Chinese Journal of Nephrology

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Combined detection of markers in the early diagnosis of acute kidney injury following cardiac surgery

CHE Miao-lin;QIAN Jia-qi;DAI Hui-li;WU Qing-wei;NI Zhao-hui;XUE Song;YAN Yu-cheng

2011, 27(3): 164-169.

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Objective To investigate the markers in early diagnosis of acute kidney injury (AKI) in patients undergoing heart surgery. Methods Markers included serum cystatin C (CyC), and urinary neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), retinol binding protein (RBP) and N-acetyl-β-D-glucosaminidase (NAG). Twenty-nine cardiac surgical patients hospitalized were enrolled in the study. Serial blood and urine samples were collected immediately before incision and at various time intervals after surgery. The primary outcome measure was AKI, defined as a 50% increase in Scr from baseline. Results The cohort consisted of 29 patients aged (62.9±13.7) years, and baseline Scr was (73.2±11.9) μmol/L. There were no significant differences in demographics between cases and controls, while the aortic clamp time was predictably longer in AKI cases as compared to controls [(60.63±13.92) vs (43.00±9.20) min, P<0.05]. Each biomarker differed significantly between cases and controls at least one time-point. Optimal AUCs were for CyC at 10 hours with sensitivity (ST) 0.71, specificity (SP) 0.92,AUC=0.83(0.67-1.00), cut-off (CO) 1.31 mg/L; NGAL at 0 hour with ST 0.84, SP 0.80, Auc=0.85(0.70-1.00), CO 49.15 μg/g Ucr; IL-18 at 2 hours with ST 0.85, SP 0.73, AUC=0.81 (0.64-0.97), CO 285.65 ng/g Ucr; RBP at 0 hour with ST 0.75, SP 0.67, AUC=0.77(0.60-0.95), CO 2934.65 μg/g Ucr and NAG at 4 hours with ST 0.86, SP 0.67, AUC=0.72(0.53-0.92), CO 37.05 U/mg Ucr. Using a combination of all the 5 biomarkers analyzed at the optimal time-point as above, an AUC of 0.98 (0.93-1.02) (P<0.01) in this limited sample was able to obtain. Conclusions Application of serum and urinary biomarkers for the prediction of AKI in patients undergoing cardiac surgery is highly dependent on the sampling time. Of the evaluated markers, uNGAL has the best predictive profile. uRBP also shows similar predictive power. Combining all the five above biomarkers is able to predict significantly more cases, suggesting that the use of more than one marker may be beneficial clinically.

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Prognostic investigation of AKIN criteria combined with APACHE Ⅱ and SOFA scoring system in acute kidney injury after cardiac surgery

JIN Wei;TENG Jie;FANG Yi;LIU Zhong-hua;SHEN Bo;XU Yan;HENG Yan-yan;YANG Zhao-hua;WANG Chun-sheng;DING Xiao-qiang

2011, 27(3): 170-175.

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Objective To explore the prognostic value of Acute Kidney Injury Network (AKIN) criteria combined with Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) and Sequential Organ Failure Assessment (SOFA) scoring system in acute kidney injury (AKI) after cardiac surgery. Methods Clinical data of patients who underwent open-heart surgery in Zhongshan Hospital, Fudan University from April 2009 to August 2009 were prospectively collected. AKI after cardiac surgery was classified by AKIN staging system. APACHEⅡ and SOFA scores were evaluated according to the worst value of physiologic variables in the 1st 24 h after surgery. Discrimination and calibration of these three models were assessed by receiver operating characteristic (ROC) curve and Hosmer-Lemeshow goodness-of-fit test. Besides, their effects on in-hospital mortality were evaluated by multivariate Logistic regression analysis. Results Of the 993 admissions, 309 patients developed AKI and the incidence was 31.1%. The median time that developed postoperative AKI and reached the Scr peak were 1 d and 2 d respectively. Either APACHEⅡ or SOFA scores, which was positively correlated with the severity of AKI (APACHEⅡr=0.37, P<0.01; SOFA r=0.42, P<0.01) was higher in AKI patients compared with that in non-AKI patients (P<0.01). The mortality rose corresponding to the severity of kidney injury. However, the predicted death rate-adjusted (PDR-A) calculated by APACHEⅡ scores was higher than the actual value in non-AKI patients and AKIN stage 1 (P<0.01), while it was lower in AKIN stage 3 (P<0.01). The areas under the ROC curve of APACHEⅡ, SOFA and AKIN criteria were all above 0.8 and the results of Hosmer-Lemeshow goodness-of-fit test indicated good calibration of three models. Multivariate analysis showed that APACHEⅡ≥19 (OR=4.26) and AKIN stage 3 (OR= 76.15) were independent predictors of in-hospital mortality. Conclusions AKI can be classified by AKIN criteria in the early stage after cardiac surgery and the AKIN staging system may serve the prediction of prognosis. The APACHEⅡ and SOFA scores just evaluated in the 1st 24 h after operation can discern the severity of patients' illness. Three models all present good discrimination and calibration in predicting patients' outcome. APACHEⅡ≥19 along with AKIN stage 3 are found to be the independent predictors of in-hospital mortality. It should be noticed that the deviation between PDR-A and the actual mortality in subgroups, dynamic evaluation may raise the accuracy of scoring system.

