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Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population., Objective: To evaluate the prevalence of RTA in individuals with ATTRv., Methods: We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 + ) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3., Results: We selected 49 individuals with a mean age of 40 (35.5-56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH<5.5 on the dipstick had 100% sensitivity and negative predictive value to exclude dRTA., Conclusion: A high prevalence of RTA was found in individuals with TTR mutations. The UpH dipstick after WDT had good accuracy for screening for dRTA. Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population.

Objective: To investigate the risk factors of renal tubular acidosis (RTA) in patients with primary Sjögren's syndrome (pSS) and create a personalized nomogram for predicting pSS-RTA patients., Method: Data from 99 pSS patients who underwent inpatient treatment at our hospital from January 2012 to January 2024 were retrospectively collected and analyzed. Bootstrap resampling technique, single-factor, and multi-factor logistic regression analyses were used to explore the risk factors for pSS-RTA. A nomogram was developed based on the results of the multivariate logistic model. The model was evaluated through receiver operating characteristic curve, C-index, calibration curve, and decision curve analysis. In addition, we graded the severity of pSS-RTA patients and used univariate analysis to assess the relationship between pSS-RTA severity and risk factors., Results: A multivariate logistic regression analysis revealed that concurrent thyroid disease, long symptom duration, subjective dry mouth, and positive RF were independent risk factors for pSS-RTA patients. Based on them, a personalized nomogram predictive model was established. With a p-value of 0.657 from the Hosmer-Lemeshow test, the model demonstrated a good fit. The AUC values in the training and validation groups were 0.912 and 0.896, indicating a strong discriminative power of the nomogram. The calibration curves for the training and validation groups closely followed the diagonal line with a slope of 1, confirming the model's reliable predictive ability. Furthermore, the decision curve analysis showed that the nomogram model had a net benefit in predicting pSS-RTA, emphasizing its clinical value.This study did not find an association between the severity of pSS-RTA and risk factors., Discussion: We developed a nomogram to predict RTA occurrence in pSS patients, and it is believed to provide a foundation for early identification and intervention for high-risk pSS patients., (© 2024. The Author(s).)

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.

Purpose of Review: The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid nephrolithiasis, two conditions characterized by an abnormally acidic urine., Recent Findings: Both type 4 RTA and uric acid nephrolithiasis disproportionately occur in patients with type 2 diabetes and/or chronic kidney disease. Biochemically, both conditions are associated with reduced renal ammonium excretion resulting in impaired urinary buffering and low urine pH. Reduced ammoniagenesis is postulated to result from hyperkalemia in type 4 RTA and from insulin resistance and fat accumulation in the renal proximal tubule in uric acid nephrolithiasis. The typical biochemical findings of hyperkalemia and systemic acidosis of type 4 RTA are rarely reported in uric acid stone formers. Additional clinical differences between the two conditions include findings of higher urinary uric acid excretion and consequent urinary uric acid supersaturation in uric acid stone formers but not in type 4 RTA., Summary: Type 4 RTA and uric acid nephrolithiasis share several epidemiological, clinical, and biochemical features. Although both conditions may be manifestations of diabetes mellitus and thus have a large at-risk population, the means to the shared biochemical finding of overly acidic urine are different. This difference in pathophysiology may explain the dissimilarity in the prevalence of kidney stone formation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

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.

Introduction: The 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., Objective: To analyse the epidemiological aspects of distal tubular acidosis in Tunisia and study its evolutionary profile., Patients and Methods: We 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)., Results: The 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 m 2 SC with stage 2 of chronic kidney disease in 50% of patients., Conclusion: Distal 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., (Copyright © 2022 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Prospective evaluation of the prevalence of incomplete distal renal tubular acidosis (idRTA) in idiopathic calcium stone formers (ICSF) diagnosed by half-dose ammonium chloride loading (NH 4 Cl, 0.05 g/kg body weight/day) and impact of alkali treatment of idRTA., Methods: Evaluation of 386 consecutive idiopathic calcium stone formers (ICSF) (280 males, 106 females) for idRTA. If screening fasting urine pH was > 5.80, 1-day NH 4 Cl loading was performed without severe adverse effects. Normally, urine pH falls below 5.45., Results: Sixty-four idiopathic calcium stone formers exhibited idRTA, one complete dRTA. Prevalence was higher in women (25.4%) than in men (13.6%). Thus, for more equilibrated comparisons, we formed pairs of 62 idiopathic calcium stone formers (ICSF) with and 62 without idRTA, matched for gender, age, BMI and serum creatinine. Idiopathic calcium stone formers with idRTA more often had hypercalciuria (p < 0.025) and urine citrate < 2 mmol/d (p < 0.05), formed calcium phosphate stones more frequently, exhibited higher numbers of stones/year (1.4 ± 1.5 vs. 0.9 ± 0.8, p = 0.034) and 2.5 times more intrarenal calcifications (4.6 ± 5.9 vs. 1.8 ± 3.6, p = 0.002). All idiopathic calcium stone formers with idRTA were recommended chronic alkali therapy. After 4-15 years of follow-up, stone events /years follow-up (stone passage or urologic intervention) were higher in patients non-adherent to alkali therapy (0.61 ± 0.92) than in patients adherent to treatment (0.11 ± 0.21, p = 0.006)., Conclusion: Incomplete distal renal tubular acidosis is 1.8-fold more prevalent among female idiopathic calcium stone formers, predicts more stone recurrences, predisposes to calcium phosphate stones and is associated with 2.5 times more intrarenal calcifications vs. non-idRTA patients. Chronic alkali treatment reduces clinical stone recurrences by 5.5 times., (© 2022. The Author(s).)

Background: Hyperchloremic metabolic acidosis (HCMA) from renal tubular acidosis (RTA) is common in kidney transplant (KT) recipients. Calcineurin inhibitors (CNIs) are a potential cause of RTA, and whether HCMA is a determinant of poor graft prognosis is controversial., Methods: The subjects were living-donor KT recipients (LDKTRs, n = 47) and matched donors (n = 43). All cases of rejection, extrarenal causes, and respiratory disorders were excluded. HCMA was defined as having a [Na+]-[Cl - ] value of ≤34 or starting alkalization. We determined the potential causes of HCMA in LDKTRs at 3 months (m) and 1 year (y) post-KT. We examined renal hemodynamic parameters in 26 LDKTRs at 1 y post-KT: namely, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF; GFR/RPF) and pre-/post-glomerular vascular resistance (pre-/postVR)., Results: The HCMA incidence in the 3-m post-KT LDKTR group was higher than that of the donors (51.0% vs. 6.9%, p < 0.001, adjusted odds ratio: 6.7-15.7). Among adjusted factors, the most dominant HCMA contributor was low hemoglobin concentration (Hb ≤ 12 g/dl). Compared to non-HCMA cases, HCMA patients had low FF and low post-VR (p = 0.008, 0.003, respectively) suggesting increased intrarenal post-glomerular blood flow. The high pathological score of alternative arteriolar hyalinosis (aah) ≥2 was a significant HCMA risk. The tacrolimus trough level was not high in HCMA but was significantly high in HCMA in the low post-VR setting (p = 0.002)., Conclusion: Among LDKTRs, low hemoglobin level is an important contributor to the manifestation of HCMA in the induction period, and increased intrarenal post-glomerular blood flow is a key condition for the development of CNI-induced RTA., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There is limited information about the incidence of metabolic acidosis (MA) after renal transplantation. This single centre prospective study aimed to delineate the incidence and risk factors of MA in the first 6 months after renal transplantation (RTX)., Design, Setting, Participants and Measurements: Patients who underwent RTX between November 2018 and July 2020 were monitored with weekly measurement of serum bicarbonate level for 6 months and those who were diagnosed with MA were evaluated further to characterize the type of MA., Results: One hundred and twenty-five patients were included in the study, 89 (71.2%) of whom developed MA. Seventy-two patients developed MA in the first month, 11 during the 2-3 months and 6 between 4 and 6 months after transplantation. Of the 89 patients, 55(61.8%) had type 1 renal tubular acidosis (T1RTA), 27 (30.3%) had type 2 RTA (T2RTA) and 7 (7.9%) type 4 RTA (T4RTA). Two patient who had T1RTA, subsequently developed high anion gap MA following severe graft rejection. On stepwise multivariate regression analysis, serum creatinine at time of diagnosis of MA [OR (95% CI): 12.02 (1.79 to 80.59), p = .01] and high tacrolimus C0 levels [OR (95% CI): 2.43 (1.0 to 5.90), p = .049], were independent risk factors for MA., Conclusion: There is a high incidence of MA in the initial 6 months post-transplant with serum creatinine and high tacrolimus C0 levels being independent risk factors., (© 2021 Asian Pacific Society of Nephrology.)

