Primary Renal Tubular Acidosis Research Articles

Primary Renal Tubular Acidosis during pregnancy, what about the perinatal prognosis?

Primary Renal Tubular Acidosis during pregnancy, what about the perinatal prognosis?

A review of renal tubular acidosis.

To review the current scientific literature on renal tubular acidosis (RTA) in people and small animals, focusing on diseases in veterinary medicine that result in secondary RTA. Scientific reviews and original research publications on people and small animals focusing on RTA. RTA is characterized by defective renal acid-base regulation that results in normal anion gap hyperchloremic metabolic acidosis. Renal acid-base regulation includes the reabsorption and regeneration of bicarbonate in the renal proximal tubule and collecting ducts and the process of ammoniagenesis. RTA occurs as a primary genetic disorder or secondary to disease conditions. Based on pathophysiology, RTA is classified as distal or type 1 RTA, proximal or type 2 RTA, type 3 RTA or carbonic anhydrase II mutation, and type 4 or hyperkalemic RTA. Fanconi syndrome comprises proximal RTA with additional defects in proximal tubular function. Extensive research elucidating the genetic basis of RTA in people exists. RTA is a genetic disorder in the Basenji breed of dogs, where the mutation is known. Secondary RTA in human and veterinary medicine is the sequela of diseases that include immune-mediated, toxic, and infectious causes. Diagnosis and characterization of RTA include the measurement of urine pH and the evaluation of renal handling of substances that should affect acid or bicarbonate excretion. Commonality exists between human and veterinary medicine among the types of RTA. Many genetic defects causing primary RTA are identified in people, but those in companion animals other than in the Basenji are unknown. Critically ill veterinary patients are often admitted to the ICU for diseases associated with secondary RTA, or they may develop RTA while hospitalized. Recognition and treatment of RTA may reverse tubular dysfunction and promote recovery by correcting metabolic acidosis.

Demographic, Clinical, and Laboratory Characteristics of Children with Renal Tubular Acidosis

This study included patients followed up for primary renal tubular acidosis (RTA) between 1991 and 2012. Clinical characteristics at presentation, physical examination findings, laboratory test results, and treatments were recorded. The patients’ laboratory results, drug doses, height, and weight were recorded every 3 months for the first year of follow-up. Standard deviation scores (Z-scores) of height and weight for age were determined and the patients’ growth rates were evaluated. Of 50 patients followed up for primary RTA, 31 (62%) had distal RTA and 19 (38%) had proximal RTA. The median age at diagnosis was 3 months (range, 1-174 months) for patients with distal RTA and 10 months (range, 2-33 months) for patients with proximal RTA. The median follow-up times in these two groups were 96 months (range, 6-204 months) and 89 months (range, 6-180 months), respectively. Family history of RTA was more common among patients with distal RTA than those with proximal RTA (p=0.013). Nephrocalcinosis and deafness were detected more frequently in the distal RTA group (p=0.001), while ocular pathologies were more common in the proximal RTA group (p<0.001). In patients with distal RTA, older age at diagnosis was associated with lower weight and height Z-scores (p<0.05). Early diagnosis had a positive effect on the growth of patients with primary RTA.

Renal Tubular Acidosis.

Renal tubular acidosis (RTA) comprises a group of disorders characterized by low capacity for net acid excretion and persistent hyperchloremic metabolic acidosis, despite preserved glomerular filtration rate. RTA are classified into chiefly three types (1, 2 and 4) based on pathophysiology and clinical and laboratory characteristics. Most patients have primary RTA that presents in infancy with polyuria, growth retardation, rickets and/or hypotonia. Diagnosis requires careful evaluation, including exclusion of other entities that can cause acidosis. A variety of tests, administered stepwise, are useful for the diagnosis and characterization of RTA. A genetic or acquired basis can be determined in majority of patients through focused evaluation. Management involves correction of acidosis and dyselectrolytemia; patients with proximal RTA with Fanconi syndrome and rickets require additional supplements of phosphate and vitamin D.

Renal tubular acidosis.

To facilitate the understanding and knowledge of renal tubular acidosis by providing a summarized information on the known clinical and biochemical characteristics of this group of diseases, by updating the genetic and molecular bases of the primary forms renal tubular acidosis and by examining some issues regarding the diagnosis of distal renal tubular acidosis (RTA) in the daily clinical practice. The manuscript presents recent findings on the potential of next-generation sequencing to disclose new pathogenic variants in patients with a clinical diagnosis of primary RTA and negative Sanger sequencing of known genes. The current review emphasizes the importance of measuring urinary ammonium for a correct clinical approach to the patients with metabolic acidosis and discusses the diagnosis of incomplete distal RTA. We briefly update the current information on RTA, put forward the need of additional studies in children to validate urinary indexes used in the diagnosis of RTA and offer a perspective on diagnostic genetic tests.

