Combination of Pentoxifylline with Angiotensin Converting Enzyme Inhibitors Produces an Additional Reduction in Microalbuminuria in Hypertensive Type 2 Diabetic Patients

Objective.?To investigate the anti proteinuric effect of pentoxifylline in diabetic patients, we prospectively studied in 25 hypertensive type 2 diabetic patients with persistent microalbuminuria and normal renal function the impact of combining pentoxifylline with an angiotensin converting enzyme inhibitor, lisinopril, on urinary albumin excretion and compared the results with those obtained in a control group of 25 type 2 diabetic patients treated with lisinopril only. Material and Methods.?Fifty hypertensive type 2 diabetic patients with persistent microalbuminuria (31 males and 19 females, aged between 47–73 years) were randomly assigned to two groups. Group A received lisinopril 10 mg/day, while group B was given lisinopril 10 mg/day and pentoxifylline 600 mg/day for nine months. There were no significant differences between serum creatinine, HbA1c, blood pressure and urinary albumin excretion in both groups (p>0.05). Results.?Serum creatinine, creatinine clearance, blood pressure, HbA1c levels did not change significantly during the study. Urinary albumin excretion decreased from 228 ± 28 to 148 ± 15 mg/day in group A (p<0.05). In group B urinary albumin excretion decreased from 219 ± 26 to 128 ± 12 mg/day (p<0.05). Pentoxifylline and lisinopril combination caused a significant additional reduction in urinary albumin excretion when compared to lisinopril regimen (p<0.05).

Conclusions.?Our findings suggest that the combination of pentoxifylline with an angiotensin converting enzyme inhibitor in hypertensive type 2 diabetic patients with persistent microalbuminuria causes a significant reduction in urinary albumin excretion and this effect seems independent from blood pressure and glycemic control.     

Albuminuria and insulin resistance in children with biopsy proven non-alcoholic fatty liver disease

Insulin resistance may favor increased urinary albumin excretion (UAE), leading progressively to chronic kidney disease (CKD). A recent study on non-alcoholic fatty liver disease (NAFLD), a condition of insulin resistance, associated this disease with the incidence of CKD in patients with type 2 diabetes. The aim of our study was to determine whether there is an association between insulin resistance and kidney function, based on estimates of UAE and creatinine clearance in children with biopsy-proven NAFLD. Kidney function was assessed in 80 patients with NAFLD and 59 individuals of normal weight matched for age and sex. Insulin resistance was measured by means of the homeostatic model assessment-insulin resistance (HOMA-IR) and limited to NAFLD patients by using the whole-body insulin sensitivity index. The HOMA-IR was found to differ significantly between the two groups (2.69 ± 1.7 vs. 1.05 ± 0.45; p = 0.002), while UAE (9.02 ± 5.8 vs. 8.0 ± 4.3 mg/24 h; p = 0.9) and creatinine clearance (78 ± 24 vs. 80 ± 29 mg/min; p = 0.8) did not. We found a significant but weak inverse correlation between insulin sensitivity and creatinine clearance in NAFLD patients (r _s = –0.25;p = 0.02). No difference was observed in kidney function between NAFLD children presenting with or without metabolic syndrome, low or normal HDL-cholesterol, and different degrees of histological liver damage (grade of steatosis ≥2, necro-inflammation, and fibrosis). Patients with hypertension had increased levels of UAE (p = 0.04). A longer exposure to insulin resistance may be required to cause the increase in urinary albumin excretion and to enable the detection of the effect of the accelerated atherogenic process most likely occurring in children with fatty liver disease. Longitudinal studies are needed to rule out any causative relationship between insulin resistance and urinary albumin excretion.     

Urinary Excretion of Vitamin A in Critically Ill Patients Complicated with Acute Renal Failure

Objective. Study the possible excretion of vitamin A in urine of critically ill patients complicated with acute renal failure. Patients and Methods. Nine Intensive z`Care Unit patients, age 71.2 ± 15.7 (mean ± SD) with acute renal failure were studied. Urinary retinol, creatinine, protein, albumin, and serum creatinine were measured. Results. All patients excreted retinol in urine; individual values ranged from 0.007 to 0.379 µmol retinol/mmol creatinine. There was no correlation of urinary retinol/creatinine ratio with serum creatinine or with urinary protein/creatinine and albumin/creatinine ratios. Conclusion. Excretion of retinol in urine may be indicative of acute renal failure in critically ill patients.     

