Evaluation Of Renal Function In Patients With Cardiovascular Diseases

Reserch backgroundRenal dysfunction and cardiovascular disease are closely related either in the early stages of cardiovascular disease or in the end-stage organ failure. Thus, even for patients with mild to moderate cardiovascular disease, evaluation and treatment of renal function are still very important. In early stage of cardiovascular disease, cardiac pump function is still capable of compensation with cardiac neurohormone-mediated cardiac remodeling. As the disease advances, heart failure gets worse because of the cardiac pump function decompensation. Reduction in cardiac output causes decreased renal blood flow, contraction of afferent arterioles, decreased glomerular filtration rate and decreased renal dysfunction. The pathophysiological changes and mutual influence between heart and kidney is a vicious cycle based on neurohormonal and renin-angiotensin aldosterone system activation. Therefore, early detection and treatment of renal dysfunction accompanied with heart failure can play an active role in the treatment of heart failure.In recent years, more and more research indicates that renal insufficiency as an independent risk factor for cardiovascular disease. Renal dysfunction in patients may suggest their worsening heart failure. The accurate assessment of glomerular filtration rate is the most preferred indicator of renal function evaluation. It has important clinical significance for the correct evaluation of renal function, the diagnosis, proper staging and treatment in chronic kidney disease (CKD) patients. Variety of eGFR estimating equations based on Scr have been proposed to compensate for the inconvenience of the clinical monitoring of GFR. cystatin C (Cys-C) has higher sensitivity, specificity and accuracy than Scr and other endogenous indicators for diagnosis of renal dysfunction. Because of its convenience and high sensitivity, Cys-C has been used in the early prediction of acute kidney injury. With the discovery and clinical application of cystatin C(Cys-C), a variety of Cys-based GFR-estimating equations have been proposed, but still have various controversial deficiencies.More and more clinical application of contrast media associated examination and treatment make the incidence of contrast induced nephropathy larger day by day. Contrast induced nephropathy(CIN) is an acute renal injury secondary to the use of contrast media, as the third cause of nosocomial acute renal failure. The threats posed by contrast media are increasingly attended by clinicians. Although the pathogenesis of contrast induced nephropathy has been in deep understanding, there was still no sure and efficient method of initiative CIN prevention so far. The prophylactic measures of CIN include the termination of nephrotoxic drugs, strict indication of use, appropriate use of contrast media, and rehydration. The commonly used drugs consist of N-acetylcysteine, adenosine receptor inhibitor, and statins.Currently the diagnosis of CIN is still based on the concentration of Serum creatinine (Scr), but a number of studies suggest that this kind of diagnosis may lead to a certain rate of misdiagnosis because of low sensitivity of Serum creatinine. The level of Serum creatinine increase up to peak 3-5 days after angiography and decrease down to normal in 1 to 3 weeks. Some patients with contrast induced nephropathy may be ignored because of discharge. They may lose the best chance for early treatment, prevention and mitigation of renal dysfunction. Cystatin C(Cys-C) has higher sensitivity, specificity and accuracy than Scr and other endogenous indicators for diagnosis of renal dysfunction. Because of its convenience and high sensitivity, Cys-C has been used in the early prediction of acute kidney injury.Some studies suggest Cys-C as an early diagnosis indicator for acute kidney injury with more and more attention and clinical application. However, further research is needed to support Cys-C as a diagnostic indicator of CIN. Moreover, an appropriate diagnostic criteria is also needed.In part one of this study, we compared eight GFR-estimating equations(CG equation, MDRD equation, simplified MDRD equation, modified MDRD equation and four kinds of