Renal tubular acidosis (RTA) comprises a group of disorders in which excretion of hydrogen ions or reabsorption of filtered HCO 3 is impaired, leading to chronic metabolic acidosis with normal anion gap. In the current review, the focus is placed on the most common type of RTA, Type 1 RTA or Distal RTA (dRTA), which is a rare chronic genetic disorder characterized by an inability of the distal nephron to secrete hydrogen ions in the presence of metabolic acidosis. Over the years, knowledge of the molecular mechanisms behind acid secretion has improved, thereby greatly helping the diagnosis of dRTA. The primary or inherited form of dRTA is mostly diagnosed in infancy, childhood, or young adulthood, while the acquired secondary form, as a consequence of other disorders or medications, can happen at any age, although it is more commonly seen in adults. dRTA is not as "benign" as previously assumed, and can have several, highly variable long-term consequences. The present review indeed reports and summarizes both clinical symptoms and diagnosis, long-term outcomes, genetic inheritance, epidemiology and current treatment options, with the aim of shedding more light onto this rare disorder. Being a chronic condition, dRTA also deserves attention in the transition between pediatric and adult nephrology care, and as a rare disease it has a place in the European and Italian rare nephrological diseases network., (© 2021. The Author(s).)

Introduction: Distal renal tubular acidosis (dRTA), or RTA type 1, a rare inherited or acquired disease, is a disorder of the distal tubule caused by impaired urinary acid secretion. Due to associated conditions and nonspecific symptoms, dRTA may go undetected. This analysis aims to estimate the prevalence of dRTA in the UK Clinical Practice Research Datalink (CPRD) databases and extrapolate it to European Union Five (EU5) populations., Methods: A retrospective analysis was conducted using the CPRD GOLD database and linked Hospital Episode Statistics (HES) data to identify diagnosed and potentially undiagnosed or miscoded patients (suspected patients). Patients' records with at least one diagnosis code for dRTA, RTA, specific autoimmune diseases, or renal disorders recorded between January 1987 and November 2017 were obtained and analyzed. An algorithm was developed to detect potentially undiagnosed/miscoded dRTA, based on associated conditions and prescriptions., Results: A total of 216 patients with diagnosis of RTA or dRTA were identified (with 98 linked to hospital data), and 447 patients were identified as having suspected dRTA. dRTA prevalence for 2017 was estimated between 0.46 (recorded cases, of which 22.1% were considered primary) and 1.60 when including suspected cases (7.6% primary) per 10,000 people. Prescription and clinical records of diagnosed patients revealed a wide range of comorbidities and a need for pharmacological treatment to manage associated symptoms., Conclusion: The study provides new estimates of dRTA prevalence in Europe and suggests that patients may often be unreported or miscoded, potentially confounding appropriate disease management., (© 2021 S. Karger AG, Basel.)

Introduction and Purpose: Distal renal tubular acidosis (DRTA) is a metabolic disorder that associates urolithiasis and urinary pH > 6. The prevalence of DRTA in patients with calcium phosphate stones is not well known. The objective is to determine the prevalence of DRTA in patients with calcium phosphate stones and urinary pH above 6 based on the furosemide test., Methods: A total of 54 patients with calcium phosphate stones and urinary pH above 6.0 were submitted to the furosemide test. The association of DRTA with age, sex, type of stone, stone recurrence, stone bilaterality, 24-h urine biochemistry, and adverse effects of the furosemide test were examined., Results: The furosemide test indicated that 19 of 54 patients (35.2%) had DRTA. The sex ratio was similar in the two groups (p < 0.776). The DRTA group was significantly younger (p < 0.001), and had a higher prevalence of bilateral stones (p < 0.001), a higher prevalence of recurrent stones (p < 0.04), a lower plasma potassium level (p < 0.001), a higher urinary Ca level (p ≤ 0.05), and a lower urinary citrate level (p < 0.001). None of the patients reported adverse effects from the furosemide test., Conclusions: There was a high prevalence of DTRA in patients with urinary pH above 6 and calcium phosphate stones. Young age, bilateral stones, stone recurrence, hypercalciuria, hypocitraturia, and plasma hypokalemia were associated with DRTA. None of the patients reported adverse effects of the furosemide test.

Introduction: Children with a solitary post-nephrectomy kidney (SNK) are at potential risk of developing kidney disease later in life. In response to the global decline in the number of nephrons, adaptive mechanisms lead to renal injury. The aim of this study was to determine the prevalence and time of onset of high blood pressure (HBP), proteinuria, glomerular filtration rate (GFR) disruption and renal tubular acidosis (RTA) in children with SNK., Materials and Methods: After obtaining the approval from our institution's ethics committee, we reviewed the medical records of patients under 18 years of age who underwent unilateral nephrectomy between January 2005 and December 2015 in three university hospitals., Results: We identifi ed 43 patients, 35 (81.4%) cases of unilateral nephrectomy (UNP) were due to a non-oncologic pathology and Wilm's tumor was identified in 8 (18.6%) cases. In patients with non-oncologic disease, 9.3% developed de novo hypertension, with an average time of onset of 7.1 years, 25% developed proteinuria de novo, with an average time of onset of 2.2 years. For GFR, 21.8% presented deterioration of the GFR in an average time of 3.4 years. Ten (43.5%) patients developed some type of de novo renal injury after UNP. Patients with oncolo-gic disease developed the conditions slowly and none of them developed proteinuria., Conclusions: Taking into account the high rate of long term postoperative renal injury, it can be considered that nephrectomy does not prevent this disease. The follow-up of children with SNK requires a multidisciplinary approach and long-term surveillance to detect renal injury., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objective: Although diabetic kidney disease (DKD) has been considered as a glomerulocentric disease in the past few decades, growing evidence demonstrated that tubular damage was indispensable in its pathogenesis and progression. This study was designed to investigate the association of urinary acidification dysfunction with the progression of DKD in type 2 diabetic patients., Methods: Here the urinary acidification functions were measured from 80 participants with renal biopsy-proven DKD. The different kinds of renal tubular transportation dysfunction were analyzed, including the dysfunction of bicarbonate reabsorption, titratable acid secretion, and ammonium secretion. In addition, patients were followed up for 17 (interquartile range, 11-32) months to evaluate the effect of urinary acidification dysfunction in the progression of DKD., Results: The most common urinary acidification dysfunction was the disorder of ammonium secretion, accounting for 53.75%. The more proteinuria excretion and the lower glomerular filtration rate (GFR) were observed in the urinary titratable acid disorder group than the normal group, and the same results were obtained for ammonium secretion disorder. Urine titratable acid was positively correlated with eGFR whereas it was inversely correlated with proteinuria, serum creatinine, and BUN. Moreover, 24 h urine protein, serum creatinine, BUN and cystatin C increased from DKD stage II to stage IV, whereas the eGFR and urine titratable acid decreased in the same way. Furthermore, Kaplan-Meier analysis and Cox regression showed that the disorder of titratable acid was an independent risk factor for DKD progression., Conclusions: The dysfunction of urinary titratable acid is a potential biomarker for the severity of proteinuria, eGFR and glomerular lesions in patients with DKD. Moreover, the titratable acid disorder is an independent risk factor of the DKD progression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There is limited literature from India with regard to the prevalence and magnitude of renal tubular and bone manifestations in Wilson's disease (WD). Thus, we studied the prevalence of renal tubular acidosis among Indian patients with WD and also evaluated bone health and body composition in them. It was a cross-sectional study conducted at a south Indian tertiary care center. Twenty-five consecutive patients with WD aged more than 12 years attending the hepatology and neurology departments and 50 age, sex and BMI-matched controls were recruited. After clinical assessment, they underwent biochemical testing to assess renal tubular dysfunction. Bone mineral density (BMD) and body composition were assessed using a dual energy X-ray absorptiometry (DXA) scanner. Fifty-six percent (14/25) of patients with WD had renal tubular acidosis (RTA). Of them, 24% were diagnosed to have distal RTA. RTA was more common in hepatic WD patients who had prolonged duration of illness. Patients with WD had significantly lower BMD as compared to control subjects (p < 0.05). Low BMI, low IGF-1 and a shorter duration of therapy were key determinants of low bone mass in them (p < 0.05). Patients with WD had significantly more body fat (p = 0.01) and lower lean muscle mass (p = 0.03) when compared to age, sex and BMI-matched controls. In conclusion, renal tubular acidosis was common in patients with Wilson's disease. These patients had a lower bone mineral density, higher body fat percentage and lower lean muscle mass as compared to controls.

