Pathogenesis Of Renal Tubular Acidosis Research Articles

Presence of serum autoantibodies to vacuolar H+ -ATPase in patients with renal tubular acidosis.

Concomitant presence of renal tubular acidosis (RTA) and autoimmune diseases is indicative of the potential role of immune factors in the pathogenesis of RTA. Our study aimed to detect the serum antibodies to renal tubular epithelial cells in RTA patients. We enrolled 11 RTA patients, eight primary Sjögren's syndrome (pSS) patients and eight healthy controls (HC). Serum biochemical test, urinary regular test, and 24hours urinary protein quantification were measured using a fully automated analyzer. Immunofluorescence assay was performed to detect the antibodies to subunit B1 and subunit B2 of v-H+-ATPases (adenosine triphosphatases) in the serum of the participants. Clinically, RTA patients showed hyperchloremia, acidosis and paradoxical alkaline urine. We detected the serum antibodies to renal tubular epithelial cells and there were 6/11 positive in RTA patients, much higher than that in the pSS group (0/8) and the HC group (0/8). Subsequently, we demonstrated that in normal renal tissue, the B1 subunit of v-H+-ATPase specifically expressed in intercalated cells, while the B2 subunit continuously expressed along the lumen of renal tubular epithelial cells. Moreover, the antibody to subunit B1/B2 of v-H+-ATPase was positive in the sera of 6 RTA patients (54%), while it was negative in both the pSS and HC group. We detected the presence of serum autoantibodies to subunit B1 and subunit B2 of v-H+ -ATPase in RTA patients. Our findings may provide novel mechanism insights into the pathogenesis of RTA and the potential diagnostic utility of antibodies to v-H+ -ATPase in the classification of RTA.

Renal Tubular Acidosis in Horses (1980–1999)

Renal tubular acidosis (RTA) is characterized by altered renal tubular function resulting in hyperchloremic metabolic acidosis. The purpose of the study was to describe RTA in 16 horses. No breed or sex predilection was found. The mean age at onset of the disease was 7 years of age. The type of diet had no apparent effect on development of RTA. The most common clinical signs were depression, poor performance, weight loss, and anorexia. Initial blood work revealed a marked hyperchloremic metabolic acidosis in all horses and a compensatory respiratory response in most horses. Sixty‐three percent (10/16) of the horses had some evidence of renal damage or disease. Initial treatment consisted of large amounts of sodium bicarbonate given intravenously and orally for the prompt correction of the acidosis. Response to treatment was largely dependent on the rate of sodium bicarbonate administration. Long‐term oral supplementation with NaHCO3was required for the maintenance of normal acid‐base status in individual horses. Recurrence of RTA was noted in 56% (9/16) of the horses. Horses with evidence of renal disease had multiple relapses. RTA should be considered as a differential diagnosis in horses with vague signs of depression, weight loss, and anorexia. The pathogenesis of RTA in horses remains uncertain, but prompt recognition and early aggressive intravenous sodium bicarbonate therapy followed by long‐term oral supplementation seem to be important to successful management.

Renal tubular acidosis in horses (1980-1999).

Renal tubular acidosis (RTA) is characterized by altered renal tubular function resulting in hyperchloremic metabolic acidosis. The purpose of the study was to describe RTA in 16 horses. No breed or sex predilection was found. The mean age at onset of the disease was 7 years of age. The type of diet had no apparent effect on development of RTA. The most common clinical signs were depression, poor performance, weight loss, and anorexia. Initial blood work revealed a marked hyperchloremic metabolic acidosis in all horses and a compensatory respiratory response in most horses. Sixty-three percent (10/16) of the horses had some evidence of renal damage or disease. Initial treatment consisted of large amounts of sodium bicarbonate given intravenously and orally for the prompt correction of the acidosis. Response to treatment was largely dependent on the rate of sodium bicarbonate administration. Long-term oral supplementation with NaHCO3 was required for the maintenance of normal acid-base status in individual horses. Recurrence of RTA was noted in 56% (9/16) of the horses. Horses with evidence of renal disease had multiple relapses. RTA should be considered as a differential diagnosis in horses with vague signs of depression, weight loss, and anorexia. The pathogenesis of RTA in horses remains uncertain, but prompt recognition and early aggressive intravenous sodium bicarbonate therapy followed by long-term oral supplementation seem to be important to successful management.

