Proximal renal tubular dysfunction in primary distal renal tubular acidosis

Low-molecular-weight (LMW) proteinuria has been described in patients with primary distal renal tubular acidosis (dRTA). However, other proximal renal tubular dysfunctions have rarely been reported. In this report we describe reversible and multiple proximal renal tubular cell dysfunctions in a patient with dRTA. A 4-year-old girl was admitted to our hospital for investigation of short stature and proteinuria. Laboratory studies revealed a hyperchloremic metabolic acidosis without aciduria, hypokalemia, hypouricemia with uricosuria, hypercalciuria, LMW proteinuria, phosphaturia, and generalized aminoaciduria. The patient was diagnosed as having dRTA with multiple proximal renal tubular dysfunctions. All proximal renal tubular dysfunction subsided 1.5 years after starting alkali therapy. The precise pathogenic mechanisms underlying the development of multiple proximal renal tubular dysfunctions in dRTA remained unclear. However, proximal renal tubular endosomal dysfunction resulting from a profound intracellular acidosis caused by vacuolar H⁺-ATPase dysfunction or hypokalemic nephropathy might contribute to the development of proximal renal tubular dysfunctions in patients with dRTA.     

Screening renal stone formers for distal renal tubular acidosis

A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted; 13 had incomplete and 1 had complete distal RTA. Distal RTA was found particularly in recurrent stone formers (17%), and especially in those with bilateral stone disease, where a distal renal tubular acidification defect was found in 50%. We have been unable to differentiate primary from secondary RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use in daily clinical practice, is applied to all stone formers and not restricted to patients with recurrent stone disease.     

Experimental models of distal renal tubular acidosis

A number of potential defects may impair acidification either directly or indirectly in the CCT, the OMCT, the IMCD, or in all segments. These defects are summarized in Table 1. Findings from studies in animal models of DRTA have enhanced out understanding of the pathophysiological basis of these disorders. Nevertheless, considerable effort needs to be directed in the future toward defining the cellular basis of these defects, especially in the inherited forms of classical hypokalemic DRTA, for which an adequate experimental model does not yet exist.     

Secondary erythrocytosis associated with distal renal tubular acidosis

AIMS: Diagnosis and classification of renal tubular acidosis (RTA) have traditionally been made on the basis of functional studies. Despite recent expanding knowledge about the molecular abnormalities involved in renal bicarbonate (HCO3-) and H+ transport, the pathophysiology of secondary erythrocytosis in association with distal RTA remains obscure. CASE HISTORY: A 2-month-old boy with severe hyperchloremic metabolic acidosis with positive urine anion gap was diagnosed with distal RTA. Replacement therapy with sodium bicarbonate and potassium citrate succeeded in improving his metabolic acidosis and growth. His renal function remained normal. He had persistent erythrocytosis. CONCLUSION: Secondary erythrocytosis is a rarely reported association of distal RTA. It may increase the risk of thromboembolism.     

Inherited renal tubular dysgenesis may not be universally fatal

Inherited renal tubular dysgenesis (RTD) is caused by mutations in the genes encoding components of the renin-angiotensin cascade: angiotensinogen, renin, angiotensin-converting enzyme (ACE), and angiotensin ΙΙ receptor type 1. It is characterized by oligohydramnios, prematurity, hypotension, hypocalvaria, and neonatal renal failure. The histological hallmark is the absence or poor development of renal proximal tubules. Except for a few cases, the prognosis has been thought to be universally poor, with patients dying either in utero or shortly after birth. We report a 3-year-old infant diagnosed clinically with RTD. The infant survived the neonatal period after 2 weeks of anuria subsequently subsiding. Hypotension and hyperkalemia normalized eventually with administration of fludrocortisone. A revision of renal tissue obtained from a sibling that died shortly after birth revealed normal glomeruli and distal tubules but no identifiable proximal tubules. A novel mutation in the ACE gene was found in the surviving child, who remains with stage 4 chronic kidney disease and normal neurodevelopment. As the number of surviving cases of RTD increases, it should be emphasized to the parents and the neonatal care team that it may not be universally fatal as previously reported. A trial of fludrocortisone may correct hyperkalemia and hypotension.     

On the mechanism of toluene-induced renal tubular acidosis

This study was aimed to investigate the pathogenesis of toluene-induced renal tubular acidosis (RTA). In 5 individuals addicted to toluene sniffing we documented the occurrence of hypokalemia and hyperchloremic metabolic acidosis associated with inability to lower urine pH below 5.5 (6.06 +/- 0.24). Overall kidney bicarbonate reabsorption was normal or enhanced, a feature characteristic of the distal form of RTA (DRTA). These findings resemble those found during the administration of amphotericin B, a drug felt to cause DRTA by increasing hydrogen ion (H+) back-diffusion in the collecting tubule. In toluene sniffers, the urine pCO2 measured in a highly alkaline urine was reduced (47 +/- 8.8 mm Hg), suggesting a decrease in the rate of collecting tubule H+ secretion rather than H+ back-diffusion. To investigate these two mechanisms of altered distal acidification more directly we studied the effect of toluene on acidification by the urinary turtle bladder, an epithelial analogue of the mammalian collecting tubule. In this preparation, toluene resulted in a decrease in the rate of H+ secretion measured by either the pH stat technique or the reverse short circuit current. When mucosal pH was progressively lowered to examine H+ secretion against an H+ gradient, toluene-treated bladders displayed a significant decrease in proton conductance but the lowest mucosal pH required to nullify H+ secretion, (MpH) JH = O, was not different from that of control bladders (4.05 +/- 0.29 and 3.90 +/- 0.13, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal tubular acidosis in recurrent renal stone formers

Renal tubular acidosis (RTA) is a well-known metabolic disturbance that may promote recurrent renal stone formation. However, its incidence, screening criteria and association with other lithogenic metabolic abnormalities are not established in recurrent nephrolithiasis. 10 of 50 consecutive recurrent renal stone formers had a persistent fasting morning urinary pH above 6.0 and/or a basal plasma bicarbonate concentration below 20.0 mM. Acid and alkaline loads disclosed RTA in 3 patients: 1 patient had incomplete type-1 distal RTA in addition to hyperoxaluria; a second patient showed complete type-2 proximal RTA, hyperoxaluria and renal hypercaliuria; and a third patient had incomplete proximal RTA without any other metabolic derangement. These results reinforce the importance of RTA as an isolated metabolic abnormality among recurrent renal stone formers. In addition, RTA appears to be more commonly associated with other lithogenic metabolic derangements than has been previously suspected. The extensive metabolic protocol used in this study provides a useful tool in the diagnosis and therapeutic considerations of recurrent nephrolithiasis.     

Familial hypophosphatemic rickets with proximal renal tubular acidosis

We have experienced 3 case of familial hypophosphatemic rickets with proximal renal tubular acidosis. Consisting of a family of 2 years old girl, 7 months old girl baby and their father aged 42 years. Roentgenological studies, biochemical tests on blood and renal function tests revealed hypophosphatemia in all these patients. Metabolic acidosis was found only in the 2 girls. Distal renal tubular acidosis was not found to be responsible for the metabolic disorder according to the sodium bicarbonate (NaHCO₃), and ammonium chloride (NH₄cl) load testing. No glycosuria, proteinuria and panaminoaciduris were detected, so that Fanconi's syndrome was ruled out and the diagnosis of hypophosphatemia was made. Based on these 3 cases, future status of untreated patients with this disease could be predicted. The course of this disease can be divided into 3 stages, infant, childfood and adult period.