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PubMed2003

Downregulation of nitric oxide synthase in nephrotic syndrome: role of proteinuria.

Blood pressure is frequently elevated, blood volume is usually normal or increased and plasma renin and aldosterone are usually low in nephrotic syndrome (NS). These observations challenge the conventional view attributing sodium retention in NS to a hypoalbuminemia-induced intravascular volume contraction. Given the pivotal role of nitric oxide (NO) in regulation of renal sodium (Na) handling, vascular resistance and sympathetic activity, we considered that Na retention and hypertension in NS may be associated with impaired NO system. Urinary excretion of Na and NO metabolites (NOx), as well as immunodetectable endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) NO synthases were determined in rats with puromycin aminonucleoside (PAN)-induced NS, rats with protein overload proteinuria, Nagase rats (NAR) with inherited analbuminemia, iNOS inhibitor (aminoguanidine)-treated rats, prenephrotic PAN-treated and placebo-treated control rats. The NS group showed marked proteinuria, hypoalbuminemia, decreased fractional excretion of Na (FENa), reduced urinary NOx excretion, and severe reduction of iNOS and nNOS protein abundance in the kidney. Similar results were found in rats with protein overload proteinuria in which proteinuria was present without hypoalbuminemia. In contrast, despite extreme hypoalbuminemia, NAR showed normal FENa, increased urinary NOx excretion and upregulations of iNOS and nNOS protein abundance in the kidney. Administration of aminoguanidine for 3 weeks lowered FENa in normal rats to levels approximating those found in the NS group. Animals studied 2 days after PAN administration (wherein proteinuria was absent) showed no abnormality. Thus, chronic PAN-induced NS results in downregulation of kidney iNOS and nNOS, which can contribute to the reduction of FENa by augmenting renal tubular Na reabsorption, and preglomerular vasoconstriction. Findings in the NAR, which had profound hypoalbuminemia without proteinuria, and in rats with protein overload proteinuria, which had proteinuria without hypoalbuminemia, point to proteinuria as the primary mediator of kidney iNOS and nNOS deficiency and impaired Na excretion in PAN-induced NS.

Animals↗
PubMed2000

Immunomorphometric studies of proteinuria in individual deep and superficial nephrons of rats.

Heterogeneity of structure and function among nephrons is a well-recognized feature of chronic renal diseases. However, only a small number of superficial nephrons per kidney are accessible for micropuncture analysis and relationships of proteinuria to structural change in individual nephrons of experimental models are not clearly established. To directly evaluate proteinuria in many individual nephrons, we developed an immunomorphometric method of analysis. This method is based on the uniformly abundant renal synthesis of Tamm-Horsfall protein (THP) in the thick ascending limb of Henle's loop (TAL). Luminal rabbit immunoglobulin G (IgG) deposits are formed in TALs of proteinuric nephrons in rats injected with heterologous IgG anti-THP antibodies. This immunomorphometric luminal deposit method of assessing proteinuria was previously validated through analysis of heterologous immune complex nephropathy. Glomerular dysfunction in several models-spontaneously hypertensive rats (SHR), aging Sprague-Dawley (SD) rats, rats with adriamycin nephropathy (ADR), and rats subjected to subtotal nephrectomy (NX)-was characterized by immunomorphometric analysis after injection of anti-THP antibodies. Luminal IgG deposits were used to identify nephrons with increased proteinuria. Nephrons were identified histologically as either long looped (LL) or short looped (SL), and frequency of luminal deposits in these nephrons was determined. Glomerular size and sclerosis in deep and superficial zones of renal cortex were determined. Luminal deposits in LL nephrons were more frequent than luminal deposits in SL nephrons in SHRs (p < .001) and aging rats (p < .001) and SL nephrons in ADR rats (p < .02). Whole kidney levels of albuminuria correlated closely with the frequency of luminal deposits in both LL and SL nephrons of SHRs and ADR rats and in LL nephrons of aging rats (p < .005). In contrast, LL and SL deposits were equal in NX rats and did not correlate with albuminuria. A majority of luminal deposits extended beyond the first medullary TAL zone of NX rats, but was confined to this zone in the other 3 models. Deep cortical glomeruli were larger with more glomerulosclerosis than superficial cortical glomeruli. Albuminuria correlated with sclerosis of both deep (p < .002) and superficial (p < .01) glomeruli in NX rats, but not in the other three models. These studies provide a detailed characterization of a new method that allows comparison of proteinuria derived from deep and superficial nephrons. They also provide evidence that pathogenesis of the glomerulosclerosis in NX rats differs from that of the other three models. Glomerulosclerosis was closely linked to the overall level of albuminuria in NX rats, but not to luminal deposits. In the other three models, albuminuria and luminal deposits were closely linked but did not correlate with glomerulosclerosis. Furthermore, LL and SL nephron proteinuria of NX rats was comparable while LL proteinuria was markedly greater than SL proteinuria in the other three models. The luminal deposit method provides a new way to analyze heterogeneity of proteinuria among nephrons and the mechanisms underlying structural change in experimental glomerular diseases.

