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Objective:To analyze the clinicopathological features in diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) patients, and provide reference for patients who will receive renal biopsy with diabetes mellitus complicated with chronic kidney disease.Methods:The patients with type 2 diabetes mellitus complicated with chronic kidney disease who underwent renal biopsy were collected through the database at the Nanfang Hospital of Southern Medical University from February 2002 to June 2018. According to the results of renal biopsy, they were divided into DKD group and NDKD group (including DKD+NDKD). The clinical manifestations and pathological types were compared between the two groups.Results:A total of 507 patients were eventually included in the study. There were 114 cases (22.5%) with DKD and 393 cases (77.5%) with NDKD. Pathologically, the most common pathological types of NDKD were membranous nephropathy (30.0%) and IgA nephropathy (19.1%). Among NDKD patients, 5.6% patients had DKD combing with NDKD. In term of the clinical manifestations, DKD patients had a longer history of diabetes (>1 year, 76.3% vs 36.1%, P<0.001), higher quantity of urinary protein [3.69(1.70, 6.74) g/24 h vs 2.21(0.91, 4.97) g/24 h, P<0.001], higher serum creatinine [117.5(85.8, 194.5) μmol/L vs 89.0(68.0, 143.8) μmol/L, P<0.001] than NDKD patients. But the hemoglobin [(105.07±20.85) g/L vs (124.41±25.02) g/L, P=0.002] and cholesterol [(5.69±1.87) mmol/L vs (6.43±2.75) mmol/L, P=0.001] in DKD patients were lower than those in NDKD patients. Logistic regression analysis showed that diabetes mellitus history ( OR=4.162, 95% CI 1.717-10.098, P=0.002) , higer systolic pressure (every 1 mmHg, OR=1.028, 95% CI 1.011-1.045, P=0.001) , history of antihypertensive medication ( OR=3.141, 95% CI 1.496-6.591, P=0.002), diabetic retinopathy ( OR=5.561, 95% CI 2.361-13.100, P<0.001) and higher glycated hemoglobin level (every 1%, OR=1.680, 95% CI 1.333-2.118, P<0.001) were related factors of DKD, while hematuria ( OR=2.781, 95% CI 1.334-5.798, P=0.006) and higher hemoglobin level (every 1 g/L, OR=1.022, 95% CI 1.008-1.037, P=0.002) were related factors of NDKD. Conclusions:There are differences in clinical manifestations and pathological types between DKD and NDKD. The history of diabetes, antihypertensive medication, fundus examination, higher of proteinuria and glycosylated hemoglobin may predict DKD, while hematuria and higher level of hemoglobin may have certain guiding significance for the diagnosis of NDKD. The indication of renal biopsy in patients with diabetes mellitus complicated with chronic kidney disease should include comprehensive clinical manifestations.
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Objective To explore the changes of renal cortical energy metabolism and its related molecular mechanisms in rats with progressive kidney disease.Methods A rat model of 5/6 nephrectomy was established as the model of progressive nephropathy.Rats were divided into surgical group (5/6Nx group) and sham-operated group (Sham group).Respectively,the rats were sacrificed at 1 week and 12 weeks after completing the model,and their blood,urine sample and kidney specimens were collected.Blood urea nitrogen,serum creatinine and 24 h urine protein were used to evaluate the renal function.Pathological changes in renal tissue were detected by PAS staining and Sirius red staining.The renal cortical energy metabolites were made quantitative analysis by liquid chromatography-mass spectrometry-based targeted metabolomics.The mRNA expressions of inflammatory cytokines (IL-6,IL-1β),fibrosis factors (fibronectin,collagen-1),glycolytic and tricarboxylic acid (TCA) cycle related enzymes were confirmed by real-time PCR.The protein expressions of fibrotic proteins (fibronectin,collagen-1),silent information regulator 1 (SIRT-1) and liver kinase B1 (LKB1) were tested by Western blotting.Results Compared with those in Sham group,the renal function indexes increased,the renal tissue pathological damage was obvious,the mRNA expressions of renal cortical inflammatory and fibrosis factors increased,and fibrotic proteins also increased in 5/6Nx group rats at 1 week and 12 weeks (all P ＜ 0.05),meanwhile,kidney damage worsened over time.Compared with those in Sham group,in the renal cortex of 5/6Nx group glycolytic metabolite lactate,the TCA cycle metabolites (citrate,isocitrate,oxaloacetate) and the oxidized phosphorylation metabolite reduced coenzyme Ⅰ were up-regulated (all P ＜ 0.05),but adenosine triphosphate (ATP) was no change at 1 week,then the abnormal metabolites increased further at 12 weeks,such as the down-regulation of pyruvate,oxidized coenzyme Ⅰ and ATP (all P ＜ 0.05).The pentose phosphate pathway metabolites (reduction and oxidized coenzyme Ⅱ) shows no statistical significant difference in the two group (all P ＞ 0.05).Compared with those in Sham group,in the 5/6Nx group the mRNA expressions of glycolytic enzyme hexokinase 2 and lactate dehydrogenase a were upregulated in the renal cortex at 1 week,whereas the mRNA expressions of pyruvate dehydrogenase α,pyruvate dehydrogenase β and succinate dehydrogenase of the TCA cycle related enzymes were downregulated (all P ＜ 0.05).Meanwhile,renal abnormal metabolic enzyme mRNA expressions were further increased in the 5/6Nx group at 12 weeks.The protein levels of SIRT-1 and LKB1 were not significantly different in the renal cortex of two group rats at 1 week,while SIRT-1 and LKB1 levels decreased in 5/6Nx group than those in Sham group at 12 weeks (all P＜ 0.05).Conclusions During the progression of nephropathy,rats accompanied with renal fibrosis and inflammatory have energy metabolism changes in the renal cortex which accompanies.The features of metabolic changes are manifested as enhanced glycolysis and decreased oxidative phosphorylation,which is aggravated gradually.Its mechanism is related to the inhibition of energy-regulating proteins LKB1 and SIRT-1.