New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies.

The diagnosis and classification of renal tubular acidosis (RTA) have traditionally been made on the basis of functional studies. On these grounds, RTA has been separated into three main categories: (1) proximal RTA, or type 2; (2) distal RTA, or type 1; and (3) hyperkalemic RTA, or type 4. In recent years significant advances have been made in our understanding of the subcellular mechanisms involved in renal bicarbonate (HCO3-) and H+ transport. Application of molecular biology techniques has also opened a completely new perspective to the understanding of the pathophysiology of inherited cases of RTA. Mutations in the gene SLC4A4, encoding Na+-HCO3- cotransporter (NBC-1), have been found in proximal RTA with ocular abnormalities; in the gene SLC4A1, encoding Cl(-)-HCO3- exchanger (AE1), in autosomal dominant distal RTA; in the gene ATP6B1, encoding B1 subunit of H+-ATPase, in autosomal recessive distal RTA with sensorineural deafness; and in the gene CA2, encoding carbonic anhydrase II, in autosomal recessive osteopetrosis. Syndromes of aldosterone resistance have been also characterized molecularly and mutations in the gene MLR, encoding mineralocorticoid receptor, and in the genes SNCC1A, SNCC1B, and SCNN1G, encoding subunits of the epithelial Na+ channel, have been found in dominant and recessive forms of pseudohypoaldosteronism type 1, respectively. It can be concluded that, although functional studies are still necessary, a new molecular era in the understanding of disorders of renal acidification has arrived.

Pathogenetic relationships between renal tubular acidosis and sodium metabolism alterations in liver cirrhosis.

5 cirrhotic patients with latent distal renal tubular acidosis (RTA) and 5 cirrhotic patients with normal distal acidification ability were studied. All the patients were maintained on a 80 mEq/day sodium diet for at least 5 days before the study. Only 2 of the 5 patients with RTA showed a reduced daily sodium excretion while the 3 other patients with RTA had a normal natriuresis. Acidification ability was retested in all the patients after increasing sodium distal delivery by intravenous administration of ethacrynic acid. Some hours after the maximal natriuretic effect induced by ethacrynic acid, a normalization of the acidification test was seen in all patients with RTA. These findings support the concept that although sodium metabolism alterations are not the only factor in the pathogenesis of RTA in liver cirrhosis, reduced availability of sodium at the distal tubule may impair tubular acidification, probably by influencing the distal transtubular potential difference.

Deficiency type rickets associated with precocious puberty, mental retardation and phthisis bulbi.

A 6-year-old female (at present 12-year-old) who had precocious puberty, mental retardation, phthisis bulbi and severe rickets, was presented. The parents were not relative. Her father and brother (the fifth brother out of 6 siblings) had slight mental retardation and ocular defects such as coloboma of the optic disc (father and brother), microphthalmia, cataract, and rotatory nystagmus (father). At the age of 3 years, the patient had suffered from pyelonephritis which was found not improved when she was admitted to our clinic at the age of 6 years 2 months. A deficiency type of rickets, which was not prevented by usual prophylactic amount of vitamin D 400 I. U. but cured with daily supplement of 2, 000-5, 000 I. U. of vitamin D, developed at the age of 6 years 6 months and persisted until the age of 12 years. The chemical analysis of the serum indicated constantly low level of phosphorus and elevated level of alkaline phosphatase, while it was otherwise normal. The oculo-cerebro-renal syndrome of Lowe1-13 and McCune-Albright syndrome14-21 were apparently different in the symptoms and laboratory findings from our patient. Chronic pyelonephritis which has a possible role in the pathogenesis of renal tubular acidosis to cause severe rickets24, 25 was also thought not to be responsible for the rickets of our patient, because our patient indicated no acidosis and normal response for ammonium chloride loading test and further, because rickets was not healed in spite of the fact that chronic pyelonephritis was cured bacteriologically and histologically at the age of 9 years. In our patient, a decreased sensitivity to vitamin D was inferred to be responsbile for the occurrence of rickets, which Soriano et al.26 recently proved in their own case, although there were marked differences in the age of onset and clinical findings between our case and Soriano et al.'s case. However, the relationship remained obscure between a decreased sensitivity to developmental failure or congenital defects such as precocious puberty, mental vitamin D and retardation and eye changes, which suggested a kind of retinal dysplasia syndrome, 29-34

Symptomatic osteomalacia secondary to clinically occult causes.

Case Reports1 June 1961SYMPTOMATIC OSTEOMALACIA SECONDARY TO CLINICALLY OCCULT CAUSESRICHARD C. POWELL, M.D., WILLIAM P. DEISS JR., M.D., F.A.C.P.RICHARD C. POWELL, M.D.Search for more papers by this author, WILLIAM P. DEISS JR., M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-6-1280 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of this report is to describe two adult patients with disabling osteomalacia. The feature worthy of emphasis in each case is the negligible symptomatology referable to the organ systems believed to be the sites of the primary defects—in the first case, the gastrointestinal tract with occult steatorrhea; in the second, the kidneys with latent tubular acidosis.CASE REPORTSCase 1. A 50-year-old housewife was first seen by us in February, 1959, complaining of stiffness and generalized aching pain in her back and both lower extremities. The pain was not well localized. The onset of symptoms was insidious, and...Bibliography1. Milkman LA: Multiple spontaneous idiopathic symmetrical fractures. Amer. J. Roentgenol. 32: 622, 1934. Google Scholar2. AlbrightReifenstein FEC: The parathyroid glands and metabolic bone disease: selected studies. The Williams and Wilkins Company, Baltimore. 1948. Google Scholar3. CameronBensleyWood DGEHP: Latent steatorrhea. Ann. Intern. Med. 37: 553, 1952. LinkGoogle Scholar4. JuergensScholzWollaeger JSDAEE: Severe osteomalacia associated with occult steatorrhea due to nontropical sprue: report of five cases. Arch. Intern. Med. 98: 774, 1956. CrossrefGoogle Scholar5. Mudge GH: Clinical patterns of tubular dysfunction. Amer. J. Med. 24: 785, 1958. CrossrefMedlineGoogle Scholar6. FossPerryWood GLCBFJ: Renal tubular acidosis. Quart. J. Med. 25: 18, 1956. Google Scholar7. SchreinerSmithKyle GELHLH: Renal hyperchloremic acidosis: familial occurrence of nephrocalcinosis with hyperchloremia and low serum bicarbonate. Amer. J. Med. 15: 122, 1953. CrossrefMedlineGoogle Scholar8. AlbrightBurnettParsonReifensteinRoos FCHWECA: Osteomalacia and late rickets. Medicine 25: 399, 1946. CrossrefMedlineGoogle Scholar9. MilneStanburyThomson MDSWAE: Observations on the Fanconi syndrome and renal hyperchloraemic acidosis in the adult. Quart. J. Med. 21: 61, 1952. MedlineGoogle Scholar10. JacksonLinder WPGC: Innate functional defects of the renal tubules, with particular reference to the Fanconi syndrome: cases with retinitis pigmentosa. Quart. J. Med. 22: 133, 1953. MedlineGoogle Scholar11. JacksonDowdleLinder WPEGC: Vitamin D-resistant osteomalacia. Brit. Med. J. 1: 1269, 1958. CrossrefMedlineGoogle Scholar12. Reynolds TB: Observations on the pathogenesis of renal tubular acidosis. Amer. J. Med. 25: 503, 1958. CrossrefMedlineGoogle Scholar13. ElkintonHuthClarkBarkerSeligson JREJJKESD: Renal tubular acidosis with organic aciduria during paraldehyde ingestion: six-year study of an unusual case. Amer. J. Med. 23: 977, 1957. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Indianapolis, Indiana*Received for publication September 14, 1959.From the Department of Medicine, Indiana University School of Medicine.Requests for reprints should be addressed to Richard C. Powell, M.D., Department of Medicine, Indiana University School of Medicine, Indianapolis 7, Ind. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDisabling osteomalacic myopathy as the only presenting feature of coeliac diseaseA patient with osteomalacia as single presenting symptom of gluten-sensitive enteropathyDas PeritoneumDie intestinale Calcium-Resorption und ihre St�rungenDie erworbenen, generalisierten OsteopathienCalcium Absorption in Health and DiseaseRecent Progress in Osteomalacia and RicketsA. ROBERT ARNSTEIN, M.D., BOY FRAME, M.D., F.A.C.P., HAROLD M. FROST, M.D.Hypocalcemia — An Unusual Metabolic Complication of Breast CancerGluten-Sensitive Enteropathy with Osteomalacia but without Steatorrhea 1 June 1961Volume 54, Issue 6Page: 1280-1289KeywordsAnemiaCalciumExcretionGastrointestinal tractKidneysLower back painStiffnessUrea Issue Published: 1 June 1961 PDF downloadLoading ...

