Ayub Akbari

Guidelines for the management of chronic kidney disease

New guidelines for the management of chronic kidney disease have been developed by the Canadian Society of Nephrology (Appendix 1 contains the full-text guidelines; available at [www.cmaj.ca/cgi/content/full/179/11/1154/DC1][1]). These guidelines describe key aspects of the management of chronic

Estimating Glomerular Filtration Rate in Kidney Transplantation: A Comparison between Serum Creatinine and Cystatin C–Based Methods

Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients. Although not accurate in renal transplantation, GFR is often estimated using creatinine-based equations. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. Equations to predict GFR based on the serum cystatin C concentration have been developed, but their accuracy in transplantation is unknown. GFR was estimated using four equations (Filler, Le Bricon, Larsson, and Hoek) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients. GFR was measured using radiolabeled diethylenetriaminepentaacetic acid (99mTc-DTPA), and the bias, precision, and accuracy of each equation were determined. The mean (99m)Tc-DTPA GFR was 58 +/- 23 ml/min per 1.73 m(2). The cystatin C-based equations of Filler and Le Bricon had the lowest bias (-1.7 and -3.8 ml/min per 1.73 m2), greatest precision (11.4 and 11.8 ml/min per 1.73 m2), and highest accuracy (87 and 89% within 30% of measured GFR, respectively). The cystatin C equations remained accurate even when the measured GFR was >60 ml/min per 1.73 m2. The creatinine-based equations were not as accurate, with only 53 to 80% of estimates within 30% of measured GFR. Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatinine-based equations. Further prospective studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function.

Pregnancy outcomes in women with chronic kidney disease: a systematic review.

BACKGROUND AND OBJECTIVES Pregnant women with chronic kidney disease (CKD) are at risk of adverse maternal and fetal outcomes. We conducted a systematic review of observational studies that described this risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched several databases from their date of inception through June 2010 for eligible articles published in any language. We included any study that reported maternal or fetal outcomes in at least five pregnant women in each group with or without CKD. We excluded pregnant women with a history of transplantation or maintenance dialysis. RESULTS We identified 13 studies. Adverse maternal events including gestational hypertension, pre-eclampsia, eclampsia, and maternal mortality were reported in 12 studies. There were 312 adverse maternal events among 2682 pregnancies in women with CKD (weighted average of 11.5%) compared with 500 events in 26,149 pregnancies in normal healthy women (weighted average of 2%). One or more adverse fetal outcomes such as premature births, intrauterine growth restriction, small for gestational age, neonatal mortality, stillbirths, and low birth weight were reported in nine of the included studies. Overall, the risk of developing an adverse fetal outcome was at least two times higher among women with CKD compared with those without. CONCLUSIONS This review summarizes current available evidence to guide physicians in their decision-making, advice, and care for pregnant women with CKD. Additional studies are needed to better characterize the risks.

The Effect of Pentoxifylline on Proteinuria in Diabetic Kidney Disease: A Meta-analysis

BACKGROUND Pentoxifylline is a potential therapeutic agent for diabetic kidney disease because it has anti-inflammatory, antifibrotic, and hemorheological properties. STUDY DESIGN Systematic review and meta-analysis of randomized controlled trials. SETTING, POPULATION, & INTERVENTION Adult patients with diabetic kidney disease who received oral pentoxifylline. SELECTION CRITERIA FOR STUDIES We searched bibliographic databases for trials involving pentoxifylline that reported proteinuria, glomerular filtration rate, or blood pressure. OUTCOMES The primary outcome measure was the effect of pentoxifylline on proteinuria stratified by whether pentoxifylline was compared with renin-angiotensin system blockade. RESULTS 10 studies including a total of 476 participants with a median duration of 6 months were identified. Pentoxifylline significantly decreased proteinuria (weighted mean difference, -278 mg/d of protein; 95% confidence interval [CI], -398 to -159; P < 0.001) compared with placebo or usual care. Compared with captopril, the decrease in proteinuria with pentoxifylline was similar (weighted mean difference, 0 mg/d of protein; 95% CI, -17 to 18; P = 0.9). Secondary analysis showed that patients with microalbuminuria had a nonsignificant decrease in protein excretion (weighted mean difference, -87 mg/d; 95% CI, -201 to 27; P = 0.1), whereas those with overt proteinuria (protein > 300 mg/d) had a significant decrease (weighted mean difference, -502 mg/d; 95% CI, -805 to -198; P = 0.001). No significant changes in systolic or diastolic blood pressure or glomerular filtration rate were found. LIMITATIONS Quality scores of studies were low, and there was significant heterogeneity. CONCLUSIONS Available evidence suggests that pentoxifylline may decrease proteinuria in patients with diabetic nephropathy. To confirm these findings, large high-quality studies are required.

