing loss due to different gene mutations in patients with dRTA. METHODS: Behavioral and electrophysiological audiological evaluations were performed after otolaryngology examination in 21 patients with clinically diagnosed dRTA. Radiological imaging of the inner ear (n = 9) was conducted and results of genetic analyses using next-generation sequencing method (n = 16) were included. RESULTS: Twenty-one patients with dRTA from 20 unrelated families, aged between 8 months and 33 years (median = 12, interquartile range = 20), participated. All patients with ATP6V1B1 mutations (n = 9) had different degrees of hearing loss. There was one patient with hearing loss in patients with ATP6V0A4 mutations (n = 6). One patient with the WDR72 mutation had normal hearing. Large vestibular aqueduct syndrome (LVAS) was detected in 6 (67%) of 9 patients whose radiological evaluation results were available. CONCLUSIONS: LVAS is common in patients with dRTA and may influence the type and severity of hearing loss in these patients. The possibility of both congenital and late-onset and progressive hearing loss should be considered in dRTA patients. A regular audiological follow-up is essential for the early detection of a possible late-onset or progressive hearing loss in these patients.

Long-term complications of primary distal renal tubular acidosis.

The clinical manifestations of primary distal renal tubular acidosis usually begin in childhood, but the disease is caused by a genetic defect that persists throughout life. This review focuses on the complications of distal tubular acidosis that occur or remain long-term such as nephrocalcinosis and urolithiasis, growth impairment, bone mineralization, severe hypokalemia, kidney cysts, and progressive kidney failure, as well as other persistent manifestations that occur independent of acidosis but are associated with some inherited forms of the disease. The pathogenic factors responsible for kidney failure are discussed in particular because it is a complication to which different publications have recently drawn attention and which affects a high percentage of adults with primary distal renal tubular acidosis. The need to maintain optimal metabolic control of the disease and scheduled clinical follow-up throughout life and the importance of organizing protocols for the transition of patients to adult nephrology services are emphasized.

Renal tubular acidosis and associated factors in patients with primary Sjögren's syndrome: a registry-based study.

OBJECTIVES: To investigate the clinical features and factors associated with primary Sjögren's syndrome (pSS)-associated renal tubular acidosis (RTA). METHOD: This case-control study was based on a multicenter pSS registry established by the Chinese Rheumatism Data Center. Patients with pSS, including those with RTA and those without renal involvement, between May 2016 and March 2020 were included in the analysis. Demographic, clinical, and laboratory data were also collected. Univariate and multivariate logistic regression analyses were used to identify factors that were associated with pSS-RTA. RESULTS: This study included 257 pSS patients with RTA and 4222 patients without renal involvement. Significantly younger age at disease onset (40.1 ± 14.1 vs. 46.2 ± 13.1 years, P < 0.001), longer diagnosis interval (15.0 interquartile range [IQR] [1.0, 48.0] vs. 6.0 IQR [0, 34.0] months, P < 0.001), higher EULAR Sjögren's syndrome disease activity index (9 IQR [5, 15] vs. 3 IQR [0, 8], P < 0.001), and a higher prevalence of decreased estimated glomerular filtration rate (25.0% vs. 6.6%, P < 0.001) were observed in pSS patients with RTA than in those without renal involvement. Factors that were independently associated with pSS-RTA included age at disease onset ≤ 35 years (odds ratio [OR] 3.00, 95% confidence interval [CI] 2.27-3.97), thyroid disorders (OR 1.49, 95% CI 1.04-2.14), subjective dry mouth (OR 3.29, 95% CI 1.71-6.35), arthritis (OR 1.57, 95% CI 1.10-2.25), anti-SSB antibody positivity (OR 1.80, 95% CI 1.33-2.45), anemia (OR 1.67, 95% CI 1.26-2.21), elevated alkaline phosphatase level (OR 2.14, 95% CI 1.26-3.65), decreased albumin level (OR 1.61, 95% CI 1.00-2.60), and elevated erythrocyte sedimentation rate (OR 1.78, 95% CI 1.16-2.73). CONCLUSIONS: Delayed diagnosis and decreased kidney function are common in pSS patients with RTA. pSS should be considered in patients with RTA, and early recognition and treatment may be useful in slowing the deterioration of renal function in patients with pSS-RTA. Key Points • pSS patients with RTA have earlier disease onset and higher disease activity than pSS patients without RTA, but the diagnosis was frequently delayed. • Decreased kidney function are common in pSS patients with RTA. • Sjögren's syndrome should be considered in young female patients with unexplained RTA, whereas RTA should be screened in pSS patients with early disease onset and elevated ALP level.