Effect of interleukin-8 on glomerular sulfated compounds and albuminuria

To evaluate the effect of interleukin-8 (IL8) on glomerular basement membrane (GBM) sulfated compounds and albuminuria, we infused IL8 in 1% bovine serum albumin (BSA) for 5 days into the left renal artery of Holtzman male rats at the rate of 10 μl/h using an osmotic pump. Control rats received 1% BSA. A significant increase in urinary albumin/creatinine ratio was seen on the last day of IL8 infusion (0.38±0.11, mean ± SEM) when compared with albumin/creatinine ratio prior to infusion (0.19±0.04, P = 0.04). No significant differences in urinary albumin excretion prior to and after infusion of 1% BSA were observed. On the last day of infusion, rats were injected with ³⁵sulfate (1.0 mCi/200 g body weight) intraperitoneally and killed after 8 h. Glomeruli were isolated and GBM obtained. After 5 days of IL8 administration, there was a significant increase in ³⁵sulfate uptake by GBM of the infused kidney (76±10 cpm/dry glomerular weight, mean ± SEM) compared with the uptake seen in the contralateral kidney (53±9, P = 0.05). The in vivo infusion of IL8 increased the ³⁵sulfate uptake by GBM and augmented the urinary albumin/creatinine ratio, suggesting that IL8 may induce albuminuria by altering the metabolism of the GBM sulfated compounds. This hypothesis needs to be confirmed by studies on glomerular charge selectivity and GBM anionic sites during the course of the infusion. Moreover, the persistence of the effect needs to be evaluated by prolonging the infusion for more than 5 days. Received June 3, 1996; received in revised form and accepted October 18, 1996     

Evaluation of lithogenic elements in urine of healthy newborns

The determination of urinary excretion of lithogenic elements in healthy newborns involves factors ranging from urine collection and data handling to maternal influences, which can cause difficulties in analyzing the results. The objective of this study was to determine normal values of parameters related to lithogenesis, such as calcium, uric acid, citrate, and oxalate, in urine of healthy newborns using isolated samples, focusing on variations according to gender, weight, milk ingestion, and family history of lithiasis. Parameters measured in isolated urine samples from 104 healthy newborns (77 males and 27 females) were corrected by creatinine. The ratios were expressed as milligram/milligram of creatinine: calcium/creatinine of 0.10±0.01 (X±SE), uric acid/ creatinine of 1.10±0.10, citrate/creatinine of 0.56±0.04, and oxalate/creatinine of 0.07±0.01. Differences were observed between males and females, in terms of uric acid (0.80±0.07 vs. 1.10±0.10 mg/mg, P<0.05), citrate (0.05±0.06 vs. 0.17±0.05, P<0.05), sodium (0.17± 0.01 vs. 0.05±0.01, P<0.001), and potassium (0.05± 0.01 vs. 0.20±0.02, P<0.001). Interestingly, the urinary concentration of protector factors such citrate and potassium was higher in females than in males with low sodium excretion. Artificial milk feeding leads to higher calcium (0.10±0.06 vs. 0.06±0.01), uric acid (1.40±0.20 vs. 0.90±0.09, P<0.05), citrate (0.90±0.09 vs. 0.50±0.04, P<0.001), and oxalate (0.17±0.03 vs. 0.05±0.01, P<0.001) excretion when compared with breast feeding. There was higher excretion of calcium and sodium in patients under 3 kg. Children with familial antecedents presented some differences in urinary excretion, with higher uric acid (1.50±0.30 vs. 0.80±0.08, P<0.05) but lower calcium (0.05±0.02 vs. 0.10±0.01, P<0.05) and sodium (0.15±0.02 vs. 0.20±0.02, P<0.05) excretion, respectively. This report provides urinary parameters obtained in healthy newborns and correlates them with factors that could be involved in the genesis of osteopenia, renal stones, and/or nephrocalcinosis. Received: 8 May 2000 / Revised: 7 June 2001 / Accepted: 12 June 2001     

