Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes mellitus and hypertension are frequently associated. Cardiovascular morbidity is a major burden in these patients. Furthermore a renal disease appears in 40% of them that may lead to chronic terminal renal failure. Whatever the stage of the renal disease, it increases the cardiovascular risk. A majority of type 2 diabetic patients will eventually died of cardiovascular complications before having reached chronic terminal renal failure. Many large clinical trials including type 2 diabetic patients with hypertension have been performed in the last 20 years with cardiovascular morbidity and mortality as primary outcomes. These trials mainly evaluated the role of glycemic control, of hypertension as well as the decrease of LDL-cholesterol. Based on these trials, the prescription type of hypertensive type 2 diabetic patient should include, besides hygienic and dietary advices, antidiabetic treatment, thiazide and/or betablocker and platelet inhibitor. Statin should be prescribed for secondary prevention if serum LDL-cholesterol is above 1,3 g/l and for primary prevention depending on serum LDL-cholesterol and on the number of cardiovascular risk factors. The objectives are an HbA1c below 6,5%, a LDL-cholesterol below 1g/l and a blood pressure below 150/80 mmHg. The appearance of diabetic nephropathy alters the treatment and the therapeutic objectives. Many large trials aimed at preventing microalbuminuria (primary prevention), macroproteinuria (secondary prevention), and chronic renal failure (tertiary prevention) have been conducted. For primary prevention, angiotensin-converting-enzyme inhibitors should be prescribed in case of hypertension because they delay the appearance of microalbuminuria. For secondary prevention, angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers decrease albuminuria excretion rate and delay the appearance of macroproteinuria whatever the blood pressure. Tertiary prevention is based on angiotensin-receptor blockers since they slow down the decrease of renal function. The objectives are a blood pressure below 130/80 mmHg and the regression or the reduction of albuminuria excretion rate. Intensified and target-driven interventions aimed at multiple risk factors implicated in cardiovascular and renal lesions, as successfully performed in the STENO-2 study, reduce the risk of cardiovascular and renal morbidity and mortality. In this article, large clinical trials having the prevention of cardiovascular and renal risks as primary outcomes were analyzed.
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PMID:[What do large clinical trials learn us about cardiovascular and renal prevention in patients with type 2 diabetes mellitus and hypertension?]. 1689 17

Diabetic nephropathy (DN) is a renal disease which develops as a consequence of diabetes mellitus. Microalbuminuria is the earliest clinical sign of DN. There are no specific diagnostic biomarkers for type 2 diabetics with nephropathy other than microalbuminuria and macroalbuminuria. However, microalbuminuria does not constitute a sole independent indicator for type 2 diabetics with nephropathy, and thus, another screening method, such as a biomarker assay, is required in order to diagnose it more correctly. Therefore, we have utilized two-dimensional electrophoresis (2-DE) to identify human serum protein markers for the more specific and accurate prediction of progressive nephropathy in type 2 diabetes patients, via comparisons of the serum proteome in three experimental groups: type 2 diabetes patients without microalbuminuria (DM, n = 30), with microalbuminuria (MA, n = 29), and with chronic renal failure (CRF, n = 31). As a result, proteins which were differentially expressed with statistical significance (p < 0.05) in MA and CRF groups as compared to those in DM group were selected and identified by ESI-Q-TOF MS/MS. Among these identified proteins, two proteins which might be useful as diagnostic biomarkers of type 2 diabetics with nephropathy were verified by Western blotting: extracellular glutathione peroxidase (eGPx) and apolipoprotein (ApoE) were found to exhibit a progressive reduction in MA and CRF groups. Notably, eGPx was further verified by ELISA using DM (n = 100) and MA (n = 96) patient samples. Collectively, our results show that the two proteins identified in this study may constitute potential biomarkers for the diagnosis of type 2 diabetics with nephropathy.
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PMID:Proteome analysis of serum from type 2 diabetics with nephropathy. 1726 29

