Urinary Β2-microglobulin Excretion Research Articles

Çocukluk Çağı Kanser Yaşayanlarında Nefrotoksisitenin İncelenmesi ve Glomerüler Filtrasyon Hızı Yöntemlerinin Karşılaştırılması

Objective: Increased survival rates in childhood cancers have led the researchers to focus on long-term side effects and possible risk factors for late nephrotoxicity related to the treatment regimens applied. Our aim is to evaluate drug-induced nephrotoxicity in survivors of childhood cancer and to investigate the compatibility of creatinine clearance with the estimated glomerular filtration rate. Methods: The presence of glomerular and tubular dysfunction has been screened among 59 childhood cancer survivors who had completed their treatment regimens with cisplatin, carboplatin, ifosfamide, and /or high dose methotrexate. Results: The mean age of patients was 10.7±5.5 years (2.5-23), and mean follow-up time was 2.6±2.1 years (0.5-8). Renal dysfunction was detected in 65% of the patients. The most prevalent manifestation of renal dysfunction was decreased glomerular filtration rate (n: 19, 32.2%), and increased urinary β2-microglobulin excretion (n: 12, 20.4%), followed by microalbuminuria (n: 6, 10.1%). Survivors treated with combined chemotherapy regimens (cisplatin, carboplatin, ifosfamide) had significantly lower tubular reabsorption of phosphate than those treated with high dose of methotrexate. The glomerular filtration rate analysis was performed using different methods, and a moderate correlation (r=0.563, p=0.00) was found between estimated glomerular filtration rates calculated according to cystatin-C-based equations and Schwartz formula. Conclusion: Childhood cancer survivors demonstrated a high frequency of renal complications in the current study. We have shown that the calculation of the estimated glomerular filtration rate using the Schwartz formula or cystatin-C-based equations is compatible with the creatinine clearance in this specific patient group. In survivors of childhood cancer who cannot perform 24-hour urine collection, determination of estimated glomerular filtration rate is a more practical approach.

Is renal tubular cadmium toxicity clinically relevant?

ABSTRACTBackgroundExposure to cadmium (Cd) has been associated with the development of hypertension, especially in women, but the mechanism of such an association is not understood. We hypothesize that Cd exposure alters renal production of 20-hydroxyeicosatetraenoic acid (20-HETE), which plays an indispensable role in renal salt balance and blood pressure control.MethodsWe examined long-term Cd exposure in relation to urinary 20-HETE excretion levels, tubular dysfunction and blood pressure measures, using data from a population-based, cross-sectional study that included 115 normotensive and 110 hypertensive women, 33–55 years of age, who lived in Cd contamination areas in Thailand.ResultsThe mean [standard deviation (SD)] blood Cd level of the study subjects was 3.57 (3.3) µg/L, while the mean (SD) urinary Cd and urinary 20-HETE levels were 0.58 (0.47) µg/g creatinine and 1651 (4793) pg/mL, respectively. Elevated 20-HETE levels were associated with a 90% increase in prevalence odds of hypertension (P = 0.029), four times greater odds of having higher urinary Cd levels (P = 0.030) and a 53% increase in odds of having higher levels of tubular dysfunction (P = 0.049), evident from an increase in urinary excretion of β2-microglobulin. In normotensive subjects, an increase in urinary 20-HETE levels from tertile 1 to tertile 3 was associated with a systolic blood pressure increase of 6 mmHg (95% confidence interval 0.3–12, P = 0.040).ConclusionsThis is the first report that links urinary 20-HETE levels to blood pressure increases in Cd-exposed women, thereby providing a plausible mechanism for associated development of hypertension.

Does Dent disease remain an underrecognized cause for young boys with focal glomerulosclerosis?

