Comparison of growth in primary Fanconi syndrome and proximal renal tubular acidosis

To compare the difference between primary proximal renal tubular acidosis (PRTA) and Fanconi syndrome (FS), and to find out possible risk factors for growth retardation, we studied the long-term growth, clinical, laboratory, and radiological findings associated with the treatment of six children with primary FS and 15 children with PRTA. The ages of the children with FS were much older than those with PRTA at initial diagnosis (7.03±3.82 vs. 1.63±1.56 years). The height standard deviation score (SDS) at the start of treatment was significantly lower in FS than in PRTA. Catch-up growth was noted in PRTA at the end of follow-up (initial height SDS –2.13±1.10 vs. last height SDS –1.33±1.43, P=0.023 by paired t-test), whereas apparent linear growth impairment was found in FS in terms of overall growth velocity index (82.70±8.37%) and height SDS (initial –3.25±0.95 vs. last –3.15±0.31, P=0.791). There was also a higher rate of rickets occurrence in FS (3/6 vs. 0/15 in PRTA). Hypophosphatemia during the follow-up period was more frequent for FS than PRTA (69.2±26.1% vs. 7.0±25.8%, P<0.001), whereas metabolic acidosis (blood HCO₃<20 mmol/l) was less efficiently corrected in PRTA (49.1±20.5% vs. 25.2±21.6% in FS, P=0.028). Moreover, the height SDS correlated well with the mean serum P level during the treatment period in these patients (R=0.528, P=0.014 for all children; R=0.917, P=0.01 for FS patients). Our data suggest that metabolic acidosis may not be the sole factor causing growth impairment in FS. Correction of metabolic acidosis may indeed improve growth in PRTA but not in FS. This study indicates that factors other than metabolic acidosis, such as phosphate depletion and delayed diagnosis/treatment, should be considered to be important causes of growth retardation in FS.     

Paraquat-induced Fanconi syndrome

The ingestion of paraquat, a non-selective herbicide, can be fatal in humans. Paraquat is toxic to multiple organs, including the kidney, heart, gastrointestinal tract and central nervous system. Although paraquat has been established as one cause of acute tubular necrosis, Fanconi syndrome presenting as severe hypophosphataemia after paraquat intoxication has not been reported. Here, we report the case of a 44-year-old Korean woman who presented with generalized proximal tubular dysfunction including aminoaciduria, phosphaturia and glycosuria after paraquat intoxication. We found that severe hypophosphataemia induces deep drowsiness. Renal biopsy findings indicated the presence of acute tubular necrosis that may be reversible.     

Hyperkalemic distal renal tubular acidosis associated with Rett syndrome

Renal function was studied in a 7-year-old girl with Rett syndrome (RS) complicated by persistent hyperchloremic hyperkalemic metabolic acidosis. The acidosis was associated with a urine pH above 5.5, positive urinary anion gap and decreased potassium excretion. Plasma renin activity, aldosterone and cortisol levels were normal. Therapy with sodium bicarbonate failed to lower urine pH below 5.5 or increase potassium excretion. Hydrochlorothiazide administration resulted in a fall in urine pH below 5.5 and an increase in potassium excretion as a result of increased distal sodium delivery and increased sodium reabsorption in the distal nephron. We conclude that a voltage-dependent type of derangement in the distal nephron, rather than aldosterone deficiency, is responsible for the impairment in urinary acidification observed in this patient. Early detection of impaired renal acidification in RS may prevent or slow the progression of growth failure.     

Neonatal Fanconi syndrome due to deficiency of complex III of the respiratory chain

Fanconi syndrome is an important presentation of respiratory chain disease. We report three patients who presented in the neonatal period with Fanconi syndrome, lactic acidosis and intrauterine growth retardation. In all three patients the major biochemical defect was in complex III of the mitochondrial respiratory chain, a relatively uncommon defect. The diagnosis could only be made by muscle biopsy as the defect was not expressed in cultured skin fibroblasts. Treatment with vitamins C and K₃ and ubiquinone did not alter the course of the disease and all patients died before the age of 4 months.     

