Renal Tubular Acidosis In Patients Research Articles

Symptomatic renal tubular acidosis (RTA) in patients with systemic lupus erythematosus: an analysis of six cases with new association of type 4 RTA

We have analysed the association between different parameters of renal tubular acidosis (RTA) with clinical and laboratory parameters in patients with systemic lupus erythematosus (SLE). Review of hospital database records between 1978 and 2003 revealed six SLE patients with RTA. Correlations and comparisons were done by Spearman rank correlation coefficient and the chi(2) test. Four patients had hypokalaemia (type 1 RTA) and two patients had hyperkalaemia (type 4 RTA). Three patients with type 1, but no patients with type 4 RTA, had medullary nephrocalcinosis. The majority of SLE patients with distal RTA (type 1 and type 4) had nephritis with proteinuria. No seronegative SLE was noted, and all patients were negative for anticardiolipin antibodies. There was a noticeable trend of higher serum potassium levels with increased SLE Disease Activity Index (SLEDAI; P < 0.1) and nephritic manifestation (haematuria, P < 0.1). The mean SLEDAI scores were 11.75 and 27.5 for type 1 and type 4 RTA patients, respectively. When present in patients with SLE, classic distal RTA (type 1) is the most common. In particular, we report here for the first time two cases of type 4 RTA in SLE patients with higher SLEDAI scores than patients with type 1 RTA. Medullary nephrocalcinosis or renal urolithiasis has not been found in our patients with type 4 RTA. Higher serum potassium levels seem to be associated with higher SLEDAI scores and more severe nephritic manifestations in patients with distal RTA.

Missense mutations in Na+:HCO3−cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis

The kidney Na(+):HCO(3)(-) cotransporter NBC1 is located exclusively on the basolateral membrane of kidney proximal tubule cells and is responsible for the reabsorption of majority of filtered bicarbonate. Two well-described missense mutations in NBC1, R510H and S427L, are associated with renal tubular acidosis (RTA). However, the exact relationship between these mutations and NBC1 dysregulation remains largely unknown. To address this question, cDNAs for wild-type kidney NBC1 and its mutants R510H and S427L were generated, fused in frame with NH(2) terminally tagged GFP, and transiently expressed in Madin-Darby canine kidney cells. In parallel studies, oocytes were injected with the wild-type and mutant NBC1 cRNAs and studied for membrane expression and activity. In monolayer cells grown to polarity, the wild-type GFP-NBC1 was exclusively localized on the basolateral membrane domain. However, GFP-NBC1 mutant R510H was detected predominantly in the cytoplasm. GFP-NBC1 mutant S427L, on the other hand, was detected predominantly on the apical membrane with residual cytoplasmic retention and basolateral membrane labeling. In oocytes injected with the wild-type or mutant GFP-NBC1 cRNAs, Western blot analysis showed that wild-type NBC1 is predominantly localized in the membrane fraction, whereas NBC1-R510H mutant was predominantly expressed in the cytoplasm. NBC1-S427L mutant was mostly expressed in the membrane fraction. Functional analysis of NBC1 activity in oocytes by membrane potential recording demonstrated that compared with wild-type GFP-NBC1, the GFP-NBC1 mutants H510R and S427L exhibited significant reduction in activity. These findings suggest that the permanent isolated proximal RTA in patients with H510R or S427L mutation resulted from a combination of inactivation and mistargeting of kidney NBC1, with H510R mutant predominantly retained in the cytoplasm, whereas S427L mutant is mistargeted to the apical membrane.

Subclinical renal tubular acidosis in patients with primary and secondary Sjögren's syndrome: a possible marker of disease progression

To clarify the prevalence of subclinical renal tubular acidosis (RTA) and its association with clinical and laboratory parameters in primary and secondary Sjögren's syndrome (SS), an acid-loading test was conducted. Subclinical RTA was found in 32% of patients with SS. The prevalence of subclinical RTA in primary and secondary SS was about the same (31.6% and 33.3%, respectively). Significant longer duration of illness, more severely decreased salivary excretion, decreased lymphocyte number, higher serum levels of IgG and IgA, and higher frequency of anti-SS-A (Ro) and SS-B (La) antibodies were found in patients with subclinical RTA. These results suggested that subclinical RTA may be a characteristic manifestation both in primary and secondary SS, along with the progression of immunologic dysfunction, when the illness seemed to be indolent.