Objective: A retrospective analysis of clinical characteristics and immunological manifestations of primary Sjogren's syndrome (pSS) patients with or without renal involvement was conducted in order to elucidate the potential risk factors of renal damage in pSS and evaluate the condition., Methods: A total of 1002 patients, who fulfilled the 2002 classification criteria for pSS from the Second Affiliated Hospital of Shanxi Medical University, were enrolled in the cross-sectional study. Clinical, immunological, and histological characteristics were compared between pSS patients with and without renal involvement, and potential risk factors of renal involvements in pSS patients were examined by multivariate analysis., Results: Among these pSS patients, there were 162 cases (16.17%) with and 840 cases (83.83%) without renal damage. Serious edema of both lower limbs, interstitial nephritis, and renal tubular acidosis were found in the pSS with renal damage group. Compared with simple pSS patients, the levels of creatinine, cystatin C, and alpha-1-microglobulin ( α 1 -MG) in the pSS with renal damage group were significantly increased. The difference between the two groups was statistically significant ( P < 0.05). The AUC of the combination of creatinine and α 1 -MG and creatinine, α 1 -MG, and creatinine was statistically larger than that of creatinine, and the biomarker of the biggest AUC is the combination of creatinine and α 1 -MG., Conclusion: The main clinical manifestations of pSS with renal damage were edema of the lower limbs, interstitial nephritis, and renal tubular acidosis. Creatinine and α 1 -MG are effective indicators for renal function in pSS, which may provide a better understanding for clinical decision-making.

Purpose of Review: To summarize the latest findings of congenital and acquired diseases related to stone formation and help understanding the multitude of cofactors related to urolithiasis., Recent Findings: Urolithiasis is related to a broad spectrum of congenital and acquired diseases and its management varies according to the stone type, underlying disease or recurrence rate, but it also changes according to recent findings and developments. As prevalence of urolithiasis is constantly increasing, identification of high-risk stone formers and early treatment is essential. Therefore, genetic evaluation like whole exome sequencing becomes a pertinent part of further diagnostics., Summary: Stone formation is a very heterogeneous pathomechanism. This prompt us to look at every patient individually particularly in high-risk patients, including stone and 24-h-urine analysis and additional diagnostic work-up based on stone type or underlying disease.

Background and Objectives: Incomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied., Design, Setting, Participants, & Measurements: We conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing., Results: Using the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH <5.3 with a plasma potassium threshold >3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis., Conclusions: The furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters., (Copyright © 2017 by the American Society of Nephrology.)

Background: Type 4 renal tubular acidosis causes hyperkalaemia, for which diabetes and medications commonly used in this patient group are aetiological factors. Here we describe the novel use of fludrocortisone in this difficult condition., Case Report: A 55-year-old woman with complex co-morbidities, including Type 2 diabetes (HbA 1c 37 mmol/mol 5.5%), was admitted with renal failure. Bloods on admission: eGFR 25 ml/min, creatinine 184 ?mol/L, urea 35.9 mmol/L, sodium 128 mmol/L, potassium 5.6 mmol/L, bicarbonate 15 mmol/L, and albumin 30 g/L. Her admission was prolonged, complicated by hospital-acquired sepsis (lower respiratory tract, urinary tract, and infected leg ulcers), poor venous access and severe depression. She had recurrent hyperkalaemia and deteriorating renal function, from presumed Type 4 renal tubular acidosis and excessive fluid losses from leg ulcers. Her renal function recurrently deteriorated, despite conventional treatment methods. After 69 days, she was commenced on fludrocortisone 50 mcg/day. Her renal function and serum potassium stabilized and she was discharged with potassium 4.3 mmol/L, eGFR 42 ml/min, and bicarbonate 23 mmol/L. She has remained stable on this treatment, without requiring further hospital admission for over 6 months, with eGFR 40 ml/min, and potassium 5.5 mmol/L, and albumin 26 g/L., Conclusion: This woman was presumed to have Type 4 renal tubular acidosis and recurrent hyperkalaemia due to renal insufficiency, in the context of underlying diabetes and chronic kidney disease, which was poorly responsive to conventional management. There is limited evidence for using fludrocortisone in this setting. Our case suggests that fludrocortisone might offer a novel therapeutic strategy when conventional management is not working., (© 2017 Diabetes UK.)

Background: Distal renal tubular acidosis (dRTA) is characterized by hyperchloraemic metabolic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis. It is due to reduced urinary acidification by the α-intercalated cells in the collecting duct and can be caused by mutations in genes that encode subunits of the vacuolar H + -ATPase (ATP6V1B1, ATP6V0A4) or the anion exchanger 1 (SLC4A1). Treatment with alkali is the mainstay of therapy., Methods: This study is an analysis of clinical data from a long-term follow-up of 24 children with dRTA in a single centre, including a genetic analysis., Results: Of the 24 children included in the study, genetic diagnosis was confirmed in 19 patients, with six children having mutations in ATP6V1B1, ten in ATP6V0A4 and three in SLC4A1; molecular diagnosis was not available for five children. Five novel mutations were detected (2 in ATP6V1B1 and 3 in ATP6V0A4). Two-thirds of patients presented with features of proximal tubular dysfunction leading to an erroneous diagnosis of renal Fanconi syndrome. The proximal tubulopathy disappeared after resolution of acidosis, indicating the importance of following proximal tubular function to establish the correct diagnosis. Growth retardation with a height below -2 standard deviation score was found in ten patients at presentation, but persisted in only three of these children once established on alkali treatment. Sensorineural hearing loss was found in five of the six patients with an ATP6V1B1 mutation. Only one patient with an ATP6V0A4 mutation had sensorineural hearing loss during childhood. Nine children developed medullary cysts, but without apparent clinical consequences. Cyst development in this cohort was not correlated with age at therapy onset, molecular diagnosis, growth parameters or renal function., Conclusion: In general, the prognosis of dRTA is good in children treated with alkali.

Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH 4 Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH 4 Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing metabolic evaluation should be screened for idRTA.

Background: It has been suggested a high prevalence of allergic disease in children with RTA., Objective: To describe the prevalence of allergic diseases in children with secondary RTA (renal tubular acidosis) in the nephrology department of the National Institute of Pediatrics (NIP), México., Methods: An observational, prospective, cross-sectional, descriptive study. Children with secondary RTA < 18 years who attended the outpatient nephrology service in the NIP for 24 months, were included. ISAAC questionnaire and the EAACI guidelines were applied. To prove a suspected allergy, skin tests, total and specific IgE, patch testing and food challenge were performed. Using SPSS 19, frequency of allergic diseases was described., Results: 113 patients were included. Age 8 to 168 months. Male: 53.9 %. RTA types: Distal (64.6 %), proximal (26.5 %), mixed (1.8 %) and undetermined (7 %). Age of onset between 1 and 96 months. Serum bicarbonate 10.1 to 20 mEq/L. Allergic diseases were found in 24.8 %: allergic rhinitis (18.4 %), food allergy (9.7 %), atopic dermatitis (8 %), asthma (8 %) and allergic conjunctivitis (6.1 %). Total IgE was increased in 9 patients. Positive skin tests in 14.2 %. Positive chemiluminescence in 18 children; positive open food challenge in 11 children and patch tests in 4., Conclusion: Secondary RTA is common in children attending tertiary care hospitals. The prevalence of allergic disease in children with secondary ATR, is similar to that described in the general population.

Objective: To study the clinical profile of hypokalemic flaccid paralysis (HKFP) and to evaluate its causes., Methods: Fifty cases of hypokalemic flaccid paralysis (HKFP) admitted between November 2012 to October 2014 were taken up in the study. Serum potassium level < 3.5 mmol/ltr has been taken as hypokalemia. All cases were studied for spot and/or 24 hour urinary sodium / potassium, serum potassium / calcium / magnesium. Hypokalemic periodic paralysis (HPP) were diagnosed if there was spot/24 hour urine potassium excretion < 20mmol/ltr in presence of hypokalemia and flaccid weakness without other causes. EMG and nerve conduction study were done to exclude polyneuropathy and myopathic cases., Results: Out of 50 cases of HKFP, male gender predominated (88%). Maximum number of cases (70%) occurred in 21 to 40 years of age. It occurred in all seasons but more in summer (58%). The precipitating factors were present in 76% of cases out of which high carbohydrate meal (28%), vomiting (16%), excessive sweating (8%), diarrhea (8%) and increased urination (12%) were present. Twenty percent of cases had recurrence (2 to 3 episodes most often) and 6% of cases had family history. Quadriparesis was seen in (54%), paraparesis (36%), hemiparesis (10%) and neck muscle weakness (32%). No case was present with respiratory paralysis or cranial nerve palsy. Twenty-one cases (42%) have very low potassium < 2.5 mmol/ltr, 11 cases (22%) with potassium level between 2.5 to 2.9 mmol/ltr and 18 cases (36%) with 3 to 3.5 mmol/ltr. There was no correlation between severity weakness and potassium level. Eleven cases (22%) had thyrotoxicosis and 3 cases (6%) were hypothyroid. Thirteen cases (26%) have excess urinary loss of potassium (≥20 mmol/ltr) of which 5 cases (10%) were distal renal tubular acidosis (dRTA), four cases (8%) were Gitelman's syndrome (GS) and in 4 cases exact cause could not be diagnosed. Non-renal / prior renal loss of potassium like diarrhea and excessive sweating was responsible in 8% cases each and vomiting in 10% of cases. One unique case of hypernatraemic hypokalemic paralysis (HHP) was found. Only 9 (18%) cases are hypokalemic periodic paralysis (HPP)., Conclusions: HKFP is a hetergenous group of disease of which a significant number of patients had thyroid disorders mostly in the form of thyrotoxicosis followed by renal tubular dysfunctions like dRTA and GS; non-renal and prior renal loss of potassium like diarrhea, excessive sweating and vomiting respectively. Early recognition and prompt management of these conditions will give gratifying result and prevent further attacks in some cases.

Objectives: Our objectives were to analyse the prevalence of distal renal tubular acidosis (dRTA) in primary SS (pSS) and to compare a novel urinary acidification test with furosemide and fludrocortisone (FF) with the gold standard ammonium chloride (NH4Cl) to detect dRTA., Methods: Urinary acidification was assessed in 57 pSS patients using NH4Cl and FF. A urinary acidification defect was defined as an inability to reach a urinary pH of <5.3 after NH4Cl., Results: The prevalence of complete dRTA (urinary acidification defect with acidosis) was 5% (3/57). All three patients had positive SSA/Ro and SSB/La autoantibodies and impaired kidney function. The prevalence of incomplete dRTA (urinary acidification defect without acidosis) was 25% (14/57). Compared with patients without dRTA, patients with incomplete dRTA had significantly lower venous pH and serum bicarbonate and higher urinary pH. SSB/La antibodies were more prevalent in the dRTA groups (P < 0.05). Compared with NH4Cl, the positive and negative predictive values of FF were 46% and 82%, respectively. Vomiting occurred more often during the urinary acidification test with NH4Cl than with FF (9 vs 0, P < 0.05)., Conclusion: Incomplete dRTA is common in pSS and causes mild acidaemia and higher urinary pH, which may contribute to bone demineralization and kidney stone formation. FF cannot replace NH4Cl in testing urinary acidification in pSS, but may be considered as a screening tool, given its reasonable negative predictive value and better tolerability., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Primary Sjögren's syndrome (pSS) is an important cause of renal tubular dysfunction in adults, mainly due to acquired type 1 distal renal tubular acidosis (RTA 1) and concentration defects (CD). This cross-sectional study evaluated renal tubular function of patients with pSS, by detecting proximal tubular injury (through measurements of urinary β2 microglobulin and albumin), RTA 1 (through an acidification protocol using furosemide and fludrocortisone), and CD (through water deprivation test, WDT). A total of 25 patients with pSS were evaluated and despite a preserved renal function (eGFR 92.5 ± 26.3 mL/min/1.73 m(2)), 24% were diagnosed as RTA 1. On the other hand, CD was diagnosed in 28% of the patients who presented worse renal function (eGFR 68.6 ± 27.7 mL/min/1.73 m(2)). Increased β2 microglobulin was found in 16% of the patients, and all of them had impaired renal function (eGFR 39.5 ± 11.9 mL/min/1.73 m(2)). These data showed a high prevalence of tubular dysfunction, mainly RTA 1 and CD, in patients with pSS, and suggest that patients with this disorder should be evaluated by the acidification protocol used in this study and WDT for proper diagnosis. Proximal tubular injury was less common, and probably associated with worsening of renal function.

