Urates in uric acid renal calculi

Objectives:   To investigate the presence of calcium urate, sodium, potassium and calcium in 'pure' uric acid calculi.
Methods:   Ten spontaneously passed uric acid urinary calculi have been examined by stereoscopic microscopy, infrared spectroscopy, scanning electron microscopy and energy dispersive X-Ray analysis.
Results:   The analysis of selected uric acid calculi revealed the presence of a near-pure calcium urate in two cases and of calcium enriched urate zones in all of the samples. Furthermore, in some cases complex urates containing sodium, potassium and calcium in different proportions appeared on the surface of the uric acid calculi studied, potassium being generally predominant. Ammonium urate was not detected.
Conclusions:   Most urinary uric acid calculi are not pure in composition. 'Complex urates', sodium, potassium and calcium were found together in various proportions in many areas of uric acid stones.     

Renal handling of uric acid under cyclosporin A treatment

The renal handling of uric acid during cyclosporin A (CyA) treatment was investigated by clearance studies using 24-h urine collections in 28 paediatric renal transplant recipients (CyA group), and the results were compared with those of 19 renal transplanted children treated with azathioprine and prednisolone (AZA group), 35 children with chronic renal failure (CRF) and 10 children with normal renal function (N group). Serum uric acid levels were significantly higher in the CyA group (567±156 mol/l) compared with the AZA group (378±98), the CRF group (415±119) and the N group (290±68). Mean uric acid clearances in each group measured 3.9±2.8 ml/min per 1.73 m² (CyA), 5.6±3.4 (AZA), 4.0±2.2 (CRF) and 8.4±3.7 (N). Calculation of the net tubular uric acid reabsorption per millilitre glomerular filtration rate revealed a significantly increased value of 0.53±0.15 mol/ml in the CyA group (P<0.01) compared with 0.34±0.08, 0.29±0.15 and 0.27±0.07 mol/l for the AZA, CRF and N groups respectively. We therefore conclude that CyA treatment is associated with an increased net tubular reabsorption of uric acid, which may lead to hyperuricaemia.     

Effect of an increase in the plasma potassium concentration on renal magnesium handling in healthy volunteers

Background: Lower plasma magnesium concentrations are associated with clinical problems such as arrhythmias and hypertension. Plasma magnesium concentration is tightly controlled by the kidney. Modifying renal magnesium threshold may provide a means to increase the plasma magnesium concentration. Since evidence has been presented that potassium deficiency by itself may increase renal magnesium loss, the hypothesis that elevating plasma potassium would result in an increase in plasma magnesium concentration was tested in healthy volunteers. Methods: Plasma potassium was raised in nine healthy volunteers by oral administration of 20 mg amiloride daily during 3 weeks. Magnesium metabolism was assessed before and after this period by plasma levels, urinary magnesium excretion and fractional magnesium excretion, and magnesium loading test (MLT). This MLT allows calculation of renal retention of magnesium load. Results: Basal plasma magnesium levels (0.84±0.07 vs 0.84±0.05 mmol/l) as well as urinary magnesium excretion (4.37±1.73 vs 3.67±1.37 mmol/day) and erythrocyte magnesium levels (1.72±0.16 vs 1.76±0.14 mmol Mg/l red blood cells) were similar before and on amiloride. Plasma potassium rose significantly on amiloride (3.64±0.24 vs 4.07±0.54 mmol/l, P <0.05). No change was observed in magnesium retention with the MLT: 22.7±26.7 vs 29.2±20.6% (P=0.5). Conclusions: Despite an increased plasma potassium concentration, no change was observed in plasma magnesium levels, urinary magnesium excretion or renal magnesium retention of an intravenously administered magnesium load. This indicates that increasing plasma potassium within the normal range does not modify the renal magnesium threshold.     

Urinary uric acid excretion in healthy male infants

  Blood and urine samples were collected from 23 healthy term male infants aged 2 – 12 months (mean 6.6 months). Data for establishing urinary uric acid reference values were obtained: urine concentration, 24-h urine output, weight-related urine output, urine output related creatinine, clearance, and fractional excretion. A negative correlation with age was demonstrated for all parameters studied. Received April 1, 1996; received in revised form March 18, 1997; accepted March 20, 1997     

Evaluation of renal handling of uric acid in essential hypertension: hyperuricemia related to decreased urate secretion.

