Progression Of Diabetic Nephropathy In Patients Research Articles

Prognostic Nutritional Index as a Predictor of Diabetic Nephropathy Progression.

Malnutrition and immunologic derangement were not uncommon in patients with chronic kidney disease (CKD). However, the long-term effects of prognostic nutritional index (PNI), an immunonutrition indictor, on renal outcomes in patients with diabetic nephropathy (DN) and type 2 diabetes mellitus (T2DM) are unknown. In this retrospective cohort study, 475 patients with T2DM and biopsy-confirmed DN from West China Hospital between January 2010 and September 2019 were evaluated. PNI was evaluated as serum albumin (g/L) + 5 × lymphocyte count (109/L). The study endpoint was defined as progression to end-stage renal disease (ESRD). The Cox regression analysis was performed to investigate the risk factors of renal failure in DN patients. A total of 321 eligible individuals were finally included in this study. The patients with higher PNI had a higher eGFR and lower proteinuria at baseline. Correlation analysis indicated PNI was positively related eGFR (r = 0.325, p < 0.001), and negatively correlated with proteinuria (r = −0.68, p < 0.001), glomerular lesion (r = −0.412, p < 0.001) and interstitial fibrosis and tubular atrophy (r = −0.282, p < 0.001). During a median follow-up of 30 months (16–50 months), the outcome event occurred in 164(51.09%) of all the patients. After multivariable adjustment, each SD (per-SD) increment of PNI at baseline was associated with a lower incidence of ESRD (hazard ratio, 0.705, 95% CI, 0.523–0.952, p = 0.023), while the hypoalbuminemia and anemia were not. For the prediction of ESRD, the area under curves (AUC) evaluated with time-dependent receiver operating characteristics were 0.79 at 1 year, 0.78 at 2 years, and 0.74 at 3 years, respectively, and the addition of PNI could significantly improve the predictive ability of the model incorporating traditional risk factors. In summary, PNI correlated with eGFR and glomerular injury and was an independent predictor for DN progression in patients with T2DM. Thus, it may facilitate the risk stratification of DN patients and contribute to targeted management.

Aspartate aminotransferase to alanine aminotransferase ratio and the risk of diabetic nephropathy progression in patients with type 2 diabetes mellitus: A biopsy-based study

PurposeTo study the relationship between baseline serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR) in both clinicopathological features and renal outcome among type 2 diabetes mellitus (T2DM) patients with biopsy-confirmed diabetic nephropathy (DN). MethodsAs a retrospective cohort study, we included 253 patients with T2DM and biopsy-confirmed DN. For receiver operating characteristic (ROC) curve showed that the optimal cut-off for AAR to predict end stage renal disease (ESRD) was 1.22. So, patients were divided into two groups according to their AAR at the time of renal biopsy: high AAR Group (those with AAR > 1.22); low AAR Group (those with AAR ≤1.22). Association between AAR and clinicopathological features as well as renal outcome were analyzed. ResultsPatients with higher AAR presented elder, more hypertensive, more insulin use, higher serum cholesterol, more proteinuria and lower estimated glomerular filtration rate (eGFR). Compared with low AAR group, patients with high AAR had more severe glomerular pathological lesions and interstitial fibrosis and tubular atrophy. For prognostic analysis, high AAR Group was associated with a higher risk of progression to ESRD in univariate analysis. No matter treated with continuous or categorical variate, higher AAR remained an independent predictor for ESRD after adjusted for various confounding factors: gender, age, the duration of diabetes, serum glucose level, hypertension, serum lipid level, smoking, insulin use, eGFR and proteinuria. ConclusionHigh AAR was associated with more severe renal pathologic lesions and worse renal function in patients with T2DM and DN, which might be a novel noninvasive predictor for ESRD. Clinical relevanceTo our knowledge, there was no biopsy-based cohort study. In our study, high AAR was associated with more severe renal pathologic lesions and worse renal function in patients with T2DM and DN, which might be a novel noninvasive predictor of ESRD for patients with DN.

The relationship between the thickness of glomerular basement membrane and renal outcomes in patients with diabetic nephropathy

Glomerular basement membrane (GBM) thickening is considered as one of the earliest detectable pathological features of diabetic nephropathy (DN). However, whether the thickness of GBM will impact the prognosis of DN remains largely unknown. Our aim was to explore the relationship between thickness of GBM and DN progression in patients with type 2 diabetes mellitus (T2DM). A total of 118 patients with T2DM and biopsy-proven DN who received follow-up for at least 1year were recruited. The patients were divided into two groups according to the median (787nm) of the GBM thickness: Group 1: GBM thickness < 787nm (n = 59), and Group 2: GBM thickness ≥ 787nm (n = 59). The GBM width was estimated by the direct GBM measurements as recently modified by Haas. Renal outcomes were defined by progression to ESRD and/or doubling of serum creatinine (D-Cr). The influence of GBM thickness on renal outcomes was assessed using Cox regression. Compared with the Group 1, patients in Group 2 had more serious renal insufficiency and glomerular lesions. During the follow-up, ESRD occurred in 39.8% of patients, and 8.5% of patients progressed to D-Cr. The univariate analysis indicated the greater width of GBM the higher risk of renal outcomes in T2DM patients with DN (HR [95% CI] = 2.180 [1.246-3.814], p = 0.006). However, the multivariate COX analysis demonstrated that the GBM thickness was not an independent risk factor for progression to ESRD or D-Cr (HR [95% CI] = 0.825 [0.404-1.685], p = 0.597) when adjusting for important clinical variables and pathological findings. In conclusion, the DN patients with greater width of GBM had relatively poorer renal prognosis, although it did not emerge as an independent indicator of disease progression.

Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy.

Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using ELISA, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in patients with type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with T2DM. Cultured immortalized rat proximal tubule cells (IRPTCs) treated with fatty acid-free BSA or advanced glycation end product-modified BSA (AGE-BSA), endocytic ligands of megalin, increased EV excretion, and their C-megalin content. C-megalin excretion from IRPTCs via extracellular vesicles was significantly blocked by an exosome-specific inhibitor, GW4869, indicating that this excretion is mainly exocytosis-mediated. AGE-BSA treatment of IRPTCs caused apparent lysosomal dysfunction, which stimulated multivesicular body formation, resulting in increased exosomal C-megalin excretion. In a high-fat diet-induced, megalin-mediated kidney injury model in mice, urinary C-megalin excretion also increased via UEVs. Collectively, exocytosis-mediated urinary C-megalin excretion is associated with the development and progression of DN in patients with T2DM, particularly due to megalin-mediated lysosomal dysfunction in proximal tubules, and hence it could be a candidate biomarker linked with DN pathogenesis.

Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia.

Beneficial effects of omega-3 fatty acid (O3FA) supplementation in a wide range of disease condition have been well studied. However, there is limited information regarding the effects of O3FAs on chronic kidney disease (CKD), especially in diabetic nephropathy (DN) with hypertriglyceridemia. We investigate whether O3FA supplementation could help maintain renal function in patients with diabetes and hypertriglyceridemia. Total 344 type 2 diabetic patients with a history of O3FA supplementation for managing hypertriglyceridemia were included. Reduction in urine albumin to creatinine ratio (ACR) and glomerular filtrate rate (GFR) were examined. Subgroup analyses were stratified according to the daily O3FA doses. Serum total cholesterol, triglyceride, and urine ACR significantly reduced after O3FA supplementation. Overall, 172 (50.0%) patients did not experience renal function loss, and 125 (36.3%) patients had a GFR with a positive slope. The patients treated with O3FAs at 4g/day showed greater maintenance in renal function than those treated with lower dosages (p < 0.001). This dose dependent effect remains significant after adjustment for multiple variables. O3FA supplementation in diabetic patients with hypertriglyceridemia shows benefits of reducing albuminuria and maintaining renal function. The effects are dependent on the dose of daily O3FA supplementation.

СHARACTERISTICS OF THE HEART FATTY ACID-BINDING PROTEIN, INTERLEUKIN-6 AND INTERLEUKIN-8 AS ALTERNATIVE MARKERS OF DIABETIC NEPHROPATHY PROGRESSION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

The aim of this work was to study the levels of the heart fatty acid-binding protein (h-FABP), interleukin6 (IL-6) and interleukin-8 (IL-8), in diabetic nephropathy (DN) in patients with type 1 diabetes mellitus (T1DM). Material and methods. We examined 87 patients aged 18 to 54 with T1DM within the study group. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients – with proteinuria. The control group consisted of 24 healthy donor aged 22 to 29. The comparison group included 22 patients aged 20 to 42 with verified diagnosis of essential arterial hypertension (AH) without carbohydrate metabolism disorders. The daily urinary albumin excretion was determined by immunoturbidimetric technique. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients with proteinuria.Calculation of glomerular filtration rate was performed according to the Hoek formula with the use of cystatinС serum concentrations. Contents of h-FABP, IL-6 and cystatin C in serum and h-FABP, IL-8 inurine were determined by enzyme-linked immunosorbent assay. Results. Analysis of the h-FABP content in serum showed that the concentration of this marker in individuals with T1DM was higher than in patients of the control group and the comparison group. Analysis of the h-FABP content in the urine revealed that individuals with essential hypertension showed an increased level of h-FABP while patients with T1DM demonstrated the highest concentration of h-FABP. The concentration of IL-6 inindividuals with T1DM and in individuals with AH significantly exceeded the control values. The contents of h-FABP and IL-6 inserum and h-FABP and IL-8 inurine increased with the progression of DN and reached maximum in individuals of the proteinuria subgroup. At the same time, the levels of h-FABP and IL-8 inthe urine of patients in the microalbuminuria (MAU) subgroup were higher compared to those in individuals of the normoalbuminuria (NAU) subgroup. Noteworthy is the fact that the h-FABP content in the urine of individuals in NAU subgroup was higher compared to the control group. Furthermore, higher rates of h-FABP and IL-8 urinary excretions were observed in individuals with CKD stage 2 as compared to individuals with CKD stage1 inthe MAU subgroup. Conclusion. Thus, the results obtained in the course of the study indicate that h-FABP and IL-8 can be considered as alternative markers of DN progression in patients with T1DM.

Influence of intensive glycemic control on development and progression of diabetic nephropathy in patients with type 2 diabetes mellitus (based on results from ADVANCE study)

Current article presents data on effects of intensive glycemic control with Diabeton MR on development and progression of diabeticnephropathy in patients with type 2 diabetes mellitus (T2DM), accumulated from ADVANCE (Action in Diabetes and Vascular Disease:Preterax and DiamicroN Modified Release Controlled Evaluation study). Influence of intensive therapy with Diabeton MR wasassessed in that study separately and in conjunction with active antihypertensive treatment with perindopril and indapamide.

Increased Carotid Intima-Media Thickness is Associated with Progression of Diabetic Nephropathy in Patients with Type 2 Diabetes

Background: Cardiovascular risk is higher among people with diabetic nephropathy than among those with normal renal function. Carotid intima-media thickness (IMT) is an independent predictor of cardiovascular mortality in type 2 diabetic patients. However, the relationship between carotid IMT and diabetic nephropathy is not well known. The aim of our study was to elucidate whether carotid IMT is associated with progression of diabetic nephropathy in type 2 diabetic patients. Methods: We recruited a total of 354 type 2 diabetic patients with diabetic nephropathy. Renal function was evaluated by serum creatinine levels, estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR). Carotid IMT was as sessed using B-mode ultrasound by measuring generally used parameters. Baseline-to-study end changes in eGFR were calculated, and the yearly change of eGFR (mL/min/yr) was computed. Results: Age, diabetes duration, ACR, and eGFR were significantly correlated with mean or maximal carotid IMT; however, lipid profiles, HbA1c, and blood pressure were not correlated. The mean yearly eGFR change was -4.9 ± 5.3 mL/min/yr. The yearly eGFR change was negatively correlated with mean and maximal carotid IMT. After adjusting for age and diabetes duration, the mean IMT is an independent predictor of yearly eGFR change. Conclusion: Carotid IMT may be a predictor of diabetic nephropathy progression in patients with type 2 diabetes. (Endocrinol Metab 26:310-316, 2011)