Distal renal tubular acidosis as presenting manifestation of Wilson disease in a 11-year-old girl.

A 11-year-old girl was referred to the pediatric nephrology services of our hospital for evaluation of vitamin-D-refractory rickets. She was born to second-degree consanguineous parents. On examination, she had wrist widening and bilateral genu varum. She had normal anion gap metabolic acidosis, hypokalemia, and hyperchloremia. The fractional excretion of bicarbonate was 3% and the urine anion gap was positive. She also had hypercalciuria, but no phosphaturia, glucosuria or aminoaciduria. In view of a family history of an elder sister having rigidity with cognitive and speech impairment, an ophthalmic evaluation by slit lamp examination was performed in the index case that revealed bilateral Kayser-Fleischer rings. Serum ceruloplasmin was low and 24-h urine copper was elevated in the index case. Whole exome sequencing unveiled a novel pathogenic variant in exon 2 of the ATP7B gene (chr13: c.470del; Depth: 142x) (homozygous) that resulted in a frameshift and premature truncation of the protein, 15 amino acids downstream to codon 157 (p. Cys157LeufsTer15; NM_000053.4) confirming Wilson disease. There were no mutations in the ATP6V0A4, ATP6V1B1, SLC4A1, FOXI1, WDR72 genes or other genes that are known to cause distal RTA. Therapy with D-penicillamine and zinc supplements was initiated. A low dose of 2.5 mEq/kg/day of potassium citrate supplementation normalized the serum bicarbonate levels. This case was notable for the absence of hepatic or neurological involvement at admission. Wilson disease is well known to cause proximal renal tubular acidosis and Fanconi syndrome, with relatively lesser involvement of the distal renal tubules in the literature. However, isolated distal renal tubular involvement as presenting manifestation of Wilson disease (without hepatic or neurological involvement) is rare and can lead to diagnostic confusion.

Distal Renal Tubular Acidosis due to Primary Sjögren's Syndrome: Presents as Hypoakalemic Paralysis with Hypokalemia-Induced Nephrogenic Diabetes Insipidus.

Classic distal renal tubular acidosis (dRTA) is characterized by inability to acidify the urine maximally (to

Renal Tubular Acidosis.

Renal tubular acidosis should be suspected in poorly thriving young children with hyperchloremic and hypokalemic normal anion gap metabolic acidosis, with/without syndromic features. Further workup is needed to determine the type of renal tubular acidosis and the presumed etiopathogenesis, which informs treatment choices and prognosis. The risk of nephrolithiasis and calcinosis is linked to the presence (proximal renal tubular acidosis, negligible stone risk) or absence (distal renal tubular acidosis, high stone risk) of urine citrate excretion. New formulations of slow-release alkali and potassium combination supplements are being tested that are expected to simplify treatment and lead to sustained acidosis correction.

Distal renal tubular acidosis secondary to vesico-ureteric reflux: A case report with review of literature.

Vesicoureteric reflux (VUR) is the most common congenital anomaly of the urinary tract that occurs in 30%-50% of children presenting with recurrent urinary tract infections. Long-standing untreated VUR results in renal scarring and hydronephrotic changes ultimately leading to chronic renal failure and arterial hypertension. However, it may also result in diffuse tubulopathy compromising the concentrating capacity of tubules and urinary acidification defects. Renal tubular dysfunction should be considered in all children with VUR presenting with failure to thrive, rickets, bony deformity/pain, hypokalemia, and metabolic acidosis. We report such a case of a 16-year-old male adolescent who presented with rickets, failure to gain weight and height, bony pains, and muscle weakness with a history of VUR. On investigation, he was found to have normal anion gap metabolic acidosis with hypokalemia suggestive of distal renal tubular acidosis. He responded well to oral alkali and potassium replacement therapy.

Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

Clinical and etiological profile of refractory rickets from western India.

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.

Hereditary hypophosphatemic rickets with hypercalciuria: case report.

