Novel Tubular Biomarkers Predict Renal Progression in Type 2 Diabetes Mellitus: A Prospective Cohort Study

Background. Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction. Methods. A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured. The primary outcome was a decline in estimated GFR of ≥25% yearly from baseline. Results. Urine tubular biomarkers of UCCR, UANG, UNGAL, and UKIM-1 were significantly higher according to the degree of albuminuria and all were significantly higher among patients with rapid decline in estimated GFR of ≥25% yearly from baseline. All biomarkers predicted primary outcomes with ROC for UCCR of 0.72; 95% CI 0.64-0.79, for UANG of 0.71; 95% CI 0.63-0.79, for UNGAL of 0.64; 95% CI 0.56-0.72, and for UKIM-1 of 0.71; 95% CI 0.63-0.79. Using multivariate Cox regression analysis, the number of patients with rapid renal progression was higher among those in the upper quartiles of all biomarkers than in those in the lower quartiles. Conclusions. Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function

Renal Effects of Sulodexide in Type 2 Diabetic Patients without Nephrotic Range Proteinuria

Background. Glycosaminoglycan plays an important role in the maintenance of glomerular charge selectivity of diabetic nephropathy. Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has shown a nephroprotective effect in an experimental model of diabetic nephropathy. Although sulodexide reduced albuminuria in patients with type 1 and type 2 diabetes, long-term effects in patients with type 2 diabetes with significant proteinuria have not been established. Objectives. The study was aimed at investigating the effects of sulodexide on proteinuria and renal function in patients with type 2 diabetes and nephropathy. Methods. Fifty-two patients with proteinuria between 500 and 3000 mg/day received sulodexide 200 mg/day for 12 months, while 56 matched patients with type 2 diabetes constituted the control group. All patients received standard metabolic and blood pressure controls. Primary outcome was evaluated as percentage of reduced proteinuria compared with the control group. Renal function was assessed using estimated glomerular filtration rate (GFR). Results. Proteinuria significantly increased in the control group [0.9 (IQR 0.3 to 1.78) to 1.16 (IQR 0.44 to 2.23) g/gCr, P=0.001], whereas it remained stable in the sulodexide group [0.66 (IQR 0.23 to 0.67) to 0.67 (IQR 0.17 to 1.51) g/gCr, P=0.108]. At 12 months, proteinuria was higher by 19.4% (IQR 10.3 to 37.6) in the control group while proteinuria was lower by -17.7% (IQR -53.1 to 3.2) in the sulodexide group with a significant difference between groups (P=0.001). Renal function was noted as a change of estimated GFR, and serum creatinine decreased significantly during the study in both groups but did not significantly differ between groups. No significant changes in the blood pressure, fasting plasma glucose, and hemoglobin A1C were reported. Conclusion. In addition to standard treatment, sulodexide is efficient in maintaining proteinuria in patients with type 2 diabetes with nonnephrotic range proteinuria, but it did not provide an additional benefit concerning renal disease progression

Safety and efficacy of low dose pioglitazone compared with standard dose pioglitazone in type 2 diabetes with chronic kidney disease: A randomized controlled trial.

BACKGROUND:Choices of hypoglycemic agents for patients with type 2 diabetes and chronic kidney disease (CKD) are limited. Available data among patients with CKD suggest that pioglitazone was effective and safe, with no increase in serious adverse effects. However, weight gain and fluid retention are major clinical problems for pioglitazone among patients with CKD. We conducted this study to compare the efficacy and side effects of low dose pioglitazone with standard dose pioglitazone among patients with type 2 diabetes and CKD. METHODS:A total of 75 patients with type 2 diabetes and CKD and inadequate glycemic control receiving any pharmacological antidiabetic treatment were randomly assigned to 2 groups. One group consisted of 37 patients treated with standard dose pioglitazone (15 mg/day) and another group consisted of 38 patients treated with low dose pioglitazone (7.5 mg/day). Glycosylated hemoglobinA1c (HbA1c) and metabolic profiles were monitored every 8 weeks for 24 weeks. Body composition was assessed using bio-electrical impedance analysis (BIA). RESULTS:After 6 months of therapy, HbA1c levels decreased in both standard and low dose pioglitazone groups. The mean changes in HbA1c for standard and low dose pioglitazone were 1.1±1.6 and -1.4±1.5 (P = 0.543), respectively. Compared with low dose pioglitazone, standard dose pioglitazone treatment led to a greater increase in body weight, fat mass, total body water and extracellular water composition. No major adverse effects including hypoglycemia, congestive heart failure and abnormal liver function were identified. CONCLUSION:Pioglitazone 7.5 mg once daily treatments presented similar glycemic control to standard dose pioglitazone and exhibited beneficial effects on weight gain and fluid retention among patients with type 2 diabetes and CKD

Clinicopathological Correlation in Asian Patients with Biopsy-Proven Lupus Nephritis

A total of 244 patients with lupus nephritis (219 women (89.8%) with a female to male ratio of 9 : 1) were included in the study. Clinical and laboratory findings at renal biopsy are clinically valuable in identifying different renal classifications of lupus pathology, activity, and chronicity index. Patients with class IVG had significantly higher proportions of microscopic hematuria, proteinuria, hypertension, impaired renal function, anemia, hypoalbuminuria, and positive anti-DNA antibody. All of these findings correlated well with high activity index and chronicity index of lupus pathology. Considering these correlations may help to determine the clinicopathologic status of lupus patients

Impaired Glomerular Filtration Rate in Type 2 Diabetes Mellitus Subjects: A Nationwide Cross-Sectional Study in Thailand