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Epidemiology investigation of chronic kidney disease in 1031 consecutive cases undergoing coronary angiography

YAN Lei;MA Gen-shan;LIU Hong;ZHANG Xiao-guo;ZHANG Li-ping;WANG Shuo-peng;LIU Bi-cheng

2011, 27(3): 176-180.

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Objective To investigate the prevalence of CKD in patients underging coronary angiography with suspected coronary heart disease (CHD). Methods A total of 1031 patients with suspected CHD undergoing coronary angiography in Zhongda Hospital from December 2008 to October 2009 were enrolled in the study. The prevalence of CKD and associated risk factors were analyzed. GFR was estimated with MDRD equation. CKD was defined as eGFR <60 ml?min-1?(1.73 m2)-1 or proteinuria. Luminal narrowing at least one lesion≥50% in the main branches of coronary artery was considered as CHD. Results The mean age of patients were (64.37±11.02) years. There were 543 males and 488 females, including 551 patients with CHD and 134 patients with CKD(13%). Patients with CHD had a significantly higher prevalence of CKD compared with patients without CHD (18.33% vs 6.88%, P<0.01). With the increasing number of stenosis coronary vessels (n=0, 1, 2, 3）, eGFR was declined [(84.25±19.00), (81.61±23.92), (75.16±20.99), (73.92±20.66) ml?min-1?(1.73 m2)-1, P<0.01], the percentage of proteinuria increased (0.42%, 0.82%, 1.96%, 3.25%, P=0.006), and the prevalence of CKD increased (6.88%, 13.11%, 21.57%, 23.38%, P<0.01). Logistic regression analysis indicated that increasing age (OR 1.094, 95%CI 1.068 to 1.120), increasing number of stenosis coronary vessels (OR 1.288, 95%CI 1.074 to 1.543), hypertension (OR 1.974, 95%CI 1.082 to 3.603), cardiac systolic insufficiency (OR 3.183, 95%CI 1.696 to 5.972), and hyperuricemia (OR 5.366, 95%CI 3.224 to 8.931) were risk factors for CKD. Conclusions The prevalence of CKD in patients with CHD diagnosed by coronary angiography is quite high. Aging, elevated number of stenosis coronary vessels, hypertension, cardiac systolic insufficiency and hyperuricemia are important risk factors for angiographic patients with CKD.

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Clinical analysis of acute kidney injury in 1113 patients after cardiac valve replacement surgery

HENG Yan-yan;FANG Yi;ZHONG Yi-hong;TENG Jie;ZOU Jian-zhou;WANG Chun-sheng;LIU Lan; DING Xiao-qiang

2011, 27(3): 181-185.