Case of hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome associated with nephrocalcinosis and distal renal tubular acidosis

Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder characterized by hypoparathyroidism, sensorineural deafness and renal dysplasia. Herein, we report a case of HDR syndrome associated with nephrocalcinosis and distal renal tubular acidosis. A 34-year-old woman was admitted to investigate recurrent stone formation and bilateral nephrocalcinosis. As a 3-year-old child, she had been diagnosed with HDR syndrome without chromosome evaluation. She had spontaneous stone passages on several occasions. On laboratory examination, serum calcium and intact parathyroid hormone at lower levels. Urinary citrate excretion was extremely low at 51.6 mg/day. On an ammonium chloride loading test, complete distal renal tubular acidosis was proved. To prevent the nephrocalcinosis from deteriorating, she was given potassium-sodium citrate. Since administration, she has not experienced spontaneous stone passage or renal colic. Nephrocalcinosis and recurrent urolithiasis will strongly affect renal prognosis in this case and we consider that citrate medication is an effective therapy in avoiding progress of her nephrocalcinosis.     

Lowe's syndrome with Fanconi syndrome for ocular surgery: perioperative anesthetic considerations

Lowe's syndrome is a rare inherited metabolic disorder characterized by mental retardation, kidney malfunction, and abnormalities of the eyes and bones. A 4 month-old child with Lowe's and Fanconi's syndrome, undergoing bilateral congenital cataract surgery, is presented. Preoperative electrolyte imbalance was corrected by potassium, calcium, magnesium, phosphate, and bicarbonate supplementation. Anesthesia was administered uneventfully using appropriate anesthetic agents and monitoring. Adequate preoperative evaluation and optimization, along with selection of anesthetic agents and fluid and electrolyte management with appropriate perioperative monitoring, is key to a successful outcome.     

Urinary L-lactate excretion is increased in renal Fanconi syndrome.

BACKGROUND: Measurement of l-lactate in body fluids is an established clinical tool to identify disorders of cellular respiration. However, there is very little known about the clinical value of urinary lactate measurements. We investigated urinary lactate excretion in children with renal Fanconi syndrome. METHODS: Freshly voided urine samples were obtained from children with Fanconi syndrome and controls both with and without renal disease. Urine lactate was estimated by conversion to pyruvate in the presence of lactate dehydrogenase and NAD. The NADH produced was measured photometrically. Urine lactate was factored for urine creatinine. RESULTS: Children with Fanconi syndrome had a significantly higher urine lactate/creatinine ratio [mean: 84 x 10(-2) mmol/mmol; 95% confidence interval (CI): 40.8-127.1 x 10(-2) mmol/mmol] than healthy controls (mean: 1.3 x 10(-2) mmol/mmol; CI: 1.1-1.5 x 10(-2) mmol/ mmol) and those with a variety of renal diseases (mean: 3.1 x 10(-2) mmol/mmol; CI: 1.8-4.5 x 10(-2) mmol/mmol). CONCLUSIONS: Urinary lactate is increased in Fanconi syndrome. The increase is likely to be due to reduced lactate co-transport in the proximal tubule. Urinary lactate/creatinine has clinical utility as a sensitive test of disordered proximal renal tubular function.     

Exfoliated human proximal tubular cells: a model of cystinosis and Fanconi syndrome

The renal Fanconi syndrome (FS) is characterised by generalised proximal tubular dysfunction. Cystinosis is the most common genetic cause of the FS and results from defective function of cystinosin, due to mutations of the CTNS gene leading to intralysosomal cystine accumulation. Despite these advances in our understanding of the molecular basis of cystinosis, the mechanisms of proximal tubular cell (PTC) dysfunction are still unknown. We have further characterised an in vitro model of cultured cells exfoliated in patients urine. We cultured cells from 9 cystinosis children, 4 children with Lowe syndrome and 8 controls. PTC phenotype and homogeneity were studied by lectin staining, immunocytochemistry (using ZO-1 as an epithelial marker) and enzyme cytochemistry (using -glutamyltransferase as a PTC marker). All cultured cells showed PTC phenotype. Cystinosin was stained using anti-cystinosin antibody and co-localised to the lysosomes with LAMP-2 antibody. Additionally, we have demonstrated significantly elevated intracellular cystine levels in cystinotic cell lines (13.8±2.3 nmol 1/2 cystine/mg protein, P <0.001) compared with controls. We believe this in vitro model will allow further investigation of cystinosis and other types of the FS.     

