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

Sirolimus is a potent immunosuppressant, which may permit the avoidance of nephrotoxic calcineurin inhibitors (CNI). However, cases of proteinuria associated with sirolimus have been reported following renal transplantation. Here, we report three cases of proteinuria (1, 2 and 7 g/day) developing during therapy with sirolimus plus low-dose tacrolimus following clinical islet transplantation (CIT) in type I diabetic subjects. The proteinuria resolved after discontinuation of sirolimus, substituted by mycophenolate mofetil (MMF) combined with an increased dose of tacrolimus. A renal biopsy in one case indicated only the presence of diabetic glomerulopathy. Five other CIT recipients developed microalbuminuria while on sirolimus which all resolved after switching to tacrolimus and MMF. The resolution of proteinuria from the native kidneys of CIT recipients after the discontinuation sirolimus suggests that, at least in some individuals, sirolimus itself may have adverse renal effects. Sirolimus should be used cautiously with close monitoring for proteinuria or renal dysfunction.
 ...
PMID:Proteinuria developing after clinical islet transplantation resolves with sirolimus withdrawal and increased tacrolimus dosing. 1609 17

Traditionally, microvascular disease resulting in a glomerulopathy and an increase in albumin excretion rate (AER) is believed to be the only significant mechanism by which diabetic renal disease develops. However, recent results have challenged the concept that a decline in renal function in patients with diabetes is always accompanied by an increased AER. This has led to the concept that subjects with diabetes, especially those with type 2 diabetes, can progress to renal impairment via either an albuminuric or non-albuminuric pathway. The natural history, renal morphological changes and exaggerated cardiovascular risk associated with the albuminuric-pathway to renal impairment have been well documented. Interventions to attenuate the progression of this pathway, especially inhibition of the renin-angiotensin system (RAS), are also a routine part of clinical practice. Subjects who follow the albuminuric pathway are detected by screening for the presence of microalbuminuria. The finding of microalbuminuria in this setting should provoke an intensified modification of the common risk factors for renal and cardiovascular disease, i.e. hyperglycemia, hypertension, dyslipidemia and smoking. In contrast, little is known about the natural history and structural basis of the non-albuminuric pathway to renal impairment and the best way to retard its progression is also not known. The prevalence of impaired renal function and normoalbuminuria is relatively common and in subjects with type 2 diabetes is at least 20% after accounting for the use of RAS inhibitors. It is therefore recommended that screening for diabetic renal disease should include an estimation of glomerular filtration rate (GFR) in addition to measuring AER. This will allow the detection of subjects following either an albuminuric or non-albuminuric pathway to renal impairment.
 ...
PMID:Albuminuric and non-albuminuric pathways to renal impairment in diabetes. 1620 6

Diabetes mellitus and arterial hypertension are the leading causes of end-stage renal disease in industrialized countries. Although attention has focused on renal disease and insulin-dependent diabetes mellitus (type 1 diabetes), a silent epidemic of renal disease caused by type 2, noninsulin-dependent diabetes mellitus is rapidly developing. The course of renal function is heterogeneous in type 2 diabetic patients and reflects heterogeneous patterns of renal lesions. A subset of patients with microalbuminuria and proteinuria is characterized by the typical diabetic glomerulopathy usually observed in type 1 diabetic patients, with altered albumin excretion rate (AER), for example, glomerular basement membrane thickening and mesangial fractional volume expansion. These patients also have diabetic retinopathy and rapidly lose renal function despite tight blood pressure control. In contrast, a second subset of type 2 diabetic patients has normal or near-normal patterns of glomerular structure, despite abnormalities of AER comparable to those of the patients with diabetic glomerulopathy. Thus abnormalities of AER have a different renal prognostic value depending on the underlying renal structure. The patients with worse clinical prognosis and typical diabetic glomerulopathy also have diabetic retinopathy, whereas those with a better course of renal function quite often have no diabetic retinopathy. Several findings, albeit not unanimous, suggest that HbA1c levels above 7.5 to 8.0 % are closely associated with a rapid decay of renal function in type 2 diabetes. Tight blood pressure control plays a further important role in determining the progression of renal a damage in type 2 diabetes mellitus. Convincing evidence has been provided that drugs capable of inhibiting the renin-angiotensin hormonal system are quite effective in preventing and delaying the evolution of renal damage in both type 1 and 2 diabetes. Equally strong data support the view that other antihypertensive compounds such as beta-blockers and calcium antagonists also delay the progression of renal damage in diabetes mellitus. Whatever the drug used to treat hypertension, the majority of the authors conclude that blood pressure levels should be maintained below 130/85 mmHg in diabetic patients. While it is well established that uncontrolled diabetes underlies the development of diabetic nephropathy, newer evidence suggests that genetically determined susceptibility to hyperglycemia-caused glomerular injury is also necessary. More information on this issue will help to design new therapeutical approaches to treat hypertension and renal complications in type 2 diabetes.
 ...
PMID:Hypertension and renal complications in type 2 diabetes. 1622 1

