Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteinuria in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplantation. We investigated the effect of proteinuria on cardiovascular disease after renal transplantation in 532 renal transplant patients with functioning grafts for more than 1 year. Patients were classified into two groups depending on the presence of persistent proteinuria. We analyzed graft and patient survival, posttransplantation cardiovascular disease, and main causes of graft loss and death. Five- and 10-year graft and patient survival rates were lower in the group with proteinuria. The main cause of death was vascular disease in both groups. The presence of posttransplantation cardiovascular disease was higher in the group with proteinuria. Persistent proteinuria was associated with graft loss (RR=4.18), patient death (RR=1.92), and cardiovascular disease (RR=2.45). In conclusion, persistent proteinuria was an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.
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PMID:The risk of cardiovascular disease associated with proteinuria in renal transplant patients. 1198 34

Idiopathic nodular glomerulosclerosis (ING) is an enigmatic condition that resembles nodular diabetic glomerulosclerosis but occurs in nondiabetic patients. We reviewed clinicopathologic features, immunohistochemical profiles, and outcomes in 23 patients with ING diagnosed from among 5,073 native renal biopsy samples (0.45%) at Columbia University from January 1996 to March 2001. This cohort, in which diabetes mellitus was excluded, consisted predominantly of older (mean age, 68.2 years) white (73.9%) men (78.3%). Clinical findings at presentation included renal insufficiency in 82.6% (mean serum creatinine = 2.4 mg/dL), proteinuria (> 3 g/d in 69.6%; mean 24-hour urine protein = 4.7 g/d), and-less frequently-full nephrotic syndrome (21.7%). There was a high prevalence of hypertension (95.7%; mean = 15.1 +/- 3.4 years), smoking (91.3%; mean = 52.9 +/- 6.9 pack-years), hypercholesterolemia (90%), and extrarenal vascular disease (43.5%). All 23 patients had prominent diffuse and nodular mesangial sclerosis, glomerular basement membrane thickening, arteriosclerosis, and arteriolosclerosis. Immunohistochemical staining for CD34, a marker of endothelial cells, showed an increased number of vascular channels within ING glomeruli compared with normal controls. Follow-up data were available for 17 patients, 6 of whom reached end-stage renal disease (ESRD) (35.3%). By Kaplan-Meier estimates, the median time after biopsy to ESRD was 26 months. Predictors of progression to ESRD included continuation of smoking (P =.0165), lack of angiotensin II blockade (P =.0007), degree of tubular atrophy and interstitial fibrosis (P =.0517), and degree of arteriosclerosis (P =.0096). In conclusion, ING is a progressive vasculopathic lesion linked to hypertension and cigarette smoking.
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PMID:Idiopathic nodular glomerulosclerosis is a distinct clinicopathologic entity linked to hypertension and smoking. 1220 16

Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.
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PMID:Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. 1243 44

Hyperuricemia is associated with renal disease, but it is usually considered a marker of renal dysfunction rather than a risk factor for progression. Recent studies have reported that mild hyperuricemia in normal rats induced by the uricase inhibitor, oxonic acid (OA), results in hypertension, intrarenal vascular disease, and renal injury. This led to the hypothesis that uric acid may contribute to progressive renal disease. To examine the effect of hyperuricemia on renal disease progression, rats were fed 2% OA for 6 wk after 5/6 remnant kidney (RK) surgery with or without the xanthine oxidase inhibitor, allopurinol, or the uricosuric agent, benziodarone. Renal function and histologic studies were performed at 6 wk. Given observations that uric acid induces vascular disease, the effect of uric acid on vascular smooth muscle cells in culture was also examined. RK rats developed transient hyperuricemia (2.7 mg/dl at week 2), but then levels returned to baseline by week 6 (1.4 mg/dl). In contrast, RK+OA rats developed higher and more persistent hyperuricemia (6 wk, 3.2 mg/dl). Hyperuricemic rats demonstrated higher BP, greater proteinuria, and higher serum creatinine than RK rats. Hyperuricemic RK rats had more renal hypertrophy and greater glomerulosclerosis (24.2 +/- 2.5 versus 17.5 +/- 3.4%; P < 0.05) and interstitial fibrosis (1.89 +/- 0.45 versus 1.52 +/- 0.47; P < 0.05). Hyperuricemic rats developed vascular disease consisting of thickening of the preglomerular arteries with smooth muscle cell proliferation; these changes were significantly more severe than a historical RK group with similar BP. Allopurinol significantly reduced uric acid levels and blocked the renal functional and histologic changes. Benziodarone reduced uric acid levels less effectively and only partially improved BP and renal function, with minimal effect on the vascular changes. To better understand the mechanism for the vascular disease, the expression of COX-2 and renin were examined. Hyperuricemic rats showed increased renal renin and COX-2 expression, the latter especially in preglomerular arterial vessels. In in vitro studies, cultured vascular smooth muscle cells incubated with uric acid also generated COX-2 with time-dependent proliferation, which was prevented by either a COX-2 or TXA-2 receptor inhibitor. Hyperuricemia accelerates renal progression in the RK model via a mechanism linked to high systemic BP and COX-2-mediated, thromboxane-induced vascular disease. These studies provide direct evidence that uric acid may be a true mediator of renal disease and progression.
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PMID:A role for uric acid in the progression of renal disease. 1244 7