Cys-C-based GFR estimation equations) to find out the most suitable GFR-estimating equation for patients with Cardiovascular diseases. Our study was based on the GFR by 99mTc-DTPA renal dynamic imaging as a reference standard. In part two of our study, we compared a variety of comprehensive indicators for renal function evaluation and find out the most suitable one for early and accurate diagnosis of contrast induced nephropathy.Part One Comparative study of eGFR by eight calculation methods in patients with cardiovascular diseasesObjectiveGlomerular filtration rate (GFR) is recognized as an important indicator for evaluation of renal function and an important basis for the diagnosis and staging of chronic kidney disease (CKD). K/DOQI guidelines made GFR-estimating equations available because of the inconvenience in clinical measurement of GFR. MDRD and Cockcroft-Gault estimating equation are more internationally accepted to estimate GFR (eGFR) at first. K/DOQI guidelines in 2002 recommended using the simplified MDRD estimating equation to facilitate the clinical need, but a number of clinical studies in China found that application of simplified MDRD estimating equation in Asian populations may underestimate the GFR and then the modified MDRD estimating equation was proposed for the domestic patients. With the discovery and clinical application of the cysteine protease inhibitor C (cystatin C, Cys-C), a variety of Cys-based GFR-estimating equations have been proposed, but still have various controversial deficiencies. In this study, we compared eight GFR-estimating equations to find out the most suitable GFR-estimating equation for patients with Cardiovascular diseases. Our study was based on the GFR by 99mTc-DTPA renal dynamic imaging as a reference standard.Methods 208 patients were involved. Scr, Cys-C and renal ECT were taken.122 cases were male and 86 females, aged 10 to 83 years(mean 50.33±14.86), renal failure diagnosed with GFR<60ml/min/1.73m2. According to K/DOQI guidelines,208 patients were divided into five stages (stage 1 with GFR≥90m1/min/1.73m2; stage 2 with GFR 60-89ml/min/1.73m2; stage 3 with GFR 30-59ml/min/1.73m2; stage 4 with GFR 15-29ml/min/1.73m2; stage 5 with GFR<15ml/min/1.73m2 or dialysis). There are 15 cases with CKD stage 1,72 cases with CKD stage 2,71 cases with CKD stage 3,34 cases with CKD stage 1 and 16 cases with CKD stage 5. We compared the GFR by 99mTc-DTPA renal dynamic imaging and eGFR by eight estimating equations to find out the most suitable GFR-estimating equation for patients with Cardiovascular diseases.SPSS13.0 statistical software was used for statistical analysis. Paired-Samples T Test was used for comparison of paired measurement data. Pearson linear correlation analysis was used for the correlation between two variables. ROC curve analysis was used for the diagnostic value of GFR-estimating equations. Two-sided test was used and the size of a test a=0.05, P<0.05 indicated significant difference, P<0.01 indicated statistically significant difference.Results:1 Evaluating renal function in all 208 patients, estimated GFR by eight estimating equations were well correlated with GFR by 99mTc-DTPA renal dynamic imaging (r> 0.8, P<0.01). Eight estimating equations didn't have any significant differences between each other. In different CKD stages, compared with Scr-eGFR estimating equations, Cys-eGFR estimating equations had less correlation with GFR by 99mTc-DTPA renal dynamic imaging in patients with CKD stage 1, but had better correlation in patients with CKD stage 2-4. In patients with CKD stage, however, Scr-eGFR estimating equations had better correlation with GFR by 99mTc-DTPA renal dynamic imaging than Cys-eGFR estimating equations.2 Evaluating renal function in all 208 patients, CG estimating equation underestimated the GFR in CKD stage 1-4 (P<0.01), simplified MDRD estimating equation underestimated the GFR in CKD stage 2 (P<0.05), Rule estimating equation underestimated the GFR in CKD stage 2 and 4, Macisaac estimating equation overestimated the GFR in CKD stage 2-5 (P<0.01), Tan estimating equation overestimated the GFR in CKD stage 2-4 (P<0.01).3 Using GFR<90mL/min/1.73m2 as critical value for the diagnosis of mild renal failure, we compared the AUCROC