Focal glomerulosclerosis (FGS) is a histologic entity that causes significant proteinuria in children. Although its etiology varies, recent reports indicated that some young male patients with FGS had underlying Dent disease. We describe the case of a 14-year-old Japanese boy who presented with persistent non-nephrotic range proteinuria, hematuria, and renal insufficiency. The patient was initially diagnosed as having FGS associated with scattered tubulointerstitial fibrosis. Although he had neither nephrocalcinosis nor family history of renal disease including urolithiasis, increased excretion of urinary β2 microglobulin was noted. Genetic analysis for Dent disease indicated a mutation (c.726 + 1G > A) in Chloride Channel, Voltage-Sensitive 5 (CLCN5). Given a recent hypothesis that Dent disease may be underrecognized in children with FGS, a careful diagnostic evaluation for possible underlying Dent disease should be considered in young boys who present with persistent albuminuria associated with high-grade low-molecular-weight proteinuria.

Effects of Dietary Calcium Supplementation on Bone Metabolism, Kidney Mineral Concentrations, and Kidney Function in Rats Fed a High-Phosphorus Diet.

We investigated the effects of dietary calcium (Ca) supplementation on bone metabolism, kidney mineral concentrations, and kidney function in rats fed a high-phosphorus (P) diet. Wistar strain rats were randomly divided into 4 dietary groups and fed their respective diets for 21 d: a diet containing 0.3% P and 0.5% Ca (C), a diet containing 1.5% P and 0.5% Ca (HP), a diet containing 0.3% P and 1.0% Ca (HCa), or a diet containing 1.5% P and 1.0% Ca (HPCa). Compared to the C group, the high-P diet increased serum parathyroid hormone concentration, markers of bone turnover, receptor activator of NF-κB ligand mRNA expression of the femur, kidney Ca and P concentrations, urinary N-acetyl-β-D-glucosaminidase activity, and urinary β2-microglobulin excretion, and decreased bone mineral content and bone mineral density of the femur and tibia. Dietary Ca supplementation improved the parameters of bone metabolism and kidney function in rats fed the high-P diet, while there were no significant differences in kidney Ca or P concentrations between the HP and HPCa groups. These results suggest that dietary Ca supplementation prevented the bone loss and decline in kidney function induced by a high-P diet, whereas dietary Ca supplementation did not affect kidney mineral concentrations in rats fed the high-P diet.

Renal and blood pressure effects from environmental cadmium exposure in Thai children

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β2-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1μg/g creatinine. The prevalence of urinary cadmium ≥1μg/g creatinine was significantly higher in girls and in those consuming rice grown in cadmium-contaminated areas. The geometric mean levels of urinary β2-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β2-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children.

Acquired Fanconi syndrome due to long-term adefovir administration in a patient with IgG-kappa monoclonal gammopathy and kappa Bence-Jones protein.

A 77-year-old man was admitted to our hospital for a right femoral neck fracture. He had been prescribed lamivudine for chronic hepatitis B infection for 11years, and adefovir was added 5years ago. After hospitalization, a right femoral head prosthesis was performed successfully, but an unknown hypokalemia was revealed. Hypophosphatemia, hypouricemia, glucosuria, and panaminoaciduria were also revealed, and multiple microfractures were detected by bone scintigraphy. We diagnosed him as 'osteomalacia associated with Fanconi syndrome,' which was likely due to the adefovir. Moreover, a monoclonal IgG-kappa and a kappa Bence-Jones protein were detected in his serum and urine, respectively. We switched from adefovir plus lamivudine to entecavir and started calcitriol. His excessive urinary β2-microglobulin excretion and glucosuria had decreased dramatically at 10weeks after the modification of drugs; those of the phosphate, uric acid and total protein, however, continued. Renal biopsy specimens obtained at 10weeks after discontinuation of adefovir revealed focal tubular atrophic changes with/without inflammatory cells, which were predominantly observed next to glomeruli. Kappa-dominant staining was not observed in either glomeruli or tubules with immunostaining by the enzyme-labeled antibody method. Electron microscopy revealed neither crystalline structures in the cytoplasm of proximal tubules nor electron-dense deposits. Because of the remarkable proportional reduction of other urinary protein fractions, urinary M-peak appeared 26weeks after discontinuation of adefovir, but the net amounts of the fraction decreased gradually.

Urinary excretion of β2-microglobulin as a prognostic marker in immunoglobulin A nephropathy.

