Renal Pathological Changes Research Articles

Renal Pathology and Cytogenetic Examination in Multiple Myeloma Patients with Renal Impairment--Retrospective Analysis

To explore the renal pathology and cytogenetic features in the multiple myeloma (MM) patients with renal impairment. The clinical data of newly diagnosed MM patients with renal impairment in our hospital from January 2009 to January 2019 were analyzed retrospectively, and the relationship between FISH results and results of renal pathological exanimation was analyzed statistically by using SPSS 20.0. A total of 20 patients underwent renal biopsy, included 12 males and 8 females. FISH result showed that out of 20 patients, 7 cases presented interstitial nephritis, among which 3 cases were negative for FISH, and in the remaining cases the rate of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 42.86%, 28.57%, 28.57%, 28.57% and 14.29% respectively, the detection positive rate was statistically significantly lower as compared with total probe positive rate (P＜0.01). There were 6 cases of cast nephropathy, among which IgH rearrangement, the rate of 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 66.67%, 50%, 66.67%, 50% and 0% respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were 4 cases of acute tubular necrosis, among which the detection rates of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion was 100%, 50%, 50%, 25% and 25%, respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were one case of amyloidosis, and one case of tubular nephropathy with amyloidosis, the detection with 5 probes were all positive. One case of light chain deposition disease was positive for RB1 gene deletion + D13S319 gene deletion. FISH in the MM patients with different renal pathological changes is characterized by heterogeneity, which can be used to predict the risk of renal damage and speculate possible renal pathological types to guide prognosis.

Increase of BACE1, Brain-Renal Risk Factor, Contributes to Kidney Damage in an Alzheimer's Disease Mouse Model.

It is believed that there is a certain correlation between the brain and kidneys, but it is poorly understood. Many findings suggested that there were previously unknown signaling pathways involving AβPP and BACE1 in the kidney. Exploring the changes of BACE1 activity in APP23 mouse kidneys, providing evidence for the function of AβPP and BACE1 activity in the kidney. The activity and expression of BACE1 were detected in the kidney of APP23 mice by enzymatic assay and western blotting. The protein expression levels of AβPP, claudin1, occludin, VE-cadherin, and Klotho (membrane-form klotho) were examined by using western blotting. The renal pathological changes of APP23 mice were examined by the routine renal pathological procedures. In this study, we found that the AβPP protein level was increased in kidneys of APP23 mice compared with wild-type (WT) mice. Additionally, the activity and expression of BACE1 were increased in kidneys of APP23 mice compared to that of WT. BACE1 was predominantly distributed on the lumen side of renal tubular epithelial cells. The protein levels of Klotho and VE-cadherin were decreased, occludin expression was also decreased, and claudin-1 expression was increased. Renal pathological damage which observed in kidneys of APP23 mice was more serious than that in kidneys of WT mice. Our findings suggest that the increase of AβPP protein levels under Thy-1 neuron promoter in the APP23 mice promoted the increase of renal BACE1 expression and enzymatic activity in the kidneys. Moreover, certain pathological damage in the kidneys of APP23 mice were observed. APP23 mice are easily affected by external risk factors compared with WT mice.

Cordyceps cicadae polysaccharides ameliorated renal interstitial fibrosis in diabetic nephropathy rats by repressing inflammation and modulating gut microbiota dysbiosis

Diabetic nephropathy (DN), a complication of diabetes mellitus, has been the leading cause of death in people with chronic kidney disease. This study was conducted to examine the potential health benefits of Cordyceps cicadae polysaccharides (CCP) on kidney injury and renal interstitial fibrosis that occur in DN rats. First, a DN model was established using SD rats fed with a high-fat diet for 8 weeks, then injected with STZ (35 mg/kg) intraperitoneally. The rats were then supplemented with CCP (75, 150 and 300 mg/kg) for 4 weeks. The results indicated that CCP improve insulin resistance and glucose tolerance in DN rats. Furthermore, CCP intervention significantly suppressed the inflammation, renal pathological changes and renal dysfunction, slowing down the progression of renal interstitial fibrosis. Moreover, high-throughput pyrosequencing of 16S rRNA suggested that CCP modulated the dysbiosis of gut microbiota by enhancing the relative abundance and proliferation capacity of probiotics. In vitro, CCP can markedly decrease LPS-induced inflammatory cytokine levels and TGF-β1-induced fibroblast activation. In summary, the results provided evidence that CCP exerted a beneficial effect on tubulointerstitial fibrosis in DN rats by possibly suppressing the inflammatory response and modulating gut microbiota dysbiosis, via blocking the TLR4/NF-κB and TGF-β1/Smad signaling pathway.