Total protein, albumin, alpha1-microglobulin, and immunoglobulin G (IgG) were analyzed in 1,622 urine samples without Bence-Jones proteinuria or gross hematuria. There was correlation with the histological picture obtained on renal biopsy in 61 patients. We established 24-h reference intervals for alpha1-microglobulin and IgG on 659 urine samples with total protein and albumin excretion rates below 100 mg/24 h and 30 mg/24 h, respectively, and creatinine clearance above 80 ml/min. The central 95% reference interval was found to be between 4 and 17 mg/24 h for alpha1-microglobulin and between 3 and 8.5 mg/24 h for IgG. In 80 urine samples with albumin excretion rate above 30 mg/24 h and alpha1-microglobulin and IgG within their reference intervals, we analyzed the 95% central interval of the distribution of the IgG/albumin ratios, and it was found to be within 0.01 and 0.20 (0.90 confidence interval: 0.17-0.24). Proteinuria was considered to be of the selective glomerular type if the albumin excretion rate was abnormal and the IgG/albumin ratio was under 0.20, even when the IgG excretion was within a pathological range. For the classification of proteinuria as predominantly tubular, we estimated the alpha1-microglobulin/albumin ratio in 173 urine samples with normal excretion rates of albumin and IgG and pathological excretion of alpha1-microglobulin. The discriminating value of 0.91 (0.90 confidence interval: 0.78-1.08) was accepted in order to define proteinuria of a tubular origin in the presence of a pathological albumin excretion rate. The association between albumin and IgG excretion rates and tubular reabsorption of the alpha1-microglobulin normally filtered by the glomerulus was studied in 33 urine samples from patients with no histologically significant tubulo-interstitial or vascular disease and a serum creatinine concentration below 141 pmol/l. The optimal curve-fitting function between albumin plus IgG and alpha1-microglobulin excretion rates was of the quadratic type (r = 0.927). Mixed proteinuria was considered when both, albumin and alpha1-microglobulin excretion rates were pathological and could not be included in the previously described groups.
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PMID:Classification of renal proteinuria: a simple algorithm. 1296 21

In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril's effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 microM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria.
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PMID:Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study. 1259 99

MN is relatively common in the elderly and can lead to significant morbidity and mortality as a result of complications of the nephrotic syndrome and end-stage renal disease. Some cases of MN may be missed as asymptomatic urinary abnormalities and progressive renal disease may be attributed incorrectly to vascular disease or normal aging. Urinary abnormalities and changes in renal function should be evaluated in the elderly using the same criteria as applied in younger individuals. When MN is diagnosed in an elderly individual, it has the same risks for progression as in younger individuals; thus, therapy for hypertension, hyperlipidemia, edema, and proteinuria should be instituted. When appropriate, elderly individuals should receive immunosuppressive therapy to induce a remission of the nephrotic syndrome and reduce the risk for progressive loss of renal function using criteria similar to younger patients. Most studies show response rates to be comparable in all age groups examined. The only consistent recommendation is to avoid high-dose corticosteroids when possible. Recognize that drug dosages need to be modified and carefully monitored and that the elderly may be particularly prone to side effects and infectious complications of immunosuppressive therapy. Although treatment of MN in the elderly has unique challenges, reducing the need for renal replacement therapy in this population merits special attention. This is a US government work. There are no restrictions on its use.
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PMID:Treatment of membranous nephropathy in the elderly. 1292 25