Animals↗
PubMed1989

Sudden onset of proteinuria in chronic serum sickness in rats.

1. Daily intravenous administration of bovine serum albumin (BSA) to rats produces chronic serum sickness glomerulonephritis, an immune-complex-mediated renal disease that is eventually always fatal. We have performed a detailed study of the onset of proteinuria in chronic serum sickness in order to assess the long-term consequences of discontinuing daily BSA injections precisely at that very early and well-defined stage of disease. 2. Urine and plasma samples from rats receiving daily BSA injections were collected and analysed daily before the onset of proteinuria, at which time the rats were divided into three groups. Group 1 continued to receive daily BSA injections, in group 2 injections were stopped on the first, and in group 3 on the third, day of proteinuria. Proteinuria began suddenly and was not preceded either by microalbuminuria or abnormalities of plasma composition. The sudden expression of proteinuria was accompanied by an equally rapid development of hypoalbuminaemia and hypercholesterolaemia. Development of the characteristic glomerular histopathology of serum sickness coincided with, but did not precede, the onset of proteinuria. Despite the discontinuation of antigen injections at the onset of proteinuria, basement membrane thickening was evident 8 weeks later; proteinuria persisted and hypercholesterolaemia increased. 3. In this model of immune complex glomerulonephritis, changes in kidney function and immunopathology were abrupt and closely linked, precluding the use of those criteria to predict when proteinuria would begin. Furthermore, extremely brief periods of active immunological injury to the peripheral capillary wall were sufficient to produce persistent abnormalities of glomerular structure and function.

Animals↗
PubMed2002

Predictors of proteinuria and renal failure among women with HIV infection.

BACKGROUND: Glomerular disease with proteinuria and renal failure are complications of human immunodeficiency virus (HIV) infection. While studies suggest risk factors for both include black race and lower CD4 lymphocyte count, they have not been established in population-based cohorts. This study examines the risk factors for proteinuria and renal failure in a large cohort of HIV-infected women not selected for the presence of renal disease. METHODS: This prospective cohort includes 2059 women enrolled in the Women's Interagency HIV study (WIHS). WIHS is a longitudinal study of the clinical course of HIV infection in which subjects are followed biannually with a detailed exam including urine analysis, serum creatinine, CD4 lymphocyte count, and HIV RNA level. Proteinuria was defined as > or =+1 on urine dipstick exam on at least two consecutive urine analyses, and renal failure was defined as a doubling of serum creatinine. Multivariable logistic regression was used to estimate the associations between clinical variables and the presence of proteinuria on initial evaluation in a cross-sectional analysis. Cox proportional hazards regression was used to estimate the associations between clinical variables and time to renal failure among study participants with proteinuria in a prospective longitudinal analysis. RESULTS: Of 2057 HIV-positive women, 32% (N=671) had proteinuria on initial evaluation. Predictors of proteinuria include increasing (log) HIV RNA level [odds ratio (OR)=1.05], black race (OR=2.0), absolute CD4 lymphocyte count < or =200 cells/mm3 (OR=1.41), and the presence of hepatitis C antibody (OR=1.27; all P < 0.0001). Absolute CD4 lymphocyte count < or =200 cells/mm3 [hazard ratio (HR)=3.57, P=0.001], detectable HIV RNA level (HR=2.33, P=0.02), increasing systolic blood pressure (HR=1.02, P=0.002), and decreasing albumin (HR=3.33, P=0.0001) and increasing creatinine (1.67, P=0.0001) were all associated with the development of renal failure. CONCLUSIONS: This analysis establishes the associations between both increasing HIV RNA level and decreasing CD4 lymphocyte count with the presence of proteinuria and occurrence of renal failure. Additionally, it demonstrates an association between proteinuria and a positive hepatitis C antibody. To lessen the presence and progression of renal disease among HIV-infected patients, future research should focus on suppression of the HIV RNA level and improvement in CD4 lymphocyte count.