Structure–activity relationship and hypoglycemic activity of tricyclic matrines with advantage of treating diabetic nephropathy

Forty−three tricyclic matrinic derivatives with a unique scaffold were prepared and evaluated for their stimulation effects on glucose consumption in HepG2 cells. The structure−activity relationship was systematically elucidated for the first time. Among them, compound 17a exhibited the most promising potency, and dose-dependently increased glucose consumption in L6 myotubes. It significantly lowered blood glucose, glucosylated haemoglobin and AGE level, and improved glucose tolerance and insulin resistance in KK-Ay mice as well. More importantly, 17a effectively ameliorated diabetic nephropathy (DN), as indicated by the improvement of renal function and pathological changes, and decrease of urinary protein. Furthermore, 17a could induce glycolysis but suppressed aerobic oxidation of glucose, in a similar mechanism to Metform. Our results indicated that in addition to hyperglycemia, 17a may be developed to treat diabetic complication such as DN.

Quantitative assessment of renal allograft pathologic changes: comparisons of mono-exponential and bi-exponential models using diffusion-weighted imaging.

Diffusion-weighted imaging (DWI) can noninvasively assess renal allograft pathologic changes that provide useful information for clinical management and prognostication. However, it is still unknown whether the bi-exponential model analysis of DWI signals is superior to that of the mono-exponential model. Pathologic and DWI data from a total of 47 allografts were prospectively collected and analyzed. Kidney transplant interstitial fibrosis was quantified digitally. The severity of acute and chronic pathologic changes was semi-quantified by calculating the acute composite scores (ACS) and chronic composite score (CCS). Mono-exponential total apparent diffusion coefficient (ADCT), and the bi-exponential parameters of true diffusion (D) and perfusion fraction (fp) were acquired. The diagnostic performances of both mono-exponential and bi-exponential parameters were assessed and compared by calculating the area under the curve (AUC) from receiver-operating characteristic (ROC) curve analysis. ADCT, D, and fp were all significantly correlated with interstitial fibrosis, ACS, and CCS. Cortical fp discriminated mild from moderate and severe ACS with the largest AUC of 0.89 [95% confidence interval (CI), 0.77-0.96]. Noticeably, only cortical fp could differentiate severe ACS from mild-to-moderate ACS (P<0.001) with an AUC of 0.80 (95% CI, 0.65-0.90) and a sensitivity of 100% (95% CI, 66.4-100%). Strikingly, the joint use of D and fp in either the cortex or the medulla could achieve a sensitivity of 100% for identifying either mild or severe interstitial fibrosis. Meanwhile, the serial use of cortical D and cortical fp showed the largest specificity for identifying both mild [88.9% (95% CI, 70.8-97.6%)] and severe [84.4% (95% CI, 67.2-94.7%)] interstitial fibrosis. For identifying mild CCS, the AUC of medullary ADCT (0.90, 95% CI, 0.78-0.97) was similar to that of cortical D (0.81, 95% CI, 0.67-0.91) and fp (0.86, 95% CI, 0.73-0.94), but statistically larger than that of medullary D (P=0.005) and fp (P=0.01). Furthermore, the parallel use of cortical D and cortical fp could increase the sensitivity to 95.0% (95% CI, 75.1-99.9%), whereas serial use of medullary D and medullary fp could increase the specificity to 100% (95% CI, 87.2-100%). The AUCs for differentiating severe from mild and moderate CCS were statistically insignificant among all parameters in the cortex and medulla (P≥0.15). Cortical fp was superior to the ADCT for identifying both mild and severe acute pathologic changes. Nevertheless, ADCT was equal to or better than single D or fp for evaluating chronic pathologic changes. Thus, both monoexponential and bi-exponential analysis of DWI images are complementary for evaluating kidney allograft pathologic changes, and the combined use of D and fp can increase the sensitivity and specificity for discriminating allograft pathologic changes severity.