Self blood pressure measurements (home BP) and/or ambulatory BP measurements are recommended in mild to moderate hypertension (140/90 - 179/109 mmHg) in order to confirm sustained hypertension and identify white coat and masked hypertension. The evaluation of target organ damages (TOD) has to be integrated in cardiovascular risk estimate and taken into account in the management of hypertensive patients. Beside echocardiography, there is a place for the screening of microalbuminuria in non diabetic hypertensive patients, but these investigations should not be performed systematically. Arterial stiffness evaluation and carotid intima-media thickness quantification are not yet recommended. Cardiovascular risk (CV risk) estimate plays a pivotal role in the therapeutic decision and strategy. The cardiovascular risk grade is based on [1] the list of cardiovascular risk factors (same list AFSSAPS recommendations on dyslipidemia), [2] the presence or absence of TOD and [3] cardiovascular complications: "low", "medium", and "high" CV risk. Lifestyle modifications are recommended in all hypertensive patients. Five antihypertensive drugs are recommended for first line therapy: beta-blockers, thiazide diuretics, ACEIs, ARA II and CCBs (and fixed low dose combinations with AFSSAPS agreement for first line). In order to initiate the treatment, Evidence-based therapy (according to clinical trials conducted in different clinical situations), certain comorbid conditions (compelling indications), efficacy and side-effects in a previous experience, and the cost are the determinants of the first choice. Most hypertensive patients require more than one agent to achieve target blood pressure and for second line therapy the recommended combinations are: betablockers-diuretics, ACEIs-diuretics, ARAII-diuretics, betablockers-CCBs (DHP), ACEIs-CCBs, ARA II-CCBs and CCBs-diuretics. The delay to establish a combination therapy depend on CV risk. The BP goals are those recommended by ESH-ESC 2003: BP<140/90 mmHg in all, BP<130/80 mmHg in diabetic patients and in patients with chronic renal failure. Beside lowering BP, the reduction in proteinuria <500 mg/24 h is a new goal in these high risk patients. These guidelines provide a tool for every day practice and applicability should be evaluated.
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PMID:[French as 2005-recommendations on the management of arterial hypertension]. 1740 53

Diabetic nephropathy is the leading cause of chronic renal failure (CRF) in Europe. About fifty percent of diabetic subjects develop microalbuminuria, which progresses towards established diabetic nephropathy in one third of patients. The treatment of type 2 diabetes in a patient with CRF is a challenge for the general practitioner, because of the accumulation of drugs and/or specific metabolites. Sulfonylureas are associated with an increased risk of hypoglycaemia. Biguanides may exceptionally cause life-threatening lactic acidosis. Glitazones have an interesting profile since they decrease microalbuminuria and blood pressure. However, their safety is not well defined in the context of CRF In the case of severe CRF, only insulin and repaglinide can be recommended.
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PMID:[Chronic kidney disease and antidiabetic treatment]. 1743 98

We examined the records of patients with hemolytic uremic syndrome, who had not undergone dialysis during the acute stage, with the aims of evaluating: (1) the outcome after at least 5 years of follow-up; (2) the value of peak serum creatinine as a prognostic marker; (3) the relationship between outcome and time to normalization of renal function. From 1968 to 2000, 1,179 patients were assisted. Forty-two patients (3.6%) died during the acute stage, 478 patients (40.5%) required dialysis and 659 patients (55.9%) did not undergo dialysis; 529 non-dialysis patients were lost to follow-up. The remaining 130 patients were classified into four groups: group I, complete recovery; group II, with two subgroups, IIa, microalbuminuria, and IIb, proteinuria and/or high blood pressure, both with normal renal function; group III, chronic renal failure; and group IV, end-stage renal disease. We analyzed the relationship between final outcome and: (1) peak creatinine (the highest of at least two determinations) during the acute stage and (2) time to normalization of urea and/or creatinine after the acute stage. After a mean follow-up time of 147.1 months (range 60-362 months), group I had 83 patients (63.9%), group IIa had 27 (20.8%), group IIb had 15 (11.5%) and group III had 5 (3.8%). The value of peak serum creatinine concentration was available for 57 patients. On the last clinical visit, eight out of 26 (30.7%) patients with peak serum creatinine equal to or higher than 1.5 mg/dl were in groups IIb and III versus one out of 31 (3.2%) patients with lower values (P < or = 0.007). Finally, six out of 28 patients (21%) whose renal function had normalized after 15 days from diagnosis were in groups IIb-III versus 8/82 (9.7%) whose renal function had normalized within 15 days (P = 0.18). After a mean period of follow-up of 12 years, 15% of a selected patient group had developed proteinuria, high blood pressure or chronic renal failure, and 21% had developed microalbuminuria. Peak serum creatinine during the acute stage was useful as a prognostic indicator. Patients whose renal function required more time to normalize did not have a worse outcome.
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PMID:Long-term follow-up of Argentinean patients with hemolytic uremic syndrome who had not undergone dialysis. 1756 28

