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Parental hypertension and proteinuria in Pima Indians with NIDDM.

To determine if parental hypertension is associated with proteinuria in offspring with non-insulin-dependent diabetes mellitus (NIDDM), 438 diabetic Pima Indians (172 men, 266 women) aged 20 years or more and both of their parents were examined. Hypertension was defined as a systolic blood pressure 140 mm Hg or more, diastolic blood pressure 90 mm Hg or more, or treatment with antihypertensive medicine. Sixty-three percent of the fathers and 80% of the mothers had diabetes at the time their blood pressure was measured. Families in which either parent had proteinuria, defined as a urine protein-to-creatinine ratio > or = 0.5 g/g were excluded; 73 (16.7%) of the offspring had proteinuria. The prevalence rates of proteinuria in the offspring were similar if neither parent or only one parent had hypertension (8.9 and 9.4%, respectively), but was significantly higher if both parents had hypertension (18.8%), after adjustment for age, sex, duration of diabetes, and 2-h post-load plasma glucose concentration in the offspring and diabetes in the parents by logistic regression. The odds for proteinuria being present in the offspring if both parents had hypertension was 2.2 times (95% confidence interval, 1.2 to 4.2) that if only one parent had hypertension. When mean arterial pressure and blood pressure treatment in the offspring were added to the model the relationship remained (odds ratio = 2.2; 95% confidence interval, 1.1 to 4.3). Hypertension in both parents is associated with the development of proteinuria in offspring with NIDDM. This relationship was present even when controlled for the effects of blood pressure and its treatment in the offspring.

Adult↗

Leucocyte count, proteinuria and smoking in type 1 diabetes mellitus.

A case-control study was carried out to analyse leucocyte counts in relation to proteinuria and smoking in type 1 (insulin-dependent) diabetes. The subjects were 180 smoking (87 women, age 32 +/- 11 years, diabetes duration 14 +/- 6 years) and 188 nonsmoking (88 women, age 32 +/- 11 years, diabetes duration, 14 +/- 6 years) type 1 diabetic patients. Leucocyte counts were higher in smokers than in nonsmokers, both in women (7.6 +/- 2.3 vs 6.8 +/- 1.9 x 10(9)/l, P < 0.01) and in men (8.1 +/- 2.7 vs 6.4 +/- 2.0 x 10(9)/l, P < 0.0001). Leucocyte counts correlated with the number of cigarettes smoked per day (r = 0.32, P < 0.0001), but were unrelated to glycosylated haemoglobin levels. Among nonsmokers, leucocyte counts were comparable between patients with normal proteinuria (6.7 +/- 2.2 x 10(9)/l, n = 106), microproteinuria (6.3 +/- 1.7 x 10(9)/l, n = 66) and macroproteinuria (6.8 +/- 1.1 x 10(9)/l, n = 16). Among smokers, patients with macroproteinuria or microproteinuria had higher leucocyte counts than those with normal proteinuria [8.9 +/- 3.0 x 10(9)/l, (n = 36) vs 8.4 +/- 2.7 x 10(9)/l (n = 61) vs 7.0 +/- 1.9 x 10(9)/l (n = 83); P < 0.0001)], a finding which was not due to differences in the number of cigarettes smoked per day. It is concluded that in these type 1 diabetic patients leucocyte counts were higher in smokers than in nonsmokers. Among nonsmokers leucocyte counts were comparable between patients with normal proteinuria and increased proteinuria, whereas among smokers leucocyte counts were higher in patients with increased proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Discelectrophoretic analysis of the tubular proteinuria (author's transl)].

The urinary protein pattern following tubular damage is different from other proteinurias. The tubular proteinuria consists of micromolecular proteins of MW 10-70000. The disturbed tubular function probably leads to a diminished reabsorption of these microproteins from the tubular fluids. By determining the molecular weight of the urinary proteins by SDS-PAA-electrophoresis tubular proteinurias may be distinguished from glomerular and extrarenal forms. Tubular proteinurias are found in inflammatory, degenerative and vascular tubulopathies. The course of acute tubular diseases reveals proteinurias of different micromolecular composition depending of the improving tubular function; this supports the concept of a selective tubular reabsorption of microproteins. Tubular proteinurias are associated with normal as well as with impaired glomerular filtration, which, in part, might influence the amount of microproteins excreted.

Acute Kidney Injury↗

Quantitative trait loci for proteinuria in the focal glomerulosclerosis mouse model.