P0139RETROSPECTIVE ANALYSIS OF RENAL PATHOLOGY AND CYTOGENETIC EXAMINATION IN PATIENTS WITH MULTIPLE MYELOMA WITH RENAL IMPAIRMENT

Abstract Background and Aims Renal impairment is one of the common implications in multiple myeloma. But the relationships between the renal pathology and cytogenetic features are not fully understood. To explore the renal pathology and cytogenetic features in patients of multiple myeloma with renal impairment. Method Retrospective of our hospital from January 2009 to January 2019, newly diagnosed multiple myeloma patients with renal impairment. The relationship between the results of Fluorescence in situ hybridization (FISH) and renal pathological findings was analyzed. Statistical analysis was performed using SPSS 20.0. Results A total of 20 patients underwent renal biopsy, included 12 males and 8 females. FISH result showed that there were 7 cases of interstitial nephritis, 3 of them were negative for FISH, and the remaining that IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection rates were 42.86%, 28.57%, 28.57%, 28.57% and 14.29%. The incidence was lower, which was statistically significant (P&amp;lt;0.01). There were 6 cases of cast nephropathy, IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection rates were 66.67%, 50%, 66.67%, 50% and 0%. Compared with the total probe positive rate, there was no statistical significance (P&amp;gt;0.05). There were 4 cases of acute tubular necrosis, IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection rates were 100%, 50%, 50%, 25% and 25%, respectively. Compared with the total probe positive rate, there was no statistical significance (P&amp;gt;0.05). There are 1 of amyloidosis and 1 of tubular nephropathy with amyloidosis were positive for 5 probes. One case of light chain deposition disease was positive for RB1 gene deletion + D13S319 gene deletion. Conclusion FISH in patients with different renal pathological changes is characterized by heterogeneity, which can be used to predict the risk of renal damage and speculate on possible renal pathological types to guide prognosis.

P1808INHIBITION OF MIR-155 IMPROVES PROGNOSIS IN AN EXPERIMENTAL FSGS MOUSE MODEL BY REGULATING AUTOPHAGY

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS), a podocytopathy, is one of the most common primary glomerular diseases causing end-stage renal disease in children. Its mechanisms remain unclear and the effective treatment lacks. MiR-155 is a typical multifunctional miRNA, which serves a crucial role in the regulation of numerous vessel cells. The present study aimed to investigate the role of miR-155 in the pathogenesis of FSGS. Method A FSGS model was establishe by injection of adriamycin in miR-155 knockout mice. Renal pathological changes were observed by Periodic Schiff-Methenamine Silver staining and Masson trichrome staining. Podocyte morphology and autophagosomes were examined with electron microscopy. Podocyte density was estimated by the Weibel-Gomez method. Expression of autophagy markers and apoptosis-associated proteins were analyzed by Western blotting analysis. Results Silencing of miR-155 significantly decreased urinary protein excretion and ameliorated glomerulosclerosis in adriamycin-induced FSGS mice. We found that adriamycin treatment led to fusion of podocyte foot processes, swelling of the podocyte body, dilated mitochondria, and podocyte loss. Inhibition of miR-155 improved podocyte depletion and the above cytopathies induced by adriamycin. In addition, the results also demonstrated that in miR-155 KO mice, the expression of LC3 and ATG5 was increased and the expression of P62 was decreased. Conclusion These suggest that modulated miR-155 can prevent podocyte damage, by regulating the level of autophagy. The present study provides a novel insight into microRNAs as potential therapeutics for the treatment of podocytopathy.