Diurnal Rhythm of Urinary Calcium Excretion in Adults

Twenty-four-hour urinary calcium excretion is normally the equivalent of daily calcium intake, and varies between 200–300 mg/dL with a calcium/creatinine ratio of 0.07–0.15. In this study, we aimed to investigate the diurnal rhythm of calcium excretion in healthy individual. Forty subjects (30 male, 10 female) were involved into the study. The spot urine samples were taken at 08:00, 14:00, and 22:00 together with a 24-hour collection. Mean spot urinary calcium levels at 08:00, 14:00, and 22:00 were 12.39 ± 8.19, 12.97 ± 8.37, and 16.95 ± 10.39 mg/dL, with calcium/creatinine ratios of 0.104 ± 5.26l, 0.119 ± 7.85, and 0.133 ± 8.17, respectively. Twenty-four-hour urinary calcium excretion was 12.74 ± 7.31 mg/dL with a calcium/creatinine ratio of 0.111 ± 5.41. The values at 08:00, 14:00, and of 24-hour collection were statistically similar (p > 0.05), but the nighttime values were significantly elevated (p < 0.05). In conclusion, calcium excretion is increased at night, and urinary calcium measurements should be interpreted accordingly.     

Is Serum Cystatin C an Accurate Endogenous Marker of Glomerular Filteration Rate for Detection of Early Renal Impairment in Patients with Type 2 Diabetes Mellitus?

Background. Researches have recently reported that serum cystatin C is a more sensitive marker of changes in glomerular filtration rate (GFR) than serum creatinine. We conducted this study to evaluate the significance of serum cystatin C as a more sensitive marker of GFR for early detection of renal impairment in special groups of patients with type 2 diabetes mellitus (DM). Methods. The present study included 40 patients with type 2 DM divided into four equal groups based on their urinary albumin excretion and renal function: group 1 was normoalbuminuric, group 2 was microalbuminuric, group 3 was macroalbuminuric, and group 4 was macroalbuminuric with renal dysfunction. All patients underwent a thorough history, full clinical examination, fasting, and renal function tests. Post-prandial blood glucose levels, glycosylated hemoglobin A1c (HbA1c), proteins, albumin in 24 hr urine, and serum cystatin C were collected. Results. Serum cystatin C and creatinine were significantly higher in macrolbuminuric type 2 diabetic patients with renal dysfunction (group 4: 2.26 ± 1.28, 4.21 ± 2.38 mg/dl, respectively; p < 0.001) than macrolbuminuric type 2 diabetic patients with normal renal function (group 3: 1.04 ± 0.24, 0.96 ± 0.20 mg/dl, respectively), the microalbuminuric group (0.87 ± 0.28, 0.71 ± 0.12 mg/dl, respectively), as well as the normoalbuminuric group (0.55 ± 0.41, 0.60 ± 0.18 mg/dl, respectively). ROC plots demonstrated that area under the curve (AUC) of cystatin C (0.74) was greater than that for creatinine clearance (cr.cl) (0.67) and serum creatinine (s‐cr) (0.74); therefore, the sensitivity and diagnostic accuracy of cystatin c was better than cr. cl., and both were better than s-cr. Serum cystatin C showed significant correlation in groups 2–4 with s-cr, cr.cl, and 24 hr urine albumin, but no correlation was found in group 1. Conclusion. Serum cystatin C is a reliable and easily performed marker for GFR to detect renal impairment in patients with type 2 DM.     

Beneficial effect of atorvastatin on erythropoietin responsiveness in maintenance haemodialysis patients

Aim: To evaluate the effect of atorvastatin on erythropoietin responsiveness and whether this effect is mediated by C‐reactive protein (CRP) reduction in prevalent dyslipidemic, haemodialysis patients. Methods: We studied prospectively 33 stable, iron‐repleted haemodialysis patients with low‐density lipoprotein cholesterol (LDL) ≥2.58 mmol/L, who received 20 mg atorvastatin aiming to achieve the target of LDL <2.58 mmol/L, over a period of 9 months. Twenty‐five patients completed the study, 15 men, with mean age 66.1 ± 8.2 years. The duration of haemodialysis was 56.6 ± 63.1 months and 5/25 patients were diabetics. Total serum cholesterol, triglycerides, high‐density lipoprotein cholesterol, LDL, haemoglobin, albumin, intact parathyroid hormone, serum iron, ferritin, total iron binding capacity, CRP and weekly dose of erythropoietin/body weight/haemoglobin were analysed. Results: Twenty of the 25 patients (80%) achieved the goal of LDL <2.58 mmol/L. There was a significant decrease in total cholesterol (5.77 ± 0.88 to 4.16 ± 0.96 mmol/L, P < 0.001) and LDL (3.59 ± 0.77 to 1.94 ± 0.77 mmol/L, P < 0.001). Haemoglobin increased from 121 ± 11 to 126 ± 7 g/L (P < 0.05), while weekly dose of erythropoietin/body weight/haemoglobin decreased significantly from 8.34 ± 3.70 to 7.87 ± 3.11 IU/kg per haemoglobin (P < 0.05). CRP decreased not significantly from 7.0 ± 6.1 to 4.5 ± 2.2 mg/L. Conclusion: Dyslipidemia of haemodialysis patients was treated safely and effectively with atorvastatin, but a fifth of the patients failed to achieve the therapeutic target. Statin therapy resulted in a significant increase of haemoglobin levels and improvement of erythropoietin responsiveness without a significant reduction in CRP levels, suggesting that the beneficial effect of statins on erythropoietin responsiveness may be driven by a mechanism other than CRP reduction.     

