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)

Diabetic nephropathy has become the single largest cause of end-stage renal disease (ESRD) worldwide. Until recently, it was thought that once a patient developed overt proteinuria, diabetic nephropathy was irreversible and inevitably progressed to ESRD. However, the reversal of lesions caused by diabetic nephropathy (e.g., glomerular basement membrane thickening and mesangial matrix increase) has been demonstrated in a series of patients who underwent a pancreas transplantation 10 years prior to the reversal. Remission of nephrotic range proteinuria has also been reported in some patients with type 1 diabetes from the Collaborative Study Group during a median follow-up of 3 years of angiotensin-converting enzyme (ACE) inhibitor administration; no deterioration of renal function was observed in these patients. Remission and regression in nephropathy of type 1 diabetes patients have also been reported when blood pressure was controlled aggressively. Recent clinical trials have demonstrated that angiotensin II receptor blocker (ARB) preserved renal function and slowed the progression of nephropathy to ESRD in patients with type 2 diabetes. Since many patients with type 2 diabetes manifest with a metabolic syndrome, multifactorial intensive treatment is necessary; such treatment includes behavior modifications, dietary intervention, exercise, and smoking cessation. In this population, pharmacological therapy targeting hyperglycemia, hypertension (including ARB/ACE inhibitor), and hyperlipidemia in cases of type 2 diabetes is also necessary.
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PMID:Remission and regression of diabetic nephropathy. 1292 17

Candesartan shows beneficial end-organ effects in the kidney. Some of these appear to be related not to the reduction in systemic blood pressure induced by candesartan, but to its blockage of intrarenal angiotensin II type I (AT1) receptors. Initial studies have shown that renal vascular resistance was reduced in patients with hypertension receiving candesartan, and urinary albumin excretion was reduced in patients with type 2 diabetes mellitus and concomitant microalbuminuria or proteinuria. These findings, together with the results of recently published large randomized studies involving diabetic patients with hypertension treated with other angiotensin II receptor blockers, indicate that this class of drugs is beneficial in preventing the development or progression of diabetic nephropathy. This review summarizes the large body of findings related to these renoprotective effects and reported during experimental and clinical research on candesartan for the treatment of diabetic nephropathy.
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PMID:Candesartan: nephroprotective effects and treatment of diabetic nephropathy. 1294 96

The inhibition of the effects of angiotensin II is necessary to ensure the best degree of renal protection by the simultaneous control of blood pressure (BP) and the achievement of the maximal antiproteinuric capacity. The inhibition can be attained through the administration of either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB). Uptitration of antihypertensive therapy is frequently required to achieve the desired BP goal in patients presenting with renal disease, with or without proteinuria. Control of BP is good for both cardiovascular and renal protection. Sometimes, in particular when BP levels are high in the absence of therapy, the simple control of BP without inhibiting the renin- angiotensin system can be accompanied by a significant drop in proteinuria. On the other hand, the possibility that an ACE inhibitor or an ARB diminishes protein excretion in urine in the absence of changes in BP has been considered after the known evidence that these classes of drugs are renoprotective independently of their effect on BP control. The aim of this paper is to briefly review the evidence in favor of uptitration of either class of inhibitors of the renin-angiotensin system as compared with the combination of the two for the control of either BP or proteinuria.
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PMID:How to titrate ACE inhibitors and angiotensin receptor blockers in renal patients: according to blood pressure or proteinuria? 1294 36

This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous.
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PMID:Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat. 1453 4

Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the patients with type 2 diabetes will develop diabetic kidney disease. In the United States, diabetes has become the most common single cause of endstage renal disease defined by the need for dialysis or transplantation. Patients with type 2 diabetes and diabetic nephropathy have a dramatically increased cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether the use of irbesartan or a calcium channel blocker would provide protection against the progression of nephropathy due to type 2 diabetes beyond that attributable to the lowering of blood pressure. In that study, 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients randomized in this trial had more than 900 mg of protein in their urine and serum creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85 mmHg or less in all groups. The primary outcome was time to a combined endpoint of doubling of their baseline serum creatinine concentration, the development of endstage renal disease, or death from any cause. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite endpoint that was 20% lower than that in the placebo group ( P = 0.02) and 23% lower than that in the amlodipine group ( P = 0.006). The risk of doubling of the serum creatinine concentration was 33% lower in the irbesartan group than in the placebo group ( P = 0.003) and 37% lower in the irbesartan group than in the amlodipine group ( P < 0.001). Treatment with irbesartan was associated with a relative risk of endstage renal disease that was 23% lower than that in both other groups. These differences were not accounted for by differences in the blood pressures that were achieved. Proteinuria was reduced on average by 33% in the irbesartan group as compared with 6% in the amlodipine group and 10% in the placebo group. The angiotensin II receptor blocker irbesartan was shown to be effective in protecting against the progression of nephropathy due to type 2 diabetes. In a study done in patients with type 2 diabetes and early nephropathy as manifested by microalbuminuria, 590 hypertensive patients with type 2 diabetes and microalbuminuria were randomized to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for 2 years. The primary outcome in that trial was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was more than 200 mg/min or at least 30% higher than the baseline level. The irbesartan 150 mg/day group demonstrated a 39% relative risk reduction versus the control group in the development of overt proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group ( P < 0.001). The albumin excretion rate was reduced in the two irbesartan groups throughout the study (-11% and -38% at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups, respectively). The albumin excretion rate remained unchanged in the control group. Irbesartan was demonstrated in the above study to be renoprotective, independent of its blood pressure-lowering effect, in patients with type 2 diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker, was demonstrated to be significantly renoprotective in patients with type 2 diabetes with either early nephropathy (microalbuminuria) or late nephropathy (proteinuria). The renoprotective effects of irbesartan were above and beyond the effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes and either early or late diabetic nephropathy should be treated with the angiotensin II receptor blocker irbesartan.
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PMID:Treatment of diabetic nephropathy with angiotensin II receptor antagonist. 1458 37