Subclinical renal tubular acidosis in patients with primary and secondary Sjögren's syndrome: a possible marker of disease progression

To clarify the prevalence of subclinical renal tubular acidosis (RTA) and its association with clinical and laboratory parameters in primary and secondary Sjögren's syndrome (SS), an acid-loading test was conducted. Subclinical RTA was found in 32% of patients with SS. The prevalence of subclinical RTA in primary and secondary SS was about the same (31.6% and 33.3%, respectively). Significant longer duration of illness, more severely decreased salivary excretion, decreased lymphocyte number, higher serum levels of IgG and IgA, and higher frequency of anti-SS-A (Ro) and SS-B (La) antibodies were found in patients with subclinical RTA. These results suggested that subclinical RTA may be a characteristic manifestation both in primary and secondary SS, along with the progression of immunologic dysfunction, when the illness seemed to be indolent.

Bone mineral density and histology in distal renal tubular acidosis

Chronic metabolic acidosis in distal renal tubular acidosis (RTA) has been implicated in the pathogenesis of enhanced bone resorption and osteopenia, resulting in a loss of bone mineral content. However, histomorphometric and bone densitometric studies of patients who suffered from long-standing distal RTA have rarely been done. A cross-sectional study to determine the alterations of bone mineral density (BMD) and histology was done in 14 nonazotemic RTA patients (11 females and 3 males) who had never received alkaline therapy before enrolling into this study. The mean age was 32.7 +/- 11.9 years. BMD measurements and transiliac bone biopsy were done in all patients. Blood chemistries, intact parathyroid hormone level, and a 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, and potassium were obtained from the RTA patients at the time of bone biopsy. Data from 28 age-, sex-, and body mass index-matched, normal controls who were residents in the same area were also obtained. Urinary excretion of calcium was 2.05 +/- 1.59 mmol/day. No patient had hypercalciuria. The serum intact parathyroid hormone level was 15.92 +/- 8.48 pg/mL. RTA patients had lower BMD in most areas when compared with normal controls. There were two patients who suffered from a pathologic fracture at the femur. Bone histomorphometry from RTA patients shows a significantly decreased bone formation rate (0.02 +/- 0.02 vs. 0.07 +/- 0.045 microm(3)/microm(2)/day, P < 0.05), not significantly decreased osteoblastic surface (0.78 +/- 1.03% vs. 2.6 +/- 1.1%) and osteoclastic surface (0.05 +/- 0.03 vs. 0.13 +/- 0.23%), but significantly increased osteoid surface (31.47 +/- 24.52 vs. 5.79 +/- 4.39%, P < 0.05) and osteoid volume (2.95 +/- 3.09 vs. 0.92 +/- 1.05%, P < 0.05) when compared with those of normal controls. There was no difference in osteoid thickness (10.65 +/- 6.10 vs. 8.69 +/- 2.14 microm). Only one distal RTA patient who had a marked increase in osteoid thickness justified the diagnosis of osteomalacia. This study demonstrates that low bone mass is common in distal RTA patients. Chronic metabolic acidosis results in suppression of bone formation and resorption, which in turn may contribute to the development of low bone mass in distal RTA patients. Although minor elevations in osteoid surface and osteoid volume are found among distal RTA patients, overt osteomalacia is not the predominant bone lesion.

Prevalence and characterization of renal tubular acidosis in patients with osteopenia and osteoporosis and in non-porotic controls.