P0140RENAL PATHOLOGICAL CHANGES AFTER SUCCESSFUL TREATMENT OF LCDD USING CYCLOPHOSPHAMIDE, THALIDOMIDE AND DEXAMETHASONE: A CASE REPORT

Abstract Background and Aims The combined of cyclophosphamide, thalidomide and dexamethasone (CTD) haven’t reported in treatment of LCDD, and how the renal pathologic injury changes after treatment is still unknown. Method Here we descript a LCDD patients who undergone repeated renal biopsy after treatment. Results We report a 56-year-old woman presented with nephrotic syndrome, impaired renal function, and serum M-protein of IgG lambda. First renal biopsy showed severe nodular glomerulosclerosis with single lambda light chain linear deposit along GBM. The patient treated with 14 cycles CTD regimen, and reached the complete hematologic response and renal response. At the 29 months of follow up, the repeated biopsy showed the glomerular nodular sclerosis attenuated significantly, only trace granular electron-dense deposits along inner side of GBM.(Details in figure 1: The pathological findings of the first (A-D) and second (E-H) renal biopsy.) Conclusion This case highlights the hematologic response not only can improve the renal function, but also alleviate the renal nodular sclerosis. And the low-cost regimen, CTD, maybe a good choice.

Effects of different varieties and processing degree grains on blood glucose and blood lipid in rats

To investigate the effects of whole grains(WG) and refined grains(RG) on blood glucose, blood lipid and inflammatory factors in normal rats, and the common effects of different whole grains. 2×2 factorial experiments were designed according to grain sources(rice &amp; wheat) and processing precision(whole grain &amp; refined grain). According to the initial body weight and fasting blood glucose, 48 male SD rats were randomly divided into four groups: RG rice group, WG rice group, RG wheat group and WG wheat group. They were fed with 45% refined rice, whole grain rice, refined wheat and whole grain wheat respectively for 18 weeks. The formula was in accordance with AIN-93 G. Food intake and body weight were monitored weekly. Fasting blood glucose, lipid, inflammatory factors and organ pathology were detected at the end of the experiment. During the experiment, the body weight growth and food intake of rats in each group were basically the same. At the end of the experiment, fatty liver appeared in varying degrees, while the kidney of rats in RG rice group and RG wheat group showed epithelial steatosis. Biochemical indexes showed that blood urea nitrogen(UN), fasting blood glucose(FBG), total cholesterol(TC), triglyceride(TG), low density lipoprotein(LDL)and monocyte chemoattractant protein-1(MCP-1)in RG wheat group were significantly higher than those in WG wheat group(P&lt;0. 05), while high density lipoprotein(HDL)level in RG wheat group was significantly lower than that in WG wheat group(P&lt;0. 05), and there was no significant difference in other indexes. The result of factorial analysis showed that the differences of FBG, serum insulin, homeostasis model assessment of insulin resistance(HOMA-IR)and C-reactive protein(CRP)caused by different grain processing degree were significant, but there was no significant difference between rice and wheat varieties(P&gt;0. 05). Studies have shown that long-term feeding of refined grains can lead to fasting blood glucose, blood lipid abnormality and renal pathological changes in rats, and proper feeding of whole grains can delay the development of adverse symptoms.

Anti-Inflammatory and Antioxidative Properties of Isoflavones Provide Renal Protective Effects Distinct from Those of Dietary Soy Proteins against Diabetic Nephropathy.

Dietary soy reportedly protects from diabetic nephropathy (DN), but its active components and mechanism of action remain unknown. In this study, KKAy mice are fed three types of diet: Dietary soy isoflavones with soy protein (Soy-IP) diet, reduced isoflavones soy protein (RisoP), and oral administration of isoflavones aglycones (IsoAgc). Albuminuria and glycosuria are decreased only in the soy-IP group. The risoP group show reduced expansion of mesangial matrix and renal fibrosis, the IsoAgc group show renal anti-fibrotic and anti-inflammatory effects; however, these renal pathological changes are repressed in the soy-IP group, suggesting the distinct protective roles of soy protein or isoflavones in DN. The isoflavone genistein has a better inhibitory effect on the inflammatory response and cellular interactions in both mouse tubular cells and macrophages when exposed to high glucose and albumin (HGA). Genistein also represses HGA-induced activator protein 1 activation and reactive oxidases stress generation, accompanied by reduced NADPH oxidase (NOX) gene expression. Finally, diabetic mice show a decrease in lipid peroxidation levels in both plasma and urine, along with lower NOXs gene expression. The data elucidate the detailed mechanism by which isoflavones inhibit renal inflammation and provide a potential practical adjunct therapy to restrict DN progression.

