Early detection of acute renal failure by serum cystatin C

BACKGROUND: Acute renal failure (ARF) is associated with high mortality. Presently, no specific therapy for ARF exists. Therefore, early detection of ARF is critical to prevent its progression. However, serum creatinine, the standard marker to detect ARF, demonstrates major limitations. We prospectively evaluated whether serum cystatin C detected ARF earlier than serum creatinine. METHODS: In 85 patients at high risk to develop ARF, serum creatinine and cystatin C were determined daily. ARF was defined according to the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and ESRD (RIFLE) classification when creatinine increased by >/=50% (R-criteria), by >/=100% (I-criteria), or by >/=200% (F-criteria). In analogy, ARF was detected when cystatin C increased by >/=50%, by >/=100%, or by >/=200%. RESULTS: Forty-four patients developed ARF and 41 served as controls. In ARF by R-, I-, and F-criteria, the increase of cystatin C significantly preceded that of creatinine. Specifically, serum cystatin C increased already by >/=50% 1.5 +/- 0.6 days earlier compared to creatinine. Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R-criteria was fulfilled by creatinine. Cystatin C detected ARF according to the R-criteria with a sensitivity of 55% and 82% on these days, respectively. Cystatin C also performed excellently, detecting ARF defined by the I- and F-criteria two days prior to creatinine, and moderately well predicting renal replacement therapy in the further course of ARF. Additionally, low T(3)- or T(3)/T(4) syndrome, glucocorticoid deficiency and excess did not affect cystatin C levels, adding to its usefulness in critically ill patients with ARF. CONCLUSION: Serum cystatin C is a useful detection marker of ARF, and may detect ARF one to two days earlier than creatinine.     

血清半胱氨酸蛋白酶抑制剂C在急性肾衰早期诊断中的价值

目的 探讨半胱氨酸蛋白酶抑制剂C（cystatin C）在早期预测和诊断急性肾衰竭（ARF）中是否优于血清肌酐（Scr）。方法 前瞻性收集我院103例重症监护室危重患者资料，每例患者每天采集血标本。同时应用酶法测Scr水平；用颗粒增强透射免疫比浊法（PETIA）检测血清cystatin C水平；用Cockroft-Gauh公式估算肾小球滤过率（eGFR）。ARF运用ADQI的RIFLE标准进行诊断（R：Scr升高≥50％基础值，I：Scr升高≥100％基础值，F：Scr升高≥200％基础值，L：肾功能丧失；E：终末期肾脏病ESRD）；同时ARF也按cystatin C升高≥50％、≥100％和≥200％的标准进行诊断。结果 27（26．2％）例患者发生不同程度ARF，其中15例经历R标准，18例经历I标准，9例经历F标准，3例经历LE标准。其余76例没有发生ARF的患者作为对照组。ARF患者的cystatinC较非ARF患者显著升高（P〈0．01），ARF患者的cystatin C与Scr（r=0．747，P〈0．01）、（cystatinC）^-1与eGFR（R=0．815，P〈0．01）呈明显线性相关。分别按照cystatin C和Scr两种方法诊断ARF，不同程度ARF诊断的中位时间是：R标准的15例患者分别为2d（1～4d）和3d（2～6d）（P=0．011）；Ⅰ标准18例患者分别为4d（1～8d）和5．5d（2～10d）（P=0．006）；F标准的9例患者分别为5d（3～lld）和6d（3～13d）（P=0．02）。ROC分析证实cystatinC在ARF诊断中的准确性高，曲线下面积为0．995，95％可信区间为0．984～1．006（P〈0．001）。当以cystatin C升高≥50％时作为ARF的诊断截点时，cystatin C在ARF诊断中的敏感性和特异性分别为93％和96％。结论 cystatin C可以作为急性肾衰竭的诊断指标：cystatin C在ARF的诊断时间上较Scr更早，可作为ARF的早期预测指标之一。     

Evaluation of serum cystatin C for diagnosis of acute rejection after renal transplantation

Objective

To evaluate the clinical value of serum cystatin C (ScysC) for the diagnosis of an acute rejection episode after renal transplantation.

Methods

The 76 recruited renal transplant patients included 43 without and 33 with an acute rejection episode. We determined the values of serum creatinine (Scr), blood urea nitrogen (BUN), β₂ microglobulin (β₂-MG), uric acid (UA), and ScysC before surgery and at 1, 3, 5, 7, 14, 30, and 90 days thereafter. The glomerular filteration rate (GFR) was measured by ^99mTc-DTPA to evaluate correlations.

