Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model), a significant decrease in renal acid excretion, glomerular filtration rate (GFR) and renal plasma flow (RPF) was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg). Four to 6 days after the induction of diabetes (DM), a group of rats were thyroparathyroidectomized (DM + TPTX). Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA) excretion was unchanged in DM (6.19 ± 0.54), decreased in TPTX (3.76 ± 0.25) and returned to normal levels in DM + TPTX (5.54 ± 0.72) when compared to the control group (6.34 ± 0.14 µmol min-1 kg-1). The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX.

Study of urinary acidification in patients with idiopathic hypocitraturia

Hypocitraturia (HCit) is one of the most remarkable features of renal tubular acidosis, but an acidification defect is not seen in the majority of hypocitraturic patients, whose disease is denoted idiopathic hypocitraturia. In order to assess the integrity of urinary acidification mechanisms in hypocitraturic idiopathic calcium stone formers, we studied two groups of patients, hypocitraturic (HCit, N = 21, 39.5 ± 11.5 years, 11 females and 10 males) and normocitraturic (NCit, N = 23, 40.2 ± 11.7 years, 16 females and 7 males) subjects, during a short ammonium chloride loading test lasting 8 h. During the baseline period HCit patients showed significantly higher levels of titratable acid (TA). After the administration of ammonium chloride, mean urinary pH (3rd to 8th hour) and TA and ammonium excretion did not differ significantly between groups. Conversely, during the first hour mean urinary pH was lower and TA and ammonium excretion was higher in HCit. The enhanced TA excretion by HCit during the baseline period and during the first hour suggests that the phosphate buffer mechanism is activated. The earlier response in ammonium excretion by HCit further supports other evidence that acidification mechanisms react promptly. The present results suggest that in the course of lithiasic disease, hypocitraturia coexists with subtle changes in the excretion of hydrogen ions in basal situations.

Study of caffeine urine and saliva of horses subjected to urinary acidification

The study of caffeine in racing horses has been of growing concern in veterinary sports medicine since the Association of Racing Commissioners International (ARCI) stated that it has no valid therapeutic use in racehorses. We examined the kinetic alterations in the urinary excretion and salivary secretion of caffeine in seven horses subjected to urinary acidification using ascorbic acid because this procedure can simulate the acidosis that follows anaerobic exercise. They participated in two treatment groups: the control group (SG) received 500 ml of saline and then 2.0 mg kg(-1) caffeine i.v. 30 min later; and the acidified group (AG) was subjected to urinary acidification with ascorbic acid at a dose of 0.5 g kg(-1) i.v. and then 2.0. mg kg(-1) caffeine i.v. 30 min later. Samples were collected 30 min before caffeine administration, immediately before caffeine administration (time zero) and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48 and 72 h afterwards. The samples were assayed by gas chromatography. The mean urinary pH for SG was 8.2, but for AG it was as low as 5.9 at 4 h, extending acidosis for up to 8 h. The kinetic curves for the two groups were similar for urinary excretion and salivary secretion. Differences occurred only in peak excretion and peak secretion in SG obtained at 1 h and 30 min, respectively, and in AG at 2 h and 1 h, respectively. This could be explained, in part, to the diuresis in AG compared with SG, resulting in less concentrated urine in the former group. The large difference between the pK(a) of caffeine and the pH of the medium may be responsible for the similar pharmacokinetics observed for the two groups. Copyright (C) 2004 John Wiley Sons, Ltd.

The Vacuolar H+-ATPase B1 Subunit Polymorphism p.E161K Associates with Impaired Urinary Acidification in Recurrent Stone Formers