Type-2 diabetes mellitus (T2DM) is a global disease and its resultant complication, diabetic nephropathy, is a leading cause of chronic renal failure. Microalbuminuria is an early indicator of diabetic nephropathy and is also an independent risk factor for cardiovascular morbidity. Data have shown that anti-hypertensives like Angiotensin receptor blockers (ARB), and Angiotensin converting enzyme inhibitors (ACEI) reduce microalbuminuria and retards the progression of renal disease effectively in hypertensive T2DM patients. But the effects ofARBs on preventing microalbuminuria and ensuing nephropathy in normotensive patients with T2DM is yet to be fully established. To assess the anti-microalbuminuric effects of losartan therapy in normotensive T2DM patients. Interventional Phase Two Clinical Trial was done. Study was done at Diabetic Clinic, Jinnah Hospital Lahore, Pakistan over 8 months. A total of 171 normotensive patients with T2DM and microalbuminuria were evaluated. After informed consent and baseline 24-hour urinary microalbuminuria quantification the selected patients were started on losartan 50 mg/day for a six-month period. Monthly follow-ups were done to monitor the blood pressure, glycemic control, urea/creatinine/potassium levels and any untoward effects of losartan therapy. Quantitative microalbuminuria was repeated at the end of study. Out of the 171 patients, 149 (87.1%) had significant albuminuria reduction >30.0% of their baseline and the variable of final outcome of intervention (urinary albumin in mg/dl) was significantly reduced (Mean 101.9 +/- SD 21.7 baseline and 47.5 +/- 12.9 post therapy) with p<0.001 and with minimal side-effects. These anti-albuminuric effects of losartan were reversible as seen on rechecking the urinary albumin two months after discontinuation of treatment. Losartan was well tolerated and demonstrated significant anti-proteinuric effects in patients with T2DM with early nephropathy independent of hypertension, warranting further long-term large-scale studies to prove its usefulness as preventive therapy for diabetic nephropathy.
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PMID:Use of losartan in reducing microalbuminuria in normotensive patients with type-2 diabetes mellitus. 1789 53

The prevalence of diabetes and its complications is increasing worldwide. Among the microvascular complications, diabetic nephropathy is the most frequent cause of end-stage renal disease. Although angiotensin-converting-enzyme inhibitors have been cited as the first line of therapy for the management of microalbuminuria, the rate of remission from microalbuminuria to normoalbuminuria has been lower than the expected. Furthermore, due to the elevated frequency of side effects of the rennin-angiotensin blockers new approaches for the treatment of microalbuminuria are needed. Pentoxifylline, a xanthine derivate drug with hemorheologic properties and primarily indicated for the therapy of disturbances of blood fluidity, is also an antagonist of adenosine 2 receptors and have anti-inflammatory and immunomodulatory effects, properties that promote beneficial changes in the blood flow conditions and kidney function. Current evidence shows that the short-term use of pentoxifylline has low side-effects, reduces both proteinuria and microalbuminuria in subjects with diabetes, and is as effective as captopril in the reduction of microalbuminuria in non-hypertensive type 2 diabetic patients. Although this data suggests that pentoxifylline could be useful for preventing the development of end-stage renal disease is necessary to conduct long-term studies to evaluate the role of pentoxifylline in the treatment of diabetic nephropathy and the prevention of chronic renal failure. In this article, we review the clinical evidence that show the efficacy of pentoxifylline in the management of microalbuminuria in diabetic patients.
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PMID:Efficacy of pentoxifylline in the management of microalbuminuria in patients with diabetes. 1822 Jun 96

