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Objective:To observe and describe the clinicopathologic manifestations of acute kidney injury (AKI) caused by immune checkpoint inhibitors (ICIs).Methods:The clinicopathologic manifestations of patients diagnosed as AKI related to ICIs in Ningbo LiHuili Hospital during the period between December 2020 to December 2021 were retrospectively analyzed, including the primary tumor disease, renal pathological features, renal function progression and therapeutic effects.Results:A total of 6 patients were enrolled, all of whom were male, aged (62±11) years old. The median time from the application of ICIs to the onset of AKI was 46 d (ranging from 31 to 95 d). The median of the peak serum creatinine was 311 (205 to 1 053) μmol/L, and 1 patient received hemodialysis treatment. Six patients received renal biopsy, among which 4 cases were acute tubulointerstitial nephritis, 1 case of tubulointerstitial nephritis with both acute and chronic changes, 1 case of chronic tubulointerstitial nephritis. Of the 6 patients, 5 received glucocorticoid therapy, and 2 of the patients completely recovered, while 3 partially recovered. One patient didn′t use glucocorticoid, but his renal function was partially restored after stopping ICIs.Conclusions:AKI caused by ICIs is mainly manifested by acute tubulointerstitial nephritis. Glucocorticoid has some therapeutic effects on AKI caused by ICIs and may be an effective treatment.
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Objective To investigate the effect and mechanism of liver X receptor ( LXR ) agonist on expression of fatty acid synthase( FAS) in diabetic kidney. Methods In the part of in vivo study, immunostaining was used to detect the FAS protein expression in kidney. 16-week-old male db/db mice on C57BL/6 background were administered via gavage a LXR synthetic agonist, TO901317, at a dose of 3 mg · kg-1 · d-1 or vehicle ( 0. 5%Carboxymethyl Cellulose Sodium, CMC-Na) alone for 7 d;Quantitative RT-PCR and Western blot were used to detect mRNA and protein levels of FAS and SREBP-1. In the part of in vitro study, MCT cell(a mouse murine proximal tubule cell line)was treated with 10μmol/L TO901317 for 24 h or transfected with active SREBP-1c expression vector (SREBP-1cN). HEK293 cells(a human renal tubule cell line)were transfected with mFAS-(1. 7 kb)-luc, LXR expression vector or SREBP-1cN for 12 h. Quantitative RT-PCR and luciferase reproter assay were utilized to examine FAS mRNA level and FAS promoter activity. Results FAS was abundantly expressed in renal cortex, with low expresson in renal glomeruli. The mRNA and protein expressious of FAS in kidney of db/db mice were lowered compared with db/m mice. TO90137 treatment increased FAS mRNA expression by 1. 3-fold. TO901317 increased expression of SREBP-1 in kidneys of db/m and db/db mice by 5. 1-fold and 17-fold, respectively. TO901317 and overexpression of SREBP-1c increased expression of FAS in MCT cells by 1. 5-fold and 1. 8-fold. Transcription activity of FAS were induced by TO901317, LXR, and SREBP-1cN overexpressions in HEK293 cells. Conclusions Both direct(LXRE)and indirect(SREBP-1c)mechanisms may contribute to the up-regulation of FAS expression by LXR in renal proximal tubule cells.
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Objective To evaluate fluid distribution in patients on maintenance hemodialysis (HD) by bioimpedance analysis and on the effect of adjusting the dry weight in hemodialysis patients.Methods Forty maintenance HD patients from the dialysis center of the Second Affiliated Hospital of Dalian Medical University were enrolled as study group.One hundred and two individuals who were tested of physical examination in the same hospital were enrolled as the control group.Sex and age of the two groups were recorded.Body weight,body high,blood pressure,bioimpedance of HD patients (pre-dialysis and post-dialysis) and controls were measured.Bioimpedance was measured by multifrequency segmental bioimpedance analysis,including right arm (RA) bioimpedance,trunk (TR) bioimpedance and right leg (RL) bioimpedance.Bioimpedance ratio (BIR) of three parts was calculated as of 100kHz and 20kHz including RA-BIR,TR-BIR and RL-BIR.Then eight HD patients who had high RA-BIA or TR-BIA according to the reference range which were obtained from 102 controls were chosen for dry weight adjustment.Post-dialysis body weight,blood pressure,and bioimpedance of the eight HD patients were measured again after adjusting the dry weight.Results (1) BIR of three parts in pre-dialysis HD patients were all significantly higher than that in the control group (P ＜ 0.05).BIR of three parts of the post-dialysis HD patients were still higher than that of the control group,but RL-BIR was not significantly (P ＞ 0.05).BIR of three parts of the post-dialysis HD patients were lower than BIR of three parts of the pre-dialysis HD patients,and there was significant different (P ＜ 0.05) with RA-BIR and RL-BIR.(2) After adjusting the dry weight,BIR of three parts of the post-dialysis HID patients were still higher than that of the control group,but none of them was significantly (P ＞0.05).BIR of three parts of the HD patients after adjusting the dry weight were lower than BIR of three parts of the HD patients before adjusting the dry weight,but there was no significant different with TR-BIR(P ＞ 0.05).After adjusting the dry weight,systolic blood pressure of the post-dialysis HD patients were significantly decrease[(150.00 ± 29.28) vs (140.63± 20.78) mm Hg,P＜ 0.05].Conclusions Bioimpedance analysis may be an effective method for adjusting dry weight in hemodialysis patients,and the bioimpedance of arms is the most effective method.The bioimpedance reference range of hemodialysis patients can be according to the reference range of normal individuals.