The tubular transport of urate was studied in 40 hypertensive patients and in 20 normal subjects by means of pyrazinamide and benzbromarone tests. There was a marked decrease in urate excretion per nephron in hyperuricemic patients with essential hypertension. Serum uric acid correlated inversely with fractional excretion of urate (r = -0.7450, p less than 0.001). Presecretory and postsecretory reabsorption of urate did not significantly differ between hypertensive patients with high uric acid levels and control subjects. Urate secretion was significantly reduced in hypertensive patients and in those with hyperuricemia showed a twofold decrease. Serum uric acid correlated inversely with tubular secretion of urate (r = -0.7091, p less than 0.001) in hypertensive patients. These findings indicate that impaired tubular secretion of urate is a potential mechanism of hyperuricemia in essential hypertension.     

Effect of cyclosporine on the renal tubular amino acid handling after kidney transplantation

The renal tubular handling of free amino acids was studied 5-6 weeks after successful renal transplantation (tx) in 20 children treated with CsA and in 10 children treated with azathioprine (Aza). The results were compared with those of 34 control children. The amino-acid clearance studies were performed in combination with short-term inulin clearance. The CsA group revealed a mean inulin clearance of 49 +/- 16.8 ml/min/1.73 m2, the Aza group of 76.9 +/- 18.2, and the controls of 114 +/- 15.6. The plasma amino-acid concentrations were not different between CsA- and Aza-treated groups; however, most of the essential amino acids were lower in transplanted children than in controls. The decrease was correlated with the GFR. The amino-acid-clearance rates were statistically not different between both transplanted groups, but lower values than in controls were found for alanine, glycine, histidine, lysine, and phenylalanine, and significantly higher values for methionine. The fractional clearance rates of most amino acids were significantly elevated in transplanted children compared to controls. In CsA-treated patients, the fractional clearance rates of arginine, glycine, and serine were higher than in Aza-treated patients. No influence of CsA blood levels or rejection episodes on the amino-acid handling were detectable. We conclude that CsA has no specific influence on the renal handling of amino acids. Most disturbances observed depend on the graft function or may be caused by injuries to the graft following the tx procedure.     

Effect of changes in renal circulation on serum uric acid levels in women with twin pregnancy

Objective  

We examined the relationship between serum uric acid levels and changes in renal circulation in women with twin pregnancy compared with those in women with singleton pregnancy.     

Dietary composition and renal function in healthy subjects

Increments in dietary protein intake can increase glomerular filtration rate (GFR) in humans, and the glomerular hyperfiltration induced by high protein intake has been incriminated in the progression of glomerulosclerosis related to age and a number of renal diseases. GFR (as 51Cr-EDTA clearance) was measured in 18 vegans, 16 lactovegetarians and 18 omnivorous control subjects, matched for age. Omnivores ate significantly more total protein and protein of animal origin than the other two groups. Vegetable protein comprised 100% of the vegans' daily protein intake and 64% of the lactovegetarians', both significantly higher than the omnivores' (32%). Vegans and lactovegetarians also ate more carbohydrate and fibre than omnivores, although fat intake was similar. Mean GFR was significantly lower in the vegans than in the omnivores (100 +/- 13 vs. 113 +/- 16 ml/min/1.73 m2; p less than 0.04) and was intermediate in the lactovegetarians (105 +/- 16 ml/min/1.73 m2). Omnivores had significantly higher mean urinary albumin excretion rate (p less than 0.05) than vegans, and higher mean diastolic blood pressure than both vegans and lactovegetarians (p less than 0.01). The vegan diet is associated with glomerular and systemic haemodynamic changes which may be beneficial in the prevention of glomerular sclerotic changes in health and disease.     

