• MeSH
• diabetické nefropatie * patologie   prevence a kontrola   terapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• BLOOD VESSELS/pathology *, DIABETES MELLITUS/complications *, KIDNEY DISEASES/etiology *,
• MeSH
• cévy patologie   MeSH
• diabetické nefropatie * MeSH
• komplikace diabetu * MeSH
• ledviny * MeSH
• nemoci ledvin etiologie   MeSH
• Publikační typ
• časopisecké články MeSH

Diabetic nephropathy (DN) develops in approximately 40% of type 1 diabetic patients and is a leading cause of end-stage renal failure. Its rate of progression varies greatly among individuals. Several factors, including genetic predisposition, metabolic and haemodynamic alterations and various growth factors, may contribute to the initiation and progression of DN. The genetic background of DN is believed to be polygenic. Polymorphisms of different genes, mainly from the renin-angiotensin system, have been studied extensively, and some of them have been suggested to contribute to the development of DN. A search for genes and combinations of genes which could influence the development and progression of DN is in progress.

• MeSH
• diabetes mellitus 1. typu komplikace   genetika   MeSH
• diabetes mellitus 2. typu komplikace   genetika   MeSH
• diabetické nefropatie epidemiologie   genetika   MeSH
• genetická predispozice k nemoci * MeSH
• hodnocení rizik MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• prognóza MeSH
• renin-angiotensin systém genetika   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• srovnávací studie MeSH

Three laboratory indicators of impaired renal function (microalbuminuria (MA), N-acetyl-beta-glucosaminidase (NAG), beta-2-microglobulinaemia (beta-2-M)) were studied in sixty diabetics of type 1. 10 times higher MA levels were found in a subgroup of diabetics with identifiable diabetic retinopathy (DR). In a subgroup of diabetics with normal values of excreted albumin the mean MA value was significantly higher than in those who had already contracted DR. Pathological levels of NAG and beta-2-M were mostly seen in those patients who also had pathological MA results. In only four cases were increased NAG or beta-2-M values as the first and only pathological parameter indicative of possible renal involvement due to diabetic nephropathy.

• MeSH
• acetylglukosaminidasa moč   MeSH
• albuminurie MeSH
• beta-2-mikroglobulin analýza   MeSH
• diabetická retinopatie diagnóza   MeSH
• diabetické nefropatie diagnóza   MeSH
• diabetické neuropatie diagnóza   MeSH
• dospělí MeSH
• imunodifuze MeSH
• lidé středního věku MeSH
• lidé MeSH
• radioimunoanalýza MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylglukosaminidasa MeSH
• beta-2-mikroglobulin MeSH

TGF-β has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-β1 activity with a TGF-β1-specific, humanized, neutralizing monoclonal antibody (TGF-β1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3-3.3 mg/dl for women and 1.5-3.5 mg/dl for men (or eGFR of 20-60 ml/min per 1.73 m2), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-β1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-β1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-β1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.

• Klíčová slova
• Diabetic Kidney Disease, Transforming growth factor beta, proteinuria, renal fibrosis,
• MeSH
• diabetické nefropatie farmakoterapie   imunologie   MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• transformující růstový faktor beta1 imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• monoklonální protilátky MeSH
• transformující růstový faktor beta1 MeSH

BACKGROUND: Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX140-B, a selective inhibitor of C-C chemokine receptor type 2 (CCR2), could further reduce albuminuria when given in addition to standard care, including ACE inhibitors or ARBs. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, we recruited patients from 78 research centres in Belgium, Czech Republic, Germany, Hungary, Poland, and the UK. We enrolled patients with type 2 diabetes aged 18-75 years with proteinuria (first morning void urinary albumin to creatinine ratio [UACR] 100-3000 mg/g), estimated glomerular filtration rate of 25 mL/min per 1·73 m(2) or higher, and taking stable antidiabetic treatment and ACE inhibitors or ARBs, for at least 8 weeks before study entry. Patients were stratified based on baseline UACR and renal function (estimated glomerular filtration rate), and then randomly assigned (1:1:1) via an interactive web response system with a minimisation algorithm to oral placebo, 5 mg CCX140-B, or 10 mg CCX140-B once a day. The 12-week dosing period in the initial protocol was extended to 52 weeks by protocol amendment. The primary efficacy measure was change from baseline in UACR during 52 weeks in the modified intention-to-treat population (all patients with uninterrupted dosing, excluding patients who stopped dosing at week 12 either permanently under the original protocol, or temporarily because of delay in approval of the protocol amendment). We did safety analyses on all randomly assigned patients who received at least one dose of study drug. According to a prespecified analysis plan, we analysed the primary endpoint with one-sided statistical testing with calculation of upper 95% confidence limits of the differences between active and control. This trial is registered with ClinicalTrials.gov, number NCT01447147. FINDINGS: The study ran from Dec 7, 2011 (first patient enrolled), until Aug 4, 2014. We enrolled 332 patients: 111 were assigned to receive placebo, 110 to 5 mg CCX140-B, and 111 to 10 mg CCX140-B. Of these, 192 were included in the modified intention-to-treat population. UACR changes from baseline during 52 weeks were -2% for placebo (95% CI -11% to 9%), -18% for 5 mg CCX140-B (-26% to -8%), and -11% for 10 mg CCX140-B (-20% to -1%). We recorded a -16% difference between 5 mg CCX140-B and placebo (one-sided upper 95% confidence limit -5%; p=0·01) and a -10% difference between 10 mg CCX140-B and placebo (upper 95% confidence limit 2%; p=0·08). Adverse events occurred in 81 (73%) of 111 patients in the placebo group versus 71 (65%) of 110 patients in the CCX140-B 5 mg group and 68 (61%) of 111 patients in the CCX140-B 10 mg group; there were no renal events during the study. INTERPRETATION: Our data suggest that CCR2 inhibition with CCX140-B has renoprotective effects on top of current standard of care in patients with type 2 diabetes and nephropathy. FUNDING: ChemoCentryx.