BACKGROUND: Black and African patients with type 2 diabetes have a greater frequency and more severe vascular complications of the disease, even after correction for socioeconomic factors. Asymptomatic sickle cell trait (SCT; hemoglobin AS) is also common among black Africans and may independently cause endothelial damage, manifested as isolated target organ complication or infarction. We examined the possibility that patients with concurrent type 2 diabetes and SCT may be predisposed to more frequent or severe diabetic macro- or microvascular complications than those without SCT. METHODS: Fifty-two type 2 diabetic patients were divided into four groups, according to gender and hemoglobin genotype (normal: AA or SCT: AS). The groups were well matched for age and for clinical and demographic parameters. Diabetic complications were assessed in each patient and scored. Hemoglobin genotype was determined by hemoglobin-gel electrophoresis. Statistical comparisons were made between the groups. RESULTS: The composite complication score for vascular disease differed significantly according to gender and genotype (p<0.027 ANOVA). Male diabetics with SCT had a higher risk ratio (RR 1.6, p<0.02) for complications than those with normal hemoglobin; however, this was not the case with female diabetics. Among the male diabetics with SCT, there was a significantly greater proportion with proteinuria (p<0.02) or retinopathy (p<0.05) than among those with a normal hemoglobin genotype. Multiple regression analysis showed that gender and SCT were independent predictors of the vascular complication severity score and that exclusion of hemoglobin genotype weakened the predictability of the regression. A significantly higher proportion of male than female diabetics had at least one detectable complication. Systolic or diastolic blood pressure had no significant impact on the regressions. CONCLUSION: Male gender and SCT may adversely affect the expression of microvascular diabetic complications in Africans. Diabetic patients from populations predisposed to the sickle gene should be screened for the trait as part of their initial risk assessment. Large-scale studies on the impact of hemoglobin genotype on diabetic complications are clearly indicated.
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PMID:Sickle cell trait and gender influence type 2 diabetic complications in African patients. 1545 Sep 89

Prolonged hyperuricemia is associated with the development of hypertension, renal arteriolosclerosis, glomerulosclerosis, and tubulointerstitial injury. It confers a greater risk than proteinuria for developing chronic renal disease and is associated with the development of hypertension. Mild chronic hyperuricemia without intrarenal crystal deposition was induced in rats by inhibiting uricase with oxonic acid. Hyperuricemic rats developed hypertension, afferent arteriolar thickening, and mild renal interstitial fibrosis. Additionally, hyperuricemia accelerated renal damage and vascular disease in rats undergoing renal ablation. To better understand the role of hyperuricemia in the kidney, micropuncture studies were performed. Hyperuricemia resulted in renal cortical vasoconstriction (single nephron glomerular filtration rate (SNGFR) 35%, P < .05) and glomerular hypertension (P < .05). The possibility that hyperuricemia could modify renal hemodynamic disturbances during progression of renal disease was tested in rats with 5/6 nephrectomy. Hyperuricemia accentuated the renal vascular damage and caused cortical vasoconstriction (SNGFR 40%, P < .05) and persistent glomerular hypertension. In conclusion, hyperuricemia impairs the autoregulatory response of preglomerular vessels, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening results in severe vasoconstriction. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis as well as arterial hypertension.
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PMID:Hemodynamics of hyperuricemia. 1566 Mar 30

Although hyperuricemia has long been associated with renal disease, uric acid has not been considered as a true mediator of progression of renal disease. The observation that hyperuricemia commonly is associated with other risk factors of cardiovascular and renal disease, especially hypertension, has made it difficult to dissect the effect of uric acid itself. However, recent epidemiologic evidence suggests a significant and independent association between the level of serum uric acid and renal disease progression with beneficial effect of decreasing uric acid levels. Furthermore, our experimental data using hyperuricemic animals and cultured cells have provided robust evidence regarding the role of uric acid on progression of renal disease. Hyperuricemia increased systemic blood pressure, proteinuria, renal dysfunction, vascular disease, and progressive renal scarring in rats. Recent data also suggest hyperuricemia may be one of the key and previously unknown mechanisms for the activation of the renin-angiotensin and cyclooxygenase-2 (COX-2) systems in progressive renal disease. Although we must be cautious in the interpretation of animal models to human disease, these studies provide a mechanism to explain epidemiologic data that show uric acid is an independent risk factor for renal progression. Although there is no concrete evidence yet that uric acid bears a causal or reversible relationship to progressive renal disease in humans, it is time to reevaluate the implication of hyperuricemia as an important player for progression of renal disease and to try to find safe and reasonable therapeutic modalities in individual patients based on their clinical data, medication history, and the presence of cardiovascular complications.
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PMID:Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease. 1566 Mar 34


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