Hypertension, impaired renal function, and proteinuria are commonly associated to the presence of diabetes. They play a major role in the development of cardiovascular and renal damage. Effective antihypertensive treatment reduces the progression of diabetic nephropathy and improves cardiovascular prognosis. Accordingly, tight BP control (<130/80 mmHg) is currently recommended in diabetic patients. Achieving BP targets represents the most important determinant of cardiovascular and renal protection. However, it has been suggested that specific classes of antihypertensive drugs may exert additional organ protection beyond their BP control. The pharmacologic blockade of the renin-angiotensin-aldosterone system has been shown to convey greater renal and cardiovascular protection compared with other classes of drugs. In particular, studies focusing on renal end point suggest that angiotensin-converting enzyme inhibitors (ACEI) are the first-choice drugs in type 1 diabetes. Both ACEI and angiotensin II receptor blockers prevent the progression from microalbuminuria to clinical proteinuria in type 2 diabetes, but angiotensin blockers provide better renoprotection in patients with overt nephropathy. Regarding cardiovascular protection, several studies (but not all) have shown that ACEI exert a protective effect on diabetic patients. Recently, interesting results in favor of angiotensin receptor blockers have been reported in the IDNT, RENAAL, and LIFE studies. It should be noted that to achieve maximal renal and cardiovascular protection, most diabetic patients require integrated therapeutic intervention, including not only several antihypertensive drugs, but statins and antiplatelet therapy as well.
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PMID:Optimizing therapy in the diabetic patient with renal disease: antihypertensive treatment. 1468 64

A 24-year-old woman was admitted to Toyosaka Hospital with proteinuria, hematuria, lymphopenia, hypocomplementemia, positive anti-nuclear antibody (ANA), and elevation of anti-streptolysin O (ASO). Renal biopsy specimen revealed diffuse mesangial and endocapillary glomerulonephritis with crescent formation and duplication of the capillary loop on light microscopic examination. Mild to moderate proliferation of mesangial matrix and cells were observed. On immunofluorescence (IF) examination, deposition of IgG, IgA, IgM, C1q, C3, and C4 to the mesangium and capillary wall were observed. By electron microscopy (EM), mesangial, subendothelial, and subepithelial deposits were recognized. However, microtubular structure in glomerular endothelial cells, fingerprint structures, and circumferential mesangial interposition were not observed by EM. The patient was referred to our hospital, but there was no change in her proteinuria 3 weeks after admission. The elevation of ASO, hypocomplementemia, and endocapillary proliferation suggested acute glomerulonephritis, while lymphocytopenia, positive ANA, the persistent hypocomplementemia, and various deposits detected by IF and EM suggested lupus nephritis; however, she did not fulfill the classification criteria of systemic lupus erythematosus. We started prednisolone (40 mg/day) with the diagnosis of chronic glomerulonephritis revealing diffuse mesangial and endocapillary proliferative glomerulonephritis, but it was not effective for the proteinuria. Quinapril (10 mg/day) and losartan (25 to 50 mg/day) were administered and the proteinuria decreased. It is possible that this use of an angiotensin converting-enzyme inhibitor and an angiotensin II receptor antagonist was effective in reducing the proteinuria in this patient.
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PMID:Patient with diffuse mesangial and endocapillary proliferative glomerulonephritis with hypocomplementemia and elevated anti-streptolysin O treated with prednisolone, angiotensin-converting enzyme inhibitor, and angiotensin II receptor antagonist. 1471 59