Egr1 Knockdown Combined with an ACE Inhibitor Ameliorates Diabetic Kidney Disease in Mice: Blockade of Compensatory Renin Increase.

BackgroundIncreased compensatory intrarenal renin diminishes the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in the treatment of diabetic kidney disease (DKD). Early growth response-1 (Egr1) is a crucial transcriptional factor in the progress of DKD and is a potential transcription factor of intrarenal renin according to bioinformatic analysis. However, whether inhibition of Egr1 can suppress compensatory renin increase in DKD is unclear.MethodsWe generated a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mouse model. The mice were treated with either enalapril (an ACEI) or enalapril combined with a shEgr1 plasmid, and age-matched DKD mice were used as controls. Urine microalbumin, urinary renin and kidney TGF-β1 were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) and Masson staining were used to determine renal pathological changes. Egr1, renin, TNF-α, and FN were measured by real-time quantitative PCR, Western blot, and immunohistochemistry. The SV40-MES13 murine mesangial cell line was transfected with pENTER-Egr1 plasmid and siEgr1.ResultsOur results showed that enalapril increased the renin level of urinary and renal in DKD mice, while shEgr1 attenuated this effect. In addition, enalapril treatment reduced the levels of urinary microalbumin, TNF-α, TGF-β1 and FN, and alleviated the pathological changes, while shEgr1 strengthened these effects. The protein and mRNA expression of renin in the SV40 MES13 cells was upregulated and downregulated following overexpression and silence of Egr1, respectively.ConclusionSilence of Egr1 could alleviate renal injury in DKD by downregulating intrarenal renin.

Implications of EET in renal ischemia/reperfusion by regulating NLRP3 expression and pyroptosis

Objective: To investigate the mechanism of epoxyeicosatrienoic acids (EET) on renal ischemia/reperfusion (I/R). Methods: Thirty 10-week male C57BL6 mice were randomly divided into five groups: sham goup, I/R group, I/R with EET group, I/R with toll-like receptor 4 (TLR4) inhibitor (TAK242) group, I/R with EET and TAK242 group. Blood urea nitrogen (BUN) and serum creatinine (Scr) as well as renal pathological changes were observed 24 h after reperfusion. The protein expression of NOD-like receptor pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (caspase-1), interleukin-1β (IL-1β), TLR4 and myeloid differentiation factor 88 (MyD88) were evaluated using Western blot. Results: Severe renal tubular epithelial cell injury and decreased renal function [BUN:(10.37±0.53) vs (6.70±0.82)mmol/L, t=9.17, P<0.001; Scr: (83.67±3.88) vs (32.50±3.51)μmol/L, t=23.96, P<0.001] occurred in I/R group. Compared to the sham group, the relative expression of NLRP3 (1.54±0.10 vs 0.71±0.05, t=13.14, P<0.001), caspase-1 (2.35±0.05 vs 0.62±0.02, t=73.77, P<0.001), IL-1β (3.11±0.11 vs 1.26±0.05, t=35.97, P<0.001), TLR4 (1.58±0.03 vs 0.39±0.01, t=86.00, P<0.001), MyD88 (0.94±0.02 vs 0.26±0.01, t=72.61, P<0.001) were significantly increased. Mice pretreated with EET analog featured lower kidney damage and diminished levels of above proteins than I/R group (all P<0.001). Besides, the co-administration of TAK242 and EET analog could even markedly reduced the expression levels of each proteins than those in I/R group and I/R with EET group (all P<0.001). Conclusion: EET exerts a protective effect on attenuating renal I/R injury possibly through inhibiting TLR4 pathway to regulate the activation of NLRP3-induced pyroptosis.

Oridonin Alleviates IRI-Induced Kidney Injury by Inhibiting Inflammatory Response of Macrophages via AKT-Related Pathways.

