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Background The prevalence of idiopathic membranous nephropathy (IMN) is increasing worldwide and the gut microbiota is recognized to play a role in its pathology. The aim of this study was to understand the involvement of the gut–kidney axis in IMN by analyzing the composition of the gut microbiota of biopsy-proven IMN patients compared with healthy controls (HC). Methods Fecal samples from 30 patients with IMN diagnosed by renal biopsy and 30 healthy co-residents (control group) were collected for analysis in the Nephrology Department of the Second Affiliated Hospital of Harbin Medical University. The microbiota composition was analyzed by a 16S rRNA microbial profiling approach. Results The results indicated that the α- and β-diversity of IMN patients differed significantly from those of the HC groups (P Faecalibacterium, Agathobacter, and Bacteroides were less abundant in the IMN group than in the HC group (LDA score > 2). Abundant bacterial functions related to lipid metabolism were observed among IMN group. Conclusion Patients with IMN appear to have an altered gut microbiome, which could provide reference for future research on the interaction mechanism between the intestinal flora and IMN.

The pathological process of glomerulonephritis (GN) includes glomerular capillary damage, and vascular endothelial growth factor (VEGF) has an important role in glomerular capillary repair in GN. We examined the effect of inhibition of glomerular capillary repair after capillary injury in GN. Experimental Thy-1 GN was induced in rats that were divided into two groups: rats that received anti-VEGF neutralizing antibody (50 μg per 100 g body weight per day) and those treated with the vehicle from day 2 to day 9. We assessed the renal function and histopathology serially until week 6. Rats of the Thy-1 GN group showed diffuse glomerular mesangiolysis with ballooning destruction of the capillary network by day 3. VEGF(164) protein levels increased in the damaged glomeruli during days 5 to 10, and endothelial-cell proliferation increased with capillary repair in the vehicle-injected group. Proliferative GN resolved subsequently with decreased mesangial hypercellularity, and recovery of most of the glomeruli to the normal structure was evident by week 6. In contrast, administration of anti-VEGF antibody significantly decreased endothelial-cell proliferation and capillary repair in glomeruli by week 2. Thereafter, glomerular mesangial-cell proliferation and activation continued with persistent infiltration of macrophages. At week 6, segmental glomerular sclerosis developed with mesangial matrix accumulation and proteinuria. Deposition of type I collagen was also noted in sclerotic lesions. We conclude that impaired capillary repair was the underlying mechanism in the prolongation of glomerular inflammation in proliferative GN and in the development of glomerular sclerosis. Capillary repair has an important role in the recovery of glomerular damage and in the resolution of proliferative GN.

Tacrolimus is an effective (but relatively expensive) immunosuppressant that is used widely in patients with membranous nephropathy. To reduce the tacrolimus dose while maintaining an equivalent therapeutic effect, we studied the clinical efficacy and pharmacoeconomic impact of co-administration of Wuzhi capsules (WZC that protects against damage to liver cells) and tacrolimus.Sixty patients with membranous nephropathy were divided randomly into two groups: experimental (tacrolimus + WZC + corticosteroids) and control (tacrolimus + corticosteroids). Each group received treatments continuously for6 months. Liver function; renal function; and whole-blood concentrations of tacrolimus, sugars, lipids, as well as 24-h urinary protein levels were used in the clinical evaluation. The cost of drugs was calculated, and the pharmacoeconomic cost-effectiveness analyses were carried out to compare indices between the two groups.Doses and costs of tacrolimus differed significantly between experimental and control groups (p0.01 or p0.05). Costs in the experimental group were 13,702.62 ± 1,458.6 CNY (2,194.10 ± 233.56 USD) and those in the control group were 17,796.87 ± 2,469.27 CNY (2,849.69 ± 395.39 USD), with clinical efficacy of 93.3 and 90.0 %, respectively. The cost-effectiveness ratios were 146.86 ± 15.63 and 197.73 ± 27.44, respectively. Compared with the experimental group, the control group showed an incremental cost-effectiveness ratio of 1,240.68 ± 306.25 CNY (198.66 ± 49.04 USD), whereas remission between the two groups was similar.Co-administration of WZCs and tacrolimus can reduce the dose of tacrolimus and decrease the costs incurred by patients within the same therapeutic window to that seen for treatment with tacrolimus alone.

Renal fibrosis is a common finding in progressive renal diseases. Matrix metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type (MMP-2⁺/⁺) mice by unilateral ureteral obstruction (UUO). Renal histopathology, EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during the development of interstitial fibrosis. UUO-renal fibrosis was also induced in MMP-2 deficient (MMP-2⁻/⁻) and MMP-2⁺/⁺ mice treated with minocycline (inhibitor of MMPs). In MMP-2⁺/⁺ mice, MMP-2 and MMP-9 were expressed in damaged tubules, and their activities increased in a time-dependent manner after UUO. Interstitial fibrosis was noted at day 14, with deposition of types III and I collagens and expression of markers of mesenchymal cells (S100A4, vimentin, α-smooth muscle actin, and heat shock protein-47) in damaged tubular epithelial cells, together with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated molecules (ILK, TGF-β1, Smad, Wnt, β-catenin, and Snail). In contrast, the kidneys of MMP-2⁻/⁻ mice and minocycline-treated MMP-2⁺/⁺ mice showed amelioration of renal fibrosis with reduced expression of markers of mesenchymal cells in tubular epithelial cells, inhibition of upregulated EMT-associated molecules, and suppression of macrophage infiltration. The results suggested that MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the induction of EMT and macrophage infiltration. Inhibition of MMPs may be beneficial therapeutically in renal fibrosis.

Background/Aims: Matrix metalloproteinases (MMPs) are zinc endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of ischemic damage in acute kidney injury (AKI). In the present study, we analyzed the role of MMP-2 in the repair process in ischemic AKI. Methods: AKI was induced in MMP-2 wild-type (MMP-2+/+) and MMP-2-deficient (MMP-2-/-) mice by 90-min renal artery clamping followed by reperfusion. Renal histology and the activity and distribution of MMP-2 were examined from day 1 to day 14. During the recovery from AKI, MMP-2+/+ mice were also treated with MMP-2/MMP-9 inhibitor. Results: In both MMP-2+/+ and MMP-2-/- mice, AKI developed on day 1 after ischemia/reperfusion with widespread acute tubular injury, but subsequent epithelial cell proliferation was evident on days 3-7. During the repair process, active MMP-2 and MMP-9 increased in regenerating tubular epithelial cells in MMP-2+/+ mice on days 7-14, and the tubular repair process was almost complete by day 14. On the other hand, in MMP-2-/- mice, less prominent proliferation of tubular epithelial cells was evident on days 3 and 7, and damaged tubules that were covered with elongated and immature regenerated epithelial cells were identified on days 7 and 14. Incomplete recovery of injured microvasculature was also noted with persistent macrophage infiltration. Similarly, treatment with MMP-2/MMP-9 inhibitor resulted in impaired recovery in MMP-2+/+ mice. Conclusion: MMP-2 is involved in tubular repair after AKI. The use of the MMP-2/MMP-9 inhibitor was a disadvantage when it was administered during the repair stage of ischemic AKI. Treatment with MMP inhibitor for AKI needs to be modified to enhance recovery from AKI.