Diabetes is the most common cause of ESRD in Western countries. This article describes the impact of glycemic control in the various stages of the disease and considers the impact of tight glycemic control on the development and progression of diabetic nephropathy (DN). The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetic Study have demonstrated in type 1 and type 2 diabetes that intensive glycemic control significantly reduces the risk for development of microalbuminuria. Although observational studies suggest an impact of glycemia also on the progression of DN, fewer data are available on the impact of improved metabolic control in secondary prevention. The long-term follow-up of the patients who participated in the Diabetes Control and Complications Trial (Epidemiology of Diabetes Interventions and Complications Study) demonstrated a sustained effect of previous tight glycemic control on both development and progression of DN. Finally, long-term normoglycemia, achieved by pancreas transplantation, is able not only to prevent the development of early diabetic glomerulopathy in kidney transplant recipients but also to halt progression and induce regression of the established diabetic renal lesions in nonuremic patients. Taken together, these studies strongly demonstrate that improvement in glucose control is the most important therapeutic approach in primary prevention. Tight glycemic control also is important in slowing progression of DN, and if blood glucose is normalized, then regression of DN can be achieved. Therefore, a target of glycated hemoglobin levels <7% should be recommended in all patients with diabetes.
 ...
PMID:Renal protection in diabetes: role of glycemic control. 1656 55

The incidence of end-stage renal failure has increased in Italy from 70-80 to 120 per 1x10(6). About 20-30% of patients with diabetes develop nephropathy, usually within 20-25 yrs after disease onset. Diet plays an essential role in the therapy of diabetic nephropathy. A well planned diabetic diet with intensive glycemic control can significantly reduce the risk of microalbuminuria development, and moderate protein restriction reduces hyperfiltration and intraglomerular pressure, and retards the progression of diabetic glomerulopathy. Various studies have shown a positive effect of diet with a protein intake of approximately 0.8 g/kg(-1)/day(-1) in patients with overt nephropathy, with a further restriction to 0.6 g/kg(-1)/day(-1) when the glomerular filtration rate begins to fall. Extra protein intake should counterbalance massive proteinuric losses.
 ...
PMID:[Nutrition in diabetic nephropathy]. 1663 99

Excess body weight may be associated with various functional/structural lesions of the kidney. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 mL/min/1.73 m2) is related to the increasing number of components of the metabolic syndrome, ie, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol, and hypertension. In the long run, end-stage renal failure may develop. An increased body mass index is particularly harmful in patients with reduced renal functional mass (unilateral renal agenesis or nephrectomy) and other renal diseases (immunoglobulin A nephritis and chronic graft dysfunction after kidney transplantation). In the pathogenesis of obesity-associated glomerulopathy, hyperfiltration is of fundamental importance. The factors involved are energy intake (high protein and salt), hyperinsulinemia, and enhanced tubuloglomerular feedback because of increased sodium reabsorption. The adrenergic and renin-angiotensin-aldosterone systems as well as glucocorticoids are stimulated. In addition, several active proteins generated in the central adipose tissue, such as leptin, proinflammatory cytokines, plasminogen activator inhibitor-1, angiotensinogen, and growth factors (transforming growth factor-beta1), as well as low levels of the protective adiponectin, may contribute to renal injury. Of greatest importance is the development of hypertension and of diabetes, which are directly related to the severity of central obesity. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise), or eventually by antiobesity medication or bariatric surgery. In the presence of glomerulopathy and/or hypertension, angiotensin converting enzyme inhibitors or angiotensin II type I receptor blockers are the drugs of choice to improve glomerular hyperfiltration.
 ...
PMID:Renal disease in obesity: the need for greater attention. 1682 23

Epidemiological studies have proven that obesity is a significant risk factor for type 2 diabetes. Long-term progression of diabetes leads to various microvascular complications, of which diabetic nephropathy has become of increasing importance, and is the main cause of end-stage renal failure in occidental countries. Microalbuminuria is the first marker of incipient diabetic nephropathy, an early stage glomerulopathy which can progress to renal failure and which historically has been treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. We report a severely obese diabetic patient on treatment for diabetic nephropathy with ACE-inhibitors and poor results, which resolved after Roux-en-Y gastric bypass.
 ...
PMID:Resolution of early stage diabetic nephropathy in an obese diabetic patient after gastric bypass. 1705 53

Obesity and being overweight are risk factors for kidney diseases. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 ml/min/1.73 m(2)) is related to the increasing number of components of the metabolic syndrome; that is, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol level and hypertension. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise) or eventually by antiobesity medication or bariatric surgery. Rimonabant, a new antiobesity medication, showed beneficial potential effect in treating clusters of metabolic syndrome, which may ultimately suggest potential benefit in treating obesity-related glomerulopathy.
 ...
PMID:Rimonabant as a potential new treatment for an emerging epidemic of obesity-related glomerulopathy? 1706 18