Although tighter blood pressure control is considered the main mechanism for preventing the progression of chronic renal failure, angiotensin-converting enzyme inhibitors and angiotensin receptors blockers seem to have an additional organ protective role. The effects of calcium antagonists in renal disease are not so clearly defined. Calcium antagonists have pleiotropic effects that might contribute to protect the kidney, such as attenuating mesangial entrapment of macromolecules, countervailing the mitogenic effect of platelet-derived growth factors and platelet-activating factors, and suppressing mesangial cell proliferation. They could also act as free radical scavengers and inhibit the renal effects of endothelin. Some evidence has been accumulated demonstrating that certain new dihydropyridinic calcium antagonists may affect postglomerular as well as preglomerular vessels, resulting in decreased filtration fraction and nephroprotective effect as renin-angiotensin axis-blocking drugs. Though there are few reports on the clinical renal effects of new calcium antagonists, they have rendered promising results. Manidipine does not increase proteinuria as do some classic calcium antagonists, and lercanidipine combined with renin-angiotensin axis-blocking drugs reduce proteinuria. Both drugs have been shown to decrease microalbuminuria when administered alone.
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PMID:Calcium antagonists and renal failure progression. 1835 Apr 43

The incidence and prevalence of chronic renal failure (CKD), defined according to the NFK-KDOQI guidelines as a glomerular filtration rate less than 60 mL/min/1.73 m2 or the presence of microalbuminuria, is increasing worldwide, leading to an increased risk of cardiovascular disease. There is general agreement about the importance of early referral to the nephrologist and predialysis educational programs because this strategy prevents the progression (by the use of renin-angiotensin system blockers, low-protein diet) and complications (arterial hypertension, anemia, malnutrition, osteodystrophy, acidosis) of renal disease. Predialysis education helps patients choose the renal replacement therapy modality (hemodialysis, peritoneal dialysis, transplantation) and improve their quality of life. Furthermore, adequate predialysis care allows the nephrologist to prepare the vascular access well in advance. In contrast to the wished-for practice of early referral, patients are often referred to the nephrologist when renal failure is already advanced. This is mainly due to the fact that non-nephrologists pay little attention to identifying patients at risk for renal failure or defining the degree of renal failure according to the KDOQI classification. In addition, serum creatinine alone provides no adequate estimate of renal function, and both the MDRD equation and the Cockcroft-Gault formula permit a more accurate estimation of the glomerular filtration rate (GFR). Using the MDRD equation, the KDOQI guidelines recommend referral when GFR is less than 30 mL/min/1.73 m2. Late nephrology referral is an independent risk factor for early death while on dialysis, as well as being associated with a more frequent use of temporary catheters, particularly in the elderly but also in patients receiving regular nephrology care. This underlines the importance of a multidisciplinary predialysis approach which may bring additional benefits - beyond referral to a nephrologists - including a reduced hospitalization rate and improved survival. The KDOQI guidelines recommend evaluating the benefits and risks of starting renal replacement therapy when patients reach stage 5 (estimated GFR <15 mL/min/1.73 m2), although the ideal time for replacement therapy initiation remains a matter of debate and the results of prospective clinical trials are awaited to resolve this issue.
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PMID:[When to start dialysis. The predialysis patient]. 1847 14

An early feature of diabetic nephropathy is the alteration of the glomerular basement membrane (GBM), which may result in microalbuminuria, subsequent macroproteinuria, and eventual chronic renal failure. Although type IV collagen is the main component of thickened GBM in diabetic nephropathy, cellular metabolism of each alpha chains of type IV collagen has not been well studied. To investigate the regulation of alpha(IV) chains in diabetic conditions, we examined whether glucose and advanced glycosylation endproduct (AGE) regulate the metabolism of each alpha(IV) chains in the diabetic tissue and glomerular epithelial cells (GEpC). Glomerular collagen alpha3(IV) and alpha5(IV) chains protein were higher and more intense in immunofluorescence staining according to diabetic durations compared to controls. In vitro, mainly high glucose and partly AGE usually increased total collagen protein of GEpC by [(3)H]-proline incorporation assay and each alpha(IV) chain proteins including alpha1(IV), alpha3(IV), and alpha5(IV) in time-dependent and subchain-specific manners. However, the changes of each alpha(IV) chains mRNA expression was not well correlated to the those of each chain proteins. The present findings suggest that the metabolism of individual alpha(IV) chains of GBM is differentially regulated in diabetic conditions and those changes might be induced not only by transcriptional level but also by post-translational modifications.
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PMID:Regulation of type IV collagen alpha chains of glomerular epithelial cells in diabetic conditions. 1979 80


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