Chronic metabolic acidosis may increase alkali mobilization from the bone and thus promote the development of osteoporosis. The objective of the current study was to compare urinary acidification in patients with reduced bone mineral content with that in control subjects with normal bone density. Forty-six subjects (41 females, 5 males) with osteopenia or osteoporosis were studied. In none of the subjects were overt metabolic acidosis, derangement of potassium homeostasis, or renal insufficiency present. Distal tubular acidification was studied by means of oral ammonium chloride loading test (0.1 g/kg body weight) and the oral frusemide test (40 mg). In addition the frusemide test was performed in 20 healthy age- and sex-matched controls (17 females, 3 males). In all control subjects a urinary pH <5. 5 was observed following the ingestion of 40 mg frusemide. In contrast, in patients with reduced bone mineral density incomplete renal tubular acidosis type I (RTA I) was diagnosed in 10 of 46 subjects (22%) by oral ammonium chloride loading test. Disorders possibly related to RTA I were detected in eight of these 10 patients. Thirty-six patients had a normal urinary pH response following oral ammonium chloride loading. Oral frusemide, 40 mg, failed to lower urinary pH <5.5 in sixteen patients (35%), these included 10 subjects with incomplete RTA I, and six subjects with a normal oral ammonium chloride loading test. An abnormal frusemide test was found in 35% of patients with reduced bone mass and in none of the normal controls (chi(2)=7.39; P<0.01). With the ammonium chloride test as the gold standard for diagnosis of distal RTA, the frusemide test showed a sensitivity of 1.0 (95% CI, 0.69-1.0) and a specificity of 0.89 (95% CI, 0.78-0.96) for the diagnosis of distal RTA. Patients with incomplete RTA I were younger than those without incomplete RTA I (42+/-16 vs 54+/-14 years; P=0.025; mean+/-SD). Basal serum bicarbonate concentrations and capillary pH did not differ between the groups. Incomplete RTA I may be prevalent in a significant proportion of patients suffering from osteopenia or osteoporosis. The outcome of the frusemide test suggests either a defect of the H(+)ATPase in the cortical collecting tubule (CCT) or a defective Na(+) reabsorption in the CCT. Prospective studies are needed to further elucidate the impact of incomplete RTA I on the development of reduced bone mineral content.

Mechanism of amphotericin B stimulation of net calcium efflux from neonatal mouse calvariae

Amphotericin B is a polyene antifungal agent that binds to membrane sterols, creating aqueous pores that permit ion fluxes sufficient to cause cell lysis. It has also been shown to alter ion transport in mammalian cells, including proton secretion from renal tubular cells. The latter effect can lead to distal renal tubular acidosis in patients treated for systemic fungal infections. Based on the understanding that osteoclast-mediated bone resorption is dependent on proton secretion, we examined the effect of amphotericin B on calcium efflux from neonatal mouse calvariae in organ culture. Amphotericin B (5 micrograms/ml) stimulated net calcium efflux from calvariae within 24 h to a level almost as great as that produced by a maximally effective concentration of parathyroid hormone. The stimulated calcium efflux was completely inhibited by both 10 ng/ml salmon calcitonin, a physiologic inhibitor of osteoclast activity, and 4 x 10(-4) M acetazolamide, a specific inhibitor of carbonic anhydrase, the enzyme necessary for substantial proton generation by osteoclasts. These results indicate a direct effect of amphotericin B on bone in vitro to stimulate osteoclast-mediated calcium efflux.

シェーグレン症候群に合併した腎尿細管性アシドーシスによる尿路結石症について

We encountered 4 patients with urolithiasis due to renal tubular acidosis (RTA) associated with Sjögren's syndrome. Laboratory results about RTA in 4 patients with Sjögrenhs syndrome were not significantly different from those in patients who suffered from urolithiasis due to RTA without Sjögren's syndrome. The incidence of urolitiasis in these cases was suspected to be higher than that in RTA patients without Sjögren's syndrome, because all 4 patients in this study had urolithiasis. When we examine patients with bilateral and multiple urolithiasis, particularly in middle-aged women, we should bear in mind that RTA and Sjögren's syndrome may exist in the background.