Prevalence and characterization of renal tubular acidosis in patients with osteopenia and osteoporosis and in non-porotic controls.

BACKGROUND: Chronic metabolic acidosis may increase alkali mobilization from the bone and thus promote the development of osteoporosis. The objective of the current study was to compare urinary acidification in patients with reduced bone mineral content with that in control subjects with normal bone density. METHODS: Forty-six subjects (41 females, 5 males) with osteopenia or osteoporosis were studied. In none of the subjects were overt metabolic acidosis, derangement of potassium homeostasis, or renal insufficiency present. Distal tubular acidification was studied by means of oral ammonium chloride loading test (0.1 g/kg body weight) and the oral frusemide test (40 mg). In addition the frusemide test was performed in 20 healthy age- and sex-matched controls (17 females, 3 males). RESULTS: In all control subjects a urinary pH <5. 5 was observed following the ingestion of 40 mg frusemide. In contrast, in patients with reduced bone mineral density incomplete renal tubular acidosis type I (RTA I) was diagnosed in 10 of 46 subjects (22%) by oral ammonium chloride loading test. Disorders possibly related to RTA I were detected in eight of these 10 patients. Thirty-six patients had a normal urinary pH response following oral ammonium chloride loading. Oral frusemide, 40 mg, failed to lower urinary pH <5.5 in sixteen patients (35%), these included 10 subjects with incomplete RTA I, and six subjects with a normal oral ammonium chloride loading test. An abnormal frusemide test was found in 35% of patients with reduced bone mass and in none of the normal controls (chi(2)=7.39; P<0.01). With the ammonium chloride test as the gold standard for diagnosis of distal RTA, the frusemide test showed a sensitivity of 1.0 (95% CI, 0.69-1.0) and a specificity of 0.89 (95% CI, 0.78-0.96) for the diagnosis of distal RTA. Patients with incomplete RTA I were younger than those without incomplete RTA I (42+/-16 vs 54+/-14 years; P=0.025; mean+/-SD). Basal serum bicarbonate concentrations and capillary pH did not differ between the groups. CONCLUSION: Incomplete RTA I may be prevalent in a significant proportion of patients suffering from osteopenia or osteoporosis. The outcome of the frusemide test suggests either a defect of the H(+)ATPase in the cortical collecting tubule (CCT) or a defective Na(+) reabsorption in the CCT. Prospective studies are needed to further elucidate the impact of incomplete RTA I on the development of reduced bone mineral content.     

原发性干燥综合征合并肾小管酸中毒患者发生骨质疏松的风险研究

目的 探讨原发性干燥综合征（primary Sjogren’s Syndrome,pSS）合并肾小管酸中毒（renal tubular acidosis,RTA）患者发生骨质疏松（osteoporosis,OP）及骨折的风险。方法 将受试者分为三组,分别为pSS合并RTA组、pSS组及健康对照组,其中pSS合并RTA组的33例受试者和pSS组的31例受试者均选自2017年-2021年在内蒙古科技大学包头医学院第一附属医院风湿免疫科接受诊疗的患者,健康对照组的31例受试者选自体检科,三组受试者的年龄及性别均无统计学差异,均行骨密度检查并评估10年内骨折风险,pSS合并RTA组与pSS组还完善了25羟基维生素D3、血钙、血钾、血磷、血沉、C-反应蛋白。结果 （1）pSS合并RTA组受试者股骨骨小梁部位的体积骨密度较pSS组明显降低（P＜0.05）;（2）pSS合并RTA组股骨颈的前、后节段、总体及股骨转子平均皮质骨厚度较pSS组明显降低（P＜0.05）;pSS组股骨颈的侧面及股骨干的前节段平均皮质骨厚度较健康对照组明显降低（P＜0.05）;（3）pSS合并 RTA组受试者股骨的BMD明显低于pSS组,pSS组受试者股骨转子的BMD明显低于健康对照组（P＜0.05）;（4）pSS合并RTA组患者10年内骨折风险明显高于pSS组及健康对照组（P＜0.05）;（5）pSS合并RTA组患者血清中的25羟基维生素D3较pSS组患者的低（P＜0.05）;pSS合并RTA组患者的血清中25羟基维生素D3与股骨颈呈正相关（r=0.359,P＜0.05）,血钙、血钾、血磷、血沉、C-反应蛋白与髋部二维BMD均无相关性（P＞0.05）;结论 pSS合并RTA发生OP及骨折的风险增加,主要表现为股骨的骨小梁BMD及股骨转子皮质骨厚度降低。     