Results

No significant difference was observed between the groups before surgery (P > .05). In the rejection-free group ScysC was decreased by 48.1% at 1/day after surgery which was greater than the other cohorts. In the rejection group at day 3 the ScysC increased which was earlier than others. The highest coefficient correlation was observed between ScysC and GFR. The AUC^ROC of ScysC was greater than all of the others.

Conclusion

ScysC was a more sensitive marker to detect changes in renal function than Scr, BUN, β₂-MG or UA; therefore it can be used to predict an acute rejection episode after transplantation.     

急性上尿路结石梗阻性肾功能不全时血清半胱氨酸蛋白酶抑制剂C的变化研究

目的探讨上尿路结石致急性梗阻性肾功能不全时血清半胱氨酸蛋白酶抑制剂C(CysC)水平变化及其与预后的关系。方法比较正常对照组及手术组间的差异,以及术前与术后CysC的变化,同时测定血清肌酐(SCr)、尿素氮(BUN)。结果术前CysC显著高于正常对照组(P0.01),术后CysC显著低于术前(P0.01);术前、术后CysC变化与SCr、BUN呈正相关。结论上尿路结石致急性梗阻性肾功能不全时血清半胱氨酸蛋白酶抑制剂C变化与肾功能的改变有较明显的相关性。CysC可以作为上尿路结石致急性梗阻性肾功能不全时解除梗阻术后肾功能恢复情况的监测指标之一。     

动态监测血清胱抑素 C 评价肾移植术后肾功能的改变

目的 监测肾移植受者血清胱抑素C(Cys C)浓度以评估移植肾功能的改变. 方法 监测58例肾移植成功受者术前及术后不同时间的血清Cys C、肌酐(SCr)、β2-微球蛋白(β2-MG)和尿素氮(BUN)水平;并于术后第7天使用99mTc-DTPA测定受者肾小球虑过滤(GFR),比较其与上述四项指标的相关性.以GFR=1.5 ml/s为临界值,绘制ROC曲线,比较各项检测指标鉴别轻度与中重度肾功能损伤的诊断性能.计算受者不同时间段血清Cys C及SCr变异系数及其比值(R值). 结果 Cys C于术后第1天下降达48.1%,明显大于其他指标的下降幅度.血清Cys C、SCr、β2-MG和BUN与GFR相关系数依次为0.876、0.691、0.589和0.516.血清Cys C、SCr、β2-MG和BUN的诊断性能:敏感性分别为91.3%、87.2%、82.6%和87.0%;特异性分别为80.0%、69.2%、71.4%和42.9%;阳性预期值分别为82.0%、73.7%、74.3%和60.4%;阳性似然比分别为4.81、2.83、2.87和1.53;ROC曲线下面积(AUC)分别为0.914、0.828、0.803和0.765.SCr的变异系数显著小于Cys C(P＜0.01),Cys C＜2 mg/L的受者R值大多＜1,Cys C＞2 mg/L的受者,伴随Cys C水平升高,R值趋近于1. 结论 Cys C与GFR相关性最好;Cys C的诊断性能及准确性均优于其他指标,即使肾功能有微小损伤,Cys C也会有显著改变.因此,肾移植术后动态监测Cys C对于及时判断移植肾存活及肾微小损伤时肾功能的改变优于其他指标.     

Evaluation of the serum cystatin C values in prediction of indications for hemodialysis in patients with chronic renal failure

Background

Indications of dialysis treatment for patients with end-stage renal disease depend on various clinical and laboratory parameters. In this study, we aimed to determine whether standardized serum cystatin C (SCC) equation may be an applicability of marker for dialysis initiation and its relationship to other clearance values among patients with advanced chronic kidney disease.

Materials and methods

A total of 84 patients (45 males, 39 females) aged 19–89 were evaluated in this study. Hemodialysis was indicated according to clinical and laboratory findings, and estimated glomerular filtration rate (eGFR) was according to four different formulas [MDRD, EpiCKD, Cockcroft Gault formula (CGF) and SCC equation].

Results

eGFR values of patients in the study were 7.23 ± 3.26, 7.86 ± 3.78, 15.09 ± 10.88 and 11.31 ± 4.54 according to MDRD, EpiCKD, SCC equation and CGF, respectively. There was a positive correlation between MDRD, EpiCKD and CGF, and between EpiCKD and CGF (p < 0.01). Also, statistically significant correlation was found between SCC equation and CGF (p < 0.05).

Conclusion

SCC equation was not seemed to be an appropriate marker for starting dialysis in patients with advanced CKD.     