Idiopathic membranous glomerulonephritis (MGN) is a rare cause of end-stage renal failure, which can lead to chronic hemodialysis. This glomerulopathy can recur after renal transplantation despite immunosuppressive therapy. To date, there is no confirmed therapy for treatment of renal grafts after recurrence of MGN. Herein, we report on a 27-year-old man who underwent cadaveric renal transplantation for MGN in September 2001. At 2 months posttransplant, a renal biopsy showed membranous deposition on immunofluorescence staining evocative of recurrence of MGN. Proteinuria developed progressively and, at one year, was estimated at 7.65 g/24 h, with hypoalbuminemia of 24 g/l. This persisted despite symptomatic treatment with anti-proteinuric agents (enalapril 20 mg/day and irbesartan 75 mg/day) and atorvastatin (10 mg/day). By March 2004, his proteinuria was 11 g/day; therefore, therapy with rituximab (monoclonal anti-CD20) at 375 mg/m(2) weekly was initiated for four consecutive weeks, followed by the same dosage every four months for one year. Biological controls performed two weeks after the fourth infusion of rituximab showed a fall in proteinuria, assessed at 1 g/24 h, with albuminemia of 29 g/l and normalized lipidic results. A renal biopsy performed 6 months after the first infusion was unchanged. Follow-up at 30 months showed consistent remission of membranous nephropathy, demonstrated by a serum creatinine level of 150 mumol/L, microalbuminuria of 107 mg/24 h and normal albuminemia of 43.7 g/l. There were no side effects; in particular, no infectious complications occurred, despite CD19 lymphocytes being still negative after 30 months. Monoclonal CD-20 antibodies have shown efficacy against MGN compared to conventional therapies in native kidneys. It has recently been shown that CD20 mRNA is overexpressed in the renal interstitium in patients suffering from MGN and that the interstitial infiltrates is mainly composed of B-cell lymphocytes in these patients. These data may explain the efficiency of rituximab in these circumstances.
 ...
PMID:[Efficiency of rituximab treatment for recurrence of membranous glomerulopathy after renal transplantation]. 1745 3

Microalbuminuria is the earliest detectable clinical abnormality in diabetic glomerulopathy. On a molecular level, metabolic pathways activated by hyperglycemia, glycated proteins, hemodynamic factors, and oxidative stress are key players in the genesis of diabetic kidney disease. A variety of growth factors and cytokines are then induced through complex signal transduction pathways. Transforming growth factor-beta 1 (TGF-beta1) has emerged as an important downstream mediator for the development of renal hypertrophy and the accumulation of mesangial extracellular matrix components, but there is limited evidence to support its role in the development of albuminuria. The loss of proteoglycans in the glomerular basement membrane (GBM) has been recently questioned as causative of the albuminuria, and current research has focused on the podocyte as a central target for the effects of the metabolic milieu in the development and progression of diabetic albuminuria. Podocyte-derived vascular endothelial growth factor (VEGF), a permeability and angiogenic factor whose expression is increased in diabetic kidney disease, is perhaps a major mediator of the increased protein filtration. Decreased podocyte number and/or density as a result of apoptosis or detachment, GBM thickening with altered matrix composition, and a reduction in nephrin protein in the slit diaphragm with podocyte foot process effacement, all comprise the principal features of diabetic podocytopathy that clinically manifests as albuminuria and proteinuria. Many of these events are mediated by angiotensin II whose local concentration is stimulated by high glucose, mechanical stretch, and proteinuria itself. Angiotensin II in turn stimulates podocyte-derived VEGF, suppresses nephrin expression, and induces TGF-beta1 leading to podocyte apoptosis and fostering the development of glomerulosclerosis. Proteinuria can then induce in tubular cells a genetic program leading to tubulointerstitial inflammation, fibrosis and tubular atrophy. Besides direct effects of albuminuria on tubular cells, pathophysiological changes in the ultrafiltration barrier lead to an increased tubular filtration of various growth factors (TGF-beta1, insulin-like growth factor I) that may further alter the function of tubular cells. Moreover, angiotensin II also stimulates uptake of ultrafiltered proteins into tubular cells and enhances the production of proinflammatory and profibrotic cytokines within the cells. Migration of macrophages and other inflammatory cells into the tubulointerstitium occurs. Increased synthesis and decreased turnover of extracellular matrix proteins in tubular cells and interstitial fibroblasts contribute to interstitial fibrosis. In addition, under locally high concentrations of angiotensin II and TGF-beta1, tubular cells may change their phenotype and become fibroblasts by a process called epithelial to mesenchymal transition (EMT) which contributes to interstitial fibrosis and tubular atrophy because of vanishing epithelia cells. An alternative explanation for the development of albuminuria in diabetic nephropathy that involves primarily an abnormality in tubular handling of ultrafiltered proteins has also been suggested, but these changes are not necessarily exclusive of the altered properties of glomerular ultrafiltration barrier.
 ...
PMID:Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. 1822 Jun 94


<< Previous 1 2 3 4 5 Next >>