View clinical trials related to Diabetic Nephropathies.
Filter by:The objective is to determine if lowering serum uric acid by means of allopurinol in the course of kidney disease may be effective in preventing or improving albuminuria and renal function in Type 1 Diabetic patients. The study is a double blinded, randomised, placebo-controlled cross-over clinical trial.
Objectives: Main objective: To assess the effect of 12 months of CPAP treatment added to conventional drug treatment on the albuminuria in patients with diabetic nephropathy and obstructive sleep apnea (OSA). Secondary objectives: To evaluate the effect of CPAP treatment on the estimated glomerular filtration rate of patients with diabetic nephropathy and OSA; determine the additional longterm CPAP effect on glycemic control, insulin resistance, lipid profile, health-related quality of life and biomarkers of cardiac function, inflammation, oxidative stress, sympathetic tone and appetite-regulating hormones in patients with diabetic nephropathy and OSA; and to identify the subgroup of patients with diabetic nephropathy and OSA in which 12 months of treatment with CPAP achieve a more pronounced reduction in albuminuria. Methodology: Randomized, multicenter, non-blinded, parallel groups, conventional treatment-controlled trial of 12 months of duration. Subjects will randomize to conventional dietary and pharmacological treatment or conventional dietary and pharmacological treatment plus continuous positive airway pressure (CPAP). Study subjects: Subjects 18 to 80 years with overweight or obesity and a clinical diagnosis of diabetic nephropathy, increased urinary albumin/creatinine ratio of 30 mg/g and an estimated glomerular filtration rate >20 ml/min/1.73 m2, and treatment with stable doses of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or anti-aldosterone drugs in the last four weeks. Efficacy variables: urinary albumin/creatinine ratio and estimated glomerular filtration rate; glycosylated hemoglobin (HbA1c); fasting glucose and insulin; homeostatic model assessment (HOMA) and QUICKI indices; total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides; Troponin I, proBNP, homocysteine and high-sensitivity C-reactive protein; systemic biomarkers (inflammation [IL-6, IL-8 and tumor necrosis factor-α], oxidative stress [8-isoprostane], endothelial damage [endothelin, VCAM-1 and ICAM-1], sympathetic activity [neuropeptide Y] and appetite-regulating hormones [leptin and adiponectin]) and clinical questionnaires: short form (SF)-12, EuroQoL and iPAQ.
The severity of the diabetic nephropathy is proportional to proteinuria rate and degree of renal interstitial fibrosis. Despite many treatments available today, diabetic nephropathy is responsible for a quarter of cases of end-stage renal disease (ESRD) requiring the use of renal replacement therapy or kidney transplantation. It develops as follows: chronic hyperglycemia of diabetes abyss renal glomeruli that allow proteins in the urine room. In response, the tubular epithelium produces monocyte chemoattractant protein-1 (MCP-1) that attracts monocytes circulating in the renal interstitium. Monocytes then differentiate into M1 or M2 macrophages. M1 macrophages increased MCP-1 production while M2 macrophages produce transforming growth factor beta (TGF-β) pro-fibrogenic. Renal fibrosis is negatively correlated with the glomerular filtration rate itself proportional to the number of nephrons. The decrease in the number of nephrons majorises secondarily proteinuria by the onset of focal segmental glomerulosclerosis lesions. Production of MCP-1 increases with the renal proteinuria because M1 macrophages earning kidneys reinforce the production of MCP-1, and fibrosis worsens because M2 macrophages infiltrate in turn kidneys and produce TGF -β. A way of limiting renal fibrosis would be to decrease renal monocytic infiltration by promoting the differentiation of monocytes towards macrophages M2. Although more numerous, M2 macrophages no longer benefit the kidneys because the decline of M1 macrophages decrease renal MCP-1 production. Ex vivo IL1-β orients the differentiation of monocytes towards macrophages M1 and IL-4 to M2. By cons in vivo, the differentiating factors are poorly known. It is remarkable that metformin and telmisartan increase M2 macrophages M1 macrophages and decrease, respectively, in humans and mice. Moreover, telmisartan reduces proteinuria more than losartan in diabetic nephropathy in humans and Metformin decreases the amount of TGF-β intra-renal mice. This effect of telmisartan is independent of the type 1 receptor of angiotensin II (AT1R) since it is not obtained with losartan. Telmisartan is a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma), the working assumption is that telmisartan fosters the transition of monocytes to macrophages M2 form, and limit the recruitment of more monocytes in the kidneys and therefore proteinuria and renal fibrosis. To show this, it will be compared the ability of monocytes to differentiate ex vivo in M1 or M2 macrophages in diabetic nephropathy patients treated with losartan or telmisartan then it will characterize the role of PPARgamma in the monocyte / macrophage transition. Finally, it will be compared the urinary excretion of amino terminal propeptide of procollagen type 3 (PIIINP), considered a marker of renal fibrosis in patients receiving losartan or telmisartan.
The aim of this study is to evaluate the safety and effects of resveratrol in treatment of diabetic nephropathy.