Adult↗
PubMed2001

Characterization of proteinuria in asymptomatic family members and household contacts of children with hepatitis B virus-associated membranous nephropathy.

The biosocial background in which the hepatitis B virus (HBV) carrier state with membranous nephropathy (MN) develops was studied by evaluating HBV carriage and proteinuria among 195 family members and household contacts of 31 index HBV carrier children with MN. Unrelated individuals from the communities of these index cases who were negative for HBV served as controls (n = 123). HBV was determined by using third-generation enzyme-linked immunosorbent assay, slot-blot hybridization, and nested polymerase chain reaction. Patterns of proteinuria were determined by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis; immunoglobulin G and haptoglobulin were suggestive of MN. Seventy-two members (36.9%) of the study group (n = 195) were HBV carriers; 21 of these carriers (29.2%) had proteinuria. Twenty-eight members (41.2%) of the study group who were HBV negative (n = 68) and 26.8% of the controls showed proteinuria. This lack of association between HBV carriage and proteinuria remained when controlled for sex and family relationship. HBV was not protective against the development of proteinuria. Proteinuria suggestive of MN was strongly associated with an abnormal protein-creatinine ratio (P: = 0.001), but was not significantly different between subjects and controls (8.7% versus 6.5%; P: = 0.5). Genetic influences or environmental exposures in these subjects may be responsible for the proteinuria, suggesting underlying glomerular basement membrane damage. Discordance between the HBV carrier state and patterns of proteinuria in the study group suggest that HBV and MN may not be causally related or may reflect exceptional interaction between specifically vulnerable individuals and HBV.

Adolescent↗
PubMed2000

Proteinuria is a key determinant of death in patients with diabetes after isolated coronary artery bypass grafting.

BACKGROUND: Proteinuria is a marker for underlying diabetic nephropathy and may be a surrogate marker for advanced atherosclerosis. It is unknown if proteinuria is a determinant of death in patients with diabetes after coronary artery bypass grafting. We hypothesized that diabetic patients with evidence of proteinuria would have increased mortality and clinical event rates after isolated coronary artery bypass grafting compared with nonproteinuric diabetic patients. METHODS AND RESULTS: We performed an observational of study of 905 diabetic patients with urinalysis and available follow-up data (nonproteinuria, n = 651; proteinuria, n = 254) after isolated coronary artery bypass grafting at the Cleveland Clinic Foundation between January 1989 and December 1992. The proteinuria group was further prospectively stratified into low-concentration (n = 225) and high-concentration (n = 29) groups. The end points of this study were all-cause mortality and the composite end point of death, nonfatal myocardial infarction, and need for repeat revascularization. The mean follow-up time was 66 months. The 5-year mortality rate for the nonproteinuria and proteinuria groups was 20.2% and 29.1% (P <.001), respectively. The 5-year rate of death, nonfatal myocardial infarction, and need for repeat revascularization for the nonproteinuria and proteinuria groups was 25.2% and 36.2% (P <.001), respectively. Significant multivariate predictors of 5-year mortality included age, not using a left internal mammary artery graft to the left anterior descending coronary artery, proteinuria, lower body weight, and increased creatinine level. CONCLUSIONS: Among diabetic patients, proteinuria appears to be an important predictor of death after isolated coronary artery bypass grafting.

Aged↗
PubMed2002

Long-term effects of losartan on proteinuria and renal function in patients with renal amyloidosis.