Mutations in the vacuolar–type H+-ATPase B1 subunit gene ATP6V1B1 cause autosomal–recessive distal renal tubular acidosis (dRTA). We previously identified a single-nucleotide polymorphism (SNP) in the human B1 subunit (c.481G.A; p.E161K) that causes greatly diminished pump function in vitro. To investigate the effect of this SNP on urinary acidification, we conducted a genotype-phenotype analysis of recurrent stone formers in theDallas and Bern kidney stone registries. Of 555 patients examined, 32 (5.8%) were heterozygous for the p.E161K SNP, and the remaining 523 (94.2%) carried two wild–type alleles. After adjustment for sex, age, body mass index, and dietary acid and alkali intake, p.E161K SNP carriers had a nonsignificant tendency to higher urinary pH on a random diet (6.31 versus 6.09; P=0.09). Under an instructed low–Ca and low–Na diet, urinary pH was higher in p.E161K SNP carriers (6.56 versus 6.01; P,0.01). Kidney stones of p.E161K carriers were more likely to contain calcium phosphate than stones of wild-type patients. In acute NH4Cl loading, p.E161K carriers displayed a higher trough urinary pH (5.34 versus 4.89; P=0.01) than wild-type patients. Overall, 14.6% of wild-type patients and 52.4% of p.E161K carriers were unable to acidify their urine below pH 5.3 and thus, can be considered to have incomplete dRTA. In summary, our data indicate that recurrent stone formers with the vacuolar H+-ATPase B1 subunit p.E161K SNP exhibit a urinary acidification deficit with an increased prevalence of calcium phosphate– containing kidney stones. The burden of E161K heterozygosity may be a forme fruste of dRTA.

Metabolic assessment in patients with urinary lithiasis

INTRODUCTION: Metabolic investigation in patients with urinary lithiasis is very important for preventing recurrence of disease. The objective of this work was to diagnose and to determine the prevalence of metabolic disorders, to assess the quality of the water consumed and volume of diuresis as potential risk factors for this pathology. PATIENTS and METHODS: We studied 182 patients older than 12 years. We included patients with history and/or imaging tests confirming at least 2 stones, with creatinine clearance > 60 mL/min and negative urine culture. The protocol consisted in the collection of 2, 24-hour urine samples, for dosing Ca, P, uric acid, Na, K, Mg, Ox and Ci, glycemia and serum levels of Ca, P, Uric acid, Na, K, Cl, Mg, U and Cr, urinary pH and urinary acidification test. RESULTS: 158 patients fulfilled the inclusion criteria. Among these, 151 (95.5%) presented metabolic changes, with 94 (62.2%) presenting isolated metabolic change and 57 (37.8%) had mixed changes. The main disorders detected were hypercalciuria (74%), hypocitraturia (37.3%), hyperoxaluria (24.1%), hypomagnesuria (21%), hyperuricosuria (20.2%), primary hyperparathyroidism (1.8%) secondary hyperparathyroidism (0.6%) and renal tubular acidosis (0.6). CONCLUSION: Metabolic change was diagnosed in 95.5% of patients. These results warrant the metabolic study and follow-up in patients with recurrent lithiasis in order to decrease the recurrence rate through specific treatments, modification in alimentary and behavioral habits.

An update on metabolic assessment in patients with urinary lithiasis

The objective of this study was to evaluate the prevalence of urinary metabolic abnormalities in patients with urolithiasis and their potential risk factors.A total of 905 stone patients were evaluated in a prospective trial from February 2000 to January 2012. Inclusion criteria were as follows: history and/or imaging tests confirming at least 2 separate or concurrent stone episodes; creatinine clearance a parts per thousand yen60 mL/min; and negative proteinuria and urine culture. Metabolic study consisted of two 24-h urine collections separated by a period of 3 months for dosing Ca, P, uric acid, Na, K, Mg, oxalate, and citrate. Serum levels of Ca, P, uric acid, Na, K, Cl, Mg, creatinine, and glucose were assessed. Urinary pH and urinary acidification tests were also performed.A total of 735 patients were included, with a mean age of the 40 +/- A 1.0 year; 96.8 % of patients presented diagnosis of one or more urinary metabolic abnormalities. The most prevalent metabolic abnormalities were hypercalciuria (50.8 %), hypomagnesuria (50.1 %), hypocitraturia (35.4 %), and hyperuricosuria (30.7 %). Body weight was significantly higher in patients with hyperuricosuria (81.20 +/- A 15.67 kg vs. 70.17 +/- A 14.13 kg, respectively, p = 0.001). Urinary sodium was significantly higher in patients with hypercalciuria than without (246.97 +/- A 103.9 mEq/24 h vs. 200.31 +/- A 91.6 mEq/24 h, p = 0.001) and hyperuricosuria compared to without (283.24 +/- A 107.95 mEq/24 h vs. 198.57 +/- A 85.3 mEq/24 h, p = 0.001).Urinary metabolic disturbances were diagnosed in 96.8 % of patients in the study. These results warrant metabolic study and follow-up in patients with recurrent lithiasis in order to decrease recurrence rate through specific treatments, modification in alimentary, and behavioral habits.

