MDRD Equation Research Articles

INFLAMMATION IS ASSOCIATED WITH EXCESSIVE BODY ADIPOSITY IN NONDIALYSED CHRONIC KIDNEY DISEASE (CKD) PATIENTS

The purpose of this study was to evaluate inflammation in non-dialysed CKD patients with normal and high body adiposity level. One hundred and thirty four CKD patients (male: 56%; age=65±12 years) under treatment for 3.0±2.0 years were evaluated in a cross-sectional study. Glomerular filtration rate (eGFR) was estimated by MDRD equation. Body adiposity was assessed by BMI and total body fat (BF; dual-energy X-ray absorptiometry). Laboratorial measurements were: albumin, pro-inflammatory cytokines by Multiplexed analysis: tumor necrosis factor-α, interferon-γ, high sensitive C reactive protein, monocyte chemotactic protein, inteleukine 6 and 8, intercellular adhesion molecule-1 and vascular adhesion molecule-1. The inflammation status was defined according to the median values for each studied pro-inflammatory cytokines: negative for inflammation (Infl-) (< median), positive for inflammation (Infl+) (≥ median). The cytokines were compared between patients with normal BMI (<25kg/m 2 ) (46%; BMI=22.2±1.9) and high BMI (≥25kg/m 2 ) (BMI=28.8±2.8). Both groups showed similar eGFR and CKD stages distribution (stage 3:42%, 4: 37%, 5: 21%). BF and all cytokines were higher in high BMI group than in normal BMI (P<0.0001). BMI and BF were correlated ( r = 0.74; P<0.0001). The Infl+ condition was more prevalent, for all cytokines, in the high BMI group (range:61–76%) than in normal (24–38%). Multivariate logistic regression analysis, for all cytokines, showed that Infl+ condition was associated with high BMI (Odds Ratio range: 2.5–4.2; 95%CI: 1.1 - 9.6; P<0.01), even after adjusted for age, gender, diabetes and eGFR. In conclusion, CKD patients with high BMI and body adiposity are at higher risk for inflammation. Therefore, the excess of adiposity should be carefully treated in these patients.

Cystatin C May Better Reflect the Effect of Obesity on Renal Function

TO THE EDITOR: We read with interest an article by Naour et al. titled “Potential Contribution of Adipose Tissue to Elevated Serum Cystatin C in Human Obesity” (1). advocating the elevation of serum cystatin C (Scys) with adiposity. However, we would like to draw attention to some issues that needs to be carefully reviewed. First, in order to confirm the association between obesity and elevated Scys, the authors attempted to discriminate the influence of reduced renal function by estimating glomerular filtration rate (GFR) based on serum creatinine (Scr). The authors found the GFR values of the participants in the range associated with normal to moderately impaired renal function. According to the K/DOQI guidelines this range concerns stage 1–3 of chronic kidney disease (CKD) (2). At stage 3, we already have a markedly affected kidney function. However, the authors reported none of the subjects had stage 3–5 of CKD. Second, the authors showed that three subjects with very low estimated GFR ( 60 ml/min, in which MDRD equation is not precise to estimate GFR (3). Finally, to determine cystatin C gene expression and secretion in adipose tissue, the authors did not mention the current renal status of the subjects recruited from the gastric surgery program. In response to hypoxic stress, the adipocytes secrete proinflammatory cytokines and adipokines. These adipokines are linked to the genesis of insulin resistance, endothelial dysfunction, metabolic syndrome, all of which have been connected with CKD and may explain the link between adipose tissue and Scys (4). Elevated Scys may be associated with the presence of early signs of atherosclerotic and end-organ damages (5). Moreover, Scys may identify an early stage defined as “preclinical kidney disease”, in which it is associated with an increased risk of CKD progression and cardiovascular mortality, more than creatinine or estimated GFR (3). A few epidemiological studies have reported positive associations of Scys with BMI in different populations and stages of CKD (6,7). However, none of these studies have used the direct measurement of GFR which means they were unable to determine if there is a bias in the estimation of GFR using creatinineor cystatin C-based equations. By contrast, other studies using direct measurement of GFR have found no association of BMI with Scys, and strong association of age with Scys and renal function, even in healthy individuals (8–10). Currently, there is no concrete evidence that would link elevated Scys to human obesity and adiposity other than its correlation with GFR. Therefore, we disagree with the authors that cystatin C may be dependent of body fat composition. DIsclOsuRE The authors declared no conflict of interest.

