Distal RTA Research Articles

Tiny Tim, Dickens, renal disease, and rickets.

Sir.—It is fitting that Lewis proposes that Charles Dickens' Tiny Tim was afflicted with renal disease,1since a number of Dickensian characters have autobiographical attributes. Charles Dickens was reported to suffer much of his life from renal colic and may have died of kidney failure.2The fact that he had strokes at a relatively young age suggests he also may have had the attendant hypertension of chronic renal failure. In addition, John Dickens, Charles' father, suffered from a form of kidney disease since his death was related to the removal of a bladder stone.2 Lewis speculates that Tiny Tim could have had distal RTA type 1, citing Dickens' descriptions of Tim's symptoms and considering the potential treatability of such an illness in 19th-century England. Other writers have suggested that poor Tim may have suffered from polio, tuberculosis of the hip, or pseudocoxalgia.3While it is

遠位型尿細管アシドーシスに骨軟化症を来した一症例

Osteomalacia is caused by distal renal tubular acidosis (distal RTA). And, secondary distal RTA is attended with autoimmunodisease. Recently, a lot of reports suggest that autoimmunodisease should be accompanied with HTLV-I infection. We report one case, a patient with Sjogren syndrome, distal RTA, osteomalacia, and positive HTLV-I antibody. We suggest sequence of these events.

Pathogenesis of distal renal tubular acidosis (incomplete form) in cirrhosis: Normal urinary Pco2 after bicarbonate loading

In liver cirrhosis, an associated defect in urinary acidification is well known but its pathophysiologic nature is not well defined. Recent studies suggest that the urine Pco2 during maximal alkalinization of the urine is an adequate index of distal hydrogen ion secretion. To evaluate the nature of distal renal tubular acidosis (distal RTA) in cirrhosis, the urine minus blood Pco2 gradient [(U – B)Pco2] in alkaline urine was determined in four patients with cirrhosis and distal RTA, and compared with that in four patients without distal RTA (control subjects), as well as with that in one patient with Sjögren's syndrome and distal RTA (subject with impaired distal acidification). As expected, the (U – B)Pco2 after sodium bicarbonate loading was low (10.6 mmHg) in the subjects with impaired distal acidification and normal (32.5 mmHg, s.e.m. = 4.8) in control subjects. By contrast, all four patients with cirrhosis and distal RTA were able to achieve a normal (U – B)Pco2 gradient (33.8 mmHg, s.e.m. = 4.0) after sodium bicarbonate loading, even in the presence of the defect in urinary acidification under acid loading. These results suggest that the pathophysiology of the urinary acidification defect in liver cirrhosis is distinct from that in ordinary distal RTA; the latter signifies a defect in H+ secretion (secretory or voltage‐dependent RTA), whereas, in cirrhosis, an increased permeability for H+ may cause the inability to acidify the urine.

Canine Distal Renal Tubular Acidosis and Urolithiasis

Distal RTA is characterized by decreased distal renal tubular hydrogen ion secretion, decreased ability to acidify urine, hypercalciuria, hyperphosphaturia, hypocitraturia, and metabolic acidosis. Because of the resulting alterations in urine composition and pH, patients with distal RTA are predisposed to urolithiasis and renal calcification. Diagnosis of distal RTA is important because it is a potentially reversible disorder that, left untreated, may cause nephrocalcinosis, recurrent urolith formation, moderate to severe metabolic acidosis, and renal failure.

Relation between urinary bicarbonate concentration and carbon dioxide tension in patients with proximal or distal renal tubular acidosis.

UEDA, H. Relation between Urinary Bicarbonate Concentration and Carbon Dioxide Tension in Patients with Proximal or Distal Renal Tubular Acidosis. Tohoku J. exp. Med., 1981, 133 (1), 21-32 The relation of urinary bicarbonate concentration (UHCO3-) to the difference between urinary pCO2 and arterial blood pCO2 (U-BpCO2) has not yet been clearly elucidated either in normal subjects or in patients with distal renal tubular acidosis (distal RTA). Nor are there any reports dealing with the relation between UHCO3- and U-BpCO2 in patients with hypokalemia or with proximal renal tubular acidosis (proximal RTA). In the present study, with the objective of analyzing the differences in the production of urinary pCO2 in different groups of patients with hypokalemia, those with distal RTA and those with proximal RTA, we loaded these patients and control subjects with sodium bicarbonate, and studied the changes in the relations between UHCO3- and U-BpCO2. The following results were obtained: (1) (a) When UHCO3- was higher than 130mEq/liter: Normal subjects had a positive correlation between UHCO3- and U-BpCO2 (p 0.7). In the patients with distal RTA, U-BpCO2 was lower than that in the control (p<0.005). (2) In the patients with hypokalemia, after the loading of potassium chloride, U-BpCO2 tended to rise compared on the same level of UHCO3-. (3) In the control subjects loaded with a large dose of phosphate, the values of U-BpCO2 compared on the same levelof UHCO3- were not distinctive compared with those in other control subjects, when UHCO3- was over 130mEq/liter. These results suggest that in the patient with proximal RTA, an increase in bicarbonate load in the distal tubule is likely to augment the formation of carbonic acid, raising the value of U-BpCO2. The fact that in the patients with distal RTA U-BpCO2 was lower than that in the control subjects seems to be attributed not only to the low value of UHCO3- due to potassium deficiency but also to the impairment of secretion of hydrogen ion in the distal tubule.