of eight estimating equation and found that Cys-eGFR estimating equations got better AUCROC than Scr-eGFR equations. Four Cys-eGFR estimating equations didn't have any significant differences between each other. Using GFR<60mL/min/1.73m2 as critical value for the diagnosis of moderate renal failure, we compared the AUCROC of eight estimating equation and found that MDRD and simplified MDRD equation had slightly higher AUCROC than other Equations. Using GFR<30mL/min/1.73m2 as critical value for the diagnosis of severe renal failure, we compared the AUCROC of eight estimating equation and found that AUCROC of Cys-eGFR estimating equations had no significant differences between that of Scr-eGFR equations.4 Of all eight estimating equations, eGFR by MDRD equation, modified MDRD equation and Arnal-Dade equation had no significant differences between the GFR by 99mTc-DTPA renal dynamic imaging in all CKD stages, better than other estimating equations.Conclusions:(1) Of four Cys-based eGFR-estimating equations, Arnal-Dade equation is better than other estimating equations. (2) For normal or mild renal failure domestic patients with cardiovascular disease, MDRD equation and modified MDRD equation are better than other equations. (3) For moderate to severe renal failure domestic patients with cardiovascular diseases, simplified MDRD equation (or modified MDRD equation) and Arnal-Dade equation are better than other equations. Key Words:GFR Estimating Equations; 99mTc-DTPA Dynamic Renal Imaging; Estimated Glomerular Filtration RatePart Two Evaluation of contrast induced nephropathy during peri-PCI periodObjective:Contrast induced nephropathy (CIN) has become one of three major reasons for hospital-acquired acute renal failure with high morbidity and mortality. Patients after PCI have high incidence of CIN because of hemodynamic instability and lack of effective prevention, which makes early diagnosis of CIN a hot topic and gains more and more attention. Currently the diagnosis of CIN is still based on the concentration of Serum creatinine (Scr), but a number of studies suggest that this kind of diagnosis may lead to a certain rate of misdiagnosis. Some studies suggest Cys-C as an early diagnosis indicator for acute kidney injury with more and more attention and clinical application. The purpose of this study is to compare a variety of comprehensive indicators for renal function evaluation and find out the most suitable one for early and accurate diagnosis of contrast induced nephropathy.Methods:168 patients who underwent PCI from January 2010 to July 2010 were involved, being excepted if with chronic infection, acute renal failure and contrast examination within 10 days. All patients were not taking nephrotoxic drugs. Of all 168 patients, 133 cases were male and 35 females, aged 33 to 84 years (mean 61.02±10.14 years). Blood testing of Scr and Cys-C were taken before and 8h,8h-24h,24h-48h after angiography. All 168 patients were divided into CIN group and Non-CIN group according to the presence and absence of contrast induced nephropathy (CIN) within 48h. SPSS13.0 statistical software was used for statistical analysis. One-factor analysis of variance(one-way ANOVA) was used for the multiple comparisons of measurement data. Analysis of variance was also used for the repeated measurement data. Chi-square test was used for comparison of enumeration data. ROC curve analysis was used to evaluate the diagnostic value of all indicators. Two-sided test was used and the size of a test a=0.05, P<0.05 indicated significant difference, P<0.01 indicated statistically significant difference.Results:1 General statisticsGeneral statistics analysis of all 168 patients were taken. Contrast induced nephropathy (CIN) was diagnosed if serum creatinine levels within 48h after the contrast examination were 25% or 0.5mg/dl higher than the baseline before the contrast examination, excluding other diseases of acute renal failure because of kidney damage factors. Finally, of all 168 patients,25 cases were diagnosed as CIN, and the incidence was 14.9%. The age, gender, incidence of hypertension and transfusion volume within 24h showed no significant difference between groups(P>0.05). In CIN group, the incidence of smoking, anemia(female