Objective: To present clinical and etiological profile of refractory rickets from Mumbai., Methods: Case records of 36 patients presenting over 2½ y with refractory rickets were evaluated with respect to clinical presentation, biochemical, radiological features and where needed, ophthalmological examination, ultrasonography and special tests on blood and urine., Results: Twenty three (63 %) patients had renal tubular acidosis (RTA)-distal RTA in 20 and proximal RTA in 3 patients; 5 (14 %) had vitamin D dependent rickets (VDDR I in 2 and VDDR II in 3 patients), 4 (11 %) had chronic renal failure (CRF) and 2 each (6 %) had hypophosphatemic rickets and chronic liver disease as cause of refractory rickets. A significant proportion of patients with RTA and VDDR showed skeletal changes of rickets in the first 2 y of life, while those with hypophosphatemic rickets presented later. Patients with hypophosphatemic rickets had predominant involvement of lower limbs, normal blood calcium and PTH levels and phosphorus leak in urine. All patients with RTA presented with failure to thrive, polyuria and marked rickets; blood alkaline phosphatase levels being normal in almost 50 % patients. Three (75 %) patients with rickets due to CRF had GFR < 30 ml/min/1.73 m(2) and hyperphosphatemia. Patients with cirrhosis due to biliary atresia had rickets inspite of taking high dose of vitamin D orally., Conclusions: Refractory rickets is a disorder of multiple etiologies; a good history and clinical examination supplemented with appropriate investigations helps to determine its cause.

Objective: Hyperkalaemia is a common feature in hospitalized patients and often attributed to drugs antagonizing the renin-angiotensin-aldosterone system (RAAS) and/or acute kidney injury (AKI), despite significantly preserved glomerular filtration rate (GFR). The objective of this study was to determine the prevalence and role of renal tubular acidosis type IV (RTA IV) in the development of significant hyperkalaemia., Design: A single-centre retrospective study., Patients: Patients admitted to a University Hospital over 12 months., Measurements: Patients with a potassium value > 6·0 mm were identified. Clinical and laboratory data were revisited, and patients with a normal anion gap metabolic acidosis were evaluated for the existence of RTA IV., Results: A total of 57 patients having significant hyperkalaemia (>6·0 mm) were identified. Twelve patients had end-stage renal disease, while 21 patients had solely AKI or progressive chronic renal failure. RTA IV was present in 24 patients (42%), of whom 71% had pre-existing renal insufficiency because of diabetic nephropathy or tubulointerstitial nephritis. All hyperkalaemic patients with urinary/serum electrolytes suggestive of RTA IV had evidence of AKI, but creatinine levels were significantly lower (P < 0·05), while the number of drugs antagonizing the RAAS was comparable., Conclusion: We demonstrated that RTA IV (i) is very common in patients with hyperkalaemia; (ii) should always be suspected in hyperkalaemic patients with only moderately impaired GFR; and (iii) may result in significant hyperkalaemia in the presence of both AKI and drugs antagonizing the RAAS., (© 2012 Blackwell Publishing Ltd.)

Background: Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations., Methods: We have collected and reviewed our own and published data on tropical dRTA to provide a comprehensive series of clinical and epidemiological studies in 78 patients., Results: Eight responsible SLC4A1 mutations have been described so far, four of them affecting multiple unrelated families. With the exception of the mutation causing South-East Asian ovalocytosis (SAO), none of these mutations has been reported outside the tropics, where dRTA caused by SLC4A1 mutations is much rarer and almost always dominant, resulting from mutations that are quite different from those found in the tropics. SLC4A1 mutations, including those causing dRTA, may cause morphological red cell changes, often with excess haemolysis. In dRTA, these red cell changes are usually clinically recessive and not present in heterozygotes. The high tropical prevalence of dRTA caused by SLC4A1 mutations is currently unexplained., Conclusion: A hypothesis suggesting that changes in red cell metabolism caused by these mutations might protect against malaria is put forward to explain the phenomenon, and a possible mechanism for this effect is proposed.

The aim of this study was to assess the prevalence of incomplete distal renal tubular acidosis (idRTA) in men with recurrent calcium nephrolithiasis and its potential impact on bone mineral density. We conducted a retrospective analysis of 150 consecutive, male idiopathic recurrent calcium stone formers (RCSFs), which had originally been referred to the tertiary care stone center of the University Hospital of Berne for further metabolic evaluation. All RCSFs had been maintained on a free-choice diet while collecting two 24-h urine samples and delivered second morning urine samples after 12 h fasting. Among 12 RCSFs with a fasting urine pH >5.8, a modified 3-day ammonium chloride loading test identified idRTA in 10 patients (urine pH >5.32, idRTA group). We matched to each idRTA subject 5 control subjects from the 150 RCSFs, primary by BMI and then by age, i.e., 50 patients, without any acidification defect (non-RTA group) for comparative biochemistry and dual energy X-ray absorptiometry (DEXA) analyses. The prevalence of primary idRTA among RCSFs was 6.7% (10/150). Patients with idRTA had significantly higher 2-h fasting and 24-h urine pH (2-h urine pH: 6.6 ± 0.4 vs. 5.2 ± 0.1, p = 0.001; 24-h urine pH: 6.1 ± 0.2 vs. 5.3 ± 0.3, p = 0.001), 24-h urinary calcium excretion (7.70 ± 1.75 vs. 5.69 ± 1.73 mmol/d, p = 0.02), but significantly lower 24-h urinary urea excretion (323 ± 53 vs. 399 ± 114 mmol/d, p = 0.01), urinary citrate levels (2.32 ± 0.82 vs. 3.01 ± 0.72 mmol/d, p = 0.04) and renal phosphate threshold normalized for the glomerular filtration rate (TmPO(4)/GFR: 0.66 ± 0.17 vs. 0.82 ± 0.21, p = 0.03) compared to non-RTA patients. No significant difference in bone mineral density (BMD) was found between idRTA and non-RTA patients for the lumbar spine (LS BMD (g/cm(2)): 1.046 ± 0.245 SD vs. 1.005 ± 0.119 SD, p = 0.42) or femoral neck (FN BMD (g/cm(2)): 0.830 ± 0.135 SD vs. 0.852 ± 0.127 SD). Thus, idRTA occurs in 1 in 15 male RCSFs and should be sought in all recurrent calcium nephrolithiasis patients. Bone mineral density, however, does not appear to be significantly affected by idRTA.

Objective: Carbonic anhydrase (CA) inhibitors topiramate and zonisamide can induce metabolic acidosis in some patients. Our aims were to assess the prevalence and severity of this acidosis and to determine its predictors., Methods: For 70 patients established on treatment with topiramate (n=55) or zonisamide (n=14) or both (n=1), we measured electrolytes, and genotyped single nucleotide polymorphisms (SNPs) in the main renal CA isoenzymes (II, IV and XII)., Results: Twenty-six percent of patients had a metabolic acidosis (serum bicarbonate <20 mmol/l). The mean serum bicarbonate of patients taking topiramate was significantly lower than those taking zonisamide (P=0.002). We found no association between serum bicarbonate and the dose of drug or the duration of treatment. Serum bicarbonate levels were associated with the CA type XII SNPs rs2306719 (P=0.006 by one-way analysis of variance) and rs4984241 (P=0.015), but this association was not strong enough to survive correction for multiple testing., Conclusion: The development of acidosis with topiramate and zonisamide is not determined by drug dose or by treatment duration, but may be influenced by polymorphisms in the gene for CA type XII. The aforementioned SNPs lie 9.8 kb apart in intron 1 of the CA type XII gene, and deserve further study in a larger cohort of patients.