HIGH BODY MASS INDEX (BMI) IS ASSOCIATED WITH ADIPOKINES AND INSULIN RESISTANCE IN NONDIALYSED CHRONIC KIDNEY DISEASE (CKD) PATIENTS

The aim of this study was to assess the association between body adiposity with adipokines and with insulin resistance in non-dialysed CKD patients. This is a cross-sectional study including CKD patients under regular treatment in an outpatient clinic. Glomerular filtration rate was estimated by MDRD equation (eGFR). The nutritional status was assessed by BMI, total body fat (BF; dual-energy X-ray absorptiometry), midarm muscle circumference and serum albumin. Laboratorial parameters included serum glucose, triglycerides; leptin and insulin (radioimmunoassay); high molecular weight adiponectin (HMWAdipo; ELISA). The insulin resistance was assessed by HOMA-IR. Data are expressed as mean + SD. One hundred and thirty four CKD patients (male=56%; eGFR= 29±13ml/min.; 65±12 years old) were included. None of the patients presented protein energy wasting and most of them had BMI≥25kg/m 2 (overweight/obese group: OwOb) ( n = 72; 54%). BMI was correlated with BF ( r = 0.74; p r = 0.58); HOMA-IR ( r = 0.36) and HMWAdipo ( r = −0.45). HOMA-IR was associated with leptin ( r = 0.28) and with HMWAdipo ( r = −0.29) (P In conclusion, BMI and BF were associated with increased leptin and HOMA-IR, but with decreased HMWAdipo. The OwOb CKD patients presented higher risk for metabolic and cardiovascular disorders.

Association of clofarabine (Clo)-associated GFR decline (GFRd) with dose and AUC.

e13120^ Background: Clo, a nucleoside analog, is approved for pediatric ALL, but also has activity in AML. We conducted a ph I-II trial of clo-melphalan-alemtuzumab for allo transplant and found grade 3-5 renal toxicity in 16 of 74 patients, despite prolonging infusion time to reduce Cmax (BBMT 2011, Epub). Methods: Clo pharmacokinetics were analyzed in 65 pts (Clo doses 10-40 mg/m2, infusion time 1 or 3 hrs) of 74 pts; baseline GFR estimated by modified MDRD equation. Clo levels were drawn at 1, 1.5, 2, 3, 5, 7, 9 and 24 hrs following the 1st and 3rd (or 4th) dose. GFRd (in ml/min/m2) between start of Clo (d-7) and day of transplant constituted the outcome of interest. Results: Median age 53 (21-73), median baseline GFR 94 ml/min/m2 (46-120). Mean (range) Cmax, clearance (CL) and AUC were 531 ng/ml (119-1010), 42002 ml/min (13979-88020) and 2052 ng*hr/ml (471-5835), respectively. Mean AUC per dose was 32.0 ng*hr/ml/mg (14-32). Systemic exposure was similar between d1 and d3. Further analyses used the highest AUC and Cmax. Decreases in GFR ranging from 10-100 ml/min/m2 (average 44 ml/min/m2) occurred in 30 of 65 patients. There was no correlation between Clo dose and GFRd (r=-0.02,p=0.87). There was a significant correlation between Clo AUC and GFRd (r=0.53, p &lt;0.0001), Clo AUC per dose and GFRd (r=0.62, p&lt;0.001) and between Clo CL and GRFd (r=-0.38, p=0.0001). There was a weaker correlation between Clo Cmax and GFRd (r=0.22, p=0.07). Clo CL was highly correlated with baseline GFR (r=0.4, p=0.0009). Of interest baseline GFR was inversely correlated with pt age (r=-0.46, p=0.0001) and age was significantly correlated with AUC (r=0.4, p=0.001), AUC per dose (r=0.36, p=0.003) and with GFRd (r=0.34, p=0.005). Conclusions: Decline in GFR is associated with inter-patient variability in exposure to Clo. Baseline GFR affects Clo CL and thus AUC, and potentially increases risk for renal toxicity. Older age is associated with decreased baseline GFR and risk for toxicity. Clo may require dose adjustment based upon renal function and/or age. These data require confirmation in further studies.