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Objective To investigate the incidence and risk factors of acute kidney injury(AKI) after different types of cardiac valve replacement surgery. Methods A single cohort of 1113 patients who received cardiac valve replacement surgery from April 2009 to March 2010 in Zhongshan Hospital, Fudan University were prospectively analyzed. Multivariate Logistic regression analysis was used to evaluate possible risk factors associated with post-operative AKI. AKI was defined as a relative 50% increase or an absolute increment of 26.4 μmol/L in Scr within 48 hours and/or urine volume <0.5 ml?kg-1?h-1 up to 6 h. Results Of the 1113 patients, the incidence of AKI was 33.24%. In-hospital mortality of AKI patients was 6.49%, which was 5.373 times higher than that of non-AKI patients (P<0.01). The incidence of AKI in patients who simultaneously received cardiac valve replacement and coronary artery bypass grafting was 75.00%, which was significantly higher as compared to other types of valve replacement surgery (P<0.01). Unconditional multivariate Logistic regression analysis revealed that male, old age, long extracorpeal circulation(CPB) time(≥120 min) and combined with coronary artery bypass grafting surgery were the independent predictors of AKI episodes, and the corresponding OR values were 1.455, 2.110, 1.768 and 2.994 respectively. Conclusions AKI is a common and serious complication after cardiac valve replacement surgery. Patients who received combined cardiac surgery as valve replacement and coronary artery bypass grafting have higher incidence of AKI. Old age, male, long CPB time (≥120 min) and combined with coronary artery bypass grafting surgery are the independent risk factors of post-operative AKI for patients undergoing cardiac valve replacement surgery.

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Clinical analysis of central venous stenosis in 5 hemodialysis patients without a previous history of catheterization

SHI Ya-xue;YE Meng;ZHANG Hao;LIANG Wei;ZHANG Ji-wei

2011, 27(3): 186-189.

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Objective To evaluate imaging findings and treatment experience in central venous stenosis without a history of previous catheterization in hemodialysis patients. Methods Clinical data of 5 haemodialysis cases of central vein stenosis without a previous catheterization history in our hospital from July 2006 to July 2008 were analyzed retrospectively. Results Patients were three women and two men aged 43 to 65 years with mean age (53±8) years and all had arm swelling as the main complaint. The vascular accesses were located at the wrist in all the patients. The mean duration of the vascular accesses from the time of creation was (33.6±35.4) months. Venography showed occlusion in 2 cases and stenosis in 3 cases of central vein including 1 case of stenosis in brachiocephalic vein, 1 case of stenosis both in branchiocephalic vein and subclavian vein, 1 case of stenosis in two segments of subclavian vein. The stenosis of branchiocephalic vein was fixed anterior to the tracheal and CT showed the compression of the vein by the aorta. Symptoms were resolved by the treatment of PTA, subclavian vein-contralateral subclavian vein bypass and ligation of the access. Conclusions Central venous stenosis in haemodialysis patients without a history of catheterization may be due to the intimal hyperplasia of the compression site or valve which is accelerated by the high flow of vascular access. Venography is the first choice for the diagnosis and the current management of central venous stenosis is far from being effective for the long term.

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Effect of olmesartan medoxomil on renal oxidative stress in mice with chronic heart failure

LU Xiao-mei;MA Ling;YU Yan-qiu

2011, 27(3): 190-193.

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Objective To investigate the effect of olmesartan medoxomil on renal oxidative stress in mice with chronic heart failure. Methods C57 mice were divided into sham operation group (SHAM group), chronic heart failure group (CHF group) and olmesartan medoxomil treatment group (OLM group). Experimental CHF model was established by coronary artery ligation, in which OLM group fed with a daily dose of 10 mg/kg. The heart rate, blood pressure, cardiac function, Scr, BUN, and plasma and kidney angiotensin (Ang) Ⅱ were measured. Real-time PCR was used to examine renal gp91phox, p22phox and NOX4 expression. AZAN and DHE staining was used to detect renal pathological change after 12 weeks． Results Compared with SHAM group, left ventricular-end diastolic dimension (LVDd) and left ventricular end-systolic dimension(LVDs) were significantly increased (P<0.05), while fractional shortening (FS) and ejection fraction (EF) were significantly decreased in CHF and OLM groups (P<0.05). Compared with SHAM group, systolic blood pressure, Scr, BUN, and AZAN and DHE staining positive area were significantly increased in CHF group (P<0.05), while above indexes were significantly lower in OLM group as compared to CHF group (P<0.05). Compared with SHAM group, plasma and kidney AngⅡ levels, gp91phox, p22phox and NOX4 expression were increased in CHF group (P<0.05), while above indexes were significantly lower in OLM group as compared to CHF group (P<0.05). Conclusions Chronic heart failure can activate intrarenal NADPH oxidase resulting in renal injury. Olmesartan medoxomil can protect kidney by inhibiting the effect of Ang Ⅱ-induced oxidative stress.