BackgroundAcute kidney injury (AKI) is one of the most common complications in clinic, but there is still no effective treatment. Oridonin, extracted from Rabdosia rubescens, has been identified to promote inhibitory effects on tumor, inflammatory and fibrosis by previous study. This study aimed to assess the kidney-protective role of Oridonin in AKI and the underlying mechanism by which Oridonin improves AKI in vivo and inhibits inflammation in LPS-induced bone marrow-derived macrophages (BMDM) in vitro.Material/MethodsSPF C57BL/6J male mice (8–10 weeks old, body weight 20–25 g) were divided into 3 groups – sham group, AKI group, and Oridonin-treated AKI group – with 6 mice in each group. In the in vitro study, LPS-induced inflammatory BMDM cells were treated with Oridonin and agonist of AKT. The expression and secretion levels of inflammation-related indicators and AKT-related signaling molecules were detected by real-time PCR, ELISA, Western blot, and immunofluorescence. Also, various methods are used to assess renal function and pathological changes.ResultsThe results showed that Oridonin treatment significantly improved the serum creatinine and BUN levels in AKI mice. Interestingly, treatment with Oridonin also resulted in decreased the infiltration of macrophages in renal tissues of AKI mice, which was associated with decreased expression and activation of AKT and its related signaling pathways, such as NF-κB and STAT3, suggesting that Oridonin attenuates AKI kidney injury via a mechanism associated with reducing the inflammatory response of macrophages in the AKI kidney. This was investigated in vitro in macrophages, and the results showed that Oridonin reduced the LPS-stimulated inflammatory response in macrophages. Mechanistically, the addition of Oridonin reversed LPS-induced downregulation of AKT, NF-κB, and STAT3 expression and inflammatory response in macrophages, suggesting that Oridonin has a protective role, via the AKT-related signaling pathways, in reducing the inflammatory response of macrophages in AKI mice. This was further confirmed by adding agonist of AKT of IGF-1 to block the inhibitory effect of Oridonin on inflammatory response in vitro.ConclusionsOridonin ameliorates AKI kidney injuries by suppressing AKT-mediated inflammatory response of macrophages.

Protective Effects of Chromium Picolinate Against Diabetic-Induced Renal Dysfunction and Renal Fibrosis in Streptozotocin-Induced Diabetic Rats.

Diabetic nephropathy (DN) is one of the most important complications of diabetes, and the leading cause of end-stage renal disease (ESRD). While Chromium picolinate (CrPic) supplementation has been found to be effective in treating diabetes, its effects on diabetic-induced nephropathy have not been studied. Therefore, in this study, CrPic (1 mg kg−1 d−1) was administered to a DN rat model by oral gavage for eight weeks to investigate its effects. The results show that CrPic supplementation caused a decrease in levels of blood glucose, serum insulin, blood urea nitrogen (BUN), serum creatinine, and urinary albumin in DN rats. It also reversed renal pathological changes, including renal glomerular sclerosis and interstitial fibrosis. In addition, the oxidative defense system in the kidneys of DN rats was found to be improved; the biological activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) increased; and the content of malondialdehyde (MDA) lowered. Immunohistochemical results reveal that the expression levels of renal transforming growth factor-β1 (TGF-β1), Smad 2, and Smad 3 decreased significantly in the kidneys of rats in the CrPic-treated group. CrPic administration was thus found to ameliorate diabetic nephropathy in SD rats via an antioxidative stress mechanism, as well the ability to inhibit TGF-β1/Smad2/3 expression. This study suggests that CrPic could be a potential renal-protective nutrient against diabetic nephropathy.

Hirudin improves renal interstitial fibrosis by reducing renal tubule injury and inflammation in unilateral ureteral obstruction (UUO) mice