Comparison of cystatin C versus creatinine for detection of mild renal failure

AIM: Serum cystatin C (SCyst) has been proposed as a novel indicator of GFR. PATIENTS AND METHODS: We compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) as gold standard. 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82) underwent simultaneous measurements. RESULTS: A highly significant correlation r = 0.70, 0.74, 0.77 (p < 0.0001) was found between 1/SCyst, 1/SCreat, C(CG), respectively, and Cin. Receiver-operating characteristic (ROC) analysis was performed on SCyst, SCreat and C(CG) using a Cin cut-off of 90 ml/min/1.73 m2. Best fit for SCyst was 0.90 mg/l with a sensitivity of 75% and a specificity of 92%. The area under the ROC curve was not significantly greater for SCreat or C(CG) than for SCyst (p = 0.91,0.13, respectively). When relationship between Cin and SCyst was plotted, experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. Additional patients were selected in our database on the basis of discordant SCreat/GFR values: false negative (n = 46 samples, 31 patients) and false positive (n = 16 samples, 9 patients). In this highly selected subgroup, 38% of the SCreat false positive had normal SCyst values and 48% of the false negative SCreat had abnormally elevated SCyst. CONCLUSION: This study suggests that SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, however, SCyst could be proposed as a confirmatory test for patients with elevated SCreat.     

海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响

目的 观察海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响.方法 20例明确诊断慢性肾脏病患者,在基础治疗上给予海昆肾喜胶囊每天6粒口服,于治疗前和治疗后8周分别检测血清胱抑素C、尿素氮、肌酐的变化.结果 海昆肾喜胶囊可明显降低慢性肾脏病患者的血清胱抑素C水平(P < 0.05);治疗前、后血清胱抑素C、血肌酐比较差异具有统计学意义(P < 0.05).结论 海昆肾喜胶囊可改善早期慢性肾脏病患者的肾功能,早期应用海昆肾喜胶囊有利于延缓慢性肾脏病的进展,具有一定临床意义.     

海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响

目的 观察海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响.方法 20例明确诊断慢性肾脏病患者,在基础治疗上给予海昆肾喜胶囊每天6粒口服,于治疗前和治疗后8周分别检测血清胱抑素C、尿素氮、肌酐的变化.结果 海昆肾喜胶囊可明显降低慢性肾脏病患者的血清胱抑素C水平(P < 0.05);治疗前、后血清胱抑素C、血肌酐比较差异具有统计学意义(P < 0.05).结论 海昆肾喜胶囊可改善早期慢性肾脏病患者的肾功能,早期应用海昆肾喜胶囊有利于延缓慢性肾脏病的进展,具有一定临床意义.     

Assessment of glomerular filtration rate in renal transplant patients using serum cystatin C

AIM: Serum cystatin C (SCysC) has been proposed as a better marker of glomerular filtration rate (GFR) than serum creatinine (Scr). However, few data are available in renal transplant patients, especially, during the early postoperative phase. METHODS: Thirty-nine renal transplant patients (22 men/17 women) were recruited for determination of SCysC and Scr before operation, at 1 week and at 4 weeks after operation. SCysC was determined by particle-enhanced turbidimetric immunoassay. Creatinine clearance (Ccr) was calculated using the Cockcroft-Gault formula. RESULTS: SCysC and Scr levels significantly decreased with the recovery of allograft function. SCysC showed a significant correlation with Scr and Ccr. The relationship between SCysC and Scr showed a positive correlation (r = .849 preoperation, and r = .940 postoperation). The relationship between SCysC and Ccr revealed a negative correlation (r = .857 preoperation, and r = .876 postoperation). At the Ccr level of 50 to 80 mL/min/1.73 m(2), the correlation between SCysC and Ccr (r = .778) was significantly better than that between Scr and Ccr (r = .553; P = .032). The concentration of SCysC was not affected by age, gender, height, body weight, hemoglobin, serum protein, glucose, or mycophenolate mofetil or azathioprine dosage. However, corticosteroids slightly increased the level of SCysC and cyclosporine (CsA) decreased it. The area under the curve of the receiver operating characteristic curve for SCysC and Scr are 0.964 and 0.915, respectively (P < .05). CONCLUSION: Although the concentration may be slightly influenced by prednisolone and CsA, SCysC is more sensitive than Scr to detect early and moderate deterioration of GFR in adult renal transplant recipients.     

