Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methods for assessment of chronic kidney disease (CKD) are advancing worldwide. To this end, the Subcommittee of Measures for Pediatric CKD in the Japanese Society for Pediatric Nephrology was started in 2006. This Subcommittee has embarked on a multidisciplinary study for determining the normal/usual baseline value of serum creatinine and cystatin C, and standardizing the method of inulin clearance in children. For adults, pharmacotherapies such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to be effective in non-diabetic nephropathy. This same treatment for childhood CKD is generally adopted, but there is no corresponding evidence of similar efficacy. We believe a randomized controlled trial to that end should be undertaken.
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PMID:[Chronic kidney disease in children]. 1878 15

Aliskiren (Rasilez) is the first oral renin inhibitor. Its present indication is essential hypertension, as monotherapy or in combination with other antihypertensive agents (diuretic, calcium antagonist, ...). It may also be associated with an angiotensin converting enzyme inhibitor (or an AT1 angiotensin receptor antagonist) in order to benefit of a dual blockade of the renin-angiotensin-aldosterone system. The usual daily dose is 150 mg, to be increased up to 300 mg if necessary. New clinical trials are ongoing to validate this novel therapeutic approach in other indications such as congestive heart failure and diabetic nephropathy.
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PMID:[Aliskiren (Rasilez), direct renin inhibitor]. 1905 13

Diabetic nephropathy management should include the use of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker with additional antihypertensive medications to reduce proteinuria and cardiovascular events. Some studies suggest that adding a nondihydropyridine rather than a dihydropyridine calcium channel blocker (CCB) may more effectively lower proteinuria. We hypothesized that a trandolapril/verapamil SR (T/V) fixed-dose combination (FDC) was superior to a benazepril/amlodipine (B/A) FDC for reducing albuminuria in 304 hypertensive diabetic nephropathy patients when treated for 36 weeks. No statistically significant differences were observed between groups in the primary end point; adjusted percentage change in urinary albumin/creatinine ratio (UACR), which increased (mean T/V, 29.29%; mean B/A, 8.49%; difference, 20.80%; P=.34); or in change in absolute UACR, which decreased (mean [g/g] T/V, -0.11; mean [g/g] B/A, -0.08; difference -0.03; P=.78). There were significant reductions in log UACR (mean change in T/V, -0.28; P<.01; mean change in B/A, -0.31; P<.001) and diastolic blood pressure in both groups and in systolic blood pressure in the B/A group. T/V was not superior to B/A for reducing UACR. Both ACEI/CCB FDCs may reduce albuminuria; in the case of T/V, this appears to be independent of systolic blood pressure reduction in patients who had previously been treated and had baseline blood pressure levels of 142/77 mm Hg.
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PMID:Effects of calcium channel blockers on proteinuria in patients with diabetic nephropathy. 1909 Aug 77

In most countries glomerulonephritis is the second most common cause of the end-stage renal disease, after diabetic nephropathy in renal replacement therapy programs. Occurence of primary glomerular diseases in young and middle aged patients, in whom they restrain their lives and professional careers, results in their particular position among causes of replacement therapy. A highly important component of the therapeutic approach to nephrotic patients is appropriate symptomatic treatment. Proteinuria reduction is crucial in the prevention of progressive kidney function decline in the course of glomerulonephritis. A long-term therapy of glomerulonephritis should be conducted both by the general internal medicine specialist and the nephrologist. The treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can be performed by the internist, but the immunosuppressive programs should be initiated and supervised by the nephrologist.
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PMID:Primary idiopathic glomerulonephritis: modern algorithm for diagnosis and treatment. 1911 18

Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can slow the progression of diabetic nephropathy. Even with ACEI or ARB treatment, the proportion of patients who progress to end-stage renal disease (ESRD) remains high. Interventions that achieve more complete blockade of the renin-angiotensin system, such as combination ACEI and ARB, might be beneficial. This approach may decrease progression of nondiabetic kidney disease. In diabetic nephropathy, combination therapy decreases proteinuria, but its effect in slowing progression is unknown. In addition, the potential for hyperkalemia may limit the utility of combined therapy in this population. VA NEPHRON-D is a randomized, double-blind, multicenter clinical trial to assess the effect of combination losartan and lisinopril, compared with losartan alone, on the progression of kidney disease in 1850 patients with diabetes and overt proteinuria. The primary endpoints are time to (1) reduction in estimated GFR (eGFR) of > 50% (if baseline < 60 ml/min/1.73 m(2)); (2) reduction in eGFR of 30 ml/min/1.73 m(2) (if baseline > or = 60 ml/min/1.73 m(2)); (3) progression to ESRD (need for dialysis, renal transplant, or eGFR < 15 ml/min/1.73 m(2)); or (4) death. The secondary endpoint is time to change in eGFR or ESRD. Tertiary endpoints are cardiovascular events, slope of change in eGFR, and change in albuminuria at 1 yr. Specific safety endpoints are serious hyperkalemia (potassium > 6 mEq/L, requiring admission, emergency room visit, or dialysis), all-cause mortality, and other serious adverse events. This paper discusses the design and key methodological issues that arose during the planning of the study.
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PMID:Design of combination angiotensin receptor blocker and angiotensin-converting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D). 1911 20

Despite the first-line use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), there is still a large need to improve the prevention and progression of diabetic nephropathy and its associated cardiovascular events. Endothelin antagonists have shown anti-inflammatory, antifibrotic, and antiproteinuric effects in experimental studies. This study was a randomized, placebo-controlled, double-blind, parallel-design, dosage-range study of the effect of the endothelin-A antagonist avosentan (SPP301) on urinary albumin excretion rate (UAER) in patients with diabetic nephropathy. We randomly assigned 286 patients with diabetic nephropathy, macroalbuminuria (UAER 0.2 to 5.6 mg/min), and BP <180/110 mmHg to 12 wk of avosentan (5, 10, 25, and 50 mg) or placebo, in addition to standard ACEI/ARB therapy. Relative to baseline, all avosentan dosages decreased mean relative UAER (-16.3 to -29.9%) compared with placebo (35.5%). Median relative UAER decreased with all avosentan dosages (-28.7 to -44.8%) compared with placebo (12.1%). Creatinine clearance and BP were unchanged at 12 wk. The main adverse events were peripheral edema (12%), mainly with high (>/=25 mg) dosages of avosentan; significant increases in liver enzymes did not occur. Twenty-one (7.3%) patients experienced adverse events that led to withdrawal from study medication. In summary, the endothelin-A antagonist avosentan given in addition to standard ACEI/ARB treatment decreases UAER in patients with diabetic nephropathy and macroalbuminuria.
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PMID:Avosentan reduces albumin excretion in diabetics with macroalbuminuria. 2013 87

Urinary neutrophil gelatinase-associated lipocalin (Ngal or lipocalin 2) is a very early and sensitive biomarker of kidney injury. Here we determined the origin and time course of Ngal appearance in several experimental and clinically relevant renal diseases. Urinary Ngal levels were found to be markedly increased in lipoatrophic- and streptozotocin-induced mouse models of diabetic nephropathy. In the latter mice, the angiotensin receptor blocker candesartan dramatically decreased urinary Ngal excretion. The reabsorption of Ngal by the proximal tubule was severely reduced in streptozotocin-induced diabetic mice, but upregulation of its mRNA and protein in the kidney was negligible, compared to those of control mice, suggesting that increased urinary Ngal was mainly due to impaired renal reabsorption. In the mouse model of unilateral ureteral obstruction, Ngal protein synthesis was dramatically increased in the dilated thick ascending limb of Henle and N was found in the urine present in the swollen pelvis of the ligated kidney. Five patients with nephrotic syndrome or interstitial nephritis had markedly elevated urinary Ngal levels at presentation, but these decreased in response to treatment. Our study shows that the urinary Ngal level may be useful for monitoring the status and treatment of diverse renal diseases reflecting defects in glomerular filtration barrier, proximal tubule reabsorption, and distal nephrons.
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PMID:Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. 1914 53