Toward More Accurate Detection and Risk Stratification of Chronic Kidney Disease

THE TERM CHRONIC KIDNEY DISEASE(CKD)WAS FIRST PROposedandsystematicallydefinedin2002,andthe5incrementalstages for thedegreeofseverityofCKDwere describedbasedontheestimatedglomerular filtration rate (GFR) (stage 1, 90; stage 2, 60-89; stage 3, 30-59; stage 4,15-29;andstage5, 15mL/min/1.73m).Stage1 is the least severeandstage5isclassifiedaskidneyfailure. Theestimated GFR (calculated from the Modification of Diet in Renal Disease [MDRD] Study equation) can be derived automatically from a single serum creatinine measurement, combined with theeasilyavailableageandsexdata,plusaqualifyingstatement on race, and without a need for patient weight. The automated estimated GFR calculation has rapidly becomearoutinecomponentofvirtually every laboratory report ofserumcreatinineconcentration.Thishasoccurredeventhough estimated GFR is not based on an accurate timed urine specimen, is only a rough estimate of a patient’s actual GFR, and is more applicable to the population than to the individual. An estimatedGFRlowerthan60mL /min/1.73m hasbeenflagged asindicatingmoderatetoseverekidneydisease andphysicians, followingtheguidelines,sometimesinformpatientsofthisfinding. The prevalence of CKD using the MDRD equation in nationally representative surveys has been estimated at 10% to 12% of the population, with CKD stage 3 (estimated GFR 3059mL/min/1.73m)comprisingthelargestcategory.Populationbasedstudieshaveconsistentlyreportedastrongandincremental association between CKD stages and risk of cardiovascular events and death, suggesting that an individual with low estimated GFR (ie, stage 3, 4, or 5) might be at increased risk. The use of the term “kidney” along with the new CKD staging and its expanded spectrum based on estimated GFR of less than 60 mL /min/1.73 m has increased awareness about and the apparent prevalence of a once underappreciated and confusingdisease state. Consequently,nephrologistshavehadan unprecedented increase in consultations to verify the diagnosis of “CKD stage 3 ” primarily because of a calculated estimatedGFRoflessthan60mL /min/1.73m.Manypatientswith thisallegeddiagnosisareanxiousuntil theyseeanephrologist, whereas thespecialist feels compelled,perhaps inpartbecause of concerns of litigation, to perform extensive and expensive workupstomoreaccuratelyassessrenal function.Someofthese patients have been stigmatized with a “preexisting condition” andhavebeendeniedinsurancecoverageuponreemployment. However, the diagnosis of stage 3 CKD for many patients cannot be substantiated other than with an estimated GFR of less than 60 mL /min/1.73 m according to the MDRD equation. Nephrologists have not adequately addressed the clinical and public health consequences of using the MDRD equation as a criterion for the detection and classification of CKD and have failed to acknowledge the many implications of the flaws in this approach. For instance, it is counterintuitive that more patients are classified as having stage 3 of a chronic disease than earlier stages, ie, stage 1 and 2 combined, in sharp contradistinction to other chronic disease states such as heart failure. The result has been that the nephrology community appears to have undermined its own important work in public health by overdiagnosing a nonexistent disease in millions of elderly persons as well as in women in whom the MDRD equation calculates a 25% worse kidney function by default, or in adults with larger muscle mass or other nutritional states associated with higher serum creatinine independent of kidney function. Use of the epidemiological classification of such an imperfect surrogate as estimated GFR does not square with the clinical reality of patient diagnosis and treatment. Many patients with so-called CKD stage 3 do not die of renal causes, and do not develop end-stage kidney disease over time, so there is a disconnect between classification based on estimated GFR equations and patients’ clinical course. At the same time, the diagnosis of true kidney disease may be missed in some persons with lower serum creatinine levels due to smaller skeletal muscle mass, low or no protein intake, or significant glomerular, tubular, or vascular kidney disease but with higher estimated GFR. As a result, and despite the overwhelming data on the association of kidney disease with cardiovascular events and death, the cardiology community has generally not considered CKD based on estimated GFR alone as a credible cardiovascular risk fac-

Comparison of prediction equations to estimate glomerular filtration rate in Chinese patients with chronic kidney disease

We sought to evaluate the applicability of formulae based on serum creatinine (SC) levels in Chinese patients with chronic kidney disease (CKD). Three hundred and twenty-seven patients with CKD who had undergone (99m) Tc-DTPA glomerular filtration rate (GFR) estimation were enrolled. The Cockcroft-Gault equation, SC-reciprocal equation, Gate equation, Hull equation, Jelliffe-1973 equation, Jelliffe-1971 equation, Mawer equation, Bjornsson equation, reexpressed 6-variable MDRD equation and reexpressed 4-variable MDRD equation were compared. Using the (99m) Tc-DTPA GFR as the standard GFR (sGFR), the accuracy of estimated GFR was compared with sGFR in various stages of CKD. Median per cents of the absolute difference ranged from 28.16% to 39.39%, accuracy with a deviation less than 30% ranging from 39.4% to 53.5%, accuracy with a deviation less than 50% ranging from 63.0% to 80.7%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from sGFR. Bland-Altman analysis demonstrated that mean difference ranged from -2.42 to 16.39 mL/min/1.73 m(2), whereas precision ranged from 82.66 to 106.15 mL/min/1.73 m(2). However, the agreement limits of all the equations exceeded the prior acceptable tolerances defined as 60 mL/min/1.73 m(2). Linear regression showed that the slopes of regression line ranged from 0.37 to 0.54 and intercepts ranged from -12.10 to 3.86. When the overall performance as well as bias and accuracy were compared in different stages of CKD, GFR estimated by Jelliffe-1973 equation, Cockcroft-Gault equation and Bjornsson equation showed promising results. When SC was measured by the enzymatic method, GFR estimation equations showed great bias in Chinese CKD patients. At present, the Jelliffe-1973 equation and Cockcroft-Gault equation may be more accurate in the Chinese ethnic group.