• MeSH
• adjuvantní chemoterapie MeSH
• albuminurie farmakoterapie   MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• diabetické nefropatie farmakoterapie   MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• receptory CCR2 antagonisté a inhibitory   MeSH
• senioři MeSH
• sulfonamidy škodlivé účinky   farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• CCR2 protein, human MeSH Prohlížeč
• CCX140-B MeSH Prohlížeč
• receptory CCR2 MeSH
• sulfonamidy MeSH

Diabetic nephropathy is one of the microvascular complications of diabetes. Its incidence is decreasing in insulin dependent patients, but extremely increasing in non-insulin dependent patients in developed countries. The development of nephropathy in an individual patient cannot be predicted in spite of new information about genetics and pathophysiology of the disease. Clinical course progresses from microalbuminuria to overt proteinuria and than to renal failure. The disease cannot be cured, but can be prevented or limited in progression. The most important measures are maintaining of normoglycaemia and blood pressure in low-normal values (best using ACE inhibitors), treatment of hypercholesterolaemia and protein restriction. Renal replacement therapy is available for all diabetic patients in our country without restriction, the best method is kidney transplantation if not contraindicated.

• MeSH
• diabetické nefropatie * diagnóza   terapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Risk factors for atherosclerosis were investigated in a group of 17 female Type II diabetic patients with microalbuminuria-urinary albumin excretion (UAE) in the range of 30-300 mg/day, and in a control group including 15 Type II diabetic females with UAE less than 30 mg/day. Significantly increased mean concentrations of total and LDL-cholesterol were measured in the group with microalbuminuria (p less than 0.05). Also mean levels of some other cardiovascular risk factors (systolic blood pressure, fibrinogen, apolipoprotein B, triglycerides and uric acid) were higher in the group of patients with microalbuminuria, although the differences in comparison to the control group did not reach the level of statistical significance. In the multiple stepwise regression analysis log transformed UAE values correlated significantly with three independent factors--uric acid (p less than 0.01), fibrinogen (p less than 0.05), and systolic blood pressure (p less than 0.05). It is concluded that a slight increase in the levels of a number of cardiovascular risk factors observed in incipient diabetic nephropathy suggests an additive effect favouring atherogenesis.

• MeSH
• albuminurie krev   komplikace   MeSH
• arterioskleróza krev   MeSH
• diabetes mellitus 2. typu krev   komplikace   MeSH
• diabetické angiopatie krev   etiologie   MeSH
• diabetické nefropatie krev   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipidy MeSH

BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273). METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier. RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found. CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

• Klíčová slova
• biomarkers, chronic kidney disease, diabetic nephropathy, diagnosis, urine proteomics,
• MeSH
• diabetes mellitus 2. typu komplikace   diagnóza   moč   MeSH
• diabetické nefropatie diagnóza   etiologie   moč   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• peptidomimetika moč   MeSH
• progrese nemoci MeSH
• prospektivní studie MeSH
• proteomika metody   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• validační studie MeSH
• Názvy látek
• peptidomimetika MeSH

Diabetic nephropathy is one of the main causes of chronic renal failure in developed countries. The genesis and development of diabetic nephropathy is associated in both types of diabetes with a more rapid progression of other secondary complications and an increased mortality, in particular cardiovascular mortality. The main causes of development of diabetic nephropathy are prolonged hyperglycaemia along with a so far not elucidated inborn disposition. The course of diabetic nephropathy is characterized more clearly in type 1 diabetes. The clinically manifest stage is already irreversible and in the course of years it develops into chronic renal failure. Preventive and curative measures include maintenance of optimal metabolic control, systematic control of blood pressure, in particular by ACE-inhibitors, and a reduction of protein intake. Systematic multidisciplinary collaboration in care for patients with diabetic nephropathy helps to prevent the progression of other secondary complications such as diabetic foot and diabetic retinopathy. At present in the Czech Republic dialysis methods substituting renal function are available to practically all patients with diabetic nephropathy. As regards survival time and quality of life the optimal method of renal function replacement for patients in the terminal stage of diabetic nephropathy is transplantation.

• MeSH
• diabetické nefropatie diagnóza   patofyziologie   prevence a kontrola   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH