Course Of Diabetic Nephropathy Research Articles

Effect of endothelial no synthase gene polymorphism on the course of diabetic nephropathy in patients with type 2 diabetes mellitus

Effect of endothelial no synthase gene polymorphism on the course of diabetic nephropathy in patients with type 2 diabetes mellitus

The relationship between polymorphic variants of the endothelial NO-synthase gene and the course of diabetic nephropathy in patients with type 2 diabetes mellitus

Objective — to identify a possible association between the endothelial nitric oxide synthase (eNOS) gene G894T (rs1799983) polymorphism and the markers of renal function and glucose metabolism in patients with type 2 diabetes mellitus (DM2) with diabetic nephropathy (DN).
 Materials and methods. Examinations 126 patients with diabetic nephropathy (DN). The control group included 20 healthy individuals. Patients with DM2 were divided into two groups depending on the eNOS rs1799983 gene polymorphism: group I — patients with DN and G/G genotype eNOS G894T gene (n=80); group II — patients with DN and G/T and T/T genotypes eNOS G894T gene (n=46). Genotyping of the of the eNOS rs1799983 gene polymorphism was performed by the Taq‑Man® Fast Universal PCR Master Mix (Applied Biosystems, USA) and TaqMan® SNP Assay (Applied Biosystems, USA).
 Results. It has been established that in patients with DN, the distribution of genotypes of the G894T polymorphism of the eNOS gene corresponded to the Hardy‑Weinberg equilibrium in all groups and does not differ significantly from European populations. In diabetic patients with DN the 3 times higher total frequency of G/T and T/T genotypes eNOS G894T gene was established when compared to the control group. These findings prove the undoubted influence of the T allele on the development of DN in this group of patients. DN patients with genotypes G/T and T/T had significantly higher blood glucose and HOMA index (p <0.05) than G homozygotes (genotype G/G). Patients with DN and G/G genotype eNOS G894T gene had better glomerular filtration rate and lower albuminuria compared to patients with G/T and T/T genotypes (p <0.05).
 Conclusions. The establishing of association of eNOS gene polymorphism with the disease and further assessment of individual genetic risk is important for the development of a differentiated approach to the prevention and treatment of DN in patients with DM2 depending on the hereditary predisposition of an individual patient. Therefore, currently one of the most progressive approaches is to develop a strategy for early diagnosis, prognosis and preventive therapy of the disease using genetic markers.

STUDY OF MICROALBUMINURIAAND ALBUMIN - CREATININE RATIO IN TYPE 2 DIABETES MELLITUS AND THEIR CORRELATION WITH GFR AND OTHER BIOCHEMICAL PARAMETERS

Diabetes mellitus (DM) is one of the primary risk factors for developing renal impairment globally. The development of microalbuminuria has been considered to be one of the rst clinical signs of a classic course of diabetic nephropathy, which leads to macroalbuminuria and then to progressive loss of glomerular ltration rate (GFR) and eventually end-stage renal disease. Both type 1 and type 2 DM may lead to chronic complication of diabetic nephropathy (DN). The development of microalbuminuria has been considered to be one of the rst clinical signs of a classic course of diabetic nephropathy, which leads to macroalbuminuria and then to progressive loss of glomerular ltration rate (GFR) and eventually end-stage renal disease. Persistent macroalbuminuria predicts loss of kidney function and, more importantly, interventions that reduce macroalbuminuria also slow the loss of glomerular ltration rate. this prospective observational study was designed in an attempt to evaluate the relationship between microalbuminuria, albumin-creatinine ratio with other biochemical parameters in type 2 DM and to examine whether this relation differs from that of non-diabet

Influence of non-alcoholic steatohepatitis on the renal functional status in patients with type 2 diabetes and diabetic kidney disease

Background. Hepatic steatosis and nonalcoholic steatohepatitis (NASH) are considered the most common liver pathologies, which in developed countries is observed in 20–30% of the adult population. Patients with diabetes mellitus (DM) often develop non-specific kidney lesions such as asymptomatic bacteriuria, pyelonephritis, kidney carbuncle, kidney abscess, kidney tuberculosis, necrotizing papillitis, or papillary necrosis, which significantly complicate the course of diabetic nephropathy (DN). DN accounts for 40% of complications in type 1 DM and 5–15% among patients with type 2 DM. The purpose of the study is to clarify the impact of non-alcoholic steatohepatitis on the renal functional status in patients with type 2 diabetes and diabetic kidney disease (DКD). Materials and methods. One hundred and sixty patients with NASH with comorbid type 2 DM of moderate severity and DКD stages I–IV were examined. A prospective study was conducted, which involved 160 patients and 30 practically healthy individuals. In particular, 25 patients with NASH and type 2 diabetes (group 1), 20 people with NASH and class I obesity (group 2), 70 patients with NASH stage I–IV (group 3), of whom 31 patients (44.3%) had DКD stage I–II (group 3a), 20 (28.6%) stage III (group 3b), 19 (27.1%) had DKD stage IV (group 3c). Results. In patients with NASH, type 2 DM, and DKD stage I–IV, hypoalbuminemia was found to be probably higher compared to that of patients with type 2 DM, DКD stage I–IV and without NASH that indicates the influence of NASH on the level of albuminemia; higher blood level of creatinine and urea; lower glomerular filtration rate, which confirms the negative effect of NASH on the course of type 2 DM with DКD. In the presence of NASH, patients with DКD had a higher level of albuminuria, urinary creatinine, albumin-creatinine ratio than if it’s absent. Conclusions. Indicators of the renal functional state in patients with NASH and type 2 DM varied depending on the presence of DКD and its stage. As the stage of DКD increased, the content of albumin in the blood decreased, the levels of creatinine and urea increased. The result of the detected changes was an increase in glomerular filtration rate, which indicates the phenomenon of hyperfiltration, which is specific for the initial stages of DКD.

РОЛЬ ПОЛИМОРФИЗМОВ ГЕНОВ СИСТЕМЫ БИОТРАНСФОРМАЦИИ КСЕНОБИОТИКОВ И АНТИОКСИДАНТНОЙ ЗАЩИТЫ В РАЗВИТИИ ДИАБЕТИЧЕСКОЙ НЕФРОПАТИИ

Introduction.The main etiopathogenetic mechanisms of the development of multifactorial diseases are genetic predisposition and environmental factors. A special role in the prognosis of type 1 diabetes mellitus is played by diabetic nephropathy, which leads to chronic kidney disease in its outcome. In the conditions of modern technogenic civilization, it is believed that the most significant contribution to the formation of predisposition to socially significant human diseases can be made by genes of enzymes of protective and adaptive systems of the body – these are, first of all, genes of enzymes of antioxidant protection and biotransformation of xenobiotics. The aim of the study was to study the role of polymorphic variants of genes of the xenobiotic biotransformation system and antioxidant protection (G681A in the CYP2C19 gene; G1293C in the CYP2E1 gene) in the development of diabetic nephropathy in patients with type 1 diabetes mellitus. Material and methods. The study included patients with type 1 diabetes mellitus (50 people) and healthy individuals (20 people). Molecular-genetic, clinical-laboratory and biochemical research methods were used. The reliability of differences in the distribution of genotype frequencies between groups of patients and healthy individuals was assessed by the test2, by the method of conjugate tables (four-field table). Results and discussion. The activity of the processes of free radical oxidation and lipid peroxidation increases many times in type 1 diabetes mellitus, which is confirmed in our study by an increase in the content of malondialdehyde products against the background of an increase in the activity of enzymes of the antioxidant defense system. This is especially evident in individuals carrying heterozygous polymorphism of the CYP2C19 (G681A) and CYP2E1 (G1293C) genes, which is also combined with a more pronounced decrease in kidney function in these patients compared with carriers of other polymorphic variants of the studied genes. Conclusion. Heterozygous polymorphism of the CYP2C19 (G681A) and CYP2E1 (G1293C) genes in combination with increased activity of antioxidant defense enzymes and xenobiotic biotransformation enzymes leads to a more severe course of diabetic nephropathy in patients with type 1 diabetes mellitus.

Recoverability of Diabetic Nephropathy of Donor Kidney After Kidney Transplantation.

Some kidney donors have diabetes, and little of their natural course of diabetic nephropathy (DN) is known. The aim of this study was to analyze the changes in pathologic lesions in the diabetic donor kidney after KT by performing protocol biopsy two weeks and one year after KT. This retrospective study included 103 patients who underwent KT, with kidneys from donors with a history of diabetes mellitus (DM). Among them, data of 34 patients who underwent biopsy two weeks and one year after KT were reviewed. Biopsy specimens were reviewed using light microscopy and electron microscopy. Glomerular basement membrane (GBM) thickness at 2 weeks and 1 year was compared. Biopsy showed that DN occurred in 29 of the 34 patients. Only trivial histological changes were observed in 22 patients (64.7%), including 5 patients who did not show DN. At one year after transplantation, there was no change in the DN histologic class in 26 patients (76.5%), and there was no statistically significant difference in the change in GBM thickness. This pattern was observed regardless of the recipient’s DM or glycemic control. With this understanding, clinicians can use kidneys from DM donors with more comfort, thereby reducing the kidney discard rate.

Neogenin pathway positively regulates fibronectin production by glomerular mesangial cells.

Neogenin, a transmembrane receptor, was recently found in kidney cells and immune cells. However, the function of neogenin signaling in kidney is not clear. Mesangial cells (MCs) are a major source of extracellular matrix (ECM) proteins in glomerulus. In many kidney diseases, MCs are impaired and manifest myofibroblast phenotype. Overproduction of ECM by the injured MCs promotes renal injury and accelerates the progression of kidney diseases. The present study aimed to determine if neogenin receptor was expressed in MCs and if the receptor signaling regulated ECM protein production by MCs. We showed that neogenin was expressed in the glomerular MCs. Deletion of neogenin using CRISPR/Cas9 lentivirus system significantly reduced the abundance of fibronectin, an ECM protein. Netrin-1, a ligand for neogenin, also significantly decreased fibronectin production by MCs and decreased neogenin protein expression in MCs. Furthermore, treatment of human MCs with high glucose (HG, 25 mM) significantly increased the protein abundance of neogenin as early as 8 h. Consistently, neogenin expression in glomerulus significantly increased in the eNOS-/-db/db diabetic mice starting as early as the age of 8 wk and this increase sustained at least to the age of 24 wk. We further found that the HG-induced increase in neogenin abundance was blunted by antioxidant PEG-catalase and N-acetyl cysteine. Taken together, our results suggest a new mechanism of regulation of fibronectin production by MCs. This previously unrecognized neogenin-fibronectin pathway may contribute to glomerular injury responses during the course of diabetic nephropathy.

Влияние растительного препарата Канефрон® H на течение диабетической нефропатии у пациентов с сахарным диабетом 2-го типа: результаты сравнительного когортного исследования

Цель исследования. Диабетическая нефропатия (ДН) является серьезным и частым осложнением сахарного диабета, ведущим к терминальной стадии почечной недостаточности у 30 % больных сахарным диабетом. Первым проявлением ДН является микроальбуминурия, которая возникает в результате снижения барьерной функции клубочковой фильтрации для альбумина. В нарушении этой функции ключевые роли принадлежат активным формам кислорода, воспалительным цитокинам и факторам роста.Экспериментальные процедуры. В ходе этого исследования пациенты с ДН получали комплексный растительный препарат Канефрон® Н для изучения его влияния на динамику микроальбуминурии и общий статус системы антиоксидантной защиты. Проведено открытое исследование с участием 59 пациентов для сравнения эффективности препарата Канефрон® Н в комплексе со стандартной антидиабетической терапией и ингибитором ангиотензинпревращающего фермента (АПФ) со стандартной терапией и лечением только ингибитором АПФ.Результаты. После 6-месячной терапии в основной группе уровень микроальбуминурии значительно снизился по сравнению с контрольной группой. Канефрон® Н позитивно влияет на статус антиоксидантной защиты и уровни перекисного окисления липидов. Кроме того, содержание аминотрансфераз печени не изменилось.Выводы. Учитывая отличную переносимость препарата Канефрон® Н, результаты исследования позволяют однозначно рекомендовать этот растительный лекарственный препарат пациентам с ДН в качестве дополнительной терапии.

Yuquan pill enhance the effect of Western medicine in treatment diabetic nephropathy: A protocol for systematic review and meta-analysis.

Background:Diabetic nephropathy is glomerular sclerosis caused by diabetic microvascular disease, which is one of the most serious complications of diabetes. At present, the traditional treatment of diabetic nephropathy is mainly based on the control of blood pressure, blood sugar, blood lipids, and other basic treatments using angiotensin converting enzyme inhibitor/angiotensin receptor blocker, the clinical reports of relying solely on angiotensin converting enzyme inhibitor/ angiotensin receptor blocker to delay the course of diabetic nephropathy are not optimistic. Yuquan pill (YQP), a classic traditional Chinese medicine prescription, has clinical reports that it can effectively assist in the treatment of diabetic nephropathy with minimal side effects. However, there has been no systematic review of the YQP in the treatment of diabetic nephropathy. This article systematically evaluated the effectiveness and safety of YQP clinical applications.Methods:The database search include seven databases, including PubMed, Embase, Cochrane Library, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wanfang database. The search date was set as a randomized controlled trial from the establishment of the database to April 21, 2021. The main outcome indicators include urinealbumin excretion rate, serum creatinine, urea nitrogen, Total effective rate. The analysis software uses Stata 15.Results:This study will analyze multiple outcome indicators such as clinical efficacy, urinary albumin excretion rate, blood creatinine value, urea nitrogen, and symptom scores. Provides a the latest evidence for YQP in the treatment of diabetic nephropathy (DN).Conclusion:The results of this study will provide evidence for the efficacy of YQP in the treatment of DN.INPLASY Registration number:INPLASY202150030.

The glycocalyx, a novel key in understanding of mechanism of diabetic nephropathy: a commentary.

Diabetes is a chronic and progressive disease that usually causes disrupts the function of the body's organs and can eventually lead to cardiomyopathy, nephropathy, retinopathy, and neuropathy. Diabetic nephropathy (DN) is the most common cause of chronic kidney disease and causes chronic structural changes in different parts of the affected kidney. Glycocalyx layer is one of the most important components of the vascular base found in the endothelium throughout the body's arteries and it has been shown that glycocalyx is also damaged during diabetic nephropathy. Our goal is to conduct this systematic review study is to find the cause-and-effect relationship between glycocalyx and diabetic nephropathy and also to clarify the role of the endothelial renal glycocalyx in understanding of mechanism of the course of diabetic nephropathy, and to provide an accurate background for further important studies. All databases included MEDLINE (PubMed), Science Direct, Scopus, Ovid and Google Scholar were systematically searched for related published articles. In all databases, the following search strategy was implemented and these key words (in the title/abstract) were used: "diabetes" AND "glycocalyx" OR "diabetic nephropathy" AND "glycocalyx". A total of 19 articles were retrieved from all databases using search strategy. After screening based on the title and abstract, number of 17 of them selected for full text assessment. Finally, after extracting the key points and making connections between the articles, we came up with new points to consider. It can be said that diabetes with the action of reactive oxygen species through oxidative stress, increases ICAM-1 and TNF-α and decreases heparanase enzyme, it affects the glomerular endothelium and eventually leads to albuminuria and destruction of the Glx layer. Diabetes causes super-structural changes in the kidney nephrons at the glomerular level. The glomerular filter barrier, which includes the epithelial cell called the podocyte, endothelial pore cells, and basal membrane of the glomerulus, plays a major role in stabilizing the selective glomerular function in healthy individuals. Diabetic nephropathy also causes changes in endothelial glycocalyx.

MO628IMPACT OF INDUCTION OF AUTOPHAGY BY RAPAMYCIN AND METFORMIN ON NATURAL HISTORY OF DIABETIC NEPHROPATHY IN RATS

Abstract Background and Aims Impaired autophagy in the kidney resulted in podocyte loss and massive proteinuria in diabetic nephropathy. Improvement of autophagy by activation of mTORC1 and reduction of AMPK and Sirt1 may be a novel therapeutic option for the suppression of diabetic nephropathy. Method This experimental work was carried out on 48 adult male Sprague dawely rats. The total duration of the study was 10 weeks. All investigation and intervention were carried out at 3 time points, 3 weeks, 6 weeks, 10 weeks. The rats were randomly divided into healthy control group (n = 12) and 3 induced diabetic groups (n = 12 each), the three groups were the non-treated, treated with rapamycin and treated with rapamycin and metformin. To study autophagy, we use electron microscopy and immunohistochemical staining of kidney tissue with LC3 antibody Results Diabetic rats treated with rapamycin alone or rapamycin and metformin showed lower level of proteinuria and almost normal serum creatinine through all intervals of the study. Also, their Kidney tissue showed increased autophagosomes and high expression of LC3 compared to diabetic rats. There are no significant differences between both treated groups in terms of induction of autophagy during the experiment period. Conclusion we concluded that using a small dose of rapamycin for short duration in early diabetic rats is beneficial in halting the course of diabetic nephropathy, adding metformin to rapamycin aiming to potentiate its effect on autophagy seems to be less beneficial.

Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study

Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1–4 respectively. Conversely, no patient who underwent KB for indications 5–7 displayed NDHKD. Logistic regression analyses identified eGFR_CKD-EPI >15 mL/min/1.73 m², urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group. Conclusion: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.

Effects of Allicin on Pathophysiological Mechanisms during the Progression of Nephropathy Associated to Diabetes.

This study aimed to assess the impact of allicin on the course of diabetic nephropathy. Study groups included control, diabetes, and diabetes-treated rats. Allicin treatment (16 mg/kg day/p.o.) started after 1 month of diabetes onset and was administered for 30 days. In the diabetes group, the systolic blood pressure (SBP) increased, also, the oxidative stress and hypoxia in the kidney cortex were evidenced by alterations in the total antioxidant capacity as well as the expression of nuclear factor (erythroid-derived 2)-like 2/Kelch ECH associating protein 1 (Nrf2/Keap1), hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), erythropoietin (Epo) and its receptor (Epo-R). Moreover, diabetes increased nephrin, and kidney injury molecule-1 (KIM-1) expression that correlated with mesangial matrix, the fibrosis index and with the expression of connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA). The insulin levels and glucose transporter protein type-4 (GLUT4) expression were decreased; otherwise, insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) expression was increased. Allicin increased Nrf2 expression and decreased SBP, Keap1, HIF-1α, and VEGF expression. Concurrently, nephrin, KIM-1, the mesangial matrix, fibrosis index, and the fibrotic proteins were decreased. Additionally, allicin decreased hyperglycemia, improved insulin levels, and prevented changes in (GLUT4) and IRSs expression induced by diabetes. In conclusion, our results demonstrate that allicin has the potential to help in the treatment of diabetic nephropathy. The cellular mechanisms underlying its effects mainly rely on the regulation of antioxidant, antifibrotic, and antidiabetic mechanisms, which can contribute towards delay in the progression of renal disease.

Normoalbuminuric chronic kidney disease in diabetes

Urinary albumin excretion (UAE) is widely used in clinical practice as indicator of diabetic kidney disease. According to the classical concept of the natural course of diabetic nephropathy, an increase in UAE usually precedes a decline in renal function. Meanwhile, a growing body of evidences indicates a high prevalence of normoalbuminuric chronic kidney disease (NA-CKD) in diabetic subjects, especially among patients with type 2 diabetes. An increase in NA-CKD prevalence can be results of improved glucose, blood pressure, and lipid control, widespread use of renin-angiotensin system blockers, and smoking cessation. It was shown that NA-CKD is more prevalent among women and is associated with arterial hypertension and coronary artery disease. The renal structure in subjects with NA-CKD is more heterogeneous when compared to patients with increased albuminuria, wherein interstitial changes and arteriolosclerosis could be the principal morphological findings, while signs of glomerulopathy may be absent. The prognostic value of NA-CKD needs to be clarified. It was shown that NA-CKD increases the risk of myocardial infarction, stroke and cardiovascular death in patients with diabetes. The search for alternative diagnostic markers for detecting of diabetic kidney disease in the absence of albuminuria, is of practical importance. The evaluations of the markers of tubular damage and interstitial fibrosis, as well as proteomic approaches, are considered as perspective diagnostic and prognostic options in NA-CKD. The study of pathogenesis, pathology, clinical course of NA-CKD in diabetic patients, as well as the development of more specific diagnostic and treatment options is a challenge for future research.

Renal experiences of bariatric surgery in patients with type 2 diabetes mellitus

The review addresses the questions of the literature devoted to the problem of the influence of bariatric surgery on the course of diabetic nephropathy in patients with diabetes mellitus type 2 after achieving a surgically induced remission. This approach was shown to have positive aspects, such as decrease in creatinine, decrease in albuminuria, an increase in GFR, normalization of glycemia and blood pressure, "incretin effect"’s influence on the kidneys. Descriptions of the currently expected pathogenetic mechanisms involved in achieving the observed improvement in microvascular complications of diabetes, namely diabetic kidney disease, are also described in details.

Normoalbuminuric chronic kidney disease in diabetes.

Urinary albumin excretion (UAE) is widely used in clinical practice as indicator of diabetic kidney disease. According to the classical concept of the natural course of diabetic nephropathy, an increase in UAE usually precedes a decline in renal function. Meanwhile, a growing body of evidences indicates a high prevalence of normoalbuminuric chronic kidney disease (NA-CKD) in diabetic subjects, especially among patients with type 2 diabetes. An increase in NA-CKD prevalence can be results of improved glucose, blood pressure, and lipid control, widespread use of renin-angiotensin system blockers, and smoking cessation. It was shown that NA-CKD is more prevalent among women and is associated with arterial hypertension and coronary artery disease. The renal structure in subjects with NA-CKD is more heterogeneous when compared to patients with increased albuminuria, wherein interstitial changes and arteriolosclerosis could be the principal morphological findings, while signs of glomerulopathy may be absent. The prognostic value of NA-CKD needs to be clarified. It was shown that NA-CKD increases the risk of myocardial infarction, stroke and cardiovascular death in patients with diabetes. The search for alternative diagnostic markers for detecting of diabetic kidney disease in the absence of albuminuria, is of practical importance. The evaluations of the markers of tubular damage and interstitial fibrosis, as well as proteomic approaches, are considered as perspective diagnostic and prognostic options in NA-CKD. The study of pathogenesis, pathology, clinical course of NA-CKD in diabetic patients, as well as the development of more specific diagnostic and treatment options is a challenge for future research.

Почечные исходы бариатрических операций у пациентов с сахарным диабетом 2-го типа

The review addresses the questions of the literature devoted to the problem of the influence of bariatric surgery on the course of diabetic nephropathy in patients with diabetes mellitus type 2 after achieving a surgically induced remission. This approach was shown to have positive aspects, such as decrease in creatinine, decrease in albuminuria, an increase in GFR, normalization of glycemia and blood pressure, "incretin effect"'s influence on the kidneys. Descriptions of the currently expected pathogenetic mechanisms involved in achieving the observed improvement in microvascular complications of diabetes, namely diabetic kidney disease, are also described in details.

DIABETIC NEPHROPATHY;

Objectives: To compare serum uric acid levels in different stages of diabeticnephropathy. Study Design: Descriptive analytical study. Setting: University of Health ScienceLahore. Period: February 2010 to January 2011. Subjects and methods: A sample size of195 diabetic subjects. They were divided among normoalbuminuric, microalbuminuric andmacroalbuminuric groups, according to their daily urinary albumin excretion rate (AER), with65 patients in each group. Their glomerular filtration rate (GFR), daily AER and serum uricacid was evaluated by conducting tests on serum and urine samples. Statistics: Kruskal-Wallis test and Mann-Whitney U test were used to observe differences of medians in differentgroups. P value less than 0.05 was taken statistically significant. Results: There was majority ofmales in microalbuminuric and macroalbuminuric groups while females were more in numberin normoalbuminuric group. Significant differences were found in serum urea concentration,serum creatinine concentration, serum uric acid concentration, glomerular filtration rate, urinarycreatinine concentration, urine flow rate, daily albumin excretion rate and urinary albuminconcentration among the three groups. Urinary creatinine concentration and glomerularfiltration rate were in the highest ranges in normoalbuminuric group and in the lowest rangesin macroalbuminuric group. While rest of the parameters (ie. age, duration of diabetes, serumurea concentration, serum creatinine concentration, urine flow rate, daily AER , urinary albuminconcentration and serum uric acid concentration) were in the lowest ranges in normoalbuminuricgroup and in the highest ranges in macroalbuminuric group. There was significant increaseserum uric acid levels in advancing stages of diabetic nephropathy. p &lt;0.05 was takenstatistically significant. Conclusion: It is concluded that serum uric acid increases with theadvancing stages of diabetic nephropathy. Progressive decline in glomerular filtration rate andgradual rise in serum creatinine level occurs throughout the course of diabetic nephropathy.

Renal Function in Type 2 Diabetes Following Gastric Bypass.

Metabolic surgery for obese patients with type 2 diabetes (T2D) yields short- and long-term remission rates of 60-90%. Its effects on diabetesassociated complications such as neuropathy and nephropathy have not been well studied to date. Hardly any data are available on this subject with respect to moderately obese patients (body mass index [BMI] 25-35 kg/m2) with insulin-dependent T2D. Our previous studies suggest that, in such patients, treatment with a Roux-en-Y gastric bypass (RYGB) improves diabetic neuropathy. In this pilot study, we investigate the course of diabetic nephropathy after RYGB surgery. 20 insulin-dependent patients whose T2D was inadequately controlled with medication, and whose BMI was in the range 25-35 kg/m2, were prospectively included in a pilot study. All patients underwent a standardized RYGB operation. Blood and urine tests for renal function were performed before surgery and 12 and 24 months afterward. The serum creatinine level fell from 0.82 ± 0.23 to 0.69 ± 0.13 mg/dL (p = 0.0025) in the first 12 months after surgery and was unchanged a further 12 months later. The glomerular filtration rate (eGFR) rose in the first 24 months after surgery from 96.4 ± 28.7 to 111.7 ± 23.3 mL/min/1.73 m2 (p = 0.0093). The urinary albumin/creatinine and high-molecular-weight adiponectin/creatinine ratios fell markedly in the first 24 months after surgery (2.89 ± 3.14 versus 1.00 ± 0.24 mg/mmol [p = 0.0491] and 0.18 ± 0.06 versus 0.04 ± 0.01 μg/g [p = 0.0392]). RYGB has positive effects on renal function and may therefore be a good treatment option for moderately obese, insulin-dependent patients whose T2D cannot be adequately controlled with medication. These results still need to be confirmed in randomized, controlled trials with longer periods of followup.

Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis.

Diabetic nephropathy constitutes a devastating complication in patients with type 1 diabetes mellitus, and its diagnosis is traditionally based on microalbuminuria. The aim of this review is to update through the medical literature the suggested early natural course of diabetic nephropathy, the theories behind the pathways of its pathogenesis, and its diagnosis. Poor glycemic control, dyslipidemia, smoking, advanced glycation end products, and environmental and genetic clues play an important role in the development of diabetic nephropathy. Microalbuminuria has been traditionally considered as a primary early marker of microvascular complication unraveling the risk for progress to the advanced stages of chronic kidney disease, but because of our inability to make an early diagnosis of diabetic nephropathy in young patients as well as nonalbuminuric diabetic nephropathy, recently, other additional markers of renal injury like serum and urinary neutrophil gelatinase-associated lipocalin, chitinase-3-like protein 1, cystatin C, and plasma growth differentiation factor 15 have been proposed to unmask early renal dysfunction, even before microalbuminuria supervenes. Copyright © 2016 John Wiley & Sons, Ltd.