Assessing Renal Function Using Cockcroft-Gault and Modification of Diet in Renal Disease Equations in Healthy South Indian Males – A pilot study

Objective: To compare the estimated GFR (eGFR) calculated by CG and MDRD formulae and to study the correlation between body mass index (BMI) and eGFR in healthy South Indian men. Material &amp; Methods: Healthy male volunteers were enrolled. eGFR was estimated by CG and MDRD equation and categorized as normal, mild, moderate, severe renal impairment and renal failure. Estimated clearance by these two methods was compared using paired student’s t test. Correlations were performed with pearson’s correlation test. Results: A total of 491 subjects were enrolled. Mean (±SD) eGFR was 91.05 (± 15.04) and 86.43 (± 13.61) by CG and MDRD equations respectively; this difference though statistically significant (p=0.01), was clinically insignificant. A reduced renal function (&lt;90ml/min) was found in 50.9% and 63.1% of population by CG and MDRD formulae respectively. BMI positively correlated with CG-GFR (r=0.471, p&lt;0.001), and negatively correlated with MDRD-GFR (r=-0.268, p&lt;0.001). Serum creatinine positively correlated with BMI (r=0.19, p&lt;0.001). Conclusion: The normal eGFR seems to be lower in the South Indian population compared to the western standards. CG and MDRD formulae may need to be validated before these can be applied for staging of kidney function in a healthy Indian population. DOI: http://dx.doi.org/10.3126/ajms.v2i3.5337 Asian Journal of Medical Sciences 2 (2011) 185-189

1289 COMPARISON OF CO-MORBIDITY AT BASELINE AND RENAL FUNCTION OUTCOME IN PATIENTS WITH NEPHRECTOMY FOR RENAL MASSES AND MATCHED LIVING RENAL DONORS

You have accessJournal of UrologyKidney Cancer: Localized II1 Apr 20121289 COMPARISON OF CO-MORBIDITY AT BASELINE AND RENAL FUNCTION OUTCOME IN PATIENTS WITH NEPHRECTOMY FOR RENAL MASSES AND MATCHED LIVING RENAL DONORS Miki Hew, Dedan Opondo, Ernesto Cordeiro, Frederike Bemelman, Mirza Idu, Jean de la Rosette, and Pilar Laguna Miki HewMiki Hew Amsterdam, Netherlands More articles by this author , Dedan OpondoDedan Opondo Amsterdam, Netherlands More articles by this author , Ernesto CordeiroErnesto Cordeiro Amsterdam, Netherlands More articles by this author , Frederike BemelmanFrederike Bemelman Amsterdam, Netherlands More articles by this author , Mirza IduMirza Idu Amsterdam, Netherlands More articles by this author , Jean de la RosetteJean de la Rosette Amsterdam, Netherlands More articles by this author , and Pilar LagunaPilar Laguna Amsterdam, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1623AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nephrectomy for renal cell carcinoma (RCC) or kidney donation can lead to chronic kidney disease (CKD), however in the literature this is less often seen in donors. Objectives were to quantify differences in co-morbidities and baseline renal function between patients with nephrectomy for RCC and renal living donors matched for age and sex. To asses postoperative differences in renal function and define predictors for new onset of glomerular filtration rate (GFR) below 60 ml/min/1.73m2. METHODS Patients between 18 and 75 years who underwent radical nephrectomy (RN) from Jan. 2000 through Jul. 2011 for localized RCC with a normal contra lateral kidney were matched by age and sex to kidney donors from the same period. Charlson co-morbidity index and incidence of hypertension, diabetes and cardiovascular diseases (CVD) were compared between groups with Chi-Square tests. Renal function was estimated using the MDRD formula and compared preoperative and 1 year after nephrectomy using the independent samples T-test. Logistic regression was used to asses predictive factors for new onset of GFR below 60 ml/min/1.73m2. RESULTS Each group contained 98 patients, mean age was resp. 60.6±9.9 and 59.5±9.2 years for RCC and donor group. Charlson score>2 was more frequent in RCC patients (23(23.5%) vs. 2(2%), p<0.001). Incidences of hypertension (36 (36.7%) vs. 22 (22.4%), p=0.03), diabetes (10(10.2%) vs. 0, p=0.001) and CVD (22(22.4%) vs. 3(3.1%), p<0.001) were higher in RCC compared to donor group. Preoperative GFR in RCC group was 84.9±21.2 and 91.8±14.7 ml/min/1.73m2 in donors (p=0.009). For renal function changes see table 1. New onset of GFR below 60ml/min/1.73m2 was only predicted by preoperative renal function (OR=0.87; 95%CI: 0.82-0.92; p<0.001). Table 1. One year postoperative renal function and changes compared to baseline renal function. Renal function was by estimated glomerular filtration rate (eGFR) using the MDRD equation. All variables are reported as mean± stand 1 year postoperative: RCC patients Donor patients p-value serum creatinine (μmol/L) 116.1±37.0 115.2±18.8 0.87 eGFR MDRD (ml/min/1.73m2) 57.4±16.3 55.2±10.1 0.37 % change eGFR (compared to baseline) 31.7±15.4% 39.0±7.9% 0.001 CONCLUSIONS Patients undergoing RN for suspicion of RCC had higher baseline co-morbidity load and lower baseline renal functions compared to patients with similar age and gender ratio who underwent donor nephrectomy. Conversely renal functions 1 year postoperative were comparable between both groups. Kidney donors had at least similar loss in renal function compared to RCC patients. Only baseline renal function predicted development of GFR below 60 ml/min/1.73m2. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e522-e523 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Miki Hew Amsterdam, Netherlands More articles by this author Dedan Opondo Amsterdam, Netherlands More articles by this author Ernesto Cordeiro Amsterdam, Netherlands More articles by this author Frederike Bemelman Amsterdam, Netherlands More articles by this author Mirza Idu Amsterdam, Netherlands More articles by this author Jean de la Rosette Amsterdam, Netherlands More articles by this author Pilar Laguna Amsterdam, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Chronic kidney disease and the risk of stent thrombosis after percutaneous coronary intervention with drug‐eluting stents

Chronic kidney disease (CKD) has been demonstrated to be associated with adverse clinical outcomes for patients with coronary artery disease (CAD). However, data on relation of CKD and stent thrombosis (ST) after drug-eluting stent (DES) implantation are limited. This study was designed to examine whether CKD is associated with higher incidence of ST after elective coronary DES implantation compared with patients with normal renal function. We consecutively enrolled 2,862 patients undergoing elective percutaneous coronary intervention (PCI) with DES. Demographic and clinical data were collected preoperatively. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min, calculated using the modified MDRD equation. The primary outcome was 1-year definite or probable ST. Four hundred and forty-five participants (15.5%) had CKD before procedure. The incidence of 1-year definite or probable ST was significantly higher in CKD patients compared with patients with normal renal function (1.8% vs. 0.6%, P = 0.014). After adjustment for multiple clinical and biochemical covariates, CKD was an independent predictor of 1-year definite or probable ST (hazard rate [HR] 0.396, 95% CI 0.165-0.951, P = 0.038). CKD is significantly associated with increased incidence of 1-year definite or probable ST in patients undergoing PCI with DES.

Abstract P099: The Relation of Kidney Disease to Measures of Digital Arterial Tonometry in the Jackson Heart Study

Background: The presence of chronic kidney disease is greater in African Americans than in non-Hispanic whites. Though there is data to show a relation between endothelial dysfunction and end-stage kidney disease, the relation to mild and moderate chronic kidney disease (particularly in African Americans) is unclear. Methods and Results: Digital arterial tonometry was performed during Exam 2 and 3 of the Jackson Heart Study using the endoPAT2000. Data from digital arterial tonometry included baseline pulse wave amplitude (BPA) as a measure of endothelial tone and reactive hyperemic index (F-RHI) as a measure of endothelial function. For this study, the estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation. Those participants with eGFR &lt; 60 ml/min/1.73m2 were defined as having CKD. Participants with eGFR &lt; 15 ml/min/1.73m2 were excluded from the analysis. Microalbuminuria in this study was defined as a urinary albumin:creatinine ratio ≥ 17mg/g in men and ≥ 25 mg/g in women. We compared the differences in least square means adjusted for age and sex, and adjusted for multiple traditional clinical covariates using a generalized linear model. Results: There were 834 participants in the study population (mean age 58.5 years, 61% women); 87 (10.4%) participants with CKD and 108 (13.0%) with microalbuminuria. In age and sex adjusted samples, we found that both BPA and F-RHI were significantly associated with CKD in the pooled samples. However in multivariable adjusted analysis the relation was no longer significant in either the pooled or sex-specific samples. In the multivariable adusted analysis,BPA was significantly (P=0.036) associated with microalbuminuria in men and F-RHI was weakly significantly (P=0.08) associated with microalbuminuria in women. Conclusion: We found that endothelial dysfunction as measured by digital arterial tonometry is not significantly associated with chronic kidney disease. There is an association of endothelial tone in men and endothelial dysfunction in women with microalbuminuria.

The Influence of Body Size Descriptors on the Estimation of Kidney Function in Normal Weight, Overweight, Obese, and Morbidly Obese Adults

Dosing adjustments for patients with impaired kidney function are often based on estimated creatinine clearance (eCrCl) because measuring kidney function is not always possible for dose adjustment. However, there is no consensus on the body size descriptor that should be used in the estimation equations. To compare the use of alternative body size descriptors (ABSDs) on the performance of kidney function estimation equations compared with measured CrCl (mCrCl). We combined 2 a Food and Drug Administration clinical trial database that includes subjects with body mass index (BMI) less than 40 kg/m(2) and published data from those 40 kg/m(2) or more. The 3 parent equations (Cockcroft-Gault [CG], Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease-Epidemiology Collaboration [CKDEPI]), and 14 ABSD-modified equations were compared with mCrCl for accuracy, bias, agreement, goodness of fit (R(2)), and prediction error. These equations were also compared across mCrCl and BMI strata. Subjects (n = 590) were aged 19-80 years; 33.9% were female and BMI ranged from 17.2 to 95.6 kg/m(2). Compared with mCrCl, the use of total weight in the CG equation yielded low accuracy (12.5%) and significant bias (-107 mL/min) in the morbidly obese group. In contrast, the use of lean body weights (BMI ≥40 kg/m(2)) and total ± adjusted weights (BMI <40 kg/m(2)) with the CG equation yielded higher accuracy, greater than or equal to 60.7% across all BMI strata, and was unbiased. Transforming the MDRD or CKDEPI equations with body surface area improved accuracy only at mCrCl of 30-80 mL/min and increased the overall prediction error. No kidney function equation was consistently accurate and unbiased across weight, mCrCl, and estimate ranges. The accuracy and overestimation bias of the CG equation in obese subjects was improved through the selective use of total, adjusted, and lean body weight by BMI strata.

Left ventricular hypertrophy and geometry in type 2 diabetes patients with chronic kidney disease. An echocardiographic study.

We assessed left ventricular structural alterations associated with chronic kidney disease (CKD) in Congolese patients with type 2 diabetes. This was a cross-sectional study of a case series. We obtained anthropometric, clinical, biological and echocardiographic measurements in 60 consecutive type 2 diabetes patients (37 females, 62% ) aged 20 years or older from the diabetes outpatient clinic, University of Kinshasa Hospital, DRC. We computed creatinine clearance rate according to the MDRD equation and categorised patients into mild (CrCl > 60 ml/min per 1.73 m(2)), moderate (CrCl 30-60 ml/min per 1.73 m(2)) and severe CKD (< 30 ml/min per 1.73 m(2)). Left ventricular hypertrophy (LVH) was indicated by a LV mass index (LVMI) > 51 g/m(2.7) and LV geometry was defined as normal, or with concentric remodelling, eccentric or concentric hypertrophy, using relative wall thickness (RWT) and LVMI. Compared to patients with normal kidney function, CKD patients had higher uric acid levels (450 ± 166 vs 306 ± 107 µmol/l; p ≤ 0.001), a greater proportion of LVH (37 vs 14%; p ≤ 0.05) and longstanding diabetes (13 ± 8 vs 8 ± 6 years; p ≤ 0.001). Their left ventricular internal diameter, diastolic (LVIDD) was (47.00 ± 6.00 vs 43.00 ± 7.00 mm; p ≤ 0.001), LVMI was (47 ± 19 vs 36.00 ± 15 g/m2.7; p ≤ 0.05) and proportions of concentric (22 vs 11%; p ≤ 0.05) or eccentric (15 vs 3%; p ≤ 0.05) LVH were also greater. Severe CKD was associated with increased interventricular septum, diastolic (IVSD) (12.30 ± 3.08 vs 9.45 ± 1.94 mm; p ≤ 0.05), posterior wall thickness, diastolic (PWTD) (11.61 ± 2.78 vs 9.52 ± 1.77 mm; p ≤ 0.01), relative wall thickness (RWT) (0.52 ± 0.17 vs 0.40 ± 0.07; p ≤ 0.01) rate of LVH (50 vs 30%; p ≤ 0.05), and elevated proportions of concentric remodelling (25 vs 15%; p ≤ 0.05) and concentric LVH (42 vs 10%; p ≤ 0.05) in comparison with patients with moderate CKD. In multivariable adjusted analysis, hyperuricaemia emerged as the only predictor of the presence of LVH in patients with CKD (adjusted OR 9.10; 95% CI: 2.40-33.73). In keeping with a higher rate of cardiovascular events usually reported in patients with impaired renal function, CKD patients exhibited LVH and abnormal LV geometry.

The estimation of glomerular filtration rate in an Australian and New Zealand cohort

Accurate estimation of glomerular filtration rate (GFR) allows early detection of renal disease and maximizes opportunity for intervention. To assess the accuracy of estimated GFR (eGFR) in an Australian and New Zealand cohort with chronic kidney disease using the 4-variable Modification of Diet in Renal Disease equation (MDRD(4V)), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and the Cockcroft and Gault equation with actual and ideal body weight. Retrospective review of patients who had measured GFR (mGFR) by 51Cr-EDTA clearance and simultaneous measurements of serum biochemistry and anthropometrics. eGFR was compared with mGFR using the concordance correlation coefficient (CCC) and Bland-Altman measures of agreement. 178 patients had 441 radioisotope measurements of GFR. Mean mGFR of was 22.6 mL/min per 1.73 m(2) . The MDRD(4V) equation using the 'black' correction factor was most accurate with a mean eGFR of 19.74 (CCC 0.733, bias -2.86). The CKD-EPI equations also using the 'black' correction factors were almost as good at 19.11 (CCC 0.719, bias -3.49). The Cockcroft-Gault creatinine clearance values had the poorest agreement with mGFR. In the 18 nonwhite non-Asian patients, the MDRD(4V) and CKD-EPI equations were generally less accurate although the use of the 'black' correction factor resulted in greater accuracy for both equations. The MDRD(4V) equation was the most accurate. However, its accuracy might be less for nonwhite non-Asian patients if the 'black' correction factor is omitted. Further study of the estimation of GFR in Australian and New Zealand ethnic subgroups would be helpful.

Maladies rénales : les nouveaux enjeux

Chronic kidney disease (CKD) affects two to four million people in France and most of them are not aware of their disease. CKD is a major, independent risk factor of cardiovascular mortality and morbidity; the cardiovascular risk increases with the severity of renal failure. Evaluation of renal function (GFR) relies on MDRD and CKD-EPI equations. The French CKD-REIN cohort with more than 3000 patients followed for 5 years, will hopefully provide substantial advances in the knowledge of CKD epidemiology, of risk factors and mechanisms of CKD progression and medical practices. Improving CKD screening based on blood pressure, proteinuria (microalbuminuria in diabetic patients) and serum creatinine, is a national duty in high risk patients (with diabetes, hypertension and cardiovascular diseases). A major research goal is to identify new therapeutic targets and biomarkers, in order to treat kidney diseases before the occurrence of renal insufficiency, to halt their progression and to decrease cardiovascular risk. Careful therapeutic education of patients is required to successfully implement established guidelines, appropriate diets and new therapeutic strategies.

