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Increasing evidence shows that diabetic nephropathy is associated with immune disorder. Macrophages are a key immune cell infiltrating the kidney in both patients and experimental animal models of diabetes, and correlate with progressive renal injury under diabetic conditions. Blockade of renal macrophage infiltration by either genetic deletion or pharmacological inhibition has been shown to improve diabetic renal injury, revealing a pathogenic role of macrophages in diabetic nephropathy. Further, studies identify that M1 macrophages are a key player responsible for diabetic renal injury by triggering renal inflammation, while M2 macrophages are highly heterogenous, and may play diverse roles in either initiating the renal repairing process if renal inflammation is resolved, or promoting progressive renal fibrosis via a macrophage-to-myofibroblast transition (MMT) process if renal inflammation is ongoing. Macrophages may also interact with intrinsic kidney cells to mediate renal inflammation or fibrosis directly or indirectly by producing a variety of proinflammatory cytokines/chemokines and growth factors, or by macrophage-derived exosomes. In summary, macrophages are immunologically important in the pathogenesis of diabetic kidney disease and may play a driving role in the progression of diabetic nephropathy. Targeting macrophages may thus be considered as a novel therapy for combatting diabetic nephropathy.

Diabetic kidney disease (DKD), as the primary cause of end-stage renal disease (ESRD), is becoming a growing public health challenge worldwide. Early intervention in conditions involving high glucose levels will prevent the progression of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) comprise a new class of medications used to reduce hyperglycemia in patients with diabetes by inhibiting renal reabsorption of filtered glucose. Interestingly, SGLT2i is not only capable of controlling the blood glucose level but also has other benefits in terms of blood pressure control, body weight decrease, and albuminuria reduction. It is assumed that various events, such as energy metabolism disorder, insulin resistance, glomerular hyperfiltration, oxidative stress, inflammation, and fibrosis, attributable to the pathogenesis of DKD, can be improved by SGLT2i. Clinical trials have demonstrated that SGLT2i can exert renoprotective effects and reduce the morbidity and mortality due to ESRD. In this review, we focus on the most recent findings from clinical trials and the underlying mechanisms by which SGLT2 inhibitors afford renal protection.

Background Renal fibrosis is one of the main characteristics of diabetic nephropathy. TGF-β1/Smad3 pathway is expected to reveal the pathogenesis of renal fibrosis in diabetic nephropathy (DN). Pyridoxamine (PM), a natural form of vitamin B6, is a powerful inhibitor of advanced glycation end products (AGEs). PM plays an anti-apoptotic, anti-oxidative stress, and fibrosis role in DN. The purpose of this study was to assess whether PM has a protective effect in renal tubular epithelial and to investigate its possible mechanism. Methods The effects of PM were investigated in HK-2 cells induced by high glucose. HK-2 cells were administered with PM at a dose of 1 mmol/L. Western blot and Realtime PCR were used to detect the expression levels of renal fibrosis related proteins. The possible mechanism of PM was examined by expression of transforming growth factor-β1 (TGF-β1)/Smad3 pathway. Results PM could reduce the expression of Fibronectin (FN) and α-smooth muscle actin (α-SMA) induced by high glucose. PM could also affect the activity of TGF-β1/Smad3 pathway in HK-2 cells. FN and α-SMA were up-regulated by overexpression of Smad3 for 48 h. After adding PM, the levels of FN and α-SMA are significantly decreased. Conclusion Our findings indicate that PM showed a protective effect in HK-2 cells through the inhibition of TGF-β1/Smad3 pathway.

Objectives To evaluate and compare the effectiveness and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the prevention and treatment of diabetic kidney disease (DKD). Methods We searched articles in PubMed, Embase, and the Cochrane Central Register of Controlled Trials, which are published from 2010 to 2021, to identify randomized controlled trials (RCTs) by comparing SGLT2 inhibitors with placebo. A network meta-analysis (NMA) was conducted within a frequency framework using a random-effects model. Results We included 16 studies involving 51,925 patients in the analysis. Only empagliflozin significantly lowered urine albumin-to-creatinine ratio (UACR) than a placebo (mean differences [MD]: −83.01, 95% confidence intervals [CI]: −117.74 to −48.27). With regard to the composite kidney outcomes, canagliflozin (relative risk [RR] = 0.74, 95% CI: 0.69–0.80), dapagliflozin (RR = 0.76, 95% CI: 0.68–0.85), empagliflozin (RR = 0.69, 95% CI: 0.63–0.76), and ertugliflozin (RR = 0.82, 95% CI: 0.68–0.99) were significantly associated with a lower risk than placebo. Conclusions The UACR-lowering effects of empagliflozin were greater than most other SGLT2 inhibitors. There were few clinically significant differences in the renal protective effects among these drugs.

Diabetic nephropathy is one of the main complications of diabetes, and is also one of the important causes of end-stage renal disease. It is characterized by pathological changes such as thickening of the glomerular basement membrane, expansion of the mesangial matrix, glomerular sclerosis, and hyalinosis of small arteries. However, diabetic nephropathy is rarely accompanied by the formation of a large number of crescents. At this time, renal puncture is required to search for the cause in diabetic nephropathy with worsening renal function. We report a case of diabetic nephropathy with the formation of a large number of crescents.