Urinary N-acetyl-β-D-glucosaminidase activity in rabbits with experimental hypercalciuria

Routinely used renal function tests remain normal in uncomplicated hypercalciuria. The aim of this study was to assess the value of N-acetyl-β-D-glucosaminidase (NAG), a sensitive marker of renal proximal tubular damage, in experimental hypercalciuria. Oral calcium providing 75 mg/kg per day elementary calcium and 20,000 IU/day vitamin D₃ was administered for 15 days to 7 rabbits (Orytolagus cuniculus-New Zealand white) and 7 rabbits were given placebo as a control group. Serum calcium, phosphorus, and alkaline phosphatase, daily urinary calcium excretion and NAG/creatinine ratio were measured before and after drug administration. Kidneys were examined macroscopically and microscopically following the study period. Serum calcium, phosphorus and urinary calcium excretion increased, while alkaline phosphatase decreased significantly in response to drug treatment [10.8±1.5 vs. 12.2±1.3 mg/dl, 4.6±0.6 vs. 6.7±0.7 mg/dl, 22.3±8.3 vs. 46.8±22.5 mg/kg per day, and 138.0±57.1 vs. 70.1±33.1 IU/l, respectively (P <0.05)]. The NAG/creatinine ratio prior to the study (0.5±0.1 mU/mg) was significantly different from that after the study (5.4±1.5 mU/mg, P <0.01). In the control group, changes in serum and urinary parameters were not significant (P >0.05). The relationship between the urinary NAG/creatinine ratio and the daily urinary calcium excretion was statistically significant (r = 0.67, P <0.05). In the study group, nephrocalcinosis was present in all rabbits except 1 (85.7%), whereas none of the control group rabbits had nephrocalcinosis. In conclusion, in rabbits urinary NAG excretion increases significantly in nephrocalcinosis induced by hypercalciuria. Received February 12, 1996; received in revised form November 25, 1996; accepted November 27, 1996     

The Course of Hypercalciuria and Related Markers of Bone Metabolism Parameters Associated with Corticosteroid Treatment

Background and objective: Prolonged corticosteroid (CS) use induces osteoporosis; the pathogenesis of this condition is multifactorial and includes CS-induced hypercalciuria. We investigated the course of hypercalciuria and related markers of bone metabolism parameters during and after the CS treatment. Materials and Methods: We recruited 42 patients who were taking at least 10 mg/day of methylprednisolone or an equivalent dose of CSs for at least 30 days. The 24-h urinary calcium and sodium, a spot urinary calcium/creatinine ratio, and urinary deoxypyridinoline were measured prior to the treatment, at day 7, at days 30–60, and after the cessation of the treatment. Additionally, the serum levels of phosphorus, calcium, alkaline phosphatase (ALP), albumin, creatinine, osteocalcin, and parathyroid hormone (PTH) were analyzed. Results: The 24-h urinary calcium excretion was significantly increased at day 7 (182.2 ± 158.6 mg/day; p < 0.001) and at days 30–60 (196.9 ± 167.8 mg/day; p < 0.001) compared with baseline (98.7 ± 88.1 mg/day) and returned to basal level after the cessation of the CSs (118.9 ± 90.2 mg/day; p = 0.725). The urinary deoxypyridinoline level was significantly higher at days 30–60 compared with basal level. The serum osteocalcin level was decreased at days 30–60 when compared with day 7. No significant changes were detected in the PTH, phosphorus, creatinine, and ALP levels. Conclusions: CS treatment induces hypercalciuria just after starting the treatment until the end of it. CS-induced hypercalciuria promptly improved after cessation of the treatment. By days 30–60, the excretion of urinary deoxypyridinoline was accompanied by hypercalciuria. The serum osteocalcin level was decreased at days 30–60 when compared with day 7.     