Hypokalemia Related to Distal Renal Tubular Acidosis as an Initial Presentation of Primary Sjogren's Syndrome.

Hypokalemia due to loss of potassium through the kidneys can be caused by distal Renal Tubular Acidosis (dRTA). The etiology of dRTA can be primary due to genetic defects or secondary to autoimmune diseases, especially Sjogren's syndrome (SS). The occurrence of dRTA in SS patients is low, at only 5% of cases. This case was interesting because dRTA was the initial clinical manifestation that led to the diagnosis of SS in the patient. A 48-year-old woman came with complaints of recurrent weakness. The patient was routinely hospitalized with severe hypokalemia and received potassium supplementation. The diagnosis of dRTA was based on repeated weakness, normal blood pressure, severe and recurrent hypokalemia, high urinary potassium, alkaline urine, low plasma bicarbonate, and standard anion gap metabolic acidosis. The diagnosis of SS in this patient was confirmed based on dry eyes, dry mouth, positive Schirmer's test, and positive autoantibodies to SS-A and Ro-52. There was a delay in the diagnosis of SS for two years in this patient because the complaints were initially subtle and non-specific. The hypokalemia in this patient was secondary to dRTA associated with primary SS. The possibility of an underlying autoimmune disorder should be considered in a patient presenting with recurrent severe hypokalemia. dRTA, as the etiology of hypokalemia, can be a gateway to the diagnosis of SS. In this patient, complaints related to dRTA appeared before the onset of sicca symptoms, and the diagnosis of SS was established.

Genotype-Phenotype correlation of distal renal tubular acidosis in Tunisia.

INTRODUCTION: Distal renal tubular acidosis (dRTA) is a rare genetic disorder due to the incapacity of the α intercalated cells to excrete protons in the collecting duct. This impaired distal acidification of urine leads to a chronic hyperchloremic metabolic acidosis with a normal plasma anion gap, hypokalemia, and hypercalciuria with hypocitraturia causing nephrocalcinosis. Primary dRTA is inherited either as an autosomal dominant (SLC1A4 gene) or autosomal recessive trait (ATP6V0A1/ATP6V1B1 genes). AIM: To analyze the genotype-phenotype correlation of dTA in Tunisia. METHODS: In this study we present all available data of patients followed in our center for dRTA over the last 28 years and who had a genetic study. This was a retrospective descriptive study from January 1991 to December 2018, conducted in the Pediatrics Department of the Charles Nicolle Hospital in Tunis. RESULTS: Twenty-five cases of dRTA were collected and were offered genetic analysis to confirm the diagnosis. The molecular mutation was confirmed in 13 patients of whom 11 had homozygous mutations in ATP6V1B1(G1) and 2 had homozygous mutations in ATP6V0A4(G2). Median age of diagnosis was 8.9 months. Severe growth retardation was documented in nine children with mutations in ATP6V1B1, in eight children with no genetic mutation and in the two patients with a mutation in ATP6V0A4. All children were found to have metabolic acidosis at initial presentation. Hypokalemia was found in 19 children. All patients were polyuric. Twenty-two patients had nephrocalcinosis (88%). The treatment was based on alkali prescription and substitution of potassium chloride. Sensorineural hearing loss (SNHL) was documented in 12 children. At the last consultation, 14 patients had chronic kidney disease (CKD) stage 2 or higher, 8 of whom were in the group with negative genetic analysis. CONCLUSION: According to the early onset in patients, the recessive mode seems to be the mode of transmission in Tunisia. dRTA was long considered to not affect renal function, but we note a decline in eDFG.