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.

Renal effects and safety of tirzepatide in subjects with and without diabetes:A systematic review and meta-analysis

BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m^(2));the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P<0.0001]and 15 mg[MD-18.03%(-28.58,-7.47),P=0.0008]were superior to placebo in percent reductions of UACR.Tirzepatide,at all doses,outperformed insulin in percent reductions of UACR.Compared to the placebo,the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D(MD-33.25%vs-7.93%;P=0.001).The CFB in eGFR with all doses of tirzepatide was comparable[5 mg:MD 0.36(-1.41,2.14);10 mg:MD 1.17(-0.22,2.56);15 mg:MD 1.42(-0.04,2.88)];P>0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD.

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.