URINARY THYMIDINE GLYCOL AS A BIOMARKER FOR OXIDATIVE STRESS AFTER KIDNEY TRANSPLANTATION

Reactive oxygen species are generated during ischemia-reperfusion tissue injury. Oxidation of thymidine by hydroxyl radicals (HO^˙) causes formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol excreted in urine can be used as a biomarker of oxidative DNA damage. The aim of this study was to investigate the oxidative DNA damage in patients showing immediate allograft function after kidney transplantation, and to find out whether this damage correlates with glomerular and tubular lesions.

Time dependent changes in urinary excretion rates of thymidine glycol, but also of total protein, albumin, low molecular weight (α₁-microglobulin, β₂-microglobulin) and high molecular weight proteins (transferrin, IgG, α₂-macroglobulin) were analyzed quantitatively and by polyacrylamide-gel electrophoresis in six patients. Urinary thymidine glycol was determined by a fluorimetric assay in combination with affinity chromatography and HPLC.

After kidney transplantation the urinary excretion rate of thymidine glycol increased gradually reaching a maximum within the first 48 hours (16.56 ± 11.3 nmol/mmol creatinine, ref. 4.3 ± 0.97). Severe proteinuria with an excretion rate of up to 7.2 g/mmol creatinine was observed and declined within the first 24 hours of allograft function (0.35 ± 0.26 g/mmol creatinine). The gel-electrophoretic pattern showed a nonselective glomerular and tubular proteinuria. The initial nonselective glomerular proteinuria disappeared within 48 hours, changing to a mild selective glomerular proteinuria. In this period (12–48 hours) higher levels of thymidine glycol excretion were observed, when compared to the initial posttransplant phase (13.66 ± 9.76 vs. 4.31 ± 3.61 nmol/mmol creatinine; p < 0.05).

An increased excretion of thymidine glycol is seen after kidney transplantation and is explained by the ischemia-reperfusion induced oxidative DNA damage in the kidney. In the second phase higher levels of excretion were observed parallel to the change from a nonselective to a selective glomerular and tubular proteinuria. An explanation may be sought in the repair process of DNA in the glomerular and tubular epithelial cells, appearing simultaneously with functional recovery.     

Effects of residual renal function in haemodialysis patients

Thirty-six haemodialysis patients on treatment for more than six months were studied for residual renal function (RRF). Twenty patients were anuric. The remaining 16 patients with RRF excreted 35–1600 ml urine/day with creatinine clearance ranging 0.17–6.95 ml/min. Patients with RRF were on dialysis therapy for shorter periods than those with anuria (25.5±18.5 vs. 101.7±14.2 months, p=0.001). Twelve out of 20 anuric patients had had previous renal transplantation, whereas none of those with RRF had been transplanted (p=0.0006). Interdialytic weight gain, serum potassium and phosphate were lower in patients with RRF. Serum phosphate and uric acid were correlated with their respective urinary excretion rates (p=0.013 and 0.005, respectively), but interdialytic weight gain could not be correlated with urinary output. Creatinine clearance significantly correlated with urinary excretion of potassium, sodium, phosphate and uric acid. In this series of patients a previous unsuccessful renal transplantation was an important factor in the loss of RRF. The presence of RRF contributed to the regulation of the blood levels of phosphate and the excretion rate of potassium, sodium and uric acid.     

Urinary enzyme changes in children undergoing cineangiographic evaluation using iopromid

Nephropathy due to radiocontrast media presents with a wide spectrum of changes from reversible renal dysfunction to oliguria requiring dialysis. Nineteen patients (mean age 4.5±3.7 years) were included. Mean±SD values of the variables obtained before and 48 hours after angiography were the following: plasma creatinine: 0.6±0.10 and 0.6±0.16 mg/dl; endogenous creatinine clearance: 76.1±17.0 and 80.9±19.3 ml/min/1.73 m²; plasma osmolality: 279±23 and 298±39 mOsm/kg H₂O; urine osmolality: 429±225 and 459±196 mOsm/kg H₂O; fractional sodium excretion: 2.1±1.3% and 2.4±1.3%; plasma uric acid: 3.9±1.3 and 3.4±1.0 mg/dl; urinary AST/creatinine: 5.2±4.8 and 4.2±2.6 mU/mg; ALT/creatinine: 16.8±12.4 and 15.3±12.6 mU/mg; LDH/creatinine: 52.0±39.6 and 42.3±31.5 mU/mg; NAG/creatinine: 20.1±2.8 and 16.8±2.3 mU/mg, respectively. The changes in renal function parameters and urinary enzyme levels were insignificant statistically (p>0.05). In conclusion, iopromid injection at maximum doses of 5 ml/kg does not result in injury to the tubular epithelium leading to increased urinary enzyme levels.     