When laboratories report estimated glomerular filtration rates in addition to serum creatinines, nephrology consults increase

Serum creatinine alone can be difficult to interpret as a measure of kidney function such that chronic kidney disease might be under-recognized in the general population. In the province of Ontario, Canada, all outpatient laboratories now report estimated glomerular filtration rate (eGFR) in addition to serum creatinine. To determine the impact of this reporting on clinical practice, we linked health administrative data for more than 8 million adults of age 25 years or older over an almost 10-year period and conducted a population-based intervention analysis with seasonal time-series modeling to determine overall trends in the number and type of patients seen by nephrologists. Compared to the period when only serum creatinines were reported, the number of patients seen in consultation by nephrologists increased after eGFR reporting by an average of 24% (an absolute increase of 2.9 consults per 100,000 adults), an increase of about 23 consults per nephrologist per year. The greatest increases were seen in women (39% increase) and those 80 years of age and older (58% increase). Our study found that eGFR reporting was associated with a sudden increase in the number of nephrology consults. However, it remains to be seen whether the routine reporting of eGFR results in improved treatment and outcomes for those with chronic kidney disease.

Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review

BACKGROUND Glomerular filtration rate (GFR) commonly is estimated in kidney transplantation by using creatinine-based estimation equations. The performance of these equations in kidney transplant recipients is unclear, with conflicting results between studies. STUDY DESIGN Systematic review. SETTING & POPULATION Stable adult kidney transplant recipients more than 6 months posttransplantation. SELECTION CRITERIA Reporting of or ability to calculate from available data the GFR estimation equation bias (mean difference between measured GFR and estimated GFR) and percent accuracy (percentage of GFR estimates within 10%, 20%, or 30% of measured GFR). INDEX TESTS Creatinine-based GFR estimation equations (Cockcroft-Gault, 6-variable Modification of Diet in Renal Disease [MDRD] Study, 4-variable MDRD Study, and Nankivell). REFERENCE TESTS GFR determination using plasma or renal clearance of inulin, radioisotopes, or nonradiographic contrast. RESULTS The search yielded 23 studies. For the 4-variable MDRD Study equation, bias ranged from -11.4 to +9.2 mL/min/1.73 m(2) (0.15 mL/s/1.73 m(2)). Only 76% of estimates were within 30% of measured GFR. For the Cockcroft-Gault equation, bias ranged from -4.0 to +16 mL/min/1.73 m(2) and 73% of estimates were within 30% of measured GFR. For the Nankivell equation, bias ranged from -1.4 mL/min to 36.3 mL/min with a 30% accuracy of only 68%. LIMITATIONS This review is limited by the inability to pool bias data, lack of calibration of serum creatinine in the majority of studies, and inclusion of nonindependent observations in many studies. CONCLUSIONS Differences in patient populations, baseline GFRs of the study group, reference standard GFR used, and creatinine assay calibration likely account for the heterogeneity in results. These factors need to be considered by investigators and clinicians when interpreting estimates of GFR in kidney transplant recipients.

Estimating Glomerular Filtration Rate in Kidney Transplantation: Is the New Chronic Kidney Disease Epidemiology Collaboration Equation Any Better?

BACKGROUND The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients (KTRs) is unknown. METHODS We used the plasma clearance of (99m)Tc-diethylenetriamine pentaacetic acid to measure the GFR in a cohort of 207 stable KTRs and estimated the GFR with the new CKD-EPI equation. RESULTS The mean bias for the CKD-EPI equation of -4.5 mL x min(-1) x (1.73 m(2))(-1) was lower than that of the 4-variable MDRD Study equation; however, the 2 equations showed similar variation of individual biases around the mean or median bias, so that only modest improvement was seen in the overall percentage of GFR estimates within 30% of the measured GFR (84% vs 77% for the CKD-EPI vs MDRD Study equations, respectively). In the cohort with a GFR >60 mL x min(-1) x (1.73 m(2))(-1) (n = 98), the CKD-EPI bias was much less than that of the MDRD Study equation [-7.4 mL x min(-1) x (1.73 m(2))(-1) vs -14.3 mL x min(-1) x (1.73 m(2))(-1)], and an accuracy of + or - 30% was seen for 89% of GFR estimates, compared with 77% with the MDRD Study equation. The variation of the individual biases around the mean bias remained substantial [SD = 13.7 mL x min(-1) x (1.73 m(2))(-1)]. CONCLUSIONS The CKD-EPI equation shows improved estimation ability, and we recommend that it replace the MDRD Study equation as the currently preferred creatinine-based estimating equation for KTRs. The precision of GFR estimates obtained with the CKD-EPI equation remains suboptimal, however, and we recommend that research on other markers of GFR, such as cystatin C and beta-trace protein, be pursued.

