Diabetic Nephropathy and Management

Chronic kidney disease affects people worldwide. Approximately 1 out of 3 adults with diabetes have kidney disease. Among several etiological factors for CKD, diabetes mellitus (DM) and hypertension are the main factors. These factors not only cause CKD but are also responsible for several complications related to CKD. In this article, we have reviewed Diabetic Nephropathy (DN) in terms of etiology, pathophysiology, diagnosis, management, current guidelines for diabetic nephropathy management, and some of the research study findings. Diabetic nephropathy (DN) is the chief factor for end-stage renal disease (ESRD) development across the globe. The primary cause of DN is Diabetes Mellitus, which is an autoimmune lifestyle disorder having several etiological factors. Checking for urine albuminuria, estimated GFR (eGFR), and blood glucose are unswerving tests for DN diagnosis and subsequent monitoring. Controlling hyperglycemia, blood pressure, and proteinuria are critical in stopping the progression of DKD. Clinical practice and evidence-based medicine demonstrated that early diagnosis followed by treatment can prevent or halt DKD progression.

Differences in Pathological Characteristics and Laboratory Indicators in Adult and Pediatric Patients with Henoch-Sch？nlein Purpura Nephritis

We aimed to investigate the differences in renal histopathological changes and laboratory parameters between adult and pediatric patients with Henoch-Sch？nlein purpura nephritis（HSPN）, and to analyze the correlation between laboratory parameters and renal histopathological grading. A total of 139 patients diagnosed with HSPN between September 2010 and December 2014 at the First Hospital of Jilin University, China, were retrospectively reviewed. The clinical and pathological characteristics were examined and compared between the adult and the pediatric patients. A majority of adult（75.0%） and pediatric（66.2%） patients were categorized as pathological grade Ⅲ HSPN. Adults having crescent lesions, interstitial fibrosis and renal artery involvement significantly outnumbered child counterparts（all P〈0.05）. Pathological grading showed a positive correlation with 24-h urine protein（r=0.307, P=0.009）, microalbuminuria（r=0.266, P=0.000） and serum globulin（r=0.307, P=0.014）, and a negative correlation with serum albumin（r=0.249, P=0.037） in pediatric patients with HSPN. Among adult patients with HSPN, histopathological grading showed a positive correlation with 24-h urine protein（r=0.294, P=0.015）, microalbuminuria（r=0.352, P=0.006）, α1-microglobulin（r=0.311, P=0.019） and immunoglobulin G（r=0.301, P=0.023） in urine, and serum creatinine（r=0.292, P=0.018）. Further, a negative correlation between serum albumin and pathological grading was also observed（r=0.291, P=0.018）. In conclusion, the severity of renal pathological lesions in HSPN patients is well reflected by the levels of proteinuria. Adult patients have more severe renal histopathological changes than pediatric patients.

Decreased Number of CD14+TLR4+ Monocytes and Their Impaired Cytokine Responses to Lipopolysaccharide in Patients with Chronic Kidney Disease

This study aimed to examine the number of circulating Toll-like receptor 4（TLR4） ＋ CD14＋ monocytes in patients with different stages of chronic kidney disease（CKD）, their responses to lipopolysaccharide（LPS）, and to explore the potential association of the number of TLR4＋CD14＋ monocytes with clinical laboratory measures. The numbers of TLR4＋CD14＋, LPS-stimulated TNF-？＋CD14＋ and interleukin（IL）-6＋CD14＋ monocytes were determined by flow cytometry in 9 patients with stage 3 CKD, 11 with stage 4 CKD, 16 with stage 5 CKD, and 19 healthy controls（HCs）. Their laboratory tests were performed by routine methods and the potential association among these measures was analyzed by Pearson＇s correlation analysis. The numbers of CD14＋, CD14＋TLR4＋, LPSstimulated TNF-？＋CD14＋ and IL-6＋CD14＋ monocytes in patients with CKD were significantly less than those of HCs（all P〈0.05）, and were negatively associated with patient disease severity. The number of CD14＋TLR4＋ monocytes was positively correlated with estimated glomerular filtration rate（e GFR, P〈0.001） and the levels of hematocrit（P〈0.01）, but negatively correlated with the levels of blood urine nitrogen, serum creatinine, and C-reactive protein（P〈0.001 for all）, in the CKD patients. Our data indicate that significant reduction in the number of TLR4＋ monocytes and their impaired responses to LPS may be associated with the progression of CKD in Chinese patients.

Mesenchymal stem cells transplantation mildly ameliorates experimental diabetic nephropathy in rats

Background Diabetic nephropathy is a common complication of diabetes mellitus. This study aimed to explore whether mesenchymal stem cells （MSCs） transplantation could attenuate diabetic nephropathy in experimental diabetic rats. Methods Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin （STZ） （60 mg/kg）. Diabetic rats were randomized to four groups： diabetes control group （DC）, ciclosporin A group （CsA）, MSC group, and MSC＋CsA group （MSCA）. Bone marrow mesenchymal stem cells were cultured, identified and labeled by 5-bromo-2＇-deoxyuridine （BrdU） in vitro. Then they were transplanted to diabetic rats via introcardiac infusion. Ciclosporin A was administered daily at 5 mg/kg. At 1,2, 4, 8 weeks after transplantation, random blood glucose, urine albumin/creatinine ratio （AIb/Cr）, endogenous creatinine clearance rate and renal mass index were tested. Renal morphology and labeled cells were examined. Results Cultured MSCs expressed mesenchymal cell phenotype, and could be multidifferentiated to osteogenic and adipogenic cells. Labeled MSCs could be detected in the kidney of nephropathic rats, mainly in renal interstitium, but they did not propagate after engrafting in kidney. Over the course of the experiment, MSCA group showed a significant decrease in blood glucose compared with MSC group, CsA group and DC group （P 〈0.05, respectively）. The AIb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group （P〈0.05）. And the AIb/Cr in MSCA group showed a significant decrease compared with MSC group （0.74 vs 0.84, P 〈0.05）. There was a significant difference in renal mass index between the MSCA group and DC group （5.66 vs 6.37, P 〈0.05）. No significant difference was found in creatinine clearance rate among 4 groups （P 〉0.05）. Treatment with MSC＋CsA significantly ameliorated the morphology of diabetic kidney. Conclusion MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose, AIb/Cr ratio and renal mass index.