Pulse pressure and isolated systolic hypertension: association with microalbuminuria. The GUBBIO Study Collaborative Research Group

BACKGROUND: The long-term risk of end-stage renal disease is high in persons with isolated systolic hypertension, that is, those with an elevation of pulse pressure and not of diastolic pressure. Other data suggest that pulse pressure is a predictor of the hypertension-induced organ damage. Microalbuminuria is considered an early sign of glomerular damage caused by hypertension. The study shows the relationship of pulse pressure and isolated systolic hypertension to microalbuminuria in nondiabetic subjects. METHODS: This is a cross sectional analysis for a population sample of 677 men and 890 women, aged 45 to 64 years, who were without diabetes mellitus and macroalbuminuria. Data collection included: overnight urinary albumin and creatinine excretion; fasting plasma glucose, cholesterol, and creatinine; creatinine clearance; and blood pressure, weight, height, medical history, and smoking habit. Pulse pressure was calculated as systolic minus diastolic pressure. Isolated systolic hypertension was defined as systolic pressure > or =140 mm Hg in persons not on antihypertensive drugs and with diastolic pressure <90 mm Hg. Microalbuminuria was defined as urinary albumin excretion > or =20 microg/min. RESULTS: Pulse pressure and isolated systolic hypertension were significantly related to urinary albumin excretion and the prevalence of microalbuminuria in univariate and multivariate analyses. Controlling for gender and other variables, the risk of microalbuminuria was 1.71 with a 15 mm Hg higher pulse pressure (95% CI, 1.31 to 2.22) and 4.95 in the presence of isolated systolic hypertension (95% CI, 3.15 to 7.76). CONCLUSIONS: In nondiabetic, middle-aged adults, pulse pressure and isolated systolic hypertension are directly related to microalbuminuria, independent of diastolic pressure and other correlates.     

Clinical and biochemical profile of patients with “pure” uric acid nephrolithiasis compared with “pure” calcium oxalate stone formers

The purpose of the present study was to compare the clinical characteristics of “pure” uric acid (UA) stone formers with that of “pure” calcium oxalate (CaOx) stone formers and to determine whether renal handling of UA, urinary pH, and urinary excretion of promoters and inhibitors of stone formation were different between the two groups. Study subjects comprised 59 patients identified by records of stone analysis: 30 of them had “pure” UA stones and 29 had “pure” CaOx nephrolithiasis. Both groups underwent full outpatient evaluation of stone risk analysis that included renal handling of UA and urinary pH. Compared to CaOx stone formers, UA stone formers were older (53.3 ± 11.8 years vs. 44.5 ± 10.0 years; P = 0.003); they had higher mean weight (88.6 ± 12.5 kg vs. 78.0 ± 11.0 kg; P = 0.001) and body mass index (29.5 ± 4.2 kg/m² vs. 26.3 ± 3.5 kg/m²; P = 0.002) with a greater proportion of obese subjects (43.3% vs. 16.1%; P = 0.01). Patients with “pure” UA lithiasis had significantly lower UA clearance, UA fractional excretion, and UA/creatinine ratio, with significantly higher serum UA. The mean urinary pH was significantly lower in UA stone formers compared to CaOx stone formers (5.17 ± 0.20 vs. 5.93 ± 0.42; P < 0.0001). Patients with CaOx stones were a decade younger, having higher 24-h urinary calcium excretion (218.5 ± 56.3 mg/24 h vs. 181.3 ± 57.1 mg/24 h; P = 0.01) and a higher activity product index for CaOx [AP (CaOx) index]. Overweight/obesity and older age associated with low urine pH were the principal characteristic of “pure” UA stone formers. Impairment in urate excretion associated with increased serum UA was also another characteristic of UA stone formers that resembles patients with primary gout. Patients with pure CaOx stones were younger; they had a low proportion of obese subjects, a higher urinary calcium excretion, and a higher AP index for CaOx.     