Evaluation of renal function in leprosy: a study of 59 consecutive patients

Background. Renal abnormalities in leprosy have been largely described in medical literature, but there are few studies evaluating renal function in these patients. Methods. This is a cross-sectional study in 59 consecutive paucibacillary (PB) and multibacillary (MB) leprosy patients. Glomerular filtration rate (GFR) was estimated by simplified-MDRD formula. Microalbuminuria was determined by 24 h urine collection. Urinary acidification capacity was measured after water deprivation and acid-loading with CaCl2. Urinary concentration capacity was evaluated after desmopressin acetate administration, using the urinary to plasma osmolality (U/P-osm) ratio. All parameters except microalbuminuria were measured in a control group of 18 healthy volunteers. Results. Age and gender were similar between leprosy (MB or PB) and control groups. GFR <= 80 ml/min/1.73 m(2) was observed in 50% of the leprosy patients. GFR and U/P-osm in leprosy patients were significantly lower than in controls (P < 0.001). Urinary acidification defect was found in 32% of PB and in 29% of MB patients and urinary concentrating ability was abnormal in 83% of PB and 85% of MB patients. Microalbuminuria was found in 4 patients (8.5%), leukocyturia was found in 13 (22%) and haematuria was present in 16 patients (27%). Plasma creatinine (P-cr) > 1.2 mg/dl was observed in 17.9% of MB patients and in none of the controls (P = 0.020). A negative correlation was observed between GFR and time of treatment (r = -0.339; P = 0.002). Age and time of treatment were independent risk factors for GFR <= 80 ml/min/1.73 m(2) in multivariate analysis. Conclusions. Asymptomatic GFR changes and renal tubular dysfunction, including urine concentration defect and impaired acidifying mechanisms, can be caused by leprosy on specific treatment and without any reaction episodes.

Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

The activity of the Na(+)/H(+) exchanger NHE3 is regulated by a number of factors including parathyroid hormone (PTH). In the current study, we used a renal epithelial cell line, the opossum kidney (OKP) cell, to elucidate the mechanisms underlying the long-term effects of PTH on NHE3 transport activity and expression. We observed that NHE3 activity was reduced 6 h after addition of PTH, and this reduction persisted almost unaltered after 24 h. The decrease in activity was associated with diminished NHE3 cell surface expression at 6, 16, and 24 h after PTH addition, total cellular NHE3 protein at 16 and 24 h, and NHE3 mRNA abundance at 24 h. The lower levels of NHE3 mRNA were associated to a small, but significant, decrease in mRNA stability. Additionally, by analyzing the rat NHE3 gene promoter activity in OKP cells, we verified that the regulatory region spanning the segment -152 to +55 was mildly reduced under the influence of PTH. This effect was completely abolished by the presence of the PKA inhibitor KT 5720. In conclusion, long-term exposure to PTH results in reduction of NHE3 mRNA levels due to a PKA-dependent inhibitory effect on the NHE3 promoter and a small reduction of mRNA half-life, and decrease in the total amount of protein which is preceded by endocytosis of the apical surface NHE3. The decreased NHE3 expression is likely to be responsible for the reduction of sodium, bicarbonate, and fluid reabsorption in the proximal tubule consistently perceived in experimental models of PTH disorders.

Cytotoxicity and Regenerative Proliferation as the Mode of Action for Diuron-Induced Urothelial Carcinogenesis in the Rat

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da acidificação urinária em ovinos com a utilização de três tratamentos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da sobrecarga calórica em ratos machos submetidos ou não a restrição protéica in útero

Pós-graduação em Biologia Geral e Aplicada - IBB

Efeito da suplementação de cloreto de amônio sobre os equilíbrios eletrolítico e ácido-básico e o pH urinário de ovinos confinados

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação clínica, laboratorial e anatopatológica do sistema urinário de ovinos confinados com e sem suplementação de cloreto de amônio

Pós-graduação em Medicina Veterinária - FMVZ