OBJECTIVE: To investigate the effect of the angiotensin II receptor antagonist losartan on proteinuria in secondary amyloidosis cases. MATERIAL AND METHODS: Sixteen patients with renal biopsy-proven AA amyloidosis with proteinuria were included in the study. All the patients had received colchicine treatment for at least 18 months. The patients were divided into two groups with similar age and gender distributions. Eight patients were given losartan at a dose of 50 mg/day for 12 months and the other 8 patients served as controls. Mean arterial blood pressure, proteinuria, serum albumin level and renal function were determined at the initiation of the study and after 1 and 12 months. RESULTS: There were no significant differences in proteinuria, serum albumin level, renal function or mean arterial blood pressure at the initiation of the study. In the losartan group daily proteinuria decreased significantly from 5.2 +/- 0.7 g at the initiation of the study to 3.9 +/- 1.2 g at 1 month and 3.6 +/- 0.8 g at 12 months, while in the control group it changed from 4.6 +/- 1.0 g to 4.7 +/- 1.0 g and 6.1 +/- 1.2 g, respectively. The increment at 12 months was significant. After 12 months of treatment with losartan, proteinuria was significantly lower in comparison to the degree of proteinuria in the control group. Serum albumin level increased significantly in the losartan group but was unchanged in the control group. In the control group, creatinine clearance showed a significant decrease. There was no significant difference in mean arterial blood pressure measurements, serum creatinine levels, total protein, albumin and creatinine clearance levels between the two groups. CONCLUSIONS: Losartan seemed to prevent an increase in proteinuria without altering the creatinine clearance level in patients with amyloidosis type AA during a 12-month period. This indicates that losartan may be used to decrease proteinuria in this patient group. However, our results are only preliminary and need to be confirmed by larger studies.

Adult↗
PubMed2006

Increase of proteinuria after conversion from calcineurin inhibitor to sirolimus-based treatment in kidney transplant patients with chronic allograft dysfunction.

BACKGROUND: Conversion from calcineurin inhibitor to sirolimus, rapamycin has become an option in patients with chronic allograft dysfunction (CAD). However, in many cases an increase of proteinuria has been observed. The aim was to characterize the course of this so far unexplained proteinuria after conversion. METHODS: In 149 renal transplant patients from various Spanish centres, proteinuria and renal function were analysed 6 months before until 6 months after conversion. Patients were divided into three groups according to mean proteinuria before conversion (1: 300-3500 mg/day; 3:>3.5 g/day). RESULTS: Generally patients showed an increase of proteinuria from 864+/-1441 (0-12125) to 1541+/-1878 (0-10976) mg/day after conversion; P<0.001. Group 1: 145+/-92 vs 669+/-868 mg/day, P<0.001; group 2: 1041+/-799 vs 1995+/-2021 mg/day, P<0.001; group 3: 6205+/-3184 vs 4859+/-2122 mg/day, P=NS. Patients with an increase of proteinuria of >500 mg/day (n=60; 40%) had a higher serum creatinine before conversion compared with patients with no or moderate increase (2.5+/-0.8 vs 2.15+/-0.72 mg/dl; P=0.002). The group that experienced an increase>500 mg/day had a higher serum creatinine after conversion compared with the patients with no or moderate increase (2.8+/-1.0 vs 2.1+/-1.2; P<0.001). Of 64 patients, 19 in group 1 showed an increase>500 mg/day. CONCLUSION: Conversion for CAD can be associated with an increase of proteinuria in patients with pre-existing renal damage; however, it preserves renal function in patients with better creatinine and proteinuria before conversion, and might not be of benefit if advanced loss of renal function and high proteinuria are already present before conversion.

Calcineurin Inhibitors↗
PubMed2006

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XL II: factors predictive of new or worsening proteinuria.

OBJECTIVES: To determine the factors predictive of new or worsening proteinuria in a large multiethnic cohort of patients with systemic lupus erythematosus (SLE). METHODS: Five hundred and twenty-nine SLE patients from a multiethnic US cohort [LUpus in MInorities: NAture versus Nurture (LUMINA)] were evaluated for new or worsening proteinuria using the categories of the Systemic Lupus Activity Measure-Revised: (1), normal; (2), trace or 1+ proteinuria on the dipstick; (3), 2-3+ proteinuria and (4), > or =4+ proteinuria. A rise in urinary protein was considered a positive event visit. Basic demographic and socioeconomic variables were assessed at baseline (T0). Clinical and immunological variables including disease features, activity, duration, comorbidities (such as hypertension and diabetes), medications and autoantibodies were assessed at the visit preceding a positive event visit. Selected HLA-DR and HLA-DQ alleles, and FCGR receptor polymorphisms were assessed. Data were analysed using logistic regression analyses and generalized estimating equations. RESULTS: There were 243 patients (59.1% of 93 Texan Hispanics, 37.0% of 100 Puerto Rican Hispanics, 58.0% of 181 African Americans and 29.7% of 155 Caucasians) with new or worsening proteinuria, and 364 positive events in 2801 visits. Younger age [Odds ratio (OR) = 1.013, 95% confidence limits (CL) = 1.001-1.024, P < 0.0334], anti-dsDNA (OR = 1.554, CL = 1.149-2.100, P < 0.0042), and HLA-DRB1*1503 (OR = 1.746, 95% CL = 1.573-2.2673, P < 0.0103) were found to independently predict the occurrence of new or worsening proteinuria. CONCLUSION: The factors predictive of new or worsening proteinuria include traditional factors associated with lupus nephritis, such as age and anti-dsDNA, as well as HLA-DRB1*1503, which has not been previously described in association with lupus nephritis, new or worsening proteinuria.