This is a multi-center, randomized, parallel study to evaluate effect of exenatide on 24h-UAER in patients with diabetic nephropathy. Screening will be made to select eligible participants before intervention. The trial will include 2-week run-in period of stable doses of glargine plus lispro insulin and 24-week treatment period. After the run-in period, patients were randomly assigned to one of two groups for antihyperglycaemic therapies for a total of 24-weeks: glargine plus exenatide and continued glargine plus lispro insulin. The treatment of exenatide will be initiated by 5ug bid, and uptitrated to 10 ug bid after 4 weeks and then maintained at 10ug bid until the completion of the study. Lispro insulin will be initially treated according to the insulin dosage of previous antihyperglycaemic therapies, and further titrated up at 4-week intervals until to reach the target fasting blood glucose (FPG).
It is estimated that approximately 30% of patients with diabetes develop diabetic nephropathy. Diabetic nephropathy is a multifactorial progressive disease that occurs through various mechanisms such as hyperglycemia, oxidative stress, inflammation and fibrosis, control or blocking these mechanisms are therefore potential therapeutical targets for this entity. Current treatment options are based on the glycemic control, blood pressure control, as well as the use of medications such as angiotensin-converting enzyme inhibitors and Angiotensin II receptor antagonists, these actions are not enough to stop progression. Pirfenidone is a drug with antifibrotic, antioxidant, and anti-inflammatory properties. Although the specific mechanism is unknown, pirfenidone interferes with the expression, secretion and the effect of the β (TGF-β) transforming growth factor. The investigators plan to carry out a controlled clinical study to evaluate the effect of pirfenidone in patients with type 2 diabetes and nephropathy. The period of time the treatment will be administered will be of 12 months, 62 patients will be included. The primary outcome will be improvement in glomerular filtration rate. The secondary outcomes will be number of patients requiring replacement therapy, 24 hour urine microalbuminuria and change in the concentration of TGF - β. Change in these parameters will be evaluated at the end of the treatment period (12 months). Throughout the study the incidence of adverse events will be recorded, wich will allow us to learn about the safety and security of the drug in this population.
Background: Worldwide, diabetic nephropathy or Diabetic Kidney Disease (DKD), is the most common cause of chronic and end-stage kidney disease. With the increasing rates of obesity and type 2 diabetes (T2DM), many more patients with DKD may be expected in the coming years. Large-sized prospective randomized clinical trials suggest that intensified glucose and blood pressure control, may halt the progression of DKD, both in type 1 diabetes and T2DM. However, despite the wide use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, a considerable amount of patients develop DKD during the course of diabetes, indicating an unmet need for renoprotective therapies. Sodium-glucose linked transporters (SGLT-2) inhibitors are novel glucose-lowering drugs for the treatment of T2DM. These agents seem to exert pleiotropic actions 'beyond glucose control', including reduction of blood pressure and body weight. In addition, SGLT-2 inhibitors decrease proximal sodium reabsorption and decrease glomerular pressure and albuminuria in rodents and type 1 diabetes patients. In rodents, SGLT-2 inhibitors also improved histopathological abnormalities associated with DKD. To date, the potential renoprotective effects and mechanisms of these agents have not been sufficiently detailed in human type 2 diabetes. The current study aims to explore the clinical effects and mechanistics of SGLT-2 inhibitors on renal physiology and biomarkers in metformin-treated T2DM patients with normal kidney function. Study Design: Randomized, double-blind, comparator-controlled, intervention trial Study Endpoints: Renal hemodynamics, i.e. measured glomerular filtration rate (GFR, ml/min) and effective renal plasma flow (ERPF, ml/min); 24-hour urinary solute excretion; markers of renal damage ; blood pressure; body anthropometrics; systemic hemodynamic variables (including stroke volume, cardiac output and total peripheral resistance); arterial stiffness will be assessed by applanation tonometry, (SphygmoCor®); insulin sensitivity and beta-cell function. Expected results: Treatment with the SGLT-2 inhibitor dapagliflozin, as compared to the sulfonylurea (SU) derivative gliclazide, may confer renoprotection by improving renal hemodynamics, and decreasing blood pressure and body weight in type 2 diabetes.
This study aims to evaluate the safety and efficacy of MT-3995 administered over the longer term, following MT-3995-J05 study.
The purpose of this study is to evaluate the effect of lipo-prostaglandin E1 （lipo-PGE1) on renal oxygenation in patients with diabetic nephropathy by blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI).patients with stable chronic kidney disease (CKD) were included. All patients were divided into two groups: diabetic nephropathy（DN) and CKD without diabetes. In addition to the conventional treatments, all patients received 10 ug lipo-PGE1 intravenously once daily for consecutive 14 days. Kidney BOLD-MRI were performed before and after lipo-PGE1 administration to acquire bilateral renal cortical R2*(CR2*) and medullary R2* (MR2*) values. Meanwhile, the clinical indexes at baseline and under lipo-PGE1 including 24 hours urinary protein and serum creatinine were collected. the investigators want to prove Lipo-PGE1 can improve kidney medullary oxygenation in patients with DN.
This study evaluates the long-term benefits of Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus, focussing on the prevalence and predictors of T2DM improvement and remission after RYGB, and subsequently relapse of type 2 diabetes mellitus after RYGB. Moreover, the study evaluates the possible effect of RYGB on diabetic microvascular complications such as nephropathy and retinopathy. Finally, the study provides insight into the factors influencing glucose-insulin homeostasis after RYGB, including altered microbiota diversity and bile acid levels.