The FGS/Kist strain of mice, a new animal model for focal glomerulosclerosis (FGS) in humans, was previously established by recurrent selection for high proteinuria, which is a principal marker of FGS, from descendants of CBA/Nga and RFM/Nga strains. We performed a genome-wide scan for quantitative trait loci (QTLs) affecting proteinuria in a population of 356 backcross progeny derived from a cross between FGS/Kist and the standard normal strain, C57BL/6J. Five proteinuria QTLs (Ptnu1-5) were detected at the genome-wide 5% or less level. Ptnu1 and Ptnu2, located on Chromosomes (Chrs) 8 and 17, respectively, had main effects on proteinuria and also interacted epistatically with each other. However, Ptnu3 on Chr 9 and Ptnu4 and Ptnu5 both on Chr 15 had epistatic interaction effects only. Except for the epistatic interaction effect of Ptnu4 and Ptnu5, all alleles derived from FGS/Kist were responsible for the high proteinuria. These results indicated that the genetic control of proteinuria is complex and the identified QTLs may provide new insights into the pathogenesis of FGS in mice as well as in humans.

Analysis of Variance↗

Effect of oral camostat mesilate on hematuria and/or proteinuria in children.

The effects of camostat mesilate (CM), a derivative of gabexate mesilate developed for oral use, on primary glomerulonephritis (GN) and chance hematuria and/or proteinuria were evaluated. Fourteen patients (6 males, 8 females) with a mean age of 11 years and 3 months (range 4-16 years) were enrolled. Histological and clinical diagnoses of the 14 patients were as follows: IgA nephropathy 3, non-IgA GN 2, and asymptomatic significant microscopic hematuria [more than 100 red blood cells per high-power field (x400)] with or without proteinuria 9. They were consecutively treated with oral CM (100 mg twice a day) when they were confirmed to have continuous significant microscopic hematuria and/or proteinuria after a few months of observational follow-up. Urinary findings were normalized in 10 of the 14 patients (85.7%) between 1 month 1 week and 10 months (mean 4 months) after administration of CM. Hematuria cleared in 11 of 13 patients, and proteinuria disappeared in 4 of 5 patients. The mean duration of CM administration was 21.7 +/- 9.1 months (range 4-37 months). At present, 3-12 years after discontinuation of CM therapy, their urinary findings remain normal at 9 years 10 months to 26 years 6 months of age. In conclusion, there appears to be an association between the oral use of CM and reduction in significant microscopic hematuria and/or proteinuria. Oral CM therapy could represent a practical primary care approach to chance hematuria and/or proteinuria in children.

Administration, Oral↗

Hematuria and proteinuria in a mass school urine screening test.

A total of 1,044 school children identified with hematuria and/or proteinuria during a mass school urine screening test were referred to pediatric nephrologists at 13 hospitals in Korea. These children had isolated hematuria (IH) (60.1%), isolated proteinuria (IP) (26.4%: transient, 19.6%; orthostatic, 4.9%; persistent, 1.9%) or combined hematuria and proteinuria (CHP) (13.5%). The patient's history, physical examination, laboratory tests, kidney ultrasound and Doppler ultrasonography were obtained. Renal biopsies were performed on 113 children who showed severe proteinuria, hypertension, abnormal renal function, family history of chronic renal disease, systemic diseases or persistent hematuria and/or proteinuria for more than 12 months. IgA nephropathy (IgAN), thin basement membrane nephropathy (TBMN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), other GN, Alport syndrome and lupus nephritis were detected. IgAN and TBMN were the most common causes in the CHP group and IH group, respectively. Abnormal findings on the renal ultrasound with or without Doppler ultrasonography were noted in 147 cases (suspected nutcracker phenomenon, 65; increased parenchymal echogenicity, 40; hydronephrosis, 15). This study showed that the use of a mass school urine screening program can detect chronic renal disease in its early stage and recommends that more attention should be paid to identifying those children with CHP and massive proteinuria. A school urine screening program can detect chronic renal disease in its early stage. When mass screening is used, the initial aggressive diagnostic procedures such as renal biopsy are not needed. In addition, a regular follow-up for those children with IH and IP is certainly warranted.

Adolescent↗

Tubular proteinuria in pre-term and full-term infants.