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Role of hypoxia inducible factor 1α-mediated signaling pathway in angiotensinⅡ- induced renal interstitial fibrosis

TANG Lin;GUO Qing;ZHANG Cui-cui;LIU Zhang-suo;ZHANG Xiao-xue

2011, 27(3): 194-197.

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Objective To explore the role of hypoxia inducible factor 1α(HIF-1α)-mediated signaling pathway in angiotensinⅡ(AngⅡ) induced renal interstitial fibrosis. Methods Renal tubular epithelial cells were cultured and treated with different concentrations (10-9-10-6 mol/L) of AngⅡfor 24 h and 48 h. Real-time quantitative PCR and Western blotting were preformed to detect the mRNA and protein expressions of HIF-1α, prolyl hydroxylase 2 (PHD2) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in renal tubular epithelial cells. Results HIF-1α mRNA level was increased with AngⅡ treatment in a concentration dependent manner. When cells were treated with AngⅡ concentration at 10-7 mol/L for 24 h, the mRNA level was markedly increased by 166%. Furthermore, by real-time quantitative PCR and Western blotting, compared with the control group, AngⅡ increased the mRNA and protein levels of HIF-1α and TIMP-1 (P<0.05, respectively), while the mRNA and protein levels of PHD2 were decreased markedly (P<0.05, respectively) in renal tubular epithelial cells. Conclusion AngⅡreduces HIF-1α degradation in renal tubular epithelial cells probably by reducing the expression of PHD2, which increases the expressions of HIF-1α and TIMP-1 involved in renal interstitial fibrosis.

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Tilting the balance of tubular cell fate toward survival contributes to ischemic tolerance in kidney

JIANG Su-hua;ZOU Jian-zhou;LIU Hong;REN Li;XU Xun-hui;CHEN Yue;DING Xiao-qiang

2011, 27(3): 198-202.

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Objective To explore the role of brief ischemia pretreatment in the induction of renal ischemic tolerance, and investigate its effects on tubular cell necrosis, apoptosis and proliferation. Methods Male Sprague-Dawley rats were randomly divided into three groups, including sham-operated group (Sham), ischemia/reperfusion injured group subjected to the occlusion of both renal pedicles for 40 min followed by reperfusion (I/R), and preconditioned group with 20-min ischemia pretreatment induced 4 days before I/R (IPC). Histological changes were evaluated by PAS staining. The ultra-structure of tubular cells was observed by transmission electron microscopy (TEM). Apoptosis was confirmed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). The proliferation of tubular cells was evaluated with proliferating cell nuclear antigen (PCNA). Results Twenty-minites ischemia pretreatment offered both promising functional and histological protection against 40-min ischemia/reperfusion injury (P< 0.01). The mortality rate was reduced from 33% in I/R group to 0 in IPC group. The renoprotection offered by 20-min ischemia pretreatment was accompanied with reduced postischemic tubular cell apoptosis and necrosis (P<0.05), and increased cell proliferation (PCNA positive) (P< 0.01). Conclusions Brief and sublethal prior ischemia can render the kidney more tolerant to subsequent prolonged I/R injury. Its ability to tilt the balance of tubular cell fate toward survival, reducing postischemic cell death and enhancing cell proliferation, may play an important role in renal protection of ischemic preconditioning.

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Intervention of azithromycin on adriamycin-induced nephropathy rats

ZHANG Bi-li;SONG Lan-yun;WANG Wen-hong;ZHANG Xuan;FAN Shu-ying;YANG Li

2011, 27(3): 203-208.