Background. Type 2 diabetic mellitus (T2DM) patients with impaired renal function have a higher risk of mortality, and often progress to end-stage renal disease. The study aims to determine the prevalence of kidney disease and investigate the relationship between various factors and impaired renal function in a large population of patients with T2DM. Methods. We conducted a cross-sectional study among 30,377 patients from a nationwide diabetes study involving 602 Thai hospitals. Impaired glomerular filtration rate (GFR) was defined as 7% (adjusted OR 2.53 (95%CI=1.38 to 4.63)) were found to be associated with a significantly increased risk of impaired GFR among T2DM patients. Conclusion. Almost 40% of patients with T2DM in a nationwide cross-sectional study in Thailand had impaired GFR. Advanced age, albuminuria, hyperuricemia, hypertension, HA1C 7% were independently associated with increased prevalence of impaired GFR

Clinical Study Effect of Sulodexide on Urinary Biomarkers of Kidney Injury in Normoalbuminuric Type 2 Diabetes: A Randomized Controlled Trial

Glycosaminoglycans or sulodexide has shown benefits in early experimental diabetic nephropathy (DN) models, but its efficacy in patients with early stage of DN is unknown. Methods. Twenty patients were randomly assigned to the placebo group and another 20 patients were randomly assigned to receive sulodexide 100 mg/day for 14 weeks. Primary outcome was a change of urinary TGF-beta1, albuminuria, and glomerular filtration rate (GFR). All patients had stable metabolic profiles for at least 90 days before randomization. Results. Urinary TGF-beta1 increased significantly in the placebo group but did not change significantly in the sulodexide group. Additionally, the mean change of urine TGF-beta1 in the placebo group was significantly higher than that in the sulodexide group (8.44 ± 9.21 versus 2.17 ± 6.96 pg/mg Cr, = 0.02). Mean changes of urinary albumin were 15.05 ± 30.09 g/mg Cr ( = 0.038) in the placebo group and 13.89 ± 32.25 g/mg Cr ( = 0.069) in the sulodexide group. No consistent patterns of side effects were observed. Conclusion. In this 14-week trial, benefits of sulodexide in preventing the increase of urinary TGF-beta1 were observed in patients with normoalbuminuric type 2 diabetes. The study suggests that sulodexide treatment may provide additional renoprotection in early stage DN. This trial is registered with TCTR20140806001

Efficacy of Weekly Split versus Single Doses of Ergocalciferol on Serum 25-Hydroxyvitamin D among Patients on Continuous Ambulatory Peritoneal Dialysis: A Randomized Controlled Trial

Background. Vitamin D deficiency is a common problem among patients on continuous ambulatory peritoneal dialysis (CAPD). Vitamin D supplementation leads to reduced serum parathyroid hormone levels and improved cardiovascular markers. Different doses and time intervals of oral vitamin D supplementation may differ in each patient on dialysis. The study aimed to evaluate the efficacy of weekly split and single dose of ergocalciferol at 60,000 IU on serum 25-hydroxyvitamin D (25(OH)D) among patients on CAPD. Methods. A randomized study was conducted among patients on CAPD with vitamin D deficiency or insufficiency (25(OH)D < 30 ng/mL). Patients were randomly assigned to two groups: the split dose group was given ergocalciferol 20,000 IU three times weekly and the single dose group was given ergocalciferol 60,000 IU once weekly for 8 weeks. Main outcomes measured serum 25(OH)D concentrations, serum calcium, serum phosphate, and intact parathyroid levels at 8 weeks after being enrolled. Results. Of 128 screened patients, 50 met the criteria for eligibility and were randomized. At 8 weeks after treatment, mean serum 25(OH)D concentrations significantly increased from baseline 22.7 ± 5.9 to 29.5 ± 9.5 ng/mL P=0.004 in the split dose group and 22.9 ± 5.3 to 31.2 ± 12.3 ng/mL P=0.003 in the single dose group. No significant change was found in increase of serum 25(OH)D between the two groups P=0.561. At the end of study, a similar proportion of patients in both groups reached the desirable serum concentration of 25(OH)D ≥ 30 ng/mL (60% in the single group vs. 40% in the split group, P=0.258). No significant cases of hypercalcemia, hyperphosphatemia, or serious adverse events occurred during the study. Conclusion. Weekly single and split doses of ergocalciferol 60,000 IU achieved similar effects on serum 25(OH)D levels among patients on CAPD with vitamin D insufficiency or deficiency, suggesting that weekly single dose would be prescribed for adequate vitamin D repletion. This trial is registered with TCTR20200821005

The Effects of Simvastatin on Proteinuria and Renal Function in Patients with Chronic Kidney Disease

Current data suggests that statins might have beneficial effects on renal outcomes. Beneficial effects of statin treatment on renal progression in advanced chronic kidney disease (CKD) are obviously controversial. In a retrospective, controlled study, the authors have evaluated the effects of 53-week treatment with simvastatin, versus no treatment on proteinuria and renal function among 51 patients with CKD stages III-IV. By the end of the 53-week treatment, urine protein excretion decreased from 0.96 (IQR 0.54, 2.9) to 0.48 (IQR 0.18, 0.79) g/g creatinine (P<0.001) in patients treated with simvastatin in addition to ACEI and ARBs, while no change was observed among the untreated patients. Moreover, a significantly greater decrease in urine protein excretion was observed in the simvastatin group as compared with the untreated group. The mean changes of serum creatinine and eGFR did not significantly differ in both groups. A significantly greater decrease in total cholesterol and LDL-cholesterol was found in the simvastatin group than in the untreated group. In summary, apart from lipid lowering among CKD patients, ingesting simvastatin was associated with a decrease in proteinuria. These statin effects may become important for supportive therapy in renal damage in the future