Adult↗
PubMed1998

Pretransplant hepatitis C virus infection: a predictor of proteinuria after renal transplantation.

BACKGROUND: Reports have suggested that hepatitis C virus (HCV)-infected kidney recipients may develop de novo glomerular lesions caused by the virus. We studied the relationships between pretransplantation anti-HCV antibodies and the occurrence of proteinuria and the link with short- and long-term patient and graft survival. METHODS: A total of 322 consecutive renal recipients treated at a single center from 1989 to 1994 whose sera were routinely assayed for anti-HCV antibodies at the time of transplantation were analyzed. The risks of persistent proteinuria (>1 g/day), graft loss, or death were estimated by Kaplan-Meier analysis. The relationship between clinical variables and each outcome was examined by Cox multivariate regression analysis. RESULTS: Before transplantation, 9.6% of the recipients were anti-HCV antibody positive. Persistent proteinuria developed in 13.6% recipients. The presence of anti-HCV antibodies was strongly associated with proteinuria (relative risk [RR]=5.36, 95% confidence interval [CI]=2.49-11.51). Proteinuria occurred more frequently in second grafts (RR=2.64, 95% CI=1.10-6.29). The number of HLA-A,B mismatches was an independent risk factor (RR=1.55, 95% CI=1.10-2.19). Recipient age (RR=0.80, 95% CI=0.63-1.02) and duration of dialysis (RR=0.86, 95% CI=0.77-0.96) were protective factors. Histology of biopsies from 26/44 recipients with proteinuria showed that de novo glomerular lesions were more frequent in HCV-positive patients, although the difference was not significant. One- and five-year graft survival rates were significantly worse in patients with proteinuria (90.7% and 41.1%) than in patients without it (95.6% and 91.8%) (P<0.00001). Despite the strong association between HCV infection and proteinuria, patient and graft survival rates in anti-HCV-positive and anti-HCV-negative recipients were similar. CONCLUSIONS: The presence of anti-HCV antibodies before renal transplantation seems to be a major risk factor of proteinuria after transplantation. This may be due to glomerular lesions caused by HCV. However, anti-HCV has no impact on 5-year patient and graft survival.

Adult↗
PubMed2002

Risk factors for proteinuria in a large, multiracial, southeast Asian population.

The factors associated with proteinuria were examined in a large multiracial Asian population participating in a screening program aimed at the early detection of renal disease. Of 213,873 adults who participated, 189,117 with complete data were included. Malay race, increasing age, both extremes of body mass index (BMI), self-reported family history of kidney disease (FKD), and higher systolic and diastolic BP measurements (even at levels classified as being within the normal range) were independently associated with dipstick-positive proteinuria. The odds ratios (OR) for proteinuria increased progressively with age. There was a J-shaped relationship between BMI and proteinuria (OR of 1.3, 1.00, 1.3, 1.6, and 2.5 for BMI of < or =18.00, 23.00 to 24.99, 25.00 to 27.49, 27.50 to 29.99, and > or =30.00 kg/m(2), respectively, compared with BMI of 18.01 to 22.99 kg/m(2)). OR for proteinuria according to systolic and diastolic BP were significantly increased beginning at levels of 110 and 90 mmHg, respectively. In addition, the Malay race was associated with a significantly higher OR for proteinuria, compared with the Chinese race (OR of 1.3). Finally, FKD was significantly associated with proteinuria (OR of 1.7), whereas a family history of diabetes mellitus and a family history of hypertension were not. When family histories were analyzed by clustering, isolated FKD remained a significant determinant of proteinuria and the magnitude of the effect was not significantly different from that observed in the presence of a coexisting family history of diabetes mellitus or hypertension. This is the first study to evaluate factors associated with proteinuria in an Asian population. The epidemiologic study of renal disease in this population suggests that risk factors for renal disease might differ significantly among racial groups.