How do laboratory specialists advise clinicians concerning the use and interpretation of renal tests?

Background. The aim of this study was to elucidate how laboratory specialists advise clinicians concerning renal parameters and to compare their advice with guideline recommendations. Methods. A questionnaire was distributed to laboratory specialists in Norway and The Netherlands together with two case histories from a primary health-care setting and one from a hospital setting, simulating questions from clinicians. The investigations that laboratory specialists suggested were compared to a test panel that was predefined based on clinical practice guideline recommendations (the ‘recommended test panel’). The critical differences between two test results (creatinine, estimated glomerular filtration rate [eGFR] and albumin/creatinine ratio [ACR]) and the anticipated precision of the MDRD equation were evaluated. Results. Fifty-two of the 100 laboratory specialists responded, and most of these were regularly contacted by clinicians to discuss laboratory results. Less than 30% would suggest using the recommended test panel to evaluate renal function in the two primary-care patients. For creatinine and eGFR, median changes stated to signal improvement or deterioration in renal function (creatinine: −14% and +14%, respectively; eGFR: + 18% and −13%, respectively) were similar to what could be calculated using information on analytical and within-subject variation from the literature. There were variable critical differences for the ACR results (median values of −50% for improvement and + 67% for deterioration). Only 23% of the participants would recommend a gold standard clearance examination for a patient who was to undergo nephrotoxic chemotherapy. Conclusion. Questions from GPs about renal parameters are answered differently by laboratory specialists, and adherences to guideline recommendations are low on some issues.

Prevalence of Chronic Kidney Disease and Its Association with Risk Factors in Disadvantageous Population

The prevalence of kidney disease, particularly diabetic and hypertensive kidney disease is increasing rapidly specially in the disadvantageous group of population throughout the world. A cross sectional survey was carried out at certain selected slum areas of Mirpur in Dhaka city of Bangladesh over the period from July 2003 to June 2005, and a total of participants ranging from 15 to 65 years were studied. The analysis discovered that 4.1% of the participants were diabetic, 11.6% were hypertensive, and 7.7% had proteinuria. Based on MDRD equation, 13.1% of the participants were detected as having chronic kidney disease (CKD) while with Cockcroft-Gault equation 16% had CKD. Accordingly, the difference between the two equations was not significant. Association of sociodemographic factors with CKD was not significant except age more than 40 years and marital status. The association between CKD and risk factors like proteinuria, obese and overweight, use of tobacco, diabetes mellitus, and hypertension was highly significant. Combined prevalence of DM, hypertension, and proteinuria among CKD group was also demonstrated to be significantly higher (3.8% with Cockcroft-Gault equation and 5.3% with MDRD equation) than that of normal population. The survey data revealed that CKD and its risk factors like DM and hypertension are alarmingly high in disadvantageous population and adding further pressure to the existing burden of CKD.

Long-Term Outcomes of Percutaneous Coronary Intervention (PCI) in Octogenarians with Chronic Kidney Disease

Background: Few studies have examined the long-term outcomes of percutaneous coronary intervention (PCI) in octogenarians (>80 years old) with chronic kidney disease (CKD). The aim of this study was to evaluate the long-term outcomes of octogenarians with CKD (eGFR < 60mL/min/1.73m2) undergoing PCI in our hospital. Methods: Retrospective data was collected for 319 consecutive patients who underwent PCI during January 2003 to December 2009. Patients were stratified on the presence of CKD (n=143) or no CKD (n=176) as defined by estimated GFR using the MDRD equation and followed for a mean of 33 months. The CKD group had higher rates of diabetes mellitus (40.4% versus 23.4%, p= <0.05), hypertension (98.6% versus 93.8%, p= <0.05), and peripheral vascular disease (19.6% versus 8.5%, p= <0.05). Other characteristics were similar among the groups. The primary outcome of the study was to compare the in-stent restenosis in octogenarians with and without CKD. All cause mortality and bleeding events post stenting were also compared.Results: A total of 59 patients developed in-stent restenosis: 16.6 % (n=29) in non CKD [17.3% with BMS (Bare metal Stents) and 14.3 % with DES (Drug Eluting Stents)] and 21 % (n=30) in the CKD group (22.8% with BMS and 16.7 % with DES) (P=0.31). There was no association of stent type and all cause death in either group; all cause death was significantly higher in the CKD patients. There was no significant difference in bleeding complications in CKD compared with non CKD groups (11.4% versus 10.5%, p= 0.85). However, CKD patients on aspirin and clopidogrel had a significantly higher incidence of bleeding (60% versus 40%, p=<0.001). Conclusion: As previously shown, CKD patients have a higher mortality than those without kidney disease. Long-term outcomes of BMS are comparable to DES in octogenarians with CKD. BMS may be preferable in CKD patients in order to avoid prolonged dual anti-platelet therapy with its attendant higher risk of bleeding in this group.