Predictors of tubular proteinuria (alpha 1-M/crea ratio >10 mg/mmol) were sought in 100 infants of 24-32 weeks' (group 1) and 69 of 34-42 weeks' gestation (group 2). Random spot urine samples were obtained in the former group at the ages of 0-3 days, at 1-2 weeks and thereafter at 2-week intervals until the disappearance of tubular proteinuria, and in the latter one sample at a mean (SD) of 3.0 days' (1.3) age. In group 1, gestational age correlated negatively with the first urinary alpha 1-M/crea ratio. The highest urinary alpha 1-M/crea ratios [median (range) 39.1 mg/mmol (9.5-268.9)] occurred at a median (range) of 5 days' (1-42) age. Low gestational age and the need for inotropes predicted tubular proteinuria early after birth, whereas low gestation and long duration of ventilator treatment predicted the highest alpha 1-M/crea ratios. Prolonged vancomycin treatment and low gestational age were associated with delayed normalization of tubular proteinuria. In group 2 no significant risk factors for tubular proteinuria were found. The urinary alpha 1-M/crea ratio seems to be a sensitive indicator of renal tubular function in neonates, with low gestational age, the need for inotropes and prolonged assisted ventilation being predictors of increased tubular proteinuria. Long vancomycin courses should be avoided in pre-term infants in view of the prolonged adverse renal effects.

Alpha-Globulins↗

Proteinuria and renal disease: prognostic value of urine dipstick testing for leukocytes.

Proteinuria is utilized to screen for underlying kidney disease and serves as a marker of disease progression. The aim of this study was to test the hypothesis that patients with proteinuria will have a higher frequency of urine dipstick positive for leukocytes as an index of noninfectious renal inflammation. In this retrospective analysis, 1,099 urine specimens were evaluated from 676 patients. Proteinuria was present in 39% of the samples and leukocyturia in 5.1%. The percentage of urines that were dipstick positive for leukocytes was similar in those specimens with or without proteinuria. However, in patients with proteinuria and concomitant leukocyturia, the mean serum creatinine concentration was higher (P=0.003) and the calculated GFR was lower (P=0.01) compared to those without this additional abnormality. These differences were noted despite similar age, gender distribution, and array of underlying diseases in these two groups. Based on these findings, urine dipstick testing for leukocytes as a primary means of screening otherwise healthy children for serious renal disease is of little value. However, in patients with established proteinuria, a positive dipstick result for leukocytes is a simple means of identifying those with more prominent noninfectious renal inflammation, a process which may promote kidney disease progression. This finding may serve as an early marker of the severity of renal injury, regardless of whether the primary process is glomerular or tubular.

Child↗

Profiling proteinuria in pediatric patients.

This study was designed to characterize proteinuria in children with kidney disease. Random urine samples from 250 pediatric patients were examined by quantitative measures of total protein (pr), albumin (Alb), and creatinine (cr). Patient diagnoses were subjectively categorized as "Glomerular" (GD) or "Tubulo-interstitial" disease (TD) in origin. Proteinuria was quantitated by the random urine protein-to-creatinine (Upr/cr) ratio, and glomerular proteinuria was assessed as the albumin-to-creatinine ratio (Ualb/cr) and percentage albuminuria (%Alb=Alb/pr*100). The non-albumin fraction (1-Alb/pr) includes low-molecular-weight proteins and micro- and macroglobulins. Of the 250 patients, 112 (45%) had GD and 138 (55%) had TD. Both proteinuria and albuminuria correlated with a decline in glomerular filtration rate (GFR) (r=-0.4; p<0.0001). Those with GD averaged significantly greater %Alb than those with TD at all levels of proteinuria (p<0.0001). With loss in GFR, %Alb increased significantly in patients with TD (18+/-13 to 47+/-30%; p<0.001) and GD (56+/-26 to 74+/-15%; p<0.01), respectively. The %Alb at all levels of GFR averaged <50% in those with TD and >50% in those with GD. In conclusion, random Ualb/cr, Upr/cr, and %Alb provide a simple and inexpensive assessment of proteinuria and may profile renal disease activity and response to therapy in pediatric patients.

Adolescent↗

Influence of blood pressure changes with and without proteinuria upon outcome of pregnancy.