海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响

目的 观察海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响.方法 20例明确诊断慢性肾脏病患者,在基础治疗上给予海昆肾喜胶囊每天6粒口服,于治疗前和治疗后8周分别检测血清胱抑素C、尿素氮、肌酐的变化.结果 海昆肾喜胶囊可明显降低慢性肾脏病患者的血清胱抑素C水平(P < 0.05);治疗前、后血清胱抑素C、血肌酐比较差异具有统计学意义(P < 0.05).结论 海昆肾喜胶囊可改善早期慢性肾脏病患者的肾功能,早期应用海昆肾喜胶囊有利于延缓慢性肾脏病的进展,具有一定临床意义.     

Refining predictive models in critically ill patients with acute renal failure

Mortality rates in acute renal failure remain extremely high, and risk-adjustment tools are needed for quality improvement initiatives and design (stratification) and analysis of clinical trials. A total of 605 patients with acute renal failure in the intensive care unit during 1989-1995 were evaluated, and demographic, historical, laboratory, and physiologic variables were linked with in-hospital death rates using multivariable logistic regression. Three hundred and fourteen (51.9%) patients died in-hospital. The following variables were significantly associated with in-hospital death: age (odds ratio [OR], 1.02 per yr), male gender (OR, 2.36), respiratory (OR, 2.62), liver (OR, 3.06), and hematologic failure (OR, 3.40), creatinine (OR, 0.71 per mg/dl), blood urea nitrogen (OR, 1.02 per mg/dl), log urine output (OR, 0.64 per log ml/d), and heart rate (OR, 1.01 per beat/min). The area under the receiver operating characteristic curve was 0.83, indicating good model discrimination. The model was superior in all performance metrics to six generic and four acute renal failure-specific predictive models. A disease-specific severity of illness equation was developed using routinely available and specific clinical variables. Cross-validation of the model and additional bedside experience will be needed before it can be effectively applied across centers, particularly in the context of clinical trials.     

狼疮肾炎患者血清胱蛋白酶抑制剂C水平与肾组织病理的关系

我们研究了狼疮肾炎(LN)患者血清胱蛋白酶抑制剂C(Cyst C)水平与肾组织病理评分的关系,以期寻找一种无创、易行的方法评价LN患者肾病理变化和肾功能损害.     

血清半胱氨酸蛋白酶抑制剂C与血肌酐的匹配研究

研究发现,半胱氨酸蛋白酶抑制剂C(CysC)不易受体内、体外因素干扰[1,2];能更早期地反映出肾小球滤过率(GFR)的降低[1,2];对儿童GFR的变化反应敏感[3].因此,被认为是一种比Scr能更好反映肾小球滤过功能的理想指标.然而CysC只是近几年才应用于临床,目前尚缺乏大样本、多中心、长时间的临床验证,严重地限制了其在临床的实际应用.因此,需要建立Scr和CysC两者的平行分析,使其互为参照,为临床提供诊断信息,共同发挥各自的优势.     

Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction

Background  

Allograft function following renal transplantation is commonly monitored using serum creatinine. Multiple cross-sectional studies have shown that serum cystatin C is superior to creatinine for detection of mild to moderate chronic kidney dysfunction. Recent data in adults indicate that cystatin C might also be a more sensitive marker of acute renal dysfunction. This study aims to compare cystatin C and creatinine for detection of acute allograft dysfunction in children using pediatric RIFLE (risk of renal dysfunction, injury to the kidney, failure or loss of kidney function, end stage renal disease) criteria for acute kidney injury.     

Outcome and predictive factors of acute renal failure in the intensive care unit

The development of acute renal failure (ARF) in the ICU setting carries a high morbidity and mortality. To assess the outcomes and its predictive factors in our ICU, we analyzed the data of patients with ARF treated during 18 months. The 33 patients included 21 men and 12 women of mean age 51 +/- 21.7 years (13 to 87). Sepsis with multi-organ dysfunction (MOD) was the leading cause of ARF (58%). Comorbid conditions were malignancy in 30% of patients, diabetes mellitus in 24%, hypertension in 21%, ischemic heart disease in 21%, liver disease in 15%, and chronic renal failure in 15%. Predisposing factors were hypotension in 67% of cases, dehydration in 36%, drug related in 33%, congestive heart failure in 24%, and liver cirrhosis in 6%. Twenty-five (76%) patients needed mechanical ventilation, 22 (67%) were anuric, 18 (55%) had MODS, and 15 (45%) needed inotropic support. Length of stay in hospital was 27.2 +/- 28.0 days (2 to 94). Nineteen patients (58%) were managed conservatively and 14 (42%) by renal replacement therapy. Patient mortality was 67% and renal mortality 52%. The impact of the following factor: was assessed on patient and renal outcome was assessed ventilation support, presence of oliguria, need for inotropes, and presence of MOD. Patient mortality was significantly influenced by an elevated odds ratios (OR) (95% CI): mechanical ventilation [OR = 34 (95% CI 1.95 to 538)], and presence of MODS [OR = 12.3 (95% CI 2 to 75)]. Renal mortality was influenced by mechanical ventilation [OR = 12.3 (95% CI 1.6 to 119)], oliguria [OR = 12 (95% CI 2 to 72)], inotrope support [OR = 10 (95% CI 2 to 52), and MOD [OR = 35 (95% CI 3.5 to 35.0)]. This study confirms the high patient and renal mortality of ARF among patients to ICU. The four parameters were excellent predictors of renal outcome, while only the need for mechanical ventilation and the presence of MOD were predictors for patient survival.     

Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement

BACKGROUND: It is well known that serum creatinine may be used as a marker of renal function only if taking into account factors that influence creatinine production, such as age, gender, and weight. Serum cystatin C has been proposed as a potentially superior marker than serum creatinine, because serum cystatin C level is believed to be produced at a constant rate and not to be affected by such factors. However, there are limited data on factors that may influence serum cystatin C levels, and there are limited data comparing cystatin C-based estimates of renal function with creatinine-based estimates that adjust for such factors, especially in individuals with normal, or mildly reduced, renal function. METHODS: This was a cross-sectional study of 8058 inhabitants of the city of Groningen, The Netherlands, 28 to 75 years of age. Serum cystatin C and serum creatinine levels were measured, and creatinine clearance was determined from the average of two separate 24-hour urine collections. We performed multivariate analyses to identify factors independently associated with serum cystatin C levels after adjusting for creatinine clearance. Then, partial Spearman correlations were obtained after adjusting for factors that may influence serum cystatin C and creatinine levels. We also compared the goodness-of-fit (R(2)) of different multivariate linear regression models including serum cystatin C level and serum creatinine level for the outcome of creatinine clearance. RESULTS: Older age, male gender, greater weight, greater height, current cigarette smoking, and higher serum C-reactive protein (CRP) levels were independently associated with higher serum cystatin C levels after adjusting for creatinine clearance. After adjusting for age, weight, and gender, the partial Spearman correlations between creatinine and, respectively, serum cystatin C level and serum creatinine level were -0.29 (P < 0.001) and -0.42 (P < 0.001), respectively. The R(2) values for serum cystatin C level and serum creatinine level adjusted for age, weight, and gender were 0.38 and 0.42, respectively. The addition of cigarette smoking and serum CRP levels did not improve the R(2) value for the multivariate serum cystatin C-based model. CONCLUSION: Serum cystatin C appears to be influenced by factors other than renal function alone. In addition, we found no evidence that multivariate serum cystatin C-based estimates of renal function are superior to multivariate serum creatinine-based estimates.     

Early detection of acute kidney injury by serum cystatin C in critically ill children

Background

We prospectively evaluated whether serum cystatin C (CysC) detected acute kidney injury (AKI) earlier than basal serum creatinine (Cr).

Methods

In 107 pediatric patients at high risk of developing AKI, serum Cr and serum CysC were measured upon admission. Baseline estimated creatinine clearance (eCCl) was calculated using a CysC-based glomerular filtration rate (GFR) equation from a serum Cr measured at the pediatric intensive care unit (PICU) entrance.

Results

The median age was 10 months (interquartile range, 3–36 months). Serum Cr, serum CysC, and eCCl (mean ± standard deviation [range]) were 0.5?±?0.18 mg/dl (0.2–1.1 mg/dl), 0.53?±?0.78 (0.01–3.7 mg/l), and 72.55 ± 28.72 (20.6–176.2) ml/min per 1.73 m², respectively. The serum CysC level in patients with AKI was significantly higher than children with normal renal function (p?<?0.001). The values for the cut-off point, sensitivity, specificity, and the area under curve (AUC) were determined for CysC as 0.6 mg/l, 73.9 %, 78.9 %, and 0.92 [95 % confidence interval (0.82–1)], respectively, and for Cr the values were 0.4 mg/dl, 68 %, 46.2 %, and 0.39, [95 % confidence interval (0.24–0.54)], respectively. The receiver operating characteristics (ROC) curve analysis revealed that CysC had a significantly higher diagnostic accuracy than eCCl (p?<?0.001).

Conclusions

Our results identify that the sensitivity of serum CysC for detecting AKI is higher than that of serum Cr in a heterogeneous pediatric intensive care unit (PICU) population.