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Objective To explore the effect of hypoxia on exosomes secreted by renal tubular epithelial cells and the function of exosomes in chronic kidney diseases.Methods (1) The supernatant of renal tubular epithelial cells which were cultured in normoxia (21％ O2) or hypoxia(1％ O2) for 48 h was collected and centrifuged gradiently to harvest exosomes.Exosomes were identified and compared by transmission electron microscope, nanoparticle tracking analysis, Western blotting and measurement of the protein concentration.(2) Primary peritoneal macrophages of rats were co-cultured with exosomes in different concentrations (1, 10, 50, 100, 300 mg/L).The expression of interleukin-6(IL-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) in cells and supernatant were separately detected by quantitative real-time PCR (qRT-PCR) and ELISA, and the expression of phospho (p)-STAT/STAT and suppressors of cytokine signaling 1 (SOCS1) in macrophages was detected by Western blotting.At last, the expression of inflammatory microRNAs (miR) in exosomes was measured by qRT-PCR.Results (1) The vesicles harvested by gradient centrifugation were less than 150 nm and expressed CD63 which was characteristic of exosomes.Hypoxia had no effect on the morphology of exosomes, but stimulated their secretion.(2) Hypoxic exosomes dose-dependently improved the expression of IL-6, TNF-α, iNOS in macrophages polarized by lipopolysaccharide (LPS) and increased the expression of p-STAT while decreased the expression of SOCS1 (P ＜ 0.01).MicroRNAs referred to inflammation such as miR-155 and miR-27a increased in hypoxic exosomes compared to that in normoxic exosomes (P ＜ 0.05).Conclusions Hypoxia makes exosomes promoted the polarization of macrophages to M1, which may account for the microinflammation in chronic kidney diseases.
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<p><b>OBJECTIVE</b>To evaluate the renal function in treatment-naive patients with hepatitis B virus (HBV) related cirrhosis and to identify the risk factors for renal impairment.</p><p><b>METHODS</b>We collected the data of 860 HBV-related cirrhosis patients hospitalized in our unit between Jan 1, 2011 and Dec 31, 2011. Liver function of the patients was assessed with Child-Pugh score system, and the renal function with estimated glomerular filtration rate (eGFR) calculated by Modification of Diet in Renal Disease (MDRD) equation recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI). We investigated the prevalence of renal impairment (eGFR>60 ml/min/1.73 m(2)) among these patients and explored the risk factors for renal impairment.</p><p><b>RESULTS</b>Of the 860 patients, 296 had complete clinical data and were included in our analysis. The overall incidence of renal impairment among the enrolled patients was 8.45% (25/296). Patients with Child-Pugh stage C showed a significantly higher incidence of renal impairment than those with stages B and A (17.17% [17/99] vs 6.67%[7/105] vs 1.09% [1/92], P<0.001). Age, history of hyperuricemia, and Child-Pugh score were identified as the risk factors for renal impairment in these patients.</p><p><b>CONCLUSION</b>In patients with HBV-related liver cirrhosis, the incidence of renal impairment increases significantly with deterioration of the liver function, and renal function should be regularly monitored in these patients for appropriate antiviral treatment.</p>
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Adult , Female , Humans , Male , Middle Aged , Glomerular Filtration Rate , Hepatitis B virus , Hepatitis B, Chronic , Incidence , Kidney , Liver Cirrhosis , Virology , Retrospective Studies , Risk FactorsABSTRACT
AIM: To investigate the influence of irbesartan (Irb), a new angiotensin II receptor 1 antagonist, on renal hypertrophy in streptozotocin (STZ)-induced diabetic rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: normal group (Group N, n=7), diabetic group (Group DN, n=6) and irbesartan treated group (Group DNI, n=7). In the experimental group, after the rats subjected to uninephrectomy, STZ was given by peritoneally injection at bolus dose of 50 mg/kg to induce diabetes. Blood glucose (BG), body weight (BW), urinary albumin excretion (Ualb), 24 hour proteinuria (24 h Upro) were measured at week 4, 8, 12, respectively. By the end of experiment at week 12, creatinine clearance (Ccr), kidney weight (KW), indicator of renal hypertrophy (KW/BW), renal total protein content (RTP), glomerular area (AG) and glomerular volume (VG) as well as glomerular basement membrane (GBM) were determined by semi-quantitative pathology technique. RESULTS: It was showed that there was no significant difference in BG between group DN and DNI, while Irb significantly reduced the increasing of Ualb, 24 h Upro in diabetic rats compared to control group (P