Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the United States and causes end-stage renal failure requiring dialysis and renal transplantation. There is no effective treatment for ADPKD in humans. However, there are now multiple clinical trials testing a host of therapeutic interventions in children and adults with ADPKD. The major therapeutic interventions being tested in patients with ADPKD include Tolvaptan, Octreotide, Sirolimus, Everolimus, and statins, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).
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PMID:Therapeutic interventions for autosomal dominant polycystic kidney disease. 1837 77

In diabetic nephropathy, glomerular mesangial cells exhibit aberrant anabolic activity that includes excessive production of extracellular matrix (ECM) proteins, leading to crowding of filtration surface areas and possible renal failure. In the present study, a murine mesangial cell line (MES-13 cells) was studied to determine the roles of the renin-angiotensin system (RAS) and the insulin-like growth factor (IGF) axis in the anabolic response to elevated glucose levels. Culture of MES-13 cells in medium containing supra-physiological glucose concentrations (>5.5 mmol/l) resulted in increased production of ECM proteins including laminin, fibronectin, and heparan sulfate proteoglycan with concurrent increases in IGF-binding protein (IGFBP)-2 production. These responses were blocked by the angiotensin receptor antagonists saralasin and losartan, while exogenous angiotensin II (Ang II) treatment directly stimulated increases in ECM and IGFBP-2. In all experiments, IGFBP-2 levels were correlated with anabolic activity implicating IGFBP-2 as a possible mediator in cellular responses to high glucose and Ang II. Such mediation appears to involve IGFBP-2 modulation of IGF-I signaling, since all responses to high glucose or Ang II were blocked by immuno-neutralization of IGF-I. These data suggest alterations in the IGF axis as key mechanisms underlying nephropathic responses of mesangial cells to Ang II and high glucose.
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PMID:Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line. 1839 86

Proteinuria is a common complication occurring after kidney transplantation. It is associated with an increased risk of renal failure and patient death. Treatment with ACE inhibitors or angiotensin receptor antagonists (blockers) has been shown to reduce proteinuria after kidney transplantation, as well as improve both graft and patient survival. An increase in proteinuria has been observed in some patients after initiation of sirolimus therapy. Although the mechanism of this remains unclear, high proteinuria at baseline and poor renal function at baseline have been identified as potential risk factors for the development of proteinuria after conversion to sirolimus. Initiation of sirolimus therapy is not recommended in patients with early histological indicators of glomerular damage; however, in patients with healthy grafts, sirolimus may prevent future glomerulosclerosis. Early treatment with an ACE inhibitor and sirolimus, prior to the appearance of glomerular changes, may result in better outcomes.
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PMID:Mechanisms and management of proteinuria in kidney transplant patients. 1844 99

In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life). The primary endpoint was the difference in the urinary albumin to creatinine ratio between the groups at 52 weeks. The geometric coefficient of variation and the mean of the urinary albumin to creatinine ratio fell in both groups at 52 weeks but both were significantly greater for the telmisartan compared to the losartan cohort. Mean systolic blood pressure reductions were not significantly different between groups at trial end. We conclude that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure.
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PMID:Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy. 2020 69

Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.
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PMID:Renal failure and concurrent RAAS blockade in older CKD patients with renal artery stenosis: an extended Mayo Clinic prospective 63-month experience. 1856 8

Acute and especially chronic renal failure (CRF) are relatively common and important risk factor for morbidity and mortality in patients after heart, lung, liver or intestine transplantation. Numerous factors contribute to the development of CRF in this group of patients, like treatment with calcineurin inhibitors and other nephrotoxic drugs in the perioperative period, hemodynamical changes during and after the surgery, preexistent renal disease, hypertension, diabetes mellitus, dyslipidemia and anemia. Pretransplant evaluation of renal function is mandatory to predict which patients have increased risk for development of CRF. In the posttransplantation course it is necessary to timely diagnose and treat renal failure, while patients with insufficient renal function have 4.55-fold increased risk of death compared to patients with normal renal function. Special problem is diagnostic approach to patients with suspected chronic renal disease who are candidates for transplantation of other parenhimatose organs. Diagnostic value of serum creatinine and estimation of renal function based on its value is very limited. Gold diagnostic standard is radioisotope estimation of glomerular filtration, but this method is not widely available. It seems that this problem may be solved with the use of cystatin C, but this approach needs to be validated in large studies. Numerous different immunosuppressive drugs available on the market enable individualization of immunosuppression. Different drugs combinations may have less nephrotoxic potential, but one must be careful because of the possible risk of organ rejection with the change of immunosuppression. Use of angiotensin convertase enzyme inhibitors and/or angiotensin receptor blockers, statins with drugs for control of hyperglycemia, may prevent or postpone development of CRF. Although technical advances of contemporary hemodialysis machines and peritoneal dialysis equipment enable well tolerated dialysis even in critically ill patients, renal transplantation remains the method of choice for treatment of patients with transplanted parenhimatous organ that developed CRF.
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PMID:[Chronic renal failure after heart, lung, liver, or intestine transplantation]. 1857 34