Approach to the patient with hypokalemia caused by Hashimoto's thyroiditis associated with primary Sjogren's syndrome and renal tubular acidosis

Hypokalemia is a common clinical symptom. It is quite important to clarify the cause of hypokalemia. Autoimmune thyroid disease and primary Sjogren syndrome(pSS)have a common genetic predisposition. The coexistence of both diseases is frequent. Renal tubular acidosis(RTA)is one of the causes of hypokalemia, which can be primary and secondary to other diseases in etiology. Primary RTA is more common in children. As for adults, RTA is often secondary to pSS. In this paper, we reported a case of hypokalemia caused by Hashimoto's thyroiditis associated with primary Sjogren's syndrome and renal tubular acidosis in order to call attention to the special cause and treatment of hypokalemia. (Chin J Endocrinol Metab, 2016, 32: 349-352) Key words: Hypokalemia; Hashimoto's thyroiditis; Primary Sjogren's syndrome; Renal tubular acidosis

Renal Tubular Acidosis

In this article, we discuss the current views on the renal regulation of acid-base metabolism and the diagnostic approach to children with metabolic acidosis, including the major characteristics of the different types of renal tubular acidosis (RTA), focusing on distal RTA (dRTA). We update progress in identifying the underlying defective transporters and gene mutations responsible for the primary forms, suggest candidate genes possibly involved in some cases, discuss the mechanisms causing growth retardation and disordered mineral metabolism, and provide the basis for differential diagnosis with other types of primary RTA.

Primary renal tubular acidosis recognized and treated at three days of age. A case report illustrating the value of routine postmortem examination.

Renal tubular acidosis should be suspected even in the very young in fant who does not thrive, and who demonstrates a hyperchloremic acidosis with urine of neutral pH. This case report details the course of an infant whose disease was diagnosed in the newborn nursery.

Primary renal tubular acidosis and secondary hyperparathyroidism

A thirty-two year old woman with primary renal tubular acidosis, severe nephrocalcinosis and reduced glomerular function had bilateral, symmetric pathologic fractures of the femoral heads secondary to atypical osteitis fibrosa generalisata. There was no evidence of concomitant osteomalacia. The clinical, roentgenographic and pathologic features indicated that the hyperparathyroidism was secondary to the renal tubular acidosis. The course of the skeletal disease was monitored by serial metabolic balance measurements, radiocalcium turnover studies, x-ray examinations and bone biopsies. Almost complete reversal of the metabolic bone disease was achieved after subtotal parathyroidectomy and calcium lactate and vitamin D 2 therapy. Nevertheless, glomerular insufficiency progressed and caused death after a total course of between four and ten years. An awareness of atypical cases of renal tubular acidosis can facilitate early diagnosis and effective management, and improve the prognosis in this unusual condition.

NEPHROLOGY: The natural history of renal tubular acidosis: Lightwood's syndrome revisitied

Twelve children with primary renal tubular acidosis (RTA) studied with HCO3− titration and NH4Cl loading have been observed 1½–8 yrs. These include 7 ♂ with proximal RTA (PRTA) dx'd at 7–18 mos, and 3 ♂ and 2 ♀ with distal RTA dx'd at 3–13 yrs. Bone disease and/or nephrocalcinosis were present in DRTA but not PRTA. GFR (CIN) at onset was normal or slightly decreased in PRTA, but 40–60% of normal in DRTA. GFR is now normal in all patients. With rx pts had accelerated growth, reaching at least the 3rd percentile in 2–3 yrs, with some achieving the 50th percentile. Five with PRTA have normal blood pH and HCO3 off rx, 5–8 yrs after dx. Two remain on rx <2 yrs after dx. The acidification defect in pts with DRTA persists. Thus PRTA appears to be a self-limited disease of bicarbonate reabsorption in male infants, characterized by growth retardation and acidemia, without bone disease and nephrocalcinosis. DRTA appears to be a permanent defect in urinary acidification, with acidemia, growth retardation, bone disease, and nephrocalcinosis. Response to rx in both groups is good, with marked improvement in growth, and normalization of GFR in DRTA despite severe degrees of initial nephrocalcinosis. On the basis of these observations, it seems likely that Light-woods's syndrome was proximal RTA—not distal RTA as has been considered heretofore.

RENAL TUBULAR DYSFUNCTION AND HYPERGAMMAGLOBULINEMIA

Abstract. A report is given on a female patient, 32 years of age, with a history of slight joint distress, recurrent dependent oedema, hypokalaemia, hypergammaglobulinaemia and positive tests for rheumatoid factor. Electrolyte balance studies revealed latent renal tubular acidosis (RTA), impaired renal pH‐regulation and impaired renal conservation of sodium and potassium. Systemic pH was found to be largely dependent on the dietary load of sodium chloride. Correction of the hypokalaemia resulted in frank systemic acidosis, whereas persistent hypokalaemia was associated with alkalosis. The situation thus differed from that found in primary RTA. Electron microscopic and light microscopic studies from a renal biopsy revealed simultaneous signs of tubular and interstitial nephritis and slight glomerular reaction. Immunoglobulin deposits were seen in the tubuli and the glomerular basement membrane by the immunofluorescence method.