Background/Aimsβ2-microglobulin (β2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary β2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear.MethodsWe included urinary β2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between β2-MG levels and clinical parameters as a prognostic biomarker of IgAN.ResultsA total of 51 patients (30 males, 21 females; mean age, 33.01 ± 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 ± 34.78 mL/min/1.73 m2 and 1.28 ± 1.75 g/day, respectively. The mean level of urinary β2-MG was 1.92 ± 7.38 µg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of β2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary β2-MG (p < 0.01). Cox regression analysis showed that albumin, β2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN.ConclusionsUrinary β2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary β2-MG may be an additional prognostic factor in patients with IgAN.

Evaluation of Renal Function in Term Babies with Perinatal Asphyxia

To study the renal function in term newborns with perinatal asphyxia including urinary excretion of β2 microglobulin (β2M). This case control study included 50 term newborn babies with perinatal asphyxia and 50 normal babies as matched controls. In all cases, asphyxia grading (using Apgar score) and Hypoxic ischemic encephalopathy (HIE) staging (Sarnat and Sarnat) were done. Blood and urinary parameters (including β2M) for renal function were done in all and Fractional excretion of sodium (FENa) and Renal failure index (RFI) were calculated. The renal parameters were compared within subgroups as well as controls using analysis of variance test and the independent samples t test. Acute kidney Injury (AKI) was noted in 56% of cases (24% prerenal and 32% intrinsic type). All 9 babies who died had AKI. Serum parameters like urea, creatinine, sodium and potassium had better correlation with the renal function as compared to urine parameters. All individual urine parameters except β2M showed wide variations. FENa, RFI and urinary β2M increased with increasing severity of asphyxia and HIE staging. AKI is common in term babies with perinatal asphyxia. FENa and RFI are useful parameters for assessing the renal function and urinary β2M is a good biomarker for diagnosis and prognosis of acute tubular injury in term babies with perinatal asphyxia.

Progress in cadmium-related health effects in persons with high environmental exposure in northwestern Thailand: A five-year follow-up

Food-borne cadmium was the principal source of exposure for persons living in the 12 cadmium-contaminated villages in Mae Sot District, Tak Province, northwestern Thailand. This report presents progress in cadmium-related health effects among persons with high cadmium exposure. The study included 436 persons who had urinary cadmium levels ≥5μg/g creatinine and were screened for urinary cadmium, renal function, hypertension, diabetes and urinary stones in 2005 (baseline) and 2010 (5-year follow-up). Study renal biomarkers included urinary excretion of β2-microglobulin (β2-MG), total protein and calcium, serum creatinine and glomerular filtration rate (GFR). The geometric mean level of urinary cadmium statistically significantly reduced from 9.5±1.6μg/g creatinine in 2005 to 8.8±1.6μg/g creatinine in 2010. Compared to baseline, the follow-up examination revealed significant increases in urinary β2-MG (tubular effect), urinary total protein and serum creatinine, and a decrease in GFR (glomerular effects). Progressive renal dysfunctions were similarly observed in persons both with and without reduction in cadmium intake. Significant increases in prevalence of hypertension, diabetes and urinary stones were also detected at follow-up. These three disorders were found to markedly impair renal functions in the study persons. Our study indicates that in persons with prolonged excessive cadmium exposure, toxic health effects may progress even after exposure reduction. Renal damage from cadmium can be due to its direct nephrotoxic effect and also through the related disorders causing nephropathy.

Early detection of renal damage caused by fumaric acid ester therapy by determination of urinary β2-microglobulin

Fumaric acid esters are considered efficacious and safe drugs for the treatment of psoriasis. Renal damage, caused either by acute renal injury or Fanconi syndrome, is a recognized side-effect of this therapy. To investigate whether the measurement of urinary excretion of β2-microglobulin, a marker of renal proximal tubular dysfunction, allows early detection of kidney damage before an increase in serum creatinine or significant proteinuria occurs. Urinary β2-microglobulin excretion was measured regularly in 23 patients undergoing fumaric acid ester therapy. Urinary β2-microglobulin remained normal in all 10 male patients. Three (23%) out of 13 female patients experienced an increase in urinary β2-microglobulin excretion. In two of these patients a sharp increase was observed in association with high doses. One further patient had moderately elevated levels on rather low doses of fumaric acid esters. After discontinuing treatment, urinary β2-microglobulin levels returned to normal within a few weeks. Determination of urinary β2-microglobulin possibly allows early detection of renal damage by fumaric acid esters. Female patients seem to be prone to this side-effect, especially when taking high doses.

Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend χ 2 = 6.4, P = 0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male non-smokers (adjusted β = 0.31, P = 0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted β = −0.38, P = 0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of β2-microglobulin ( P = 0.02) and N-acetyl-β- d-glucosaminidase ( P = 0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend χ 2 = 4.3, P = 0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure.

Many confounding factors influencing urinary β2-microglobulin excretion in premature newborns

Many confounding factors influencing urinary β2-microglobulin excretion in premature newborns

Transferrinuria in type 2 diabetic patients with early nephropathy and tubulointerstitial injury

Background: Transferrinuria is thought to be a marker for early stages of diabetic nephropathy. Transferrin has also been proposed as a mediator of tubular toxicity because the reabsorption of transferrin results in the release of reactive iron in proximal tubular cells, promoting the formation of hydroxyl radicals. We evaluated the role of urinary transferrin excretion in diabetic patients with early nephropathy by comparing tubulointerstitial injury in renal biopsy specimens. Patients and methods: 45 type 2 diabetic patients with normoalbuminuria (urinary albumin excretion <30 mg/24 h) or microalbuminuria (30–300 mg/24 h) were studied. All patients with microalbuminuria underwent renal biopsy, and the severity of the tubulo-interstitial lesions was determined by a semiquantitative estimate of interstitial fibrosis, tubular atrophy, and interstitial inflammatory infiltrates. Subjects were classified into group A (normoalbuminuria, n=25), group B (microalbuminuria without tubulointerstitial changes, n=11) or group C (microalbuminuria with tubulointerstitial changes, n=9). Results: Urinary transferrin excretion (UTf), as well as UTf/creatinine clearance (Ccr), and transferrin clearance (CTf/Ccr), was significantly higher in groups B and C than in group A, and it was significantly higher in group C than in group B. There were no significant differences in urinary albumin excretion or mesangial expansion rate (MR% estimated by quantitative morphometric studies) between groups B and C. Although urinary β2-microglobulin excretion was significantly higher in group C than in groups A and B, urinary N-acetyl-β- d-glucosaminidase activity was significantly higher in groups B and C than in group A. Conclusions: Increased transferrinuria in the microalbuminuric stage may lead to the development of tubulointerstitial injuries in type 2 diabetic patients.

EFFECT OF NICARDIPINE VERSUS ENALAPRIL ON PLASMA ENDOTHELIN-1 IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS

We compared the effects of dihydropyridine type Ca channel blocker slow-release nicardipine and angiotensin converting enzyme inhibitor enalapril on plasma endothelin-1 (ET-1) levels in hypertensive type 2 diabetic patients (n = 20). Nicardipine or enalapril was administered for 6 months by a crossover design. Nicardipine and enalapril comparably lowered blood pressure. Enalapril significantly reduced urinary albumin excretion in microalbuminuric patients, whereas nicardipine did not. Urinary β2-microglobulin excretion was significantly increased during nicardipine treatment. However, both drugs significantly reduced plasma ET-1 as compared with pretreatment levels, close to that in healthy control (2.9 ± 0.3 pg/ml in control, 4.8 ± 0.3 pg/ml before treatment, 3.2 ± 0.3 pg/ml during nicardipine vs before treatment p<0.05, 2.9 ± 0.4 pg/ml during enalapril vs before treatment p<0.01). The decrease in plasma ET-1 was significantly correlated with the increase in natriuresis in normoalbuminuric patients treated with enalapril (r=−0.82, p<0.01) but not in those treated with nicardipine. Although nicardipine and enalapril had different renal effects, both drugs equally suppressed plasma ET-1 levels in hypertensive patients with type 2 diabetes.

