CYP3A5*1/*3 polymorphisms are associated with tacrolimus pharmacokinetics and dose requirements in renal transplant recipients. Pharmacogenetic methods could be employed prospectively to help initial dose selection and to individualize immunosuppressive therapy.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is purified from rhubarb (Rheum officinale), a widely used traditional Chinese herb. In our previous studies, rhein was shown to be effective in ameliorating diabetic renal pathological changes and attenuating hyperlipidemia. Statins have also been proven to ameliorate renal pathological changes associated with diabetic nephropathy (DN) through lipid-dependent and -independent mechanisms. We here study the protective and regulatory effects of rhein on renal injury and dyslipidemia in db/db mice with DN, using simvastatin as the control, and provide information on the mechanisms by which rhein protects against renal damage from DN. The results indicated that urinary albumin excretion (UAE) was reduced after 8 weeks of treatment in the rhein group, and 12 weeks in the simvastatin group. The morphometric analysis revealed that levels of extracellular matrix (ECM) significantly decreased in the rhein group after the full treatment course, but not in the simvastatin group. The more powerful effects of rhein on decreasing transforming growth factor-beta1 (TGF-beta1) and fibronectin immunohistochemistry expression in renal tissue were also observed. And the plasma levels of cholesterol (Chol), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoE all decreased in both the rhein and the simvastatin groups. Together, our data suggested that both rhein and simvastatin regulate dyslipidemia. The powerful effect of rhein in renal protection is due to its widespread effects. Rhein is a new drug that can decrease lipid levels and protect against DN progression in a different fashion with simvastatin.

There appeared to be a similar renal protective effect of rhein compared with benazepril in diabetic nephropathy. A combined therapy may offer a more beneficial complementary effect on kidney injury in db/db mice, as reflected by urinary albumin excretion, renal function and histological changes. Our findings suggest that a therapeutic approach that combines rhein with ACEI provides a more effective therapy for DN than does either agent alone.

Aims/hypothesis Increased renal mast cells have been detected in diabetic nephropathy. However, only a few patients have been examined. Evidence of the involvement of mast cells in diabetic nephropathy is still scarce, and no observation of mast cells during the development of diabetic nephropathy has yet been reported in humans. Here, we examined changes in renal mast cells in patients at different stages of diabetic nephropathy and related these to the development of the disease. Methods Eighty patients at different clinical stages of diabetic nephropathy and 16 normal kidney donors were recruited. Immunohistochemical staining for tryptase, chymase, TGF-β1, renin and TNF-α was done on renal sections from patients and control participants. Changes in mast cell number, degranulation, subtype and phenotype were examined. Correlation between mast cells and patients' clinical and pathological indices was analysed. Results With progression of diabetic nephropathy, the number and degranulation level of mast cells increased. Increase in mast cell number and degranulation level correlated significantly with tubular interstitial injury. Almost all renal mast cells in patients with diabetic nephropathy were found to produce chymase, renin, TGF-β1 and TNF-α. The level of TNF-α in mast cells increased with progression of diabetic nephropathy. Conclusions/interpretation This study suggests that mast cells are involved in development of diabetic nephropathy. Through release of bioactive substances, such as tryptase, chymase, TGF-β1, renin and TNF-α, into the tubular interstitium by degranulation, mast cells could promote renal inflammation and fibrosis, and thus contribute to diabetic nephropathy.

Background: Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus. However, the underlying mechanisms remain unclear. We studied the expression characteristics of angiopoietin-like 2 (ANGPTL2), a novel DN-associated growth factor identified in our previous gene chip screening. Methods: Glomeruli were microdissected from renal biopsies from 24 patients with DN and 8 donor controls. The expression of ANGPTL2 was assessed by RT-PCR and immunohistochemistry, and then correlated with clinical and pathological indices of glomerular injury. Results: Consistent with the results of the gene chip experiment, abundant expression of ANGPTL2 was found more frequently in diabetic glomeruli as compared to donor controls (95 vs. 38%, χ² = 15.9, p < 0.01). ANGPTL2 mRNA upregulation was more prominent in glomeruli with less microaneurysm (22 vs. 66%, p < 0.05), inflammatory influx (6 vs. 50%, p < 0.05) or endothelial foam cell formation (11 vs. 53%, p < 0.05). Immunostaining revealed an upregulation of ANGPTL2 protein in hypertrophied diabetic glomeruli, mainly distributed in podocytes, which were supposed to be the origin of ANGPTL2. Conclusion: The upregulation of ANGPTL2 in diabetic glomerulopathy shows a close relationship to abnormal microvasculature and endothelial inflammation. ANGPTL2 may play an important role in the pathogenesis of diabetic glomerulopathy.

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Aims/Introduction The aim of the present study was to obtain a full view of the changes of urinary complement activation products in the development of diabetic nephropathy and explore their possible significance in the disease process. Materials and methods A total of 62 patients at different stages of diabetic nephropathy, 20 diabetes patients without nephropathy and 20 healthy persons were enrolled. Urinary complement activation products, including C3a, C5a and C5b‐9, were measured, and their associations with the progression of the disease were analyzed. Results The urinary complement activation products increased markedly since the proteinuria stage, and were parallel with the progression of diabetic nephropathy. More severe renal tubular damage was observed in patients with higher levels of urinary complement activation products. The urinary complement activation products levels correlated closely with renal tubulointerstitial injury score and relative tubular interstitial volume. Multivariate regression analysis showed that elevated urinary complement activation products were independent risk factors for tubular injury in diabetic nephropathy patients. Conclusions Urinary complement activation might have a role in renal tubular interstitial injury in patients with diabetic nephropathy, especially in patients at a later stage of the disease.

KDF1 has been identified as a key regulator of epidermal proliferation and differentiation, but it is unknown whether KDF1 is involved in the pathogenesis of malignancy. No study has reported the expression and function of KDF1 in renal cancer. To explore the pathologic significance of KDF1 in clear cell renal cell carcinoma (ccRCC), the expression level of KDF1 protein in the tumor tissue of ccRCC patients was examined by immunohistochemistry and Western blot while the expression level of KDF1 mRNA was analyzed by using the data from TCGA database. In vitro cell experiments and allogeneic tumor transplantation tests were performed to determine the effects of altered KDF1 expression on the phenotype of ccRCC cells. Both the KDF1 mRNA and protein were found to be decreasingly expressed in the tumor tissue of ccRCC patients when compared with the adjacent non-tumor control tissue. The expression level of KDF1 in the tumor tissue was found to correlate negatively with the tumor grade. Patients with higher KDF1 in the tumor tissue were found to have longer overall survival and disease-specific survival time. KDF1 was shown to be an independent factor influencing the disease-specific survival of the ccRCC patients. Overexpression of KDF1 was found to inhibit the proliferation, migration and invasion of ccRCC cells, which could be reversed by decreasing the expression of KDF1 again. ccRCC cells with KDF1 overexpression were found to produce smaller transgrafted tumors. These results support the idea that KDF1 is involved in ccRCC and may function as a tumor suppressor.