To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA), we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive urine anion gap. In those patients who had fasting urine pH >5.5 with normal baseline systemic pH and bicarbonate levels (incomplete RTA), acid load test with ammonium chloride was done. A cause of dRTA could be established in 53 (54%) patients. Urological defect in children (22/44) and autoimmune disease in adults (11/52) were the commonest causes. Hypokalemic paralysis, proximal muscle weakness and voiding difficulty were the common modes of presentation. Doubling of serum creatinine during the study period was noted in 13 out of 27 patients who had GFR <60 mL/min at presentation whereas in only one of the 70 with initial GFR >60 mL/min (P <0.005). In conclusion, urological disorders were the commonest cause of dRTA in children while autoimmune disorders were the commonest asso-ciation in adults. Worse baseline renal function, longer duration of disease and greater frequency of nephrolithiasis/nephrocalcinosis and urological disorders were noted in those who had wor-sening of renal dysfunction during the study period.

Objective: To asses the prevalence of post-transplant renal tubular acidosis (RTA) and its associated risk factors., Methods: A cross-sectional study was conducted on 100 live related renal transplant recipients, with a transplant duration of more than one year and an estimated GFR > 40 ml/min/1.73m2. Patients with acute graft rejection within last 6 months, unstable graft function, acute urinary tract infection and diarrhoea were excluded. Renal Tubular Acidosis (RTA) was diagnosed on the basis of plasma bicarbonate, venous pH, urine and serum anion gap measurements., Results: Out of 100 patients (74 male, 26 female) RTA was observed in 40 (29 male, 11 female). Patients with RTA had a lower GFR (65.87 +/- 12.35 versus 74.23 +/- 14.8 ml/min/1.73m2, P = 0.004) and higher number of previous acute rejections. Lower bicarbonate was associated with higher serum chloride (108.2 +/- 3.19 versus 105.72 +/- 3.9 mEq/L, P = 0.001) and higher potassium concentration (3.95 +/- 0.53 vs 3.61 +/- 0.46 mg/dl, P = 0.001). Higher phosphorous level (3.46 +/- 0.71 in RTA vs 3.19 +/- 0.59 mg/dl in non-RTA, P = 0.045) but lower total serum calcium concentrations were found in patients with RTA. Intake of angiotensin converting enzyme inhibitors (ACE 1) was associated with the development of RTA. Calcineurin inhibitor (CNI) therapy was not associated with an increased likelihood of RTA. While no difference was noted in sex, age, pre-transplant dialysis duration, post transplant period, body mass index and serum albumin levels., Conclusion: There is a high prevalence of RTA in renal transplant recipients. In most of the patients, this is subclinical and does not require treatment.

Aims: To investigate clinically and genetically all the distal renal tubular acidosis (dRTA) cases in Cyprus, to study one more family from Greece and to perform the first dRTA prenatal diagnosis. We also tried to find any association with sensorineural hearing loss (SNHL) onset and particular mutations., Methods: Nine dRTA families from Cyprus and one from Greece were analyzed for mutations in ATP6V1B1 gene by DNA resequencing and PCR-RFLPs. Clinical diagnosis was performed by standard criteria. Prenatal diagnosis was performed for one Cypriot family., Results: Results show that 7/9 dRTA cases in Cyprus are caused by 229+1G>T and R157C founder mutations in ATP6V1B1 gene. 229+1G>T mutation was estimated to be older than 400 years. No genotype- phenotype correlation was found with SNHL. A known (L81P) and a novel mutation (912delT) were found in the Greek family. Prenatal diagnosis was performed for one Cypriot family, after parents' demand, showing that the embryo was a heterozygous carrier., Conclusion: Existence of only two ATP6V1B1 mutations in the Cypriot population is a diagnostic advantage. The age of onset of SNHL varies in our patients and probably is not related to ATP6V1B1 genotypes. Effective therapy for most of the syndrome symptoms is not satisfactory for some parents who choose prenatal diagnosis to ensure their child's health., (Copyright © 2010 S. Karger AG, Basel.)

Background: In the Sub Saharan Africa Rickets has now been established to be due primarily to calcium deficiency and sometimes in combination with vitamin D deficiency. The main thrust of management is calcium supplementation with or without vitamin D. An observation was made that some children with nutritional rickets do not respond to this management modality. The recently reported high prevalence of Incomplete Distal Renal Tubular Acidosis (idRTA) in adults with osteoporosis as brought to fore the possibility of this being a possible cause of calcium wastage and therefore the poor response in these group of children with rickets., Aim: To determine the prevalence of idRTA amongst a cohort of subjects with ricketsTo show a relationship between rickets and incomplete distal renal acidosisTo determine the response of children with rickets and idRTA to addition of Shohl's solution to therapy, Methodology: Two separate cohorts of children with rickets performed the ammonium chloride loading test to detect those with incomplete renal tubular acidosis. Following identification for idRTA, Shohl's solution was added to therapy of calcium and vitamin D supplementation and their response compared to those without idRTA on calcium and vitamin D supplementation solely., Results: 50 children with rickets aged from two to six years of age and composed of 29 females and 21males were investigated. Incomplete renal tubular acidosis was found in 38% of them. Prevalence of idRTA was highest amongst those aged 3-6 years of age. Those with idRTA had worse limb deformities, biochemical and radiological parameters than those who hadn't. Rate of response on those with idRTA treated with Shohl's solution was at par with those without idRTA., Conclusion: Incomplete idRTA exist amongst children with rickets and should be looked out for in severe rickets and older children. Treatment of idRTA will lead to optimal response and healing of rickets.

Aim: We aimed to investigate the prevalence, type, and possible risk factors of renal tubular acidosis (RTA) in Turkish patients with renal transplantation., Patients and Method: The study included 66 adult renal transplantation recipients. We recorded the parameters of venous blood gas analysis including serum pH value, serum bicarbonate (HCO(3)) concentration, presence of metabolic acidosis, which was defined as low HCO(3) (<22 mEq/L), and serum pH value (<7.35) together, and base excess and urine pH at the last follow-up. Creatinine clearance was determined from 24-hour collected urine samples. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap., Results: Mean age of 66 patients was 37.0 +/- 10.4 years; 48 of 66 patients were male. RTA was found in 14 (21.2%) patients. Considering for differential diagnosis of RTA, 4 patients had type 2 RTA and 10 had type 1 RTA. On the contrary, type 4 RTA was observed in no patients. Creatinine clearance was meaningfully lower in acidosis group than in those of the nonacidosis group (55.16 +/- 23.27 vs. 71.06 +/- 28.14 mL/min; p = 0.028). HCO(3) was correlated with hemoglobin level (r = 0.423, p = 0.001) and creatinine clearance (r = 0.262, p = 0.034). It was inversely correlated with cyclosporine A (CsA) level (r = -0.499, p = 0.035)., Conclusion: RTA is a common complication after kidney transplantation. It is related with low creatinine clearance, low hemoglobin level, and high CsA level. Particularly, the value of creatinine clearance is lower and the possibility of RTA is higher.

The hyperammonemia in distal renal tubular acidosis, previously only described in two cases, is considered an unusual occurrence. After the report published in 2005, we observed plasma ammonia levels above normal range during metabolic decompensation in two other consecutive pediatric patients suffering from distal renal tubular acidosis. The ammonia plasma levels returned to normal range after treatment with sodium bicarbonate and potassium salt. In distal renal tubular acidosis, hyperammonemia is probably the result of an imbalance between the increased ammonia synthesis, in response to metabolic acidosis, and the impaired ammonia excretion, typical of distal renal tubular acidosis. According to this physiopathological mechanism, our observation shows that hyperammonemia is not an uncommon finding in distal renal tubular acidosis, and should be included among differential diagnosis of hyperammonemia in infants and children.