A follow-up study on renal tubular dysfunction in women living in the cadmium-polluted Jinzu River basin in Toyama, Japan. Part 1. Changes in the level of exposure to cadmium after soil replacement of polluted paddy fields and the related effects on the prognosis of renal tubular dysfunction

A follow-up study on renal tubular dysfunction was carried out on 193 female inhabitants of the cadmium (Cd)-polluted Jinzu River basin and 40 reference subjects living in an adjacent area in 1994-95. They were 54 to 70 years old when the initial examination was conducted in 1983-84. In the Cd-polluted Jinzu River basin, extensive reclamation of polluted rice fields has been conducted since 1979; as a result, the average Cd concentrations in polished rice consumed by the subjects in the 1994-95 study (0.12 ppm in 1994, 0.14 ppm in 1995) were significantly lower than those in the 1983-84 study (0.26 ppm in 1983, 0.29 ppm in 1984). The average Cd levels in urine in the follow-up study (7.5 micrograms/g Cr. in 1994, 7.7 micrograms/g Cr. in 1995) were also significantly lower than those in the initial study (13.5 micrograms/g Cr. in 1983, 13.3 micrograms/g Cr. in 1984). However, the mean values for urinary excretion of beta 2-microglobulin (beta 2-m) (3.9 mg/g Cr. in 1994, 3.7 mg/g Cr. in 1995) and glucose (203 mg/g Cr. in 1994, 251 mg/g Cr. in 1995) in the follow-up study were significantly higher than those obtained at the initial examination (2.0 mg/g Cr. and 125 mg/g Cr. in 1983 and 1.1 mg/g Cr. and 78 mg/g Cr. in 1984 for beta 2-m and glucose excretion, respectively). The magnitude of increase in urinary excretion of beta 2-m and glucose in inhabitants of the Cd-polluted area was significantly higher than that of the inhabitants of the reference area. Moreover, an increase was observed in the prevalence of renal tubular dysfunction determined by urinary beta 2-m exceeding 10 mg/g creatinine and urinary glucose exceeding 150 mg/g creatinine only among inhabitants of the Cd-polluted area; it is noteworthy that 31 new cases of renal tubular dysfunction were observed in the follow-up study. These results indicate that renal tubular dysfunction among inhabitants of the Cd-polluted Jinzu River basin is irreversible and progressive, and many new cases of renal tubular dysfunction were also noted over a period of 11 years, despite the fact that Cd exposure had decreased over the past 11 years.

Frequent episodes of acute renal failure and a complication of Fanconi's syndrome in a patient with paroxysmal nocturnal hemoglobinuria

A 41-year-old man with aplastic anemia and paroxysmal nocturnal hemoglobinuria complex presented with complaints of frequent episodes of acute renal failure associated with hemolytic attacks. In the last admission he suffered from severe renal dysfunction that required hemodialysis for 3 weeks. A renal biopsy sample showed normal appearing of glomeruli and a moderate degree of tubular atrophy, probably due to massive ferrous deposition which was confirmed by x-ray analysis. He was found to have Fanconi's syndrome, with phosphaturia, uricosuria, acidic aminoaciduria, and excessive urinaryβ2-microglobulin excretion. This is a case in which paroxysmal nocturnal hemoglobinuria caused frequent episodes of acute renal failure and a coincident Fanconi's syndrome.

Percutaneous Reduction of Cyst Volume of Polycystic Kidney Disease: Effects on Renal Function

Percutaneous reduction of cyst volume was performed in 10 patients with autosomal dominant polycystic kidney disease and its effects on renal function were studied. Although creatinine clearance, urinary excretion of β2-microglobulin and N-acetyl-β-D-ghicosaminidase, and renal uptake of 99mtechnetium-dimercaptosuccinic acid did not change significantly, a transient increase in urinary protein and a decrease in inulin clearance were observed. Complications, such as hematuria, fever and decreases in hematocrit, were slight and transient in most patients. This procedure holds little promise for altering the course of polycystic kidney disease.