缬沙坦对糖尿病肾病大鼠肾间质纤维化的作用

目的 探讨缬沙坦在防治糖尿病肾病(DN)大鼠肾间质纤维化( RIF)中的作用及其机制.方法 54只大鼠随机被分为对照组(C组)、DN模型组(D组)和缬沙坦治疗组(T组).D组和T组大鼠分别给予链脲菌素( STZ)一次性腹腔注射建立糖尿病大鼠模型.造模后T组给予缬沙坦混悬液40 mg· kg-1·d-1,分别于实验第4周、第8周和第12周末测血糖、血浆白蛋白、Scr、尿蛋白.Masson染色观察RIF面积.免疫组化法检查肾组织缺氧诱导因子1α( HIF-1α)、金属蛋白酶1组织抑制剂(TIMP-1)、基质金属蛋白酶9(MMP-9)的表达.实时荧光定量PCR测定其mRNA表达.结果 与C组比较,D组及T组大鼠24 h尿蛋白量、Scr均显著升高,肾组织RIF面积、HIF-1α、TIMP-1蛋白及mRNA表达均显著增加,血清白蛋白及肾组织中MMP-9蛋白及其mRNA表达均明显减少,差异均有统计学意义(均P＜0.05).与同时间点D组比较,T组在实验第8周末、第12周末24h尿蛋白、Scr均显著降低,肾组织中RIF面积、HIF-1α、TIMP-1蛋白及其mRNA表达均显著减少,血清白蛋白及肾组织中MMP-9及其mRNA表达均显著增多,差异均有统计学意义(均P＜0.05).结论 缬沙坦可能通过下调HIF-1α、TIMP-1表达,上调MMP-9表达,延缓肾间质纤维化.     

The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects

BACKGROUND: Trimethoprim used in combination with other antibiotics, has been implicated in causing hyperkalemia and hypouricemia in patients with acquired immune deficiency syndrome (AIDS). In experimental animal models, trimethoprim has been demonstrated to block sodium channels and Na+-K+-ATPase in the distal nephron and thus impair potassium excretion. Although the data from the experimental models suggest that trimethoprim reduces urinary potassium excretion, the retrospective clinical studies have confounding factors that prevent a rigorous demonstration that the hyperkalemia and hypouricemia are due solely to the effects of trimethoprim on solute excretion. AIM: The purpose of this study was to evaluate the effect of trimethoprim on potassium and uric acid balance in normal human subjects. METHODS: Five normal human subjects were admitted to the general clinical research center and placed on a fixed metabolic diet. After a 4-day control period, the subjects were given trimethoprim (15 mg/kg/day) orally for 5-7 days followed by a 4-day recovery period. Free-flow blood samples and 24-hour urine collections were obtained daily. RESULTS: Treatment with trimethoprim resulted in a significant increase in plasma potassium concentration (4.5 +/- 0.1 versus 3.7 +/- 0.1 mmol/l, p < 0.005) and significant decrease in serum uric acid concentration (3.8 +/- 0.4 versus 5.6 +/- 0.5 mg/dl, p < 0.001). Treatment with trimethoprim significantly increased the urinary excretion of uric acid, but did not significantly decrease potassium excretion during the 7-day treatment period. There was, however, a significant decrease in potassium excretion observed during the first 48 hours of trimethoprim treatment. In one subject where repeat studies were performed using different dosages, the effect on potassium and uric acid levels appeared to be dose-dependent. CONCLUSIONS: Trimethoprim increases plasma potassium concentration probably by reducing urinary potassium excretion. Trimethoprim decreases serum uric acid levels by augmenting urinary uric acid excretion. This uricosuric effect may be due to the ability of trimethoprim to impair urate reabsorption by the urate-anion exchanger in the proximal tubule.     

Management of uric acid renal obstruction by intravenous lactate

6 patients presenting with uric acid renal obstruction were managed by alkalization of urine using intravenous perfusion of 0.16 (1/6) M sodium lactate. Despite obstructive renal failure in 3 patients, rapid relief of obstruction was obtained and surgery was not necessary in any patient. Lysis of uric acid stones by urine alkalization is well documented [1, 4-12]. Intravenous infusion of 0.16 (1/6) M sodium lactate provides rapid urinary alkalization and is effective in the relief of obstruction by dissolution of uric acid calculi.     