This retrospective survey examines the etiology of nephrocalcinosis (NC) in 40 patients (26 boys), over an 8-year period. The median age at onset of symptoms and presentation was 36 months and 72 months, respectively. Clinical features included marked failure to thrive (82.5%), polyuria (60%) and bony deformities (52.5%). The etiology of NC included distal renal tubular acidosis (RTA) in 50% patients and idiopathic hypercalciuria and hyperoxaluria in 7.5% each. Other causes were Bartter syndrome, primary hypomagnesemia with hypercalciuria, severe hypothyroidism and vitamin D excess. No cause for NC was found in 12.5% patients. Specific therapy, where possible, ameliorated the biochemical aberrations, although the extent of NC remained unchanged. At a median (range) follow up of 35 (14-240) months, glomerular filtration rate (GFR) had declined from 82.0 (42-114) ml/min per 1.73 m2 body surface area to 70.8 (21.3-126.5) ml/min per 1.73 m2 body surface area (P = 0.001). Our findings confirm that, even with limited diagnostic facilities, protocol-based evaluation permits determination of the etiology of NC in most patients.

Background: Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid and kidney anion (chloride-bicarbonate) exchanger 1 may result in hereditary distal renal tubular acidosis (dRTA). Hemoglobinopathies are common in Thailand. We analyzed AE1 and hemoglobin mutations in children in Thailand with dRTA to evaluate their association with clinical manifestations., Study Design: Case series., Setting & Participants: 17 patients were recruited from 6 referral hospitals in 4 regions of Thailand., Predictors: AE1 mutations were detected by means of nucleotide sequence alterations. Hemoglobin E (HbE) was detected by means of hemoglobin typing, and thalassemia, by means of analysis of globin genes. Hemolytic anemia was indicated by decreased hemoglobin and hematocrit values in the presence of reticulocytosis., Outcomes & Measurements: Leading clinical manifestations in patients were failure to thrive and muscle weakness. Compensated or overt anemia was identified in some cases. Coexistence of AE1 mutations with HbE or alpha(+)-thalassemia was present in a number of patients., Results: 12 of 17 patients (70%) carried AE1 mutations, 7 patients (41%) had HbE, and 1 patient (6%) had alpha(+)-thalassemia. Patients with AE1 mutations presented with compensated hemolysis when they had metabolic acidosis. A patient with compound heterozygous Southeast Asian ovalocytosis/G701D and heterozygous alpha(+)-thalassemia showed severe hemolytic anemia., Limitations: 5 patients (30%) without detectable AE1 mutation also were unknown for other genetic abnormalities., Conclusions: Most of the patients with dRTA studied carried autosomal recessive AE1 mutations. Metabolic acidosis, which could be alleviated by adequate alkaline therapy, induced variable degrees of hemolysis in patients with dRTA associated with autosomal recessive AE1 mutations, especially in the presence of thalassemia.

Objective: To survey the urinary risk factors associated with recurrent calcium stone and the contribution of renal tubular acidosis to the prevalence of recurrent calcium stone formation in Thai recurrent stone formers., Material and Method: There were 86 consecutive recurrent calcium stone formers. Three-day dietary record, serum biochemical parameters, first morning urine pH, and two 24-hour urine collections were obtainedfrom each subject. Urinary risk factors for calcium stone formation were determined from the average of the 2-day urine collection. Normal controls were 34 subjects matched for aged, sex, and weight, and without a history of renal stone formation., Results: Seven patients (8.1%) were diagnosed as incomplete renal tubular acidosis (iRTA). Among the 79 idiopathic calcium stone formers (ISF), 69.6%, 15.2%, 10.1%, 7.2% and 1.3% of patients were hypocitraturia, hypercalciuria, low urinary volume, hyperuricosuria and hyperoxaluria, respectively. The common combinations of risk factors were hypocitraturia plus low urine output (8.9%) or plus hypercalciuria (7.6%). There were significant differences between ISF and normal controls in urinary oxalate excretion (0.16 +/- 0.01 vs 0.12 +/- 0.01, p < 0.05), urinary calcium/citrate ratio (4.49 +/- 0.50 vs 2.83 +/- 0.34, p < 0.01) and ion activity product for calcium oxalate stone (0. 46 +/- 0.03 vs 0. 33 +/- 0.03, p < 0. 05). Urinary citrate in ISF varied directly with net alkaline absorption (r = 0.34, p < 0.005) and urinary potassium (r = 0.54, p < 0.001). There were significant correlations between urinary calcium excretion and both sodium excretion (r = 0.42, p < 0.001) and urea excretion (r = 0.41, p < 0.001) in ISE There were seven (8.1%) with incomplete renal tubular acidosis. Patients with iRTA tended to have less urinary citrate and higher calcium/citrate ratio than did ISF, but hypercalciuria was uncommon., Conclusions: Hypocitraturia was the most common urinary risk factor found in Thai recurrent idiopathic calcium stone formers followed by hypercalciuria and low urinary volume. Almost one-fourth of the stone formers had multiple risk factors. Hypocitraturia might result from low potassium and low alkaline intake. iRTA was common among recurrent calcium stone formers. Determination of morning urine pH should be a part of the investigations for urinary risk factors to avoid overlooking the diagnosis of iRTA.

Background: Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Although calcineurin inhibitors, suboptimal allograft function, donor age and acute rejection have been associated with RTA, no detailed study has been conducted to investigate the prevalence and clinical implications of RTA in long-term kidney recipients., Methods: In this cross-sectional study, we enrolled 109 patients (74 males, 35 females) for the study [patients with glomerular filtration rate (GFR) <30 ml/min/1.73 m(2), unstable allograft function, diarrhoea, and respiratory disease were excluded]. Thirty-six patients (33%) were found to have RTA on the basis of plasma bicarbonate, arterial pH, urine and serum anion gap measurements., Results: Deceased donor transplantation [P = 0.034, 95% confidence interval (CI): 1.10-13.27], female gender (P = 0.017, 95% CI: 1.23-8.50), and lower GFR (55.8 +/- 19.4 in RTA and 66.1 +/- 15.9 ml/min/1.73 m(2) in non-RTA, P = 0.002, 95% CI: 1.10-13.27) were independent risk factors for RTA. Also, C-reactive protein was found to be higher in the RTA group (2.7 +/- 1.5 vs 2.0 +/- 1.5 mg/dl, P = 0.03), while no difference was noticed in body mass index or serum albumin. Analysis of the prevalence of osteoporosis and osteopenia in patients with RTA and without RTA, respectively, revealed no difference in frequency of osteoporosis (33% vs 31%) or osteopenia (33% vs 47%)., Conclusion: Although long-term kidney recipients have a relatively high prevalence of RTA, it is usually mild and subclinical. Further studies are needed to clarify long-term effects of RTA in kidney recipients.

Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical H(+) ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL), whereas ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal hearing. The phenotype and genotype of 39 new kindreds with recessive dRTA, 18 of whom were consanguineous, were assessed. Novel and known loss-of-function mutations were identified in 31 kindreds. Fourteen new and five recurrent mutations of the ATP6V0A4 gene were identified in 21 families. For the ATP6V1B1 gene, two new and two previously described mutations were identified in 10 families. Surprisingly, seven probands with ATP6V0A4 gene mutations developed severe early SNHL between the ages of 2 mo and 10 yr. No mutation was detected in eight families. These data extend the spectrum of disease-causing mutations and provide evidence for genetic heterogeneity in SNHL. The data also demonstrate that mutations in either of these genes may cause early deafness, and they highlight the importance of genetic screening for recessive forms of dRTA independent of hearing status.