Hypertension continues to be a major public health issue in the world. To combat this problem, many anti-hypertensive drugs have been developed and proven effective at controlling blood pressure in the last half century. In recent decades, antihypertensive drugs have been shown to have cardiovascular benefits beyond the reduction of blood pressure, and the focus has shifted to clarification of these effects. Angiotensin II receptor antagonists and calcium channel blockers are the most widely used antihypertensive drugs in Japan. However, these two classes of drugs have not yet been compared with respect to their efficacy for treating cardiovascular events. The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial described herein is a prospective, multicenter, randomized, open-label, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration and blinded assessment of endpoints in high-risk hypertensive patients treated with either an angiotensin II receptor antagonist (candesartan cilexetil) or a third-generation calcium channel blocker (amlodipine besilate). The eligibility criteria in this study were 1) age between 20 and 85 years; 2) systolic blood pressure (SBP) > or = 140 mmHg in those below 70 years of age or > or = 160 mmHg in those above 70 years of age or diastolic blood pressure (DBP) > or = 90 mmHg on two consecutive measurements at clinic; and 3) at least one of the following high risk factors for cardiovascular events: a) SBP > or = 2180 mmHg or DBP > or = 110 mmHg on two consecutive visits, b) type 2 diabetes mellitus (fasting blood glucose > or = 126 mg/dl, casual blood glucose > or = 200 mg/dl, HbA1c > or = 6.5%, 2 h blood glucose on 75 g oral glucose tolerance test (OGTT) > or = 200 mg/dl, or current treatment with hypoglycemic therapy), c) history of cerebral hemorrhage, cerebral infarction, or transient ischemic attack until 6 months prior to the screening, d) left ventricular hypertrophy on either echocardiography or ECG, angina pectoris, or history of myocardial infarction until 6 months prior to screening, e) proteinuria or serum creatinine > or = 1.3 mg/dl, and f) symptoms of arteriosclerotic artery obstruction. The therapeutic goals of blood pressure control were set as follows: SBP < 130 mmHg and DBP < 85 mmHg for patients below 60 years of age, SBP < 140 mmHg and DBP < 90 mmHg for those in their 60s, SBP < 150 mmHg and DBP < 90 mmHg for those in their 70s, and SBP < 160 mmHg and DBP < 90 mmHg for those in their 80s. A total of 3,200 patients, equally allocated to each of the two treatment arms, were required based on a two-sided alpha level 0.05 and 90% power. The CASE-J is also the first study to employ the newly developed Automatic Bar Code Data-Capturing/Allocation, Booking & Trial Coding, Data Management (ABCD) system for data collection and management. Enrollment of patients started in September 2001 and ended in December 2002. Follow-up data will be collected every 6 months until December 2005. The CASE-J trial will provide important evidence on the comparative effectiveness of candesartan cilexetil and amlodipine besilate on cardiovascular morbidity and mortality among Japanese. In addition, the use of the ABCD system is expected to contribute to the development of more efficient data management systems for large-scale clinical trials.
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PMID:Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial of cardiovascular events in high-risk hypertensive patients: rationale, design, and methods. 1471 41

The prevalence of chronic kidney disease (CKD) is on the rise in all ethnic groups. This is because of the increased prevalence of obesity, diabetes mellitus, the metabolic syndrome, and the inadequate control of elevated blood pressure and other cardiovascular-renal risk factors, especially in ethnic minority populations. The implications of the aforementioned trends in risk factor prevalence and control are profound. Moreover, these trends negatively impact patient quality of life and place an enormous financial burden on the health care system for the provision of care to patients with CKD, end-stage renal disease (ESRD), and/or cardiovascular disease (CVD). Thus, it is of utmost importance to devise strategies that prevent kidney disease and delay progressive loss of kidney function in persons with CKD. Proven strategies include pharmacological interventions that lower blood pressure to less than target levels (<130/80 mm Hg), attainment of optimal glycemic control (Hb A1c <7%), and reducing urinary protein excretion. It is also possible, although yet unproven, that correction of anemia and aggressive treatment of dyslipidemia may forestall the loss of kidney function. In general, ethnic minorities are underrepresented in most large trials. Recently, a few outcome clinical trials in blacks have reinforced the lessons of kidney function preservation already learned in nonblack populations. That is, the reversible risk factors for CKD appear to be virtually identical and, at least in nondiabetic CKD, pharmacological targeting of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers preserves kidney function better than non-RAAS blood pressure-lowering regimens, especially when significant proteinuria exists. Although more CKD studies in ethnic minorities are needed, until they become available, the best available evidence from the existing clinical trial database should be applied to minorities with CKD-even when specific data are not available for a specific racial or ethnic group. Why this approach? First, there are no known unique risk factors for kidney disease in any ethnic group. Second, poor control of reversible risk factors for CKD is universal, particularly in blacks and other ethnic minorities. Thus, it is logical to predict that more efficient use of strategies proven to forestall loss of kidney function will reduce the excess of CKD and ESRD in ethnic minorities relative to non-minority populations. However, medical-based strategies alone are probably not enough. The global epidemic of obesity will fuel the growing population of persons, especially among ethnic minorities, with diabetes, the main cause of CKD, ESRD, and CVD. The obesity and diabetes epidemics are unlikely to abate without innovative and ultimately effective public health approaches.
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PMID:Pharmacological strategies for kidney function preservation: are there differences by ethnicity? 1473 May 36

Microalbuminuria and proteinuria have been determined to be modifiable risk factors for the progression of chronic kidney disease as well as risk factors for cardiovascular events. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers have been demonstrated to decrease proteinuria at all stages and slow the progression of renal disease. Proteinuria can be used as a marker of successful treatment in patients with chronic kidney disease in combination with other established targets. This article discusses the various diagnostic tests used for the detection of microalbuminuria and proteinuria and appropriate pharmaceutical treatment.
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PMID:Proteinuria, a modifiable risk factor: angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). 1475 1


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