We report a case of a male aged 50 years who consulted for renal disease recurrent lithiasis and nephrocalcinosis. The clinical examination showed external signs of rickets/osteomalacia and biochemical data as well as a severe loss of renal phosphate with hypophosphatemia, normal 25 OH vitamin D, high 1,25 OH vitamin D and hypercalciuria. Parathyroid hormone was low and renal ultrasound confirmed the existence of severe bilateral medullary nephrocalcinosis. They also found incipient chronic renal failure and incomplete renal tubular acidosis, both secondary to nephrocalcinosis and unrelated to the underlying disease. The molecular study found a change in homozygosity in intron 5 of gene SLC34A3 (NM_080877.2:c[ 448 +5G>A] + [ 448 +5G>A] ). His three children were carriers of the same variant in heterozygosis and although they were clinically asymptomatic two of them had hypercalciuria. All these data suggest that the patient had hereditary hypophosphataemic rickets with hypercalciuria (HHRH) secondary to an alteration in the sodium dependent phosphate cotransporter located in proximal tubule (NaPi-IIc). The HHRH is transmitted by autosomal recessive inheritance and is an extremely rare form of hypophosphatemic rickets. The diagnosis and treatment are essential to prevent bone sequelae of rickets and nephrocalcinosis. A correct differential diagnosis with other forms of hypophosphatemic rickets has implications on the treatment, as the management based only on phosphorus supplementation usually corrects all clinical and biochemical abnormalities, except for the loss of phosphorus in the urine. The exogenous supply of calcitriol, as advised in other hypophosphatemic rickets, may induce renal calcium deposits and nephrocalcinosis and worsens the prognosis.

Renal tubular acidosis due to Wilson's disease presenting as metabolic bone disease.

Two sisters presented with lower limb deformity and difficulty in walking without support. Both had short stature; however, neurodevelopment and secondary sexual characters were normal. Abdominal examination revealed splenomegaly and ophthalmic examination showed presence of Kayser-Fleischer (K-F) rings. Diagnosis of Wilson's disease was confirmed with low serum copper and ceruloplasmin levels. Further investigations revealed urinary acidification defect with hypercalciuria pointing towards distal renal tubular acidosis. Both patients were started on copper chelation therapy and showed gradual radiographic improvement in osteopaenia.

Relationship between rickets and incomplete distal renal tubular acidosis in children.

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.

[Osteomalacia revealing Sjögren's syndrome: a case report]. / Ostéomalacie révélatrice d'un syndrome de Gougerot-Sjögren : à propos d'un cas.

INTRODUCTION: The most common renal disease in Sjögren's syndrome is tubulo-interstitial nephritis, responsible for tubular acidosis in around 20 % of patients. Osteomalacia exceptionally occurs as the first manifestation of a renal tubule disorder due to a Sjögren's syndrome. EXEGESIS: We report a case of a 20-year-old woman with tubular acidosis induced osteomalacia secondary to primary Sjögren's syndrome. Improvement was obtained with bicarbonates, vitamin D, calcium and high-dose steroid therapy. CONCLUSION: During Sjögren's syndrome, osteomalacia can complicate the distal renal tubular acidosis. In spite of the rare cases of osteomalacia revealing Sjögren's syndrome, this auto-immune disease must appear in the list of the aetiologies of osteomalacia.

Combined renal tubular acidosis and diabetes insipidus in hematological disease.

BACKGROUND: A 39-year-old male with multiple myeloma was admitted for treatment with melphalan and autologous stem cell reinfusion. He presented with hypokalemia and hyperchloremic non-anion-gap metabolic acidosis with a high urinary pH. He also had hypomagnesemia, hypophosphatemia, hypouricemia, proteinuria and glucosuria. The patient subsequently developed polyuria with a low urine osmolality, hypernatremia and, finally, acute renal failure. INVESTIGATIONS: Physical examination, blood and urine analyses, kidney biopsy and tonicity balance. DIAGNOSIS: Fanconi syndrome with proximal (type II) renal tubular acidosis caused by myeloma kidney. Renal tubular acidosis was complicated by probable nephrogenic diabetes insipidus and acute renal failure. MANAGEMENT: Potassium supplementation, sodium bicarbonate therapy, intravenous fluid therapy and dialysis.

Respiratory paralysis in Sjogren syndrome with normal renal function.

We report a 28-year-old woman who presented with quadriparesis and respiratory failure, and had severe hypokalaemia and distal renal tubular acidosis. She recovered completely on potassium and alkali supplementation. Biopsy and scintigraphy of the minor salivary glands confirmed the presence of Sjogren syndrome. A 6-month course of prednisolone did not correct the distal renal tubular acidosis.