Adult↗
PubMed2007

Clinical significance of proteinuria in pregnancy.

UNLABELLED: Urinary protein excretion is considered abnormal in pregnant women when it exceeds 300 mg/24 hours at anytime during gestation, a level that usually correlates with 1+ on urine dipstick. Proteinuria documented before pregnancy or before 20 weeks' gestation suggests preexisting renal disease. The National High Blood Pressure Education Program Working Group recommended that that the diagnosis of proteinuria be based on the 24-hour urine collection. Preeclampsia is the leading diagnosis that must be excluded in all women with proteinuria first identified after 20 weeks of gestation. Given the vasospastic nature of this condition, when it is present, the degree of proteinuria may fluctuate widely from hour-to-hour. Hypertension or proteinuria may be absent in 10-15% of patients with HELLP syndrome and in 38% of patients with eclampsia. The acute onset of proteinuria and worsening hypertension in women with chronic hypertension is suggestive of superimposed preeclampsia, which increases adverse outcomes. However, because proteinuria is not independently predictive of adverse outcome, an exclusive proteinuric criterion as an indication for preterm delivery in preeclampsia should be discouraged. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that measurement of urinary protein levels by simple techniques are not sensitive or specific, recall that both hypertension and proteinuria may be absent in patients with preeclampsia, and explain that proteinuria is not predictive of adverse outcomes and that delivery should not be based on protein excretion alone.

Female↗
PubMed1987

Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus.

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.

Adult↗
PubMed1990

Proteinuria and progression in human glomerular diseases.

Proteinuria is characteristic of many glomerular conditions, and often exceeds 2-3 g/24 h. There are several possible routes by which such profuse proteinuria might contribute to progression of the underlying pathology, whatever its type. First, proteinuria leads to a transit of protein through glomerular structures, including the glomerular capillary basement membrane, the mesangium and the epithelial cells, and to increased traffic of protein through the proximal tubules by pinocytosis of filtered protein. This traffic may be toxic to the cells concerned, and there is some evidence from 'overload' proteinuria induced in animals that this is so. Second, proteinuria leads to secondary hyperlipidemia with raised lipoproteins: mesangial cells have receptors for lipoproteins and in vitro, they are damaged by high concentrations, and there is evidence that hyperlipidemia leads to glomerulosclerosis. Third, proteinuria leads to hyperaggregability of platelets through alterations in plasma proteins, principally a fall in concentration of serum albumin and a rise in that of the von Willebrand factor, and possibly to increases in humoral coagulation cascades as well through losses of regulator proteins such as antithrombin III. There is evidence that anticoagulation and antiplatelet drugs will inhibit glomerulosclerosis in animals. Whether all or any of these mechanisms operate in human disease is not known; however, prognosis correlates well with duration and intensity of proteinuria in almost all proteinuric states and with the appearance and persistence of proteinuria in hematuric conditions. Therapies designed to reduce proteinuria per se may have a role in the treatment of glomerulopathies.

Animals↗
PubMed1983

Characteristics of proteinuria in endemic nephropathy.

Subjects living in the endemic area of Posavina round Slavonski Brod have a significantly greater incidence of proteinuria (13.6%) than those living under the same conditions in the area where endemic nephropathy has not been observed (5.5%). Following determination of the grade and type of proteinuria, physiologic proteinuria was found in 36% of subjects from the endemic area. In nonphysiologic proteinuria the incidence of tubular proteinuria was 41%. A slight selective glomerular proteinuria was found in 51%, and other types of proteinuria in 8% of subjects. Tubular proteinuria was significantly higher in the endemic area than in the control area. The subjects with tubular proteinuria from the endemic area excrete significantly greater amounts of beta 2-microglobulin and light immunoglobulin chains.

Adolescent↗
PubMed1994

Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease.