Renal tubular acidosis.

Renal tubular acidosis (RTA) is recognized to occur in several forms. Primary proximal RTA presents in infancy, almost exclusively in males, and is the only form of primary RTA that is transient. Distal RTA is encountered in familial and sporadic forms, the latter predominantly in females. A severe form of distal RTA in infancy, recently recognized, may represent still another type of the disease.

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

Metabolic balance studies in primary renal tubular acidosis: Effects of acidosis on external calcium and phosphorus balances

The relationship between acidosis and calcium metabolism was investigated in a 4-year-old child with primary renal tubular acidosis uncomplicated by either skeletal changes or renal insufficiency. The results of metabolic balance studies obtained from an initial period of complete correction of the acidosis through the development of acidosis by cessation of alkali therapy and during the subsequent correction of the acidosis indicate that metabolic acidosis is associated with a negative calcium balance. An altered intestinal transport of calcium was found to be the major factor responsible for the negative calcium balance. Complete correction of the acidosis resulted in restoration of a positive calcium balance. The relationship between acidosis and calcium metabolism was investigated in a 4-year-old child with primary renal tubular acidosis uncomplicated by either skeletal changes or renal insufficiency. The results of metabolic balance studies obtained from an initial period of complete correction of the acidosis through the development of acidosis by cessation of alkali therapy and during the subsequent correction of the acidosis indicate that metabolic acidosis is associated with a negative calcium balance. An altered intestinal transport of calcium was found to be the major factor responsible for the negative calcium balance. Complete correction of the acidosis resulted in restoration of a positive calcium balance.

Studies of muscle cell composition in children with renal tubular dysfunction

Studies on skeletal muscle composition were performed in one child with primary renaltubular acidosis and in two children with the Fanconi syndrome. A low concentration of intracellular potassium was found in each of them. A decreased renal capacity to conserve potassium was demonstrated by adequate challenges (acetazoleamide, nonreabsorbable anion load). The composition of the muscle cell with regard to several intermediates of the glycolytic pathway and citric acid cycle, as well as the related enzyme activities, was also very abnormal in comparison with values obtained in normal subjects. The possible significance of these observations is discussed. Studies on skeletal muscle composition were performed in one child with primary renaltubular acidosis and in two children with the Fanconi syndrome. A low concentration of intracellular potassium was found in each of them. A decreased renal capacity to conserve potassium was demonstrated by adequate challenges (acetazoleamide, nonreabsorbable anion load). The composition of the muscle cell with regard to several intermediates of the glycolytic pathway and citric acid cycle, as well as the related enzyme activities, was also very abnormal in comparison with values obtained in normal subjects. The possible significance of these observations is discussed. ErratumThe Journal of PediatricsVol. 69Issue 3Preview Full-Text PDF

The renal excretion of hydrogen ion in renal tubular acidosis: III. An attempt to detect latent cases in a family; comments on nosology, genetics and etiology of the primary disease

We have presented herein a study of the family of one patient with primary renal tubular acidosis associated with nephrocalcinosis and nephrolithiasis. A genetic factor in the disease in this patient is suggested by the following observations. The patient's father had unilateral nephrocalcinosis, staghorn calculus and hydronephrosis; one brother and three children were found to have mild depression of the serum carbon dioxide level but no other clinical signs or symptoms. Two of these three children were found to show a low or borderline hydrogen ion “clearance” index when loaded with ammonium chloride. The study illustrates the possibility of detecting latent impairment of the ability of the kidney to excrete acid by use of a standardized provocative test assessed by careful criteria. We have reviewed and analyzed 162 cases in the literature of primary renal tubular acidosis, excluding certain syndromes with multifactorial defects (e.g. the Fanconi syndrome, Lowe's syndrome, and some secondary types). The 162 cases appear to fall into at least two disease groups: (1) infantile primary renal tubular acidosis with appearance in the first year of life, a high rate of recovery, and a preponderance of males involved; and (2) late primary renal tubular acidosis appearing after the first year of life and through adult life, showing a low recovery rate and a preponderance of females involved. The disease in the infantile group may be due to a recessive gene or a delay in maturation of renal function due to some other cause; in the late group, the disease may be due to an autosomal dominant gene with fuller expressivity and penetrance in females. Although the underlying biochemical disorder in the disease is not known, some inconclusive data are cited to suggest that it may be in the Krebs citric acid cycle. Some patients in the late group may have acquired the syndrome from pyelonephritis or renal calcific damage of other origins, but the evidence on this question is scanty.