Distal renal tubular acidosis in children with chronic hydronephrosis

The difference between the PCO2 of alkalinized urine and the PCO2 of blood has been proposed as an indirect means of assessing distal nephron H+ secretion. Following oral bicarbonate loading and alkalinization of the urine to pH greater than or equal to 7.2, eight of nine children with chronic hydronephrosis and four children with idiopathic distal RTA had low (U-B)PCO2 values when compared with seven normal subjects. This findings leads us to conclude that chronic hydronephrosis may cause a form of distal RTA which persists many years after surgical diversion procedures have been carried out.

Persistent and Transient Distal Renal Tubular Acidosis with Bicarbonate Wasting

Bicarbonate titration studies were performed on two patients with bicarbonate wasting distal renal tubular acidosis (RTA; patients 1 and 2) and on three patients (3,4, and 5) with classic distal RTA. Daily requirements of alkali were 4.5 mEq/kg body wt in patient 1, a 3-year-old boy, and 16 mEq/kg in patient 2, a 5-month-old male infant. In contrast, only 1.5-2 mEq/kg/24 hr alkali were required in the three patients with classic distal RTA (age 8 1/2- 22 years). Patient 1 had glucose-6-phosphate dehydrogenase deficiency and patient 3 had inner ear deafness as an associated anomaly. In patient 2, the acidification defect was transient. Mean fractional excretion of bicarbonate (ChCO3-/Cin) times 100 at a plasma concentration of HCO3 below 20 mmol/liter was 5.1% in patient 1, 11.6% in patient 2, and 1.7% in patients 3-5. Minimal urine pH during the study was 7.38 in patient 1, 7.66 in patient 2, and 6.78-6.97 in the other patients. Values of net acid excretion at plasma HCO3 = 16 mmol/liter were strongly negative in patients 1 and 2 (-75 and -195 mumol/100 ml glomerular filtrate (GF), respectively) but slightly positive in the three patients with classic RTA (+3 to +20 mumol/100 ml GF). The two patients with bicarbonate wasting distal RTA were thus clearly separated from the group of patients with classic distal RTA.

Distal renal tubular acidosis in infancy: A bicarbonate wasting state

Three unrelated infants with apparently distal RTA were investigated. Growth retardation, polyuria, nephrocalcinosis, inappropriately high urinary pH, and marked dependence of bicarbonate excretion on urinary flow were characteristic of the distal or classic form of RTA, but the urinary loss of bicarbonate at normal serum values exceeded that usually found in children or adults with this disorder. Renal tubular function was studied during hypotonic saline diuresis in the three patients and in seven healthy control infants of similar age. Fractional delivery of sodium to the distal nephron was significantly higher in the patients than in control subjects. Sodium transport at the diluting segment was not impaired. The results support the assumption that the bicarbonate wasting was the consequence of an increased delivery of this substance to an already impaired distal nephron and thus further inhibited the distal mechanisms of net acid excretion.

Diagnosis and therapy of renal tubular acidosis in infancy

While distrubances of the acid-base balance are frequently seen in infancy, renal tubular acidosis is a rather rare disease but should be considered as differential diagnosis if metabolic acidosis persists after adequate treatment. Proximal and distal tubular acidosis with primary and secondary forms can be differentiated. Proximal RTA is characterized by the loss of bicarbonate, distal RTA by a defect to establish a hydrogen ion gradient and thus to accomplish acidification of urine. In addition to these two basic forms a bicarbonate wasting state in distal RTA has been described. A patient with these clinical features is presented. He was admitted to our hospital at the age of 1 month with meningitis, enteritis and marked dystrophy. A persistant hyperchloraemic acidosis with concomitant hypokalaemia was present. The ammonium chloride loading test confirmed the diagnosis of primary distal RTA. Renal biopsy performed with 1 year of age revealed nephrocalcinosis of the inner medullary region of the kidney while the cortex was not affected. The patient first needed alkali doses of 12 mEq/kg/day which could be gradually reduced to 3.5 mEq/kg/day. Under additional potassium substitution of 5 mEq/kg/day he was thriving well. Differential diagnosis and the particular clinical features of this case are discussed.

Renal excretion of ammonium in renal tubular acidosis.

In 10 patients with distal renal tubular acidosis (distal RTA), 8 with multiple tubular dysfunction, and 15 with primary hyperparathyroidism including 8 of skeletal syndrome, the rates of ammonium excretion without the influence of any medications were determined in respective specimens of 24-hour urine. In the majority of the patients with either distal RTA, multiple tubular dysfunction, or skeletal syndrome of primary hyperparathyroidism, the rates of ammonium excretion corrected for creatinine clearance were significantly higher than conceivable in reference to the urinary pH levels. The rates of increase in ammonium excretion tended to be higher in the cases with than in those without metabolic acidosis and/or hypokalemia. Metabolic acidosis attributable to RTA was observed in all cases with skeletal syndrome but in none without this syndrome among the patients with primary hyperparathyroidism. It is concluded that in the patients with RTA, proximal and distal alike, urinary excretion of ammonium is generally increased. This may well be attributed to the increased renal ammonium production in response to acidosis and/or potassium deficiency. The greater secretion of parathyroid hormone in cases with skeletal syndrome than in cases with other syndromes of primary hyperparathyroidism is regarded accounting for the higher incidence of RTA in the former than in the latter.ammonium excretion; renal tubular acidosis; hyperparathyroidism