Metabolic risk factors in patients with renal stones in KwaZulu Natal: an inter-racial study (Asian and Whites)

OBJECTIVE: To identify any differences between Whites and Indians in KwaZulu Natal province, South Africa, in the metabolic risk factors which predispose them to urinary stone formation. PATIENTS AND METHODS: Urinary stone disease is often a manifestation of an underlying metabolic disorder in most patients. Intrinsic and extrinsic factors affect the susceptibility of an individual to develop urinary stones. Although South African-born Indians and Whites in KwaZulu Natal share some of the same extrinsic factors, diet and genetic factors differ between the groups. In a study from April 1999 until April 2001, 140 patients were included who had a radiological diagnosis of renal calculi; they were evaluated metabolically using previously recommended methods. RESULTS: All the patients had at least one identifiable metabolic risk factor; the prevalence of the common metabolic risk factors was similar in the two groups. The prevalence of complete renal tubular acidosis (type 1) was significantly higher in the Indian patients. The most common metabolic abnormalities were hypomagnesuria and hypocitraturia, followed by low urinary volume. Hypercalciuria was not significant in this population. While Indians had lower urine volumes than Whites, Whites had significantly higher urinary calcium excretion than Indians. CONCLUSION: There were a few variations in the metabolic risk factors between Indians and Whites, and the differences could be attributed to genetic or dietary habits. The high incidence of renal tubular acidosis in Indian patients could explain the higher prevalence of urinary stone disease in this group than in other racial groups.     

Transient neonatal distal renal tubular acidosis with secondary hyperparathyroidism

We describe a neonate with distal renal tubular acidosis with secondary hyperparathyroidism manifesting as hyperchloraemia, hypercalcaemia, elevated serum parathyroid hormone (PTH) and life-threatening metabolic acidosis. He exhibited general weakness, tachypnoea, dry skin and weight loss. Urinary excretion of titratable acid and ammonium was decreased. Daily alkali (2.5 mEq/kg body weight) was required to maintain a normal plasma bicarbonate (HCO₃–). With alkali therapy, the fractional excretion of HCO₃– was below 5%. Serum calcium and PTH were restored to normal promptly on initiation of alkali therapy. After 5 months of alkali therapy, normal growth and urine acidifying ability were restored and alkali therapy was discontinued. The acidification defect in this patient was transient. We consider this patient to be consistent with Lightwood's syndrome of transient infantile renal tubular acidosis.     

Evaluation of renal function in leprosy: a study of 59 consecutive patients.

BACKGROUND: Renal abnormalities in leprosy have been largely described in medical literature, but there are few studies evaluating renal function in these patients. METHODS: This is a cross-sectional study in 59 consecutive paucibacillary (PB) and multibacillary (MB) leprosy patients. Glomerular filtration rate (GFR) was estimated by simplified-MDRD formula. Microalbuminuria was determined by 24 h urine collection. Urinary acidification capacity was measured after water deprivation and acid-loading with CaCl(2). Urinary concentration capacity was evaluated after desmopressin acetate administration, using the urinary to plasma osmolality (U/P(osm)) ratio. All parameters except microalbuminuria were measured in a control group of 18 healthy volunteers. RESULTS: Age and gender were similar between leprosy (MB or PB) and control groups. GFR 1.2 mg/dl was observed in 17.9% of MB patients and in none of the controls (P=0.020). A negative correlation was observed between GFR and time of treatment (r= -0.339; P=0.002). Age and time of treatment were independent risk factors for GFR 相似文献