Pre-eclampsia affects approximately 5% of pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity in the United States and the world. The clinical hallmarks of this maternal disorder include hypertension, proteinuria, endothelial dysfunction and placental defects. Advanced-stage clinical symptoms include cerebral hemorrhage, renal failure and the HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome. An effective treatment of pre-eclampsia is unavailable owing to the poor understanding of the pathogenesis of the disease. Numerous recent studies have shown that women with pre-eclampsia possess autoantibodies, termed AT(1)-AAs, that bind and activate the angiotensin II receptor type 1a (AT(1) receptor). We show here that key features of pre-eclampsia, including hypertension, proteinuria, glomerular endotheliosis (a classical renal lesion of pre-eclampsia), placental abnormalities and small fetus size appeared in pregnant mice after injection with either total IgG or affinity-purified AT(1)-AAs from women with pre-eclampsia. These features were prevented by co-injection with losartan, an AT(1) receptor antagonist, or by an antibody neutralizing seven-amino-acid epitope peptide. Thus, our studies indicate that pre-eclampsia may be a pregnancy-induced autoimmune disease in which key features of the disease result from autoantibody-induced angiotensin receptor activation. This hypothesis has obvious implications regarding pre-eclampsia screening, diagnosis and therapy.
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PMID:Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. 1868 93

In patients with severe hypertension a search for a renal cause, particularly for a renal artery stenosis, needs to be undertaken with 24-hour blood pressure measurement, urinary examination, determination of renal function and duplex sonography of the kidneys.--Sympathetic hyperactivity, which is associated with an increased cardiovascular risk, may already be found in an early stage of renal diseases. There is evidence that administration of an ACE inhibitor or an angiotensin receptor antagonist (ARB) may induce a decrease of sympathetic hyperactivity as well as a reduced rate of adverse cardiovascular events in patients in renal failure.--In patients with renal disease and high proteinuria antihypertensive therapy with ACE-inhibitors or ARB delays the progression of chronic renal failure. Combined therapy of ACE-inhibitors plus ARB may reduce proteinuria more than that would be the case with either of these drugs alone. However, there is no evidence that combination of these two drugs improves renal function more than monotherapy.--Renal artery stenosis of > 70% should be treated by dilatation, if there is evidence of fibromuscular dysplasia. Dilatation and/or stent implantation in an atherosclerotic renal artery stenosis of > 70% should be performed if indicated by the patient's clinical state. i.e. severe hypertension has proved to be resistant to triple drug antihypertensive therapy or pulmonary edema has occurred frequently. Preservation of renal function by angioplasty of an atherosclerotic renal artery stenosis remains a challenge. However, exact criteria for such intervention need to be established. But so far there have not been adequate data from controlled prospective trials.
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PMID:[The kidneys and hypertension]. 1877 Apr 87

Preservation of residual renal function (RRF) after the start of peritoneal dialysis (PD) is essential for both patient and technique survival. Nephroprotection methods of proven efficacy in chronic renal failure may maintain their efficacy after the start of dialysis. This study shows that candesartan, at doses ranging from 16 and 32 mg/day, is well tolerated in normotensive patients on PD and reduces progression of renal failure from 8 mL/min/year in the pre-dialysis period to 2 mL/min/year after PD start. Proteinuria is also decreased to a half at the end of the first year, with no harmful effects seen on anemia control. It is concluded that angiotensin receptor blockade should be maintained after the start of PD, irrespective of blood pressure control, in order to reduce RRF impairment in these patients.
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PMID:[Preservation of residual renal function in peritoneal dialysis by angiotensin receptor blockade]. 1895 12

Hypertension is a common comorbidity in patients with diabetes, and adequate control of blood pressure significantly reduces the risk of macrovascular and microvascular complications. Patients with diabetes should achieve a target blood pressure of less than 130/80 mm Hg. The use of angiotensin-converting enzyme inhibitors may slow progression to kidney failure and cardiovascular mortality; these agents are the preferred therapy for managing coexisting diabetes and hypertension. Angiotensin receptor blockers can prevent progression of diabetic kidney disease and are a first-line alternative for patients intolerant of angiotensin-converting enzyme inhibitors. Thiazide diuretics provide additional antihypertensive effects when combined with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. With lower doses of these drugs, the risk of clinically significant metabolic alterations is minimal. Beta blockers and calcium channel blockers also have beneficial effects in managing hypertension in patients with diabetes. Beta blockers reduce cardiovascular events and are useful in a multidrug regimen. Dihydropyridine calcium channel blockers should be reserved for patients intolerant of preferred agents or those who need additional therapy to achieve target blood pressure. Many patients with diabetes require combination therapy with multiple antihypertensive agents.
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PMID:Pharmacologic management of hypertension in patients with diabetes. 2035 38


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