Glomerular and tubular function of transplanted kidneys were assessed in 46 children aged 15.7 +/- 4.6 yr, 4.2 +/- 2.8 yr after renal transplantation. There were 34 cadaveric, and 12 living-related donors. Twelve patients (26%) had acute episodes (acute tubular necrosis, rejection, or urinary tract infection) during follow-up. All patients were on triple immunosuppression. The mean serum creatinine was 1.5 +/- 0.6 mg/dL. Creatinine clearance (Ccreat) calculated from a 24-h urine collection was 48.0 +/- 19.7 mL/min/1.73 m(2), and that estimated from the Schwartz formula, 61.0 +/- 22.5 mL/min/1.73 m(2). A positive correlation was found between the calculated and estimated clearances. Mean urine concentrating ability was 487 +/- 184 mOsmol/kg, with a value lower than 400 mOsmol/kg in 35% of patients. There was a positive correlation between urine osmolality and estimated Ccreat. Metabolic acidosis (bicarbonate <22 mmol/L) was found in 41% of patients, with relatively alkaline urine and high chloride level. Fractional excretion (FE) of sodium was above 1% in 68% of patients (mean 1.66 +/- 1.06%), and FE(Mg) was above 3% (mean 10.9 +/- 5.2%) in 93% of patients. Tubular reabsorption of phosphate (TP)/glomerular filtration rate (GFR) was 3.2 +/- 0.8 mg/dL glomerular filtrate (GF). FE(K), FE(UA), and Ca/creatinine in urine were normal. There were no functional group differences between the cadaveric and living-related kidneys. Significant group differences were found in those with acute episodes and those with a normal course. Estimated Ccreat was 54 +/- 20 vs. 67 +/- 20 mL/min/1.73 m(2) in the acute episodes and the normal course groups, respectively. Also, the FE(NA), FE(UA), and FE(Mg) were higher in the acute episodes group -2.3 +/- 1.6, 10.6 +/- 4.4, and 14.8 +/- 6.5%, respectively, compared with the normal course group -1.4 +/- 0.6, 8.2 +/- 2.8, and 9.6 +/- 4.0%, respectively. There were no between-group differences in plasma bicarbonate, FE(K), TP/GFR, and urine osmolality. We believe that most, if not all tubular dysfunctions in the transplanted kidney are secondary to renal failure and interstitial damage from acute episodes and nephrotoxic drugs. These dysfunctions are similar to those in chronic renal failure, where interstitial fibrosis plays a role in kidney function deterioration.

Background: Chronic kidney disease (CKD) is associated with the reduction of haemoglobin concentration and a variety of biochemical abnormalities including changes in serum concentration of sodium, potassium, calcium, phosphate, bicarbonate, and hydrogen ions. However, data concerning epidemiology of these abnormalities are rare and incomplete, especially among subjects with mild to moderate CKD., Patients and Methods: Patients with a serum creatinine concentration > 110 micromol/l hospitalized in the Department of Nephrology, Endocrinology and Metabolic Diseases Medical University of Silesia from 1998 to 2002 were analyzed. Patients with acute renal failure or chronic renal failure treated with renal replacement therapy were excluded from this study. A total of 653 patients (262F and 391M) were divided into 9 subgroups differing from each other by progressive decline of glomerular filtration rate (GFR)., Results: A statistically significant decrease in haemoglobin concentration and increase in the prevalence of anaemia were found in patients with GFR < 50 ml/min. In a large number of patients with a GFR < 80 but > 50 ml/min, Hb concentration <11 g/dl was observed. Mean MCV, MCH and serum iron concentration were similar in all studied subgroups. A progressive increase in serum phosphorus concentration and decrease of calcaemia was found in patients with GFR < 30 ml/min. The elevated Ca x P product (> 4.44 mmol2/12) was noticed almost exclusively in patients with GFR< 30 ml/min. A decompensated metabolic acidosis was observed in 29.8% of patients with GFR <30 ml/min., Conclusions: Anaemia is an early symptom of chronic kidney disease preceding disturbances of calcium, phosphate and hydrogen ions metabolism. These abnormalities seem to be of therapeutic relevance.

Premature infants undergo intensive growth during the postnatal period. Adequate mineralization is dependent on sufficient intake of calcium (Ca) and phosphorus (P). However, Ca and P supplementation can be associated with some risks, for example development of nephrocalcinosis. We investigated pathophysiological risk factors in premature very low birth weight (VLBW) infants associated with the development of nephrocalcinosis. From June 1994 to September 1995 all preterm neonates with a birth weight below 1,500 g were screened prospectively. At regular intervals of 2 weeks, ultrasonography (US) of the kidneys was performed and parameters of mineral metabolism were assessed in blood and spot urine samples. For analysis, premature infants with nephrocalcinosis (group N) were compared with infants without nephrocalcinosis (group R) and with a retrospectively pair-matched subgroup of premature infants without nephrocalcinosis (control group C) taken from the same study. Nephrocalcinosis was detected in 20 of 114 preterm neonates (group N, 17.5%). Of these 20 infants with nephrocalcinosis, 16 presented with a tendency towards systemic acidosis (pH<7.25) on day 2-7, compared with only 4 of 20 premature infants of the control group. Premature infants of group N had a lower serum P at 2 weeks of life and 5 (versus 0 patients of the control group C) had transient hypophosphatemia (serum P<1.6 mmol/l). Moreover, the Ca/creatinine ratio in spot urine specimens tended to be higher (P<0.1) in patients developing nephrocalcinosis. There were no significant differences in the duration of ventilation, the length of stay in the intensive care unit, and duration and frequency of furosemide and steroid treatment between the groups N and C. VLBW premature infants developing nephrocalcinosis frequently presented with slightly impaired acid-base homoeostasis within the 1st week, followed by signs of impaired mineralization (and immature or impaired renal function) within 2 weeks. In VLBW premature infants, close observation of acid-base status and regular analysis of spot urine specimens (Ca, P, creatinine) during the first weeks of life may help to identify those premature infants at risk for nephrocalcinosis.

Distal renal tubular acidosis (dRTA) is generally associated with hypercalciuria, hypocitraturia, and nephrolithiasis. Our intention was to study glycosaminoglycans (GAGS) and nephrocalcin (NC), two well-known crystal growth inhibitors, in a population with endemic dRTA and nephrolithiasis in northeast (NE) Thailand. We studied 13 patients, six with dRTA and seven with nephrolithiasis with normal or undefined acidification function. Six healthy adults living in the same area as the patients and another six from the Bangkok (BKK) area were used as controls. We measured urinary pH, ammonia, calcium, citrate, magnesium, oxalate, potassium, sodium and uric acid. GAGS were determined by an Alcian blue precipitation method and were qualitated by agarose gel electrophoresis after being isolated using 5% cetyltrimethylammonium bromide at pH 6.0. NC isoforms were isolated as previously described by Nakagawa et al. Citrate was higher in BKK controls ( p<0.04). There was a striking difference among GAGS from BKK when compared with other groups (103.85+/-10.70 vs. 23.52+/-8.11 for dRTA, 22.36+/-14.98 for kidney stone patients and 14.73+/-2.87 mg/ml in controls from the NE region, ( p<0.0001). dRTA and stone-forming patients excrete proportionally more (C+D) than (A+B) NC isoforms ( p<0.05). Also, their NC showed a 100-fold weaker binding capacity of calcium oxalate monohydrate crystals. The ratio of chondroitin sulfate/heparin sulfate in GAGS was approximately 9/1. In addition to the traditional risk factors for nephrolithiasis in dRTA, GAGS and NC might play an important role in the pathogenesis of stone formation in this population.