Pharmacokinetics of recombinant human superoxide dismutase in healthy volunteers

We studied the pharmacokinetics and effects of recombinant human superoxide dismutase (rhSOD) in 32 normal human volunteers after intravenous bolus doses from 1 mg/kg to 45 mg/kg in a single-blind, placebo-controlled, crossover design. The drug was well tolerated. Neither cardiovascular nor renal function, such as the echocardiographically determined cardiac index, insulin or para-aminohippurate clearance, or the urinary excretion of beta 2-microglobulin or N-acetylglucosaminidase, was affected. Pharmacokinetic analysis by use of noncompartmental methods showed an overall half-life of rhSOD to be about 4 hours for doses from 3 mg/kg to 45 mg/kg. The peak concentrations ranged from 24 to 837 mg/L, and urinary excretion increased from 3% to 57% of total dose after single intravenous bolus administrations of the drug from 1 mg/kg to 45 mg/kg. The mean renal clearance of rhSOD initially increased with dose then plateaued at the highest dose, whereas the nonrenal clearance decreased with dose to a plateau; total clearance remained essentially constant. The progressive increase in renal clearance may be explained by saturation of the tubular reabsorption and degradation of the protein, a mechanism previously described in animal models.

Changes in urinary proximal tubule parameters in neonatal rats exposed to cadmium chloride during pregnancy

Pregnant Sprague-Dawley rats were injected intraperitoneally with physiological saline solution (vehicle) or cadmium chloride (CdCl2) at 2.0 or 2.5 mg kg-1 on days 8, 10, 12 and 14 of gestation. On postnatal day (PND) 3, 12 or 49, the offspring were examined for 8- or 24-h urinary excretion of beta 2-microglobulin (beta 2-m), metallothionein (MT) and urinary activity of three proximal tubular enzymes: gammaglutamyl transferase (GGT), alkaline phosphatase (ALP) and N-acetyl-beta-glucosaminidase (NAG). Treatment with CdCl2 did not affect growth or survival of offspring. Significant decreases in the urinary excretion of GGT, ALP and NAG were observed on PND 3, at both doses. Exposure to 4 x 2.5 mg kg-1 resulted in functional deficit of the proximal tubule on PND 3, as evidenced by the significant increase in beta 2-m. Except for a slight but significant increase of beta 2-m in 49-day-old males, all the other urinary parameters returned to control values on PND 12. There was no effect on MT. Results from this study show that prenatal exposure to CdCl2 can induce significant changes in the kidney biochemistry of rats in the early postnatal period.

Urinary Albumin Excretion in Patients with Non-Insulin-Dependent Diabetes mellitus in an Early Microalbuminuric Stage

We investigated the urinary albumin excretion and renal hemodynamics of normotensive nonobese patients with impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) in an early microalbuminuric stage (defined by albuminuria less than 30 mg/day). In comparison with normal subjects, a significant increase in urinary albumin excretion was observed already in the IGT stage [U-albumin/U-creatinine: NL (20 subjects), 5.3 +/- 1.7 mg/g Cr; IGT (23 subjects), 11.9 +/- 6.7 mg/g Cr; DM (20 subjects), 12.8 +/- 5.7 mg/g Cr]. A 3-week diet therapy combined with physical exercise prescribed for 53 normotensive non-obese mild NIDDM patients resulted in improvement in glucose tolerance, concomitant with lowered systemic blood pressure and a decrease in urinary albumin excretion (SBP: 128.4 +/- 13.0 to 106.4 +/- 10.2 mm Hg, p less than 0.01; DBP: 78.2 +/- 10.8 to 66.0 +/- 8.0 mm Hg, p less than 0.01; U-albumin: 19.4 +/- 10.3 to 10.1 +/- 9.1 mg/day, p less than 0.01). However, glomerular filtration rate, renal plasma flow, filtration fraction and urinary beta 2-microglobulin excretion remained unchanged. From these results, we hypothesized that focal glomerular hyperperfusion increases urinary albumin excretion in patients with early NIDDM.