Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium–glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin–angiotensin–aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.

Background/Aims: Clinically, there is lack of predictors for diabetic nephropathy (DN) in diabetes mellitus (DM) without microalbuminuria, macroalbuminuria or retinopathy. Methods: PubMed, Chinese Biomedical Database, Cochrane Library, EMBASE and Elsevier Database were searched from inception to August 13, 2016. Studies involving patients with DM and containing data on cystatin C measurements and the measured glomerular filtration rate (mGFR) were included. Pooled sensitivity, specificity, positive predictive value, negative predictive value and other diagnostic indices were evaluated using a random effect model. Results: The meta-analysis enrolled 9 studies with 1417 patients. The pooled sensitivity and specificity of serum cystatin C for predicting DN were 0.88 (95% CI 0.85 - 0.91) and 0.85 (95% CI 0.82 - 0.87), respectively. The pooled positive and negative predictive values of serum cystatin C for predicting DN were 7.04 (95% CI 4.33 - 11.43) and 0.13 (95% CI 0.09 - 0.20), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.9549, and the diagnostic odds ratio was 66.80 (95% CI 27.92 - 159.86). Conclusion: Serum cystatin C is an early predictor of DN among patients with DM.

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