Renal interstitial fibrosis (RIF) often occurs in many chronic kidney diseases (CKD). Hirudin now is applied to treat fibrosis in some organs. In this study, we verified the treatment effects of hirudin on RIF in vivo and in vitro with the underlying mechanism. The RIF in vivo was the unilateral ureteral obstruction (UUO) model and RIF in vitro was the renal tubular epithelial cells induced by TGF-β. The renal pathological changes and renal fibrosis were observed by hematoxylin and eosin (H&E) staining and Masson staining. The α-SMA in renal tissues was detected by immunohistochemistry. The inflammatory factors were analyzed by the ELISA assay. The cell apoptosis was observed by TUNEL assay. The related proteins of fibrosis, epithelial-mesenchymal transition (EMT) and apoptosis were assessed by western blot analysis. The experimental data demonstrated that hirudin decreased fibrosis, EMT, inflammation and cell apoptosis in renal tissues of UUO rats and TGF-β-induced renal tubular epithelial cells. Furthermore, hirudin also reduced the expression of collgen-I, FN, α-SMA, N-cad, slug, E-cad, IL-1β, IL-6 and TNF-α in mice serum and TGF-β-induced renal tubular epithelial cells. The apoptosis related proteins (pro-caspase3, pro-caspase9, bcl2 and bax) expression was also down-regulated in renal tissues of UUO rats. In conclusion, hirudin depressed the fibrosis in renal tissues and renal tubular epithelial cells by inhibiting the inflammation, regulating the related proteins of fibrosis and ETM and decreasing the apoptosis of renal tubular epithelial cells. These findings may offer an effective treatment method for RIF.

Leptospirosis in slaughtered cows in the Triangulo Mineiro, Minas Gerais: prevalence, serological profile and renal lesions

Leptospirosis is a zoonosis that affects several species of domestic and wild animals and is an important cause of economic losses in cattle in Brazil. In this study, we determined the prevalence of bovine leptospirosis in the Triângulo Mineiro region, Minas Gerais, Brazil, identified the most frequent serovars of Leptospira interrogans, and examine the renal pathological changes associated with the disease. Samples of blood serum and kidney fragments from 100 bovine females were collected in cattle abattoir. In the serological investigation 48% of the cows were positive. The serovars for which there were more reactive animals were Wolffi (24%), Hardjo (21%) and Hebdomadis (18%). Among the positive samples, 14/48 showed antibody titers greater than 1:100, and 70.83% of the seropositive animals responded to more than one Leptospira interrogans serovar. Only one farm did not have seropositive cows and in nine farms studied, six (66.66%) presented seropositive animals to the Hebdomadis serovar. At the histopathological examination, the most frequent microscopic lesions in positive animals were hyalinization (81.25%), congestion (81.25%) and hydropic degeneration (70.83%). However, these histopathological alterations were also found in kidneys of animals negative to serology, such as hyalinization (80.77%), congestion (48.07%) and hydropic degeneration (55.77%) and these findings are unrelated to positivity. Histopathological examination of the kidneys is not indicated to replace the serological diagnosis of leptospirosis, and may be used only as a complementary examination. Despite the low frequency of seropositive animals in the Triângulo Mineiro region, the disease is present in a large number of farms. Noteworthy is the high frequency of serovar Hebdomadis and it can be considered an emerging serovar in the region. The evaluation of the frequency of this serovar in other regions becomes important, and once verified should result in the recommendation of the inclusion of this serovar in the leptospirosis control.

Establishment of a rat model of nonalcoholic steatohepatitis and histopathological changes of the pancreas and the kidney