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Objective To investigate the effects of azithromycin on serum indicators, urine indicators, renal pathology, intercellular adhesion molecule-1 (ICAM-1), nephrin and podocalyxin in adriamycin（ADR）-induced nephropathy(ADN) rats. Methods ADR nephropathy was induced by a tail intravenous injection of ADR. The rats were randomly divided into azithromycin-treated group, prednisone -treated group, integrated treatment group, model group and control group. Serum index and 24 h urine protein were measured serially at 0, 4th, 8th weeks. The values of creatinine clearance (Ccr) were calculated. Kidney tissues were collected for microscopy observation. The expressions of nephrin, podocalyxin and ICAM-1 in renal tissue were detected by immunohistochemistry SP. Results Compared with normal control group, at the 4th week， 24 hours urine protein and albumin reached the level of ADR nephropathy model. Compared with model group, at the 8th week, 24 h urine protein, cholesterol, serum creatinine, renal pathology changes in the three treated group rats were significantly reduced(P<0.05), serum total protein, albumin and Ccr (except C group) significantly raised(P<0.05), ECM/GA and renal pathology score significantly reduced (P<0.01), ICAM-1 significantly decreased (P<0.01), nephrin and podocalyxin significantly increased. Besides, the curative effect of integrated treatment was better than other treatment group. Conclusions Azithromycin induces similar responses in ADR nephropathy as prednisone, but its early protective effect of renal function is worse than prednisone. The integrated treatment of azithromycin and prednisone has a synergistic effect, and the efficacy is superior to each drug alone.

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MG132 enhances the renal anti-oxidative ability in diabetic nephropathy rats

LUO Zhi-feng;QI Wei;ZENG Wei;PANG Qi;GUO Yan-hong;MU Jiao;FENG Bing

2011, 27(3): 209-214.

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Objective To investigate the effects of MG132 on diabetic nephropathy (DN) rats induced with streptozocin. Methods Seventy-two male SD rats were randomly divided into three groups: normal control group (NC, n=24), DN group (n=24) and DN treated with MG132 group (DN+MG132, n=24). At the end of 4, 8 and 12 weeks, 24 hour urinary protein excretion rate (UPER) was detected. Morphology of kidney was examined by special staining of periodic acid-schiff (PAS). Renal 26S proteasome activity was determined by quantifying the hydrolysis of S-LLVY-AMC in a fluorescence reader. Urinary malondialdehyde (MDA) level and renal SOD and GSH-PX activity were detected by commercial kits. Renal SOD, GSH-PX and p47phox mRNA expressions were determined by real-time fluorescence PCR. Renal p47phox protein expression was determined by Western blotting. Results Compared with NC group, the DN group showed a significant increased of UPER at week 4, 8, 12 (all P<0.05), of mesangium proliferation and mesangial matrix expansion at week 12. In DN+MG132 group, UPER was significantly decreased compared with DN group at the end of 4, 8 and 12 weeks(P<0.05, respectively), and the glomeruler pathological alteration induced by diabetes was attenuated. Increased renal 26S proteasome activity in DN rats was significantly inhibited after MG132 administration (P<0.05). Moreover, renal p47phox mRNA expression in DN group was 155%, 149% and 120% more than those in NC group at 3 time points (all P<0.05), and so was the renal p47phox protein expression, 139%, 152% and 186% more (all P<0.05). Urinary MDA levels in DN group were 1.95-, 2.04- and 2.62-folds more than those in NC group (all P<0.05). In addition, compared with NC group at 3 time points, in DN group, renal SOD activity was decreased by 23.09%, 33.59% and 53.31% (all P<0.05); renal GSH-PX activity was decreased by 28.57%, 33.06% and 48.76% (all P<0.05); renal SOD mRNA was decreased by 38.09%, 61.44% and 76.53% (all P<0.05); renal GSH-PX mRNA group was decreased by 29.16%, 37.26% and 62.40% (all P<0.05). Compared with DN group, renal p47phox mRNA and protein expression, and urinary MDA levels were significantly lower in DN+MG132 group (all P<0.05); renal SOD and GSH-PX activity as well as mRNA expression were significantly increased in DN+MG132 group (all P<0.05). Conclusions MG132 treatment can provide renoprotection for DN rats effectively maybe through enhancing renal anti-oxidative ability.

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肾脏病与心血管专题

基础研究

肾脏病与心血管专题

基础研究