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Sixty-two patients with type 2 diabetes were treated with acarbose combined intensive insulin therapy( combined intensive group)or intensive insulin therapy alone (simple intensive group).As the blood glucose control reached the target,the mean amplitude of glycaemic excursion (MAGE),the absolute difference between the mean of daily differences ( MODD ),and standard deviation of blood glucose (SDBG) in combined intensive group were lower than those in simple intensive group [ ( 3.76 ± 1.47 vs 6.52 ± 1.57 ) mmol/L,( 0.57 ±0.49 vs 1.10 ±0.69 )mmol/L,( 1.44±0.60 vs 2.42±0.92 ) mmol/L,all P＜0.01 ].Daily mean blood glucose (MBG) of the former group was better than that of the latter group [ (7.08±0.69 vs 8.27 ± 1.31 ) mmol/L,P＜0.01 ].By the end of treatment,HbA1c [ 6.77％ ± 0.57％ vs 7.21％ ±0.83％,P＜0.05 ],incidence of hypoglycemia( 29％ vs 48％,P＜0.01 ),and body mass index[ (24.14±2.7 vs 27.63±3.41 ) kg/m2,P＜0.01 ] in combined intensive group were statistically improved more than those in the simple intensive group.
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Objective To assess the prevalence of hyperuricemia and its risk factors in Dalian Zhangzidao.Methods 1021 residents of Dalian Zhangzidao were randomly selected and examined.General conditions,life style,behaviors,and family histories were investigated.And physical examination and corresponding lab indexes were recorded.Data were analyzed by SPSS 13.0.Results The prevalence rate was 9.50% for all,with higher in men(11.75%) than in women(7.32%)(?2=5.83,P
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Objective To observe the expression of bone morphogenetic protein 7 (BMP-7) in different stages of diabetic rats and investigate the potential role of BMP-7 in diabetic nephropathy (DN). Methods Wistar rats were divided into diabetes mellitus(DM) group induced by intravenous injection of streptozotocin (65 mg/kg) , and normal control group injected with citrate buffer. The rats were sacrificed at day 30,60,90,120,150 and 180 following injection, respectively. The blood glucose,Scr, urinary albumin and urinary creatinine were measured in each rat before sacrifice. The renal pathological changes were examined with hematoxylin and eosin (HE),periodic acid-silver-methenamine staining (PASM) and protein expression of collagenⅣ(ColⅣ). The mRNA and protein expression of BMP-7 and TGF-?1 in kidney were detected by reverse transcription-polymerase chain reaction (RT-RCR) and immunohistochemical staining respectively, and were quantified by computer image analysis system. Results The levels of blood glucose and urinary albumin in diabetic group were remarkably higher than those in control group (P
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Objective To observe the expression of tissue transglutaminase (tTG) in renal tissues of diabetic nephropathy rats, and to investigate its contribution to the progression of diabetic nephropathy. Methods Streptozotocin-induced diabetic rats were sacrificed at 30 d, 60 d, 90 d, and 120 d respectively. Albuminuria excretion rate (AER), kidney weight index and serum creatinine (Scr) of the rats were measured. Hematoxylin and eosin (HE) staining and periodic acid-silver-methenamine (PASM) staining were used to observe the renal pathological changes. CollagenⅣ(ColⅣ) and soluble tTG protein in kidney were examined by immunohistochemistry,insoluble tTG by immunofluorescence. Expression of total tTG mRNA in kidney was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results AER, kidney weight index and Scr of diabetic rats were all progressive during the period of the experiment. Compared with control group, the levels of ColⅣ, soluble tTG and insoluble tTG protein in kidneys of hyperglycemic rats were significantly increased at 30 d, 60 d, 90 d and 120 d(P
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As constructive cells of the glomerular filtration barrier, podocytes plays an essential role in the maintenance of the glomerular blood filtration, and also in the prevention of protein loose from blood. Many factors cause podocyte injury, and consequently contribute to the onset and progression of glomerular lesions. This review focuses on relationship between podocyte injury and glomerular disease.