Objective To establish a rat model of nonalcoholic steatohepatitis,and to investigate the histopathological changes of the extrahepatic organs of the pancreas and the kidney. Methods A total of 20 Sprague-Dawley rats were selected,among which 6 were randomly selected as the observation group(group B). The remaining 14 rats were paired into seven groups according to body weight,then a random number table was used to select 1 rat from each group and assign them into the experimental group(group C),and the remaining 7 rats were assigned to the control group(group A). The rats in groups B and C were given high-fat diet,while those in group A were given a normal diet. In group B,two rats each were killed at weeks 4,8,and 12 of the experiment,liver tissue was extracted for HE staining,and liver pathological sections were observed under a microscope to see whether steatohepatitis was achieved. The model was successfully established at the end of week 12. All rats in groups A and C were sacrificed,and the serological markers alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transpeptidase(GGT),triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDL),glucose(GLU),insulin(INS),and homeostasis model assessment of insulin resistance(HOMA-IR) were measured. HE staining was performed for liver tissue and pancreatic tissue to observe the changes in pancreatic acini and pancreatic islets. PAS staining was performed for kidney tissue,and immunohistochemical desmin-staining was performed to observe the expression of desmin in glomerular podocytes. The t-test was used for comparison of continuous data between two groups. Results Compared with group A,group C had significantly higher pathological score and serum levels of ALT,GGT,LDL,TG,TC,GLU,INS,and HOMA-IR(t = 4. 67,2. 83,2. 34,4. 58,4. 78,3. 00,2. 97,3. 80 and 4. 10,all P < 0. 05). Liver pathological changes were observed in the high-fat group from week 4 to week 12,i. e.,the lobular structure was gradually destroyed,the small fat vacuoles in the cytoplasm of the hepatocytes gradually developed into large fat vacuoles,and inflammatory cell infiltration gradually appeared in the portal area. Pancreatic pathological changes were observed in the high-fat group at the end of week 12,i. e.,apoptosis and atrophy of pancreatic acinar cells were observed,and no significant abnormalities were observed in pancreatic islet cells. Renal pathological changes were observed in the high-fat group at the end of week 12,i. e.,therewere significant increases in the substances with positive PAS staining results,the glomerular volume,and the thickness of the glomerular capillary basement membrane,with disordered arrangement of capillary loops,hyperplasia of the mesangial area,swelling of renal tubular epithelial cells,and stenosis of some lumens. Immunohistochemical staining showed an increase in the expression of desmin in glomerular podocytes in the high-fat group. Conclusion A rat model of nonalcoholic steatohepatitis is successfully established by high-fat diet.Nonalcoholic steatohepatitis in rats may lead to apoptosis and atrophy of pancreatic acinar cells,increase in glomerular volume,thickening of the capillary basement membrane,mesangial hyperplasia,and podocyte injury.

Assessment of Bailing Capsule in the Treatment of Chronic Glomerulonephritis: A Meta-analysis

The aim of the study is to provide evidence-based information for the efficacy, range of adaptation, dosage and course of treatment and adverse reactions for the treatment of chronic glomerulonephritis using Bailing capsule. Computer and manual retrieval was used to collect the clinical literature on treatment of chronic glomerulonephritis with Bailing capsule. A total of 661 patients (330 cases in the treatment group and 331 cases in the control group) in 8 reported studies were included as per inclusion criteria. RevMan 4.2 software was used to analyze the overall efficacy, the change of urine protein within 24 h before and after treatment, course of treatment, dosage, and adverse reactions. The total effect of Bailing capsule in the treatment of chronic glomerulonephritis was better than that in the control group. Compared to the control group, Bailing capsule exerted better control on urine protein without serious adverse reactions. There was a certain publication bias against the included cases. Bailing capsule brought urine protein from nephritis under control, but it is still necessary to make further investigation into the effect of Bailing capsule on different renal pathological changes of chronic glomerulonephritis, the best dosage and course of treatment.

Therapeutic Effects of Fibroblast Growth Factor-21 on Diabetic Nephropathy and the Possible Mechanism in Type 1 Diabetes Mellitus Mice.

BackgroundFibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN.MethodsFour-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups.ResultsThe results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression.ConclusionTherefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.

Cryptococcal meningitis in patients with lupus nephritis.

Cryptococcal meningitis (CM) is a rare condition in patients with lupus nephritis (LN). Here, we describe the clinical characteristics, possible risk factors, and outcomes of LN patients with CM. A systematic review of medical records from16 LN patients with CM admitted to our hospital was performed. A total of 32 cases were randomly selected as controls from LN patients without infection during the same period. The mean age of patients with CM at presentation was 35.1 years, and the female-to-male ratio was 15:1.The most common clinical manifestation was headache (93.7%); patients with CM had a significantly higher prednisone dose at the time of hospitalization, a higher SLE Disease Activity Index (SLEDAI), a higher urine protein/creatinine ratio, and a lower CD4+ T cells count than those without infection (p < 0.05). Patients with CM also had significantly higher activity index and more moderate and severe mesangial proliferation than those without infections (p < 0.001 and p = 0.025, respectively). Serious renal pathological changes, mass proteinuria, higher SLEDAI, higher prednisone dose, and a decline in CD4+ T cells could be risk factors for CM in patients with LN. Key Points ⦁ LN patients with CM had more serious renal pathological changes than those without infections; serious renal pathological changes could be a major risk factor for CM in patients with LN.