The amount of proteinuria is a prognostic indicator in a variety of glomerular disorders. To examine the importance of urinary protein excretion in autosomal dominant polycystic kidney disease, this study determined the clinical characteristics of autosomal dominant polycystic kidney disease patients with established proteinuria and the frequency of microalbuminuria in hypertensive autosomal dominant polycystic kidney disease patients without proteinuria. In 270 autosomal dominant polycystic kidney disease patients, mean 24-h urinary protein excretion was 259 +/- 22 mg/day. Forty-eight of 270 autosomal dominant poly-cystic kidney disease patients had over proteinuria (> 300 mg/day). The patients with established proteinuria had higher mean arterial pressures, larger renal volumes, and lower creatinine clearances than did their nonproteinuric counterparts (all P < 0.0001), a greater pack year smoking history (P < 0.05), and the projection of a more aggressive course of renal disease (P < 0.05). All autosomal dominant polycystic kidney disease patients with established proteinuria were hypertensive, as compared with 67% without established proteinuria (P < 0.001). Forty-nine patients with hypertension and left ventricular hypertrophy without established proteinuria were examined for microalbuminuria; 41% demonstrated microalbuminuria. Those with microalbuminuria had higher mean arterial pressure, larger renal volumes and increased filtration fraction. Therefore, established proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease patients are associated with increased mean arterial pressure and more severe renal cystic involvement.

Adult↗
PubMed1988

Effect of proteinuria on mortality in NIDDM.

The effect of proteinuria (greater than or equal to approximately 1 g/day) on mortality in non-insulin-dependent diabetes mellitus (NIDDM) was assessed in Pima Indians aged greater than or equal to 45 yr. Among 1426 subjects, 48% with NIDDM at the beginning of followup, there were 489 deaths in 13,345 person-yr of observation. The age- and sex-adjusted mortality rate was 32.7/1000 person-yr (95% Cl = 27.6, 37.8) in diabetic subjects without proteinuria, similar to the rate of 30.1/1000 person-yr (95% Cl = 25.7, 34.4) in nondiabetic subjects without proteinuria. By contrast, in diabetic subjects with proteinuria the mortality rate was 121.4/1000 person-yr (95% Cl = 97.5, 145.3). When controlled for age, sex, and diabetes duration, diabetic subjects with proteinuria had a death rate 3.5 times as high (95% Cl = 2.8, 4.4) as those without proteinuria. Of the excess mortality associated with NIDDM in Pima Indians, 97% was found in subjects with proteinuria. The death rate in diabetic subjects without proteinuria was not appreciably greater than the rate in nondiabetic subjects. Mortality rates from uremia and cardiovascular disease were significantly higher in diabetic Pima Indians with proteinuria than in those without. These relationships are similar to observations reported in people with insulin-dependent diabetes.

Aged↗
PubMed2002

Proteinuria as a predictor of total plasma homocysteine levels in type 2 diabetic nephropathy.

OBJECTIVE: Patients with diabetes who manifest proteinuria are at increased risk for cardiovascular events. Some studies suggest that proteinuria exerts its cardiovascular effects at least partly through a positive association with total plasma homocysteine (tHcy). Modestly sized but better designed contrary studies find no such link through a limited range of serum creatinine and proteinuria. We tested the hypothesis that proteinuria independently predicts tHcy levels in a larger cohort of type 2 diabetic patients with nephropathy throughout a much broader range of kidney disease and proteinuria. RESEARCH DESIGN AND METHODS: Baseline data for the cross-sectional study were obtained from 717 patients enrolled in the multicenter Irbesartan Diabetic Nephropathy Trial. All subjects had type 2 diabetes, hypertension, and proteinuria and were between 29 and 78 years of age. Data included age, sex, BMI, serum creatinine and albumin, LDL and HDL cholesterol, triglyceride, proteinuria and albuminuria, plasma folate, B12, and pyridoxal 5'-phosphate (PLP) (the active form of B6), HbA(1c), and tHcy levels. Unadjusted and multivariable models were used in the analysis. RESULTS: Crude analyses revealed significant associations between tHcy and age (r = 0.074; P = 0.008), creatinine (r = 0.414; P < 0.001), PLP (r = -0.105; P = 0.021), B12 (r = -0.216; P < 0.001), folate (r = -0.241; P < 0.001), and HbA(1c) (r = -0.119; P = 0.003), with serum albumin approaching significance (r = 0.055; P = 0.072). Only serum creatinine, plasma folate, B12, serum albumin, sex, HbA(1c), and age were independent predictors of tHcy after controlling for all other variables. CONCLUSIONS: By finding no independent correlation between proteinuria (or albuminuria) and tHcy levels, this study improves the external validity of previous negative findings. Therefore, it is unlikely that the observed positive association between proteinuria and cardiovascular disease is directly related to hyperhomocysteinemia.

Cholesterol, HDL↗