Hb<110g/L, male Hb<120g/L), heart failure(EF<50%), renal failure(eGFR<60ml/min/1.73m2) and diabetes were significantly higher than that in non-CIN group (P<0.05).2 Logistic analysisLogistic analysis of some risk factors were taken to find out independent risk factors of CIN. The statistical model was statistically significant (χ2=27.855, P=0.000). Of all involed factors such as age, gender, hypertension, diabetes, smoking, anemia, heart failure and renal failure, anemia (OR=3.444, P=0.036), heart failure (OR=4.412, P=0.006), renal failure (OR=3.595, P=0.039) and diabetes (OR=3.938, P=0.028) were independent risk factors of CIN.3 Scr, Cys-C, eGFR-MDRD2, eGFR-Arnal-Dade levels during peri-PCI periodBlood testing of Scr and Cys-C were taken before and 8h,8h-24h,24h-48h after angiography. eGFR-MDRD2 was estimated by simpled MDRD estimating equation, and eGFR-Arnal-Dade was estimated by Cys-based Arnal-Dade estimating equation. The analysis of variance for the repeated measurement data of all 168 patients showed that the level of Scr decreased first within 8h after angiography, then increased 8h-24h after angiography, and up to peak 48h after angiography. Cys-C levels decreased first within 8h after angiography, then increased 8h-24h after angiography, and decreased again 24-48h after angiography. eGFR-MDRD2 levels increased first within 8h after angiography, then decreased 8h-24h after angiography, and down to minimum 48h after angiography. eGFR-Arnal-Dade levels increased first within 8h after angiography, then decreased 8h-24h after angiography, and increased again 24-48h after angiography. All 168 patients were divided into CIN group(n=25) and Non-CIN group(n=143) according to the presence and absence of contrast induced nephropathy (CIN) within 48h. Analysis of variance for repeated measurement data of patients in non-CIN group showed that the level of Scr decreased first within 8h after angiography, then increased 8h-24h after angiography, and up to peak 48h after angiography. Cys-C levels decreased first within 8h after angiography, then increased 8h-24h after angiography, and decreased again 24-48h after angiography. eGFR-MDRD2 levels increased first within 8h after angiography, then decreased 8h-24h after angiography, and down to minimum 48h after angiography. eGFR-Arnal-Dade levels increased first within 8h after angiography, then decreased 8h-24h after angiography, and increased again 24-48h after angiography. Analysis of variance for repeated measurement data of patients in CIN group showed that the level of Scr decreased first within 8h after angiography, then increased 8h-24h after angiography, and up to peak 48h after angiography. Cys-C levels decreased first within 8h after angiography, then increased 8h-24h after angiography, and decreased again 24-48h after angiography. eGFR-MDRD2 levels increased first within 8h after angiography, then decreased 8h-24h after angiography, and down to minimum 48h after angiography. eGFR-Arnal-Dade levels increased first within 8h after angiography, then decreased 8h-24h after angiography, and increased again 24-48h after angiography.4 AUCROC AnalysisAUCR Analysis was used to evaluate the diagnostic value of Scr and Cys-C levels increasement 8 hours,24 hours,48 hours after angiography,25% higher compared with that before angiography respectively. We compared the sensitivity and specificity and find that if 25% increasement of Cys-C level 24 hours after angiography than that before angiography was used as a predictor of contrast induced nephropathy, the sensitivity was 84%, superior to 52% of Scr.25% increasement of Cys-C level 24 hours after angiography compared with that before angiography was implied as a better predictor for earlier diagnosis of contrast induced nephropathy.Conclusions:(1)The incidence of CIN was 14.9%. (2)Anemia, renal failure, heart failure and diabetes were independent risk factors of CIN. (3) Cys-C levels after angiography increased up to peak earlier than Scr, implied that it can be used as a predictor of early diagnosis of CIN. (4) 25% increasement of Cys-C level 24 hours after angiography compared with that before angiography was implied as a better predictor for earlier diagnosis of contrast induced nephropathy, with the sensitivity 84%.