Familial renal hypouricemia with intact reabsorption of uric acid

Three patients with renal hypouricemia in the same family are described. Serum urate levels in the mother were in the low normal range and were below normal in her 2 sons. In all 3 patients, the ratios of renal urate clearance to creatinine clearance were abnormally elevated. Clear responses to either pyrazinamide or probenecid administration were observed in these ratios. These results suggest that these 3 patients had renal hypouricemia with normal reabsorption of urate as judged by the criteria for differentiating abnormalities in renal urate handling. This corresponds to the previously postulated mechanism as renal urate hypersecretion. Possible limitations to the diagnostic use of probenecid and pyrazinamide are also discussed.     

Effect of serum uric acid level on renal function in elderly hypertensive patients: a retrospective cohort study

Objective To explore the relationship of serum uric acid level with estimated glomerular filtration rate (eGFR) of elderly patients with hypertention based on a retrospective cohort study. Method The subjects included 465 cases who had a readmission after 3 years of follow-up in an original cohort of 1648 patients with diagnosis of essential hypertension in Fujian Provincial Hospital from August 2007 to September 2009. Multiple regression analysis was performed to examine the effect of serum uric acid level on renal function. Results Four hundred and sixty-five subjects were followed up for an average of 3.9 years. Mean patient age was 68.3±9.7 years. There was no significant difference in uric acid between the baseline and 3 years later (P＞0.05). Multiple regression analysis showed that after adjustment for age, gender, diabetes, body mass index, blood pressure etc, each 100 μmol/L-higher uric acid at baseline was associated with 4.40 ml•min-1•(1.73m2)-1 decrease in eGFR[95% confidence interval (CI): -6.25--2.55, P＜0.01]. According to the alteration of the serum uric acid, all patients were divided into the group with decreased uric acid and the group with increase uric acid. The eGFR was lower in patients with increased uric acid than that in patients with decreased uric acid 3 years later [(70.63±21.54) ml•min-1•(1.73m2)-1 vs (79.62±21.16) ml•min-1•(1.73 m2)-1, P＜0.01] and there was no significant difference at baseline between the two groups (P＞0.05). Multiple logistic regression analysis showed that after adjusting for aging, gender, diabetes, alteration of blood pressure etc, baseline uric acid was associated with a higher risk for eGFR decreasing more than 10 ml•min-1•(1.73m2)-1 3 years later [hazard ratio (HR)=2.11, 95%CI: 1.24-3.59, P＜0.01]; increased uric acid 3 years later resulted in a higher risk for renal function deterioration (HR=2.60, 95%CI: 1.67-4.07, P＜0.01). Conclusions Elderly hypertensive patients with baseline hyperuricemia have a lower eGFR, resulting an increased risk of chronic kidney disease. While the patients with declined uric acid had a lesser imparied renal function. It suggests that the improvement of uric acid may help to slow down the deterioration of renal function in elderly hypertensive patients.     

Renal handling of urea in subjects with persistent azotemia and normal renal function

Fourteen subjects with persistent azotemia and normal glomerular filtration rate were studied by renal clearances and hormonal determinations to establish the nephron site of altered urea transport and the mechanism(s) responsible for their azotemia. During constant alimentary protein, urea nitrogen appearance was normal and urea clearance was much lower than in 10 age-matched control subjects (23.3 +/- 2.1 ml/min and 49.6 +/- 2.6 ml/min per 1.73 m2, P less than 0.001). Inulin and para-aminohippurate clearances, blood volume and plasma concentration of antidiuretic hormone were within normal limits. During maximal antidiuresis, in spite of greater urea filtered load, the urinary excretion of urea was less, and both the maximum urinary osmolality and the free-water reabsorption relative to osmolar clearance per unit of GFR were greater than in control subjects. After sustained water diuresis, the plasma urea concentration markedly decreased to near normal levels in azotemic subjects. The basal urinary excretion of prostaglandins E2 was significantly reduced in azotemic subjects and was directly correlated with fractional urea clearance (r = 0.857, P less than 0.001). An additional group of control subjects (N = 8) showed a marked reduction of fractional clearance of urea after inhibition of prostaglandin synthesis (P less than 0.01). These data suggest that azotemia is due to increased tubular reabsorption of urea in the distal part of nephron, presumably because of increased back diffusion in the papillary collecting duct, accounting for the enhanced maximum urinary osmolality and free-water reabsorption. Renal prostaglandin E2 may participate in the pathogenesis of azotemia by altering recycling of urea in the medulla.