Impact of Estimated GFR Reporting on Patients, Clinicians, and Health-Care Systems: A Systematic Review

BACKGROUND Many laboratories now report estimated glomerular filtration rate (eGFR) when a serum creatinine measurement is ordered. A summary of the impact of eGFR reporting in health care systems around the world for which it has been adopted is lacking. STUDY DESIGN Systematic review of MEDLINE, EMBASE, other major databases, and conference proceedings of major nephrology meetings. SETTING & POPULATION Any health care system in which eGFR reporting was introduced. SELECTION CRITERIA FOR STUDIES Published studies or abstracts reporting patient, clinician, or health system outcomes of eGFR reporting. INTERVENTION eGFR reporting. OUTCOMES Volume of referrals or consults seen by nephrologists, changes in characteristics of patients who were seen, and prescription rates of kidney-related medications. RESULTS 22 studies (10 full text and 12 conference abstracts) were identified in 2004-2010 from 5 countries. Nephrologist referrals and consultations increased after eGFR reporting, ranging from 13%-270%. The greatest increases in referrals were seen for the elderly, females, and those with stage 3 or higher chronic kidney disease (eGFR <60 mL/min/1.73 m(2)). Change in renin-angiotensin-aldosterone system-blocking drug use ranged from increases of 0%-6%. LIMITATIONS Studies were highly variable in definition of outcomes. Reports were not available for many health care systems in which eGFR reporting was implemented. CONCLUSIONS eGFR reporting has been associated with greater identification of patients with decreased kidney function in most health care systems that have reported its impact.

Cystatin-C and beta trace protein as markers of renal function in pregnancy

Objective  To assess the validity of Cystatin‐C (Cys‐C) and beta trace protein (BTP) as clinical markers of glomerular filtration rate (GFR) in pregnant women.

Prevention of Contrast-Induced Acute Kidney Injury: Is Simple Oral Hydration Similar To Intravenous? A Systematic Review of the Evidence

Background Pre-procedural intravenous fluid administration is an effective prophylaxis measure for contrast-induced acute kidney injury. For logistical ease, the oral route is an alternative to the intravenous. The objective of this study was to compare the efficacy of the oral to the intravenous route in prevention of contrast-induced acute kidney injury. Study Design A systematic review and meta-analysis of randomised trials with a stratified analysis and metaregression. Databases included MEDLINE (1950 to November 23 2011), EMBASE (1947 to week 47 2011), Cochrane CENTRAL (3rd quarter 2011). Two reviewers identified relevant trials and abstracted data. Settings and Population Trials including patients undergoing a contrast enhanced procedure. Selection Criteria Randomised controlled trial; adult (>18 years) population; comparison of oral versus intravenous volume expansion. Intervention Oral route of volume expansion compared to the intravenous route. Outcomes Any measure of acute kidney injury, need for renal replacement therapy, hospitalization and death. Results Six trials including 513 patients met inclusion criteria. The summary odds ratio was 1.19 (95% CI 0.46, 3.10, p = 0.73) suggesting no difference between the two routes of volume expansion. There was significant heterogeneity (Cochran’s Q = 11.65, p = 0.04; I2 = 57). In the stratified analysis, inclusion of the five studies with a prespecified oral volume expansion protocol resulted in a shift towards oral volume expansion (OR 0.75, 95% CI 0.37, 1.50, p = 0.42) and also resolved the heterogeneity (Q = 3.19, P = 0.53; I2 = 0). Limitations Small number of studies identified; lack of hard clinical outcomes. Conclusion The oral route may be as effective as the intravenous route for volume expansion for contrast-induced acute kidney injury prevention. Adequately powered trials with hard endpoints should be done given the potential advantages of oral (e.g. reduced patient burden and cost) over intravenous volume expansion.