Renal Tubular Acidosis Syndrome Research Articles

Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy.

Carbonic anhydrase II (CAII) deficiency in humans is associated with a syndrome of renal tubular acidosis, osteopetrosis, and cerebral calcification. A strain of mice of CAII deficiency due to a point mutation also manifests renal tubular acidosis. We report here that retrograde injection of cationic liposome complexed with a CAII chimeric gene, using a cytomegalovirus (CMV) promoter/enhancer as an expression cassette to drive human CAII cDNA, into the renal pelvis of CAII-deficient mice results in expression of CAII in the kidney. The levels of both the CAII gene and its corresponding mRNA were highest by day 3 after treatment, diminishing thereafter, but remaining detectable by 1 mo. After gene therapy, CAII-deficient mice restored the ability to acidify urine after oral administration of ammonium chloride. The ability to acidify urine was maintained at 3 wk after gene therapy, and was eventually lost by 6 wk. Immunohistochemistry studies using anti-CAII antibodies showed that CAII was expressed in tubular cells of the outer medulla and corticomedullary junction. The gene therapy was not associated with nephrotoxicity as assessed by blood urea nitrogen levels and renal histology. To our knowledge, this is the first successful gene therapy of a genetic renal disease. Our results demonstrate the potential of gene therapy as a novel treatment for hereditary renal tubular defects.

The syndrome of renal tubular acidosis and nerve deafness. Discordant manifestations in dizygotic twin brothers

The syndrome of renal tubular acidosis (RTA) and nerve deafness is a distinct nosological entity that is inherited as an autosomal recessive trait. We studied a pair of dizygotic twin brothers both with nerve deafness but only one with RTA. Distal RTA was diagnosed in twin A because of inappropriately high urinary pH (6.9) and low net acid excretion (40.0 muEq/min per 1.73 m2) in the presence of hyperchloraemic metablic acidosis, and fractional bicarbonate excretion of 1.6% at a normal serum bicarbonate concentration. The urine minus blood PCO2 differences (U-B PCO2) during a neutral sodium phosphate load and in alkaline urine induced by bicarbonate supplementation were: 11 and 0 mm Hg, respectively. Twin A developed nephrocalcinosis and, after a 9.5-year follow-up period, was 5.3 cm taller than his brother. Twin B remained asymptomatic. Periodic determinations of blood pH and serum bicarbonate were normal and urine pH decreased to 4.6 in the face of ammonium chloride-induced metabolic acidosis. The U-B PCO2 assessed in alkaline urine was 33.5 mm Hg. Audiograms demonstrated bilateral nerve deafness in both brothers. The presence of deafness without RTA has not been previously reported in this syndrome. This report also shows that a primary distal acidification defect is responsible for the RTA observed in this syndrome.

Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis.

The syndrome of renal tubular acidosis has been categorized into three physiologic types that have different clinical findings and prognostic and therapeutic implications. We reviewed radiographs of the skeleton and kidneys in 92 patients (56 children and 36 adults) with renal tubular acidosis in order to determine whether the radiologic findings could be related to the type of syndrome. Forty-four patients had Type 1 renal tubular acidosis, 18 had Type 2, and 30 had Type 4. Evidence of skeletal abnormalities was uncommon (17 per cent) and was confined to patients who had the Type 2 disorder or azotemia. The children with Type 2 and skeletal abnormalities had rickets; the adults had osteopenia without pseudofractures. Nephrocalcinosis was evident in approximately one fourth of the group (29 per cent) and was restricted to patients with the Type 1 syndrome. In patients with Type 4, osteopenia was evident in 12 per cent, all of whom were azotemic. Our observations indicate that the radiographic manifestations of renal tubular acidosis are influenced by the physiologic type of renal tubular acidosis.

Renal tubular acidosis: practical guides to diagnosis and treatment.

The syndrome of renal tubular acidosis in some one of its various forms should be suspected when an infant or child has failure to thrive, metabolic acidosis, constipation, diarrhea, vomiting, anorexia, polyuria, or dehydration in infancy. Confirmatory biochemical findings include an inappropriately high urinary pH, inadequate acid excretion and/or abnormal tubular reabsorption of filtered bicarbonate. Growth can be normal when there is sustained correction of the metabolic acidosis through appropriate alkaline therapy.

Nephrotoxic effects of amphotericin B, including renal tubular acidosis

A detailed study of the effects of amphotericin B on renal function in a patient receiving this drug revealed that inulin clearance (C IN), p-aminohippurate clearance (C PAH) and the maximal tubular secretory capacity for p-aminohippurate (Tm PAH) decreased during therapy to about one third of their pretreatment values. Concentrating ability was impaired. Urinary potassium losses became excessive, with severe hypokalemia. Urinary calcium and magnesium excretion rates were depressed. Of special interest was the development of a syndrome of renal tubular acidosis. After twenty days of amphotericin B administration, the minimum urinary pH achieved in response to an ammonium chloride load was 6.7, and the excretion of titratable acid was severely impaired. This represents the second occasion on which a syndrome of renal tubular acidosis has been detected in patients receiving amphotericin B. Two months after amphotericin B therapy was stopped, acid excretion, concentrating ability and electrolyte excretion had returned to normal, and Tm PAH was 89 per cent of its pretreatment value, but C IN and C PAH were still moderately impaired. The findings of the study emphasize the severity of the renal damage and electrolyte changes that can be produced by amphotericin B therapy, and the need to assess renal function during and after the period of treatment. Prevention of dehydration and also of hypokalemia, by early oral administration of potassium supplements, are suggested as ways to help reduce the nephrotoxic effects of this drug. In view of the development of a renal tubular acidosis syndrome, concurrent alkali (citrate) therapy may be useful.

Familial renal tubular acidosis.

Editorial Notes1 June 1968Familial Renal Tubular AcidosisVARDAMAN M. BUCKALEW JR., M.D.VARDAMAN M. BUCKALEW JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-6-1367 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is now well-established that the syndrome of renal tubular acidosis (RTA), in which the primary defect is an inability to lower urinary pH normally, occurs as a familial disease in a small percentage of cases. However, the mode of transmission is not entirely clear. In a recent review, Seldin and Wilson (1) summarized the evidence in 14 families suggesting that familial RTA is due to an autosomal dominant gene. The strongest evidence favoring this view is found in the two families originally reported by Pitts, Schulte, and Smith (2) and subsequently by Randall and Taggart (3) and by Schreiner,...

Hereditary elliptocytosis and primary renal tubular acidosis in a single family.

HEREDITARY elliptocytosis is characterized by the presence of oval or elliptical-shaped red blood cells. Approximately 12% of affected individuals have an uncompensated hemolytic anemia. 1 Hyperchloremic acidosis, rickets, or osteomalacia and severe potassium depletion characterize the syndrome of renal tubular acidosis; hypercalcinuria, nephrolithiasis, and nephrocalcinosis are commonly associated. 2,3 Hereditary elliptocytosis and renal tubular acidosis are distinct genetically determined conditions with no apparent biochemical relationship to one another. Although hereditary elliptocytosis has been reported in association with various other genetically determined disorders 4-8 its association with renal tubular dysfunction has not been previously documented. This paper describes two siblings with a renal tubular defect having all the features of persistent primary renal tubular acidosis. Elliptocytosis was proven in one sibling and in the father, and was inferred retrospectively in the second sibling. The family pedigree is outlined in Fig 1. Report of Cases Case1 (III 3).—A girl, born following