Rapid improvement of osteomalacia by treatment in a case with Sjögren's syndrome, rheumatoid arthritis and renal tubular acidosis type 1.

We present here a case of Sjögren's syndrome (SjS) with osteomalacia based on renal tubular acidosis type 1 (RTA-1). A 53-year-old woman, diagnosed as having rheumatoid arthritis (RA) at the age of 33, was admitted to our hospital because of sicca complex, fatigability and worsening general aching. The activity of RA had been low, but it was complicated by SjS, RTA-1 and remarkable osteomalacia. Acidosis was corrected by alkali supplement therapy. By treatment with a regimen consisting of alfacalcidol, calcium L-aspartate, elcatonin and ipriflavone, her bone mineral density (BMD) was remarkably improved within months and the generalized aching gradually diminished.

Proximal renal tubular acidosis associated with osteomalacia.

Vitamin D deficiency is relatively common among older persons and those with spinal cord injuries. We report a case of proximal renal tubular acidosis in a 44-year-old quadriplegic nursing home resident who had limited sunlight exposure. Laboratory studies showed a low level of serum bicarbonate, a normal serum anion gap, and a positive urine anion gap. There was no history of diarrhea. Serum calcium and phosphorus levels were 6.9 mg/dL and 3.7 mg/dL, respectively. Proximal renal tubular acidosis due to osteomalacia was suspected, which was confirmed by a low serum 25-hydroxycholecalciferol level (< 5 ng/mL) with an elevated serum parathyroid hormone level. Treatment with vitamin D and a calcium supplement led to normalization of laboratory values.

Absence of cytochrome c oxidase activity in a boy with dysfunction of renal tubules, brain and muscle.

We report on a boy who developed proximal renal tubular acidosis with loss of carnitine at the age of about 6 months. A few months later he began to suffer from progressive muscular weakness and neurological disturbances. Blood biochemistry showed elevated lactate and beta-hydroxybutyrate with increased lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios. A high urinary excretion of lactate and citric acid cycle intermediates was found. These results indicated a defect of the mitochondrial respiratory chain. Analysis of biopsy material from skeletal muscle revealed low activities of all respiratory chain complexes. In muscle and fibroblasts cytochrome c-oxidase (complex IV) was absent. Despite high dose multi-vitamin therapy the boy died at the age of 30 months from central respiratory failure. At autopsy the neuropathological diagnosis of Leigh disease was made.

Osteomalacia secondary to renal tubular acidosis in a patient with primary Sjögren's syndrome.

We report a case of a 41-year-old woman whose disease manifested as osteomalacia and whose etiological investigation revealed renal tubular acidosis secondary to primary Sjögren's syndrome. Proximal tubular dysfunction was also present and was documented by increased urinary excretion of beta-2-microglobulin and retinol-binding protein. The patient showed clinical and laboratory improvement after treatment with oral potassium citrate, calcium supplements and steroids.

Effects of dietary acidification and potassium depletion on acid-base balance, mineral metabolism and renal function in adult cats.

Effects of dietary potassium restriction, with or without dietary acidification, on acid-base balance, mineral metabolism and renal function were evaluated in 12 adult cats. Six cats were fed a potassium-restricted diet (0.2% potassium) for 8 wk, and six cats were fed the same potassium-restricted diet plus a dietary acidifier (0.8% NH4Cl) for 8 wk. Both groups of cats were then fed the same diet supplemented with potassium gluconate (0.7% dietary potassium) for an additional 4 wk. Renal function was evaluated before treatment and again at 8 and 12 wk. Serum potassium concentration declined in all cats by wk 1 and was also lower in NH4Cl-treated cats at 2, 3, 6 and 8 wk than in control cats. Metabolic acidosis developed in both groups of cats. Dietary balance studies indicated negative potassium balance in NH4Cl-treated cats. Glomerular filtration rate declined significantly in NH4Cl-treated cats after 8 wk but was unchanged in control cats. From the results of this study, we conclude that adding a dietary acidifier to a potassium-restricted diet worsens hypokalemia, possibly by affecting gastrointestinal potassium handling, and induces severe metabolic acidosis and renal dysfunction in adult cats.