Cardiac troponin I and creatine kinase MB isoenzyme in patients with chronic renal failure.

The aim of our study was to evaluate cut-off values for acute coronary syndrome (ACS) diagnosis in patients with chronic renal failure (CRF) for the cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK-MB) as compared to the cut-off values proposed by the manufacturers and those frequently used in the laboratory. We performed a prospective study in patients with CRF with a glomerular filtration rate estimated by the MDRD-4 equation <60 mL/min and admitted with suspected acute coronary syndrome due to clinical history, physical examination, and electrocardiography. cTnI and CK-MB measurements were assessed upon hospitalisation and six months later using two different analytical methods (for cTnI: Access® and Vidas® analysers, and for CK-MB: Access® and Vitros® analysers). During the study period, 484 patients with CRF and suspected ACS were assessed. ACS was diagnosed in 12% of patients (58/484), while we found other cardiac pathologies (OCP) in 29% of patients (140/484) and other non-cardiac pathologies (ONCP) in 59% of patients (286/484). For cTnI assessed using the Access® analyser with the usual cut-off value (≥ 0.5 ng/mL), sensitivity was 43% and specificity was 94%, while for the proposed cut-off value (≥ 0.11 ng/mL), the values were 68% and 83%, respectively. For cTnI assessed using the Vidas® analyser with the usual cut-off value (≥ 0.11 ng/mL), sensitivity was 64% and specificity was 87%, while for the proposed cut-off value (≥ 0.06 ng/mL), the values were 75% and 79%, respectively. The sensitivity and specificity for both CK-MB were lower compared with cTnI. The cut-off values proposed in this study for both cTnI in patients with CRF (stage 3 to 5) to diagnose ACS are significantly different from that of the general population.

Gender Difference in the Association of Hyperuricemia with Chronic Kidney Disease in Southern China

Background: The effect of hyperuricemia on chronic kidney disease (CKD) is controversial, and little is known about gender as it relates to hyperuricemia and CKD. Methods: This was a cross-sectional study of 7,053 adults in the general Chinese population in Southern China using a multi-stage stratified sampling method. In which associations between hyperuricemia and indicators of CKD (defined by albuminuria (urinary albumin-to -creatinine ratio ≥ 30mg/g) or decreased modified MDRD equation estimated GFR (<60ml/min per 1.73m²) were tested using multivariate logistic regression. Results: After adjustment for potential confounders, hyperuricemia was associated with increased risk of reduced renal function and CKD but not albuminuria, with odds ratios (ORs) (95% CI) of 4.39 (3.38-5.70, P <0.001), 1.54 (1.31-1.82, P <0.001) and 0.96 (0.78-1.17, P =0.671), respectively. The interaction between gender and hyperuricemia with CKD was significant (P =0.010); and stratified analysis showed a stronger association of hyperuricemia with CKD in males (OR (95% CI): 2.04 (1.56-2.67), P <0.001) than in females (1.45 (1.17-1.80), P =0.001). Conclusions: We observed an independent association of hyperuricemia with CKD that was stronger in males, and this independent association in male might imply some gender specific mechanisms. These results should be confirmed in future prospective studies.

Estimation of renal function in lung cancer patients

IntroductionIn lung cancer patients treated with chemotherapy, renal function is an important parameter to be monitored. Since measurement of renal function with either isotope or creatinine clearance is time consuming and expensive, we evaluated which of the following equations: Cockcroft–Gault (CG), Wright, modification of diet in renal disease equation (MDRD), MDRD adjusted for body surface area (BSA) and chronic kidney disease epidemiology collaboration (CKD-EPI) best resembles endogenous creatinine clearance (ECC) and could therefore replace its measurement in clinical practice. Methods218 lung cancer patients, who had their 24-h creatinine secretion in urine measured prior to the start of any chemotherapy, were included. Estimation of renal function was calculated and compared to ECC. ResultsThere were no major differences in the performance of the tested equations. Mean percentage error of more than 20% and general underestimation was common to all equations. Wright equation performed best although it describes only 43% of ECC variability. Mean measured ECC was 94mL/min (95% confidence interval [CI]: 90–98mL/min) and 90mL/min for Wright equation (95% CI: 87–93mL/min) (Supp. Fig. 3). MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. Large deviations of differences were observed, with a median standard deviation of more than 20% and deviations from ECC exceeding 100%. Wright equation performed best, whereas, despite their leading role in the detection of renal diseases, the MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. In the range of ECC<50mL/(min×1.73m2), the CG equation most often detected a contraindication for cisplatin use. Differences between ECC and calculated values correlated with patients’ weight, BSA and body mass index when these were not included in the equation itself. ConclusionsIn evaluating the renal function of lung cancer patients, equations adjusted for body size descriptors should be preferred. Estimated renal function should be interpreted against the characteristics of patient's body size and special attention is needed when these are reaching the extremes.