Renal Tubular Acidosis

In 1946, Albright et al. 1 described the disorder of acidosis resulting from tubular insufficiency without glomerular insufficiency. Since then a number of reports and reviews of this condition have appeared under a variety of titles, such as renal acidosis, renal hyperchloremic acidosis, and renal tubular acidosis. 2-6 The clinical features may be polyuria and polydipsia; the presence of renal calculi, muscular weakness, paralysis, or cramps due to hypokalemia, and bone pains resulting from osteomalacia. The diagnosis depends upon the presence of a systemic acidosis, manifested by a low blood pH, hyperchloremia and a low CO 2 content, and the excretion of a dilute urine that is alkaline or only slightly acid. A striking contrast exists between the degree of systemic acidosis and the high urinary pH. Hypokalemia is usually present. Nephrocalcinosis and osteomalacia are frequently encountered. Theories regarding the etiology and pathogenesis of renal tubular acidosis include infection,

Observations on the pathogenesis of renal tubular acidosis

The responses of five adult patients with renal tubular acidosis to maneuvers designed to elucidate tubular function are compared to the responses of control subjects. After oral administration of ammonium chloride, a greater degree of acidosis developed in the patients with renal tubular acidosis than in the control subjects, they excreted less NH 4 + and HCO 3 − in the urine, and had a smaller drop in urine pH. The failure of HCO 3 − excretion to increase in three of these patients when their serum HCO 3 − levels were raised to normal indicates that diminished tubular HCO 3 − reabsorptive capacity is not the fundamental lesion in the disease. Urinary NH 4 + levels in renal tubular acidosis, although low in relation to the degree of systemic acidosis, proved to be higher than in the urines of equivalent pH of control subjects, suggesting that the capacity for tubular NH 4 + formation is not impaired in renal tubular acidosis. Inability to lower the pH of the urine appropriately is considered to be the primary disorder in renal tubular acidosis, continued HCO 3 − excretion and subnormal ammonia transfer into the urine being secondary phenomena. In spite of the relatively low urinary concentration of free hydrogen ion in renal tubular acidosis the total combined urinary hydrogen (titratable acidity) could be markedly increased by oral or intravenous phosphate loads. Orally administered neutral sodium phosphate (pH 7.4) corrected metabolic acidosis in one patient with renal tubular acidosis by increasing urinary titratable acidity without lowering pH. An adequate explanation for the inability of the patient with renal tubular acidosis to acidify the urine was not provided. Carbonic anhydrase deficiency seems an unlikely possibility because of the demonstrated ability of the patient with renal tubular acidosis to increase HCO 3 − reabsorbtion and titratable acidity.