A prospective study of 10,074 white gravidas and 2,880 black gravidas carried out during the years 1959 to 1967 has been analyzed with respect to the impact of elevated blood pressures and/or proteinuria upon pregnancy outcome. Edema was not considered because no evidence is available to indicate that its occurrence increases risk. The mean arterial pressure exhibited during the fifth and sixth months of pregnancy was found to be of significance, as well as the absolute levels of blood pressure attained prior to labor and delivery. The degree of rise in blood pressure was not of importance in itself. However, categories with significant proteinuria had greater increases in mean arterial pressure than did comparable categories without it. Significant proteinuria alone but especially with hypertension was also detrimental to pregnancy outcome. Eight categories incorporating early and late hypertension with and without proteinuria were created, and these were given descriptive diagnostic labels. Only "gestational hypertension," as defined, proved to be essentially devoid of risk to the fetus. In all other non-normotensive categories there was an increase in the stillbirth rate, the perinatal mortality rate, the frequency of intrauterine growth retardation, and neonatal morbidity. In every category, each of these untoward events was greater in black than in white gravidas, and a higher percentage of blacks was noted in each of the hypertensive categories. It is believed that hypertension, significant proteinuria, or both are associated with decreased uteroplacental blood flow which is the common denominator for all of these deleterious effects. The study suggests that "gestational hypertension" occurring late but without proteinuria may or may not represent an early stage of "pre-eclampsia" but does not, at least, place the infant at any substantially increased risk.

Black or African American↗

Proteinuria and blood glucose levels in a population with diabetic retinopathy.

In a population-based study of all insulin-treated diabetic patients on the Swedish island of Gotland, we compared the prevalence and severity of retinopathy with those of nephropathy as measured by proteinuria and serum creatinine levels. Of 365 diabetic patients, 66 (18%) had proteinuria. Of these 66, 39 (59%) had retinopathy. Proteinuria and serum creatinine correlated with increasing severity of retinopathy (P less than .001). Of 47 patients with proliferative retinopathy, 19 (40%) had proteinuria. Of 124 patients with retinopathy of other grades of severity, 20 (16%) had proteinuria. Visual acuity in the best eye was negatively correlated to proteinuria, which was present in 17 of 203 (8.4%) patients with a visual acuity of 20/20, compared with eight of 15 (53%) of those with a visual acuity of 20/200 or less. Blood glucose, determined two hours postprandially, was satisfactory (less than 10 mmol/l) in 162 patients (44%), unsatisfactory (10 to 14 mmol/l) in 89 (24%), and poorly regulated (greater than 14 mmol/l) in 114 (31%). Increasing mean blood glucose correlated to retinopathy (P less than .05).

Adolescent↗

Does labetalol influence the development of proteinuria in pregnancy hypertension? A randomised controlled study.

It is the development of proteinuria in pregnancy-induced hypertension which is associated with an increased perinatal mortality. There is some evidence to suggest that labetalol may diminish the amount of proteinuria in patients who have already developed proteinuric pre-eclampsia. A randomised controlled study design was used to investigate whether labetalol treatment, started when a persistent diastolic blood pressure greater than 90 mmHg was observed, influenced the subsequent development of proteinuria. One hundred and fourteen women with singleton pregnancies and hypertension in the absence of proteinuria were randomised to receive either labetalol or no antihypertensive therapy. At recruitment maternal age, blood pressure and gestation were similar in both the labetalol and control groups. There was no difference in the frequency, quantity or timing of subsequent proteinuria between treatment and control groups. Overall 34% of primigravidae and 10% of parous women developed proteinuria. Labetalol did, however, control the blood pressure in 45 of the 51 treated women (88%) within 24 h. This effect was often shortlived requiring dose escalation after 3 to 5 days in the majority of cases. Labetalol was well tolerated and no significant maternal toxicity was noted.

Adult↗

Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients.

Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U-test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann-Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Experimental confirmation in rats of the mixed type proteinuria observed in workers exposed to cadmium.

Recently we have reported that the proteinuria developed by workers exposed to cadmium was characterized by an increased excretion of high and low molecular weight proteins. These observations were confirmed experimentally. Female rats which were injected intraperitoneally with CdCl2 (1 mg Cd2+/kg) 5 times a week developed after 2 months of treatment a proteinuria qualitatively similar to that observed in workers exposed to cadmium. The analysis of this proteinuria by electrophoresis and gel filtration revealed an increased excretion of low and high molecular weight proteins. This animal study, which confirms previous observations on man, strengthens our hypothesis that the cadmium-induced proteinuria, classically considered as a tubular type proteinuria, is in fact a mixed type proteinuria, involving not only the tubule but also the glomerulus.

Animals↗

Early proteinuria is a strong indicator of donor renal lesions, ischemia-reperfusion injury and immunological aggression.

BACKGROUND: Early proteinuria is associated with reduced long-term graft survival. However, the determinants and mechanisms of proteinuria early after transplantation have not been identified. METHODS: Parameters associated with proteinuria within the first 3 months following transplantation were retrospectively assessed among 484 renal transplant recipients. RESULTS: Proteinuria was more abundant in patients with a history of two or more rejection episodes (0.42 +/- 0.68 vs 0.18 +/- 0.39 g/d; P = .02). Proteinuria was greater when donor age was 60 or more (OR: 4.43; P = .003), when recipient death was due to cardiovascular causes (OR: 1.98; P = .002), or when cold (OR: 1.77; P = .006) or warm (1.21; P = .09) ischemia times were prolonged. CONCLUSIONS: Proteinuria early after transplantation was related to pretransplant renal lesions, ischemia-reperfusion, and immunologic injuries.

Biomarkers↗

Pregnancy aggravates proteinuria in subclinical glomerulonephritis in the rat.

Because subclinical renal disease may be aggravated during pregnancy--as reflected in the occurrence of proteinuria, for example--we investigated whether a subclinical glomerulonephritis (SG) in the non-pregnant rat (passive Heymann nephritis), a condition without proteinuria, is aggravated when the animals become pregnant and, if so, whether this is associated with a glomerular inflammatory reaction. SG was induced in non-pregnant rats 8 days before pregnancy. On day -1, part of the group of rats became pregnant. Three experiments were performed. In experiment 1, 4-hour urine albumin excretions and blood pressure (tail cuff) were measured. In experiment 2, the glomerular filtration rate (GFR) was measured with the chromium 51-labeled ethylenediaminetetraacetic acid method, while in experiment 3, parameters characteristic of a glomerular inflammation were studied. Experiment 1 revealed that non-pregnant rats with SG did not exhibit proteinuria. However, after the rats became pregnant, a significant proteinuria occurred, without an increase in systolic blood pressure. Experiment 2 revealed that the GFR did not increase in pregnant rats with SG, while experiment 3 showed that only pregnant animals exhibited a significant glomerular inflammation; this glomerular inflammation was characterized by intraglomerular influx of polymorphonuclear cells and monocytes. The results suggest that an SG in the rat may flare up during pregnancy. This exacerbation is characterized by proteinuria and coincides with a glomerular inflammatory reaction. It is suggested that proteinuria and the glomerular inflammatory reaction are causally related and promoted by the pregnant condition.

Albuminuria↗

Isolated proteinuria: analysis of a school-age population.

Proteinuria was found in at least one of four specimens in 10.7% and in at least two of four specimens in 2.5% of 8,594 schoolchildren, ages 8 to 15 years. To determine the risk of renal disease in isolated proteinuria, the screening program was followed by a systematic clinical evaluation of the proteinuric children. After those with both proteinuria and hematuria were excluded, none of the remaining children was found to have an overt renal disease. Despite urinary protein concentrations in excess of 1,000 mg/dl and protein excretion rates of up to 1 gm in 24 hours, proteinuria proved to be transient or intermittent in every child when a large enough number of urine samples was tested. Children with the highest protein excretion rates (more than 6 mg/hour/m2 at night or more than 20 mg/hour/m2 during the day) and those with the most persistent patterns of proteinuria underwent renal function studies, intravenous pyelography, and renal biopsy. No significant abnormalities was found. Mild nonspecific changes were seen in 12 of 28 biopsies, with mesangial deposits in four. The results show that if hematuria and other signs have been excluded, a benign renal morphologic picture is almost invariably to be expected in intermittent proteinuria; renal biopsy, therefore, is not indicated.

Adolescent↗

Selectivity as a clue to diagnosis of postural proteinuria.

In 14 patients with fixed and reproducible postural proteinuria and 14 patients with histologically proven glomerulonephritis, the selectivity of proteinuria was measured separately in the day and night urine collections. The selectivity of proteinuria in the urine collected in recumbency was lower in patients with glomerulonephritis than in patients with postural proteinuria. All patients with postural proteinuria showed an increment of the selectivity from day to night of at least 13 degrees, whereas the maximum increment in patients with glomerulonephritis was 5 degrees. The changes in selectivity from day to night in patients with postural proteinuria and patients with glomerulonephritis were significantly different and seem to be a useful discriminatory test.

Adolescent↗