Chronic kidney disease (CKD) shares major risk factors with cardiovascular disease(CVD), including hypertension and diabetes mellitus. In patients with hypertensive kidney disease and diabetic nephropathy, inhibitors of the renin-angiotensin system (RAS) significantly reduce the risk of renal and cardiovascular endpoints. Whether the renoprotective effects of RAS inhibitors can be fully accounted for by blood pressure reductions or whether other mechanisms are involved has not been clearly established. Because RAS inhibitors reduce albuminuria and slow progression of kidney disease, they are recommended as fi rst-line antihypertensive agents in patients with CKD, who often require aggressive treatment with > or = 2 drugs to reach the goal blood pressure (< 130/80 mm Hg). Greater RAS inhibition with higher-than-usual doses of a single agent or dual RAS inhibition with an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker may be necessary for maximum renoprotective effects. Ongoing clinical trials assessing treatment and prevention of CKD may resolve unanswered questions about RAS inhibition in patients with hypertension and/or diabetes.
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PMID:The renoprotective effects of RAS inhibition: focus on prevention and treatment of chronic kidney disease. 1917 17

Benidipine, an L- and T-type calcium channel blocker, dilates both efferent and afferent arterioles and reduces glomerular pressure. Thus, it may exert renoprotective effects. We conducted an open-labeled, randomized trial to compare the blood pressure (BP)-lowering effect and antiproteinuric effect of benidipine with those of amlodipine in hypertensive patients with moderate-to-advanced-stage chronic kidney disease (CKD) (stages 3-5). These patients were already being administered the current maximum recommended doses of angiotensin receptor blockers (ARBs). Patients with BP >or=140/90 mm Hg, despite treatment with the maximum recommended dose of ARBs, were randomly assigned to two groups. The patients received either of the following treatment regimens: 4 mg day(-1) of benidipine, which was increased up to a dose of 16 mg day(-1) (B group; n=24), and 2.5 mg day(-1) of amlodipine, which was increased up to a dose of 10 mg day(-1) amlodipine (A group; n=23). After 6 months of treatment, a significant and comparable reduction in the systolic and diastolic BP was seen in both groups. The decrease in the urinary protein to creatinine ratio in the B group was significantly lower than that in the A group. Benidipine exerted antiproteinuric effect to a greater extent than did amlodipine, even in patients with diabetic nephropathy. We conclude that the addition of benidipine, rather than amlodipine, ameliorates urinary protein excretion in hypertensive patients with CKD who are already being administered ARBs. Therefore, we propose a combination therapy with benidipine and ARBs, even for patients with moderate-to-advanced-stage CKD.
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PMID:Comparison of the antiproteinuric effects of the calcium channel blockers benidipine and amlodipine administered in combination with angiotensin receptor blockers to hypertensive patients with stage 3-5 chronic kidney disease. 1926 95

With the arrival of a new class of drugs for the management of hypertension comes the need to define its role. Aliskiren, an orally administered direct renin inhibitor, has been approved by the US Food and Drug Administration for the treatment of hypertension. Currently, the recommendation for choice of agent in the treatment of uncomplicated hypertension is a thiazide diuretic, and for patients with diabetic nephropathy, heart failure, or coronary artery disease, an angiotensin-converting enzyme inhibitor. Patients for whom an angiotensin-converting enzyme inhibitor is indicated who are intolerant as a result of side effects should take an angiotensin receptor blocker. A new class of medicines that specifically inhibits renin is an exciting addition to the armamentarium in the treatment of hypertension. This article explores the role of aliskiren in treating hypertension as well as its side effects and appropriate dosing.
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PMID:Renin inhibition for hypertension: selecting the right role for a new class of drug. 1943 72


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