黄芪水提物对健康人尿钠排泄的影响及机制研究

目的 探讨黄芪水提物（ARE）对健康人的利尿利钠作用及其机制。方法 采用双盲交叉试验。12名健康男性志愿者口服生理盐水（10ml／kg）后随机分为ARE组和安慰剂组，2周洗脱期后再进行试验。结果 与安慰剂组相比，ARE组尿钠排泄量（UNaV）在1．5h和2h分别增加73％和43％，2h时达高峰[（0．30±0．05）比（0．21±0．02）mmol／min，P〈0．05]，4h时作用基本消失。尿钠排泄分数（FENa）和尿氯排泄量（UαV）也显著增加，均在2h达高峰，而尿量、尿钾及尿肌酐排泄量在服药4h内均无增加，12h和24h尿量及尿电解质排泄量也无改变。口服ARE后血浆心钠素浓度（pANP）、尿环磷酸鸟苷排泄量（UcGMPPV）及UcGMP V／pANP比值均在2h显著增加（P〈0．05）。U Na V与血浆pANP、UcGMPV及UcGMPV／pANP比值正相关（P均〈0．05），而与Ccr无相关（r=0．153，P〉0．05）。结论 ARE能增加健康人尿钠排泄，其机制与ARE促进ANP产生以及增加ANP肾脏活性有关。     

Apolipoprotein B Attenuates Albuminuria-Associated Cardiovascular Disease in Prevention of Renal and Vascular Endstage Disease (PREVEND) Participants

Whether urinary albumin excretion relates to higher levels of atherogenic apolipoprotein B fractions in the nondiabetic population is uncertain. Such a relationship could explain, in part, the association of elevated urinary albumin excretion with cardiovascular disease risk. We assessed the relationship of urinary albumin excretion with apolipoprotein B fractions and determined whether the association of elevated urinary albumin excretion with incident cardiovascular events is modified by high apolipoprotein B fraction levels. We performed a prospective study on 8286 nondiabetic participants (580 participants with cardiovascular disease; 4.9 years median follow-up time) with fasting lipids, apolipoprotein B, and urinary albumin excretion determined at baseline. With adjustment for sex and age, micro- and macroalbuminuria were associated with increased apolipoprotein B fractions (non-HDL cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B). All four apolipoprotein B fractions modified associations of urinary albumin excretion with incident cardiovascular disease (hazard ratios for interaction terms ranged from 0.89 to 0.94 with 95% confidence intervals ranging from 0.84 to 0.99 and P values ranging from 0.001 to 0.02 by Cox proportional hazards modeling). These interactions remained present after additional adjustment for conventional risk factors, eGFR, cardiovascular history, and lipid-lowering and antihypertensive drug treatments. Such modification was also observed when urinary albumin excretion was stratified into normo-, micro-, and macroalbuminuria. We conclude that there is an association between elevated urinary albumin excretion and apolipoprotein B fraction levels and a negative interaction between these variables in their associations with incident cardiovascular events. Elevated urinary albumin excretion may share common causal pathways with high apolipoprotein B fractions in the pathogenesis of cardiovascular disease.     

Urinary nitrite excretion and urinary variables in patients with primary nocturnal frequency of micturition: effects of indomethacin suppositories

Urinary nitrite excretion was measured in patients with primary nocturnal frequency of micturition (PNFM) and in normal individuals. Effects of indomethacin suppository on urine volume and other urinary variables were evaluated. The study comprised seven patients with PNFM and seven healthy control (age range 30–45 years). Nitrite was assayed in spot morning urine samples; urine volume, urine osmolality and electrolytes, serum osmolality and electrolytes and functional bladder capacity (FBC) were assayed. Both groups were then given 100 mg of indomethacin suppository daily for a maximum of 10 days and urinary variables were re-evaluated during day 10. Results showed that urinary nitrite excretion of patients with PNFM was greater than that of the normal subjects (230±62 umol/l vs. 42±30 umol/l, P<0.05). The mean (SD) 24 h urine volume and osmolality, the night urine volume and osmolality, serum osmolality, FBC, creatinine clearance, fractional excretion of sodium (FENa), fractional excretion of potassium (FEK), and urinary excretion of glucose and potassium were lower in patients with PNFM as compared with normal individuals, although not statistically significantly so, except for FBC that was significantly lower in the patients. Urinary excretion of sodium, calcium, chloride, phosphorus, magnesium, day-night urinary volume ratio, spot morning osmolality, nocturnal index, and nocturnal polyuria index were higher in patients with PNFM. Indomethacin decreased the 24 h urinary volume by 21%, creatinine clearance by 12%, osmolar clearance by 14% and urinary protein excretion by 38% in the patients. These variables decreased by 26, 45, 17 and 12% respectively in the healthy subjects, whereas 24 h urinary protein excretion increased mildly by 9%. Indomethacin increased day-night urinary volume ratio by 73% in the healthy subjects. It might be concluded that urinary nitrite excretion, urinary excretion of sodium, chloride, phosphorus, calcium, and magnesium increased and FBC decreased in patients with PNFM; Indomethacin decreased urinary volume, FENa, FEK, osmolar clearance, and free water clearance in the healthy subjects and the patients. These might explain the mechanism of action of indomethacin to reduce frequency of voiding. The possible interaction of prostaglandin and NO in the pathogenesis of PNFM is discussed.     

Urinary inhibitors of crystallization in hypercalciuric children with hematuria and nephrolithiasis

Urinary inhibitors are suggested to play a significant role in reducing crystallization in calcium (Ca) stone former and idiopathic hypercalciuria (IH). Urinary inhibitors such as magnesium (Mg), citrate, and glycosaminoglycans (GAGs) were evaluated, as well as urinary Ca and creatinine (Cr), in IH children with nephrolithiasis (LIT) or with hematuria plus IH (HEM) and were compared with a control group. The mean 24-h urinary excretion of Mg was similar in all groups. However, the urine Ca/Mg ratio was significantly increased (P <0.005) in LIT and HEM groups. A higher mean value for GAGs and citrate was found in the HEM group, but a very low level of GAGs (less than 60% of the normal value) and citrate (less than 30% of the normal value) was found in the LIT group. These data suggest that, despite a high urinary Ca excretion (3.6±0.1 mg/kg per day) in the HEM group, elevated urinary GAGs (32.0±1.0 mg/g Cr) and a normal urinary citrate (428.7±62.3 mg/24 h) excretion may prevent Ca crystallization and thus renal stones. In contrast, in the LIT group low urinary GAG (10.3±0.9 mg/g Cr) and citrate (235.2±52.3 mg/24 h) excretion may precipitate stone formation in the presence of a high urinary Ca excretion. Thus, it is reasonable to suggest that patients with hematuria and IH may not develop overt renal stone due to the presence of normal levels of renal stone inhibitors. Received October 30, 1995; accepted December 15, 1995     

Three-year randomized controlled trial of dipyridamole and low-dose warfarin in patients with IgA nephropathy and renal impairment

Summary: Activation of platelets and the coagulation pathway are factors which may contribute to the progression of renal disease in IgA nephropathy (IgAN). Of 21 patients with IgAN and serum creatinines between 1.6 and 3.0 mg/dL, 10 were assigned to treatment with dipyridamole and low-dose warfarin (keeping the thrombotest between 30 and 50%) and 11 to no treatment in a prospective randomized 3-year study. At entry into the trial, patients in the treatment group were younger (35 ± 6 years vs 42 ± 9 years) and had worse histological scores for tubular atrophy (1.7 ± 0.7 vs 1.1 ± 0.5) and arteriolar hyperplasia (1.4 ± 0.7 vs 0.7 ± 0.8) than those in the non-treatment group. There were no differences in serum creatinine values, creatinine clearances, urinary protein excretions, serum albumins or urinary erythrocyte counts. At the end of the trial, patients on treatment did not experience a significant increase in serum creatinine values (1.9 ± 0.3 mg/dL to 2.5 ± 1.2) or reduction in creatinine clearances (52 ± 20mL/min to 52 ± 27). Untreated patients, however, experienced a significant rise in serum creatinine values (2.1 ± 0.5 mg/dL to 3.3 ± 1.1, P < 0.01) and a fall in creatinine clearances (51 ± 26 mL/min to 31 ± 22, P = 0.06). There was no significant change in the proteinuria in either group (treatment group: 1.2 ± 1.2 g/day to 1.3 ± 1.1, non-treatment group: 1.9 ± 1.4 to 1.5 ± 1.1) and there was also no change in serum albumins and urinary erythrocyte counts. Four untreated and one treated patient developed end-stage renal failure during the course of the trial. This study suggests that treatment of patients with IgAN and renal impairment with dipyridamole and low-dose warfarin retards the deterioration of renal function, as measured by the serum creatinine and creatinine clearance.