Evan Lee

GFR Estimating Equations in a Multiethnic Asian Population

BACKGROUND Clinical practice guidelines recommend using equations for estimating glomerular filtration rate (GFR) in chronic kidney disease (CKD) management and research. The MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (CKD Epidemiology Collaboration) equations originally were derived from a North American population and had an ethnic coefficient adjustment for African Americans. A Chinese coefficient for the MDRD Study equation subsequently was determined, but this has not been externally validated. We compared the accuracy of the equations, evaluated the ethnic coefficients, and assessed the equations for disease staging in a multiethnic Asian population with CKD. STUDY DESIGN A diagnostic test study comparing the Asian coefficient (and subgroups)-modified MDRD Study and CKD-EPI equations and a cross-sectional study assessing disease staging. SETTING & PARTICIPANTS 232 outpatients (52% men; 40.5% Chinese, 32% Malay, and 27.5% Indian/other) with stable CKD. INDEX TEST Asian and ethnicity-based modifications of the MDRD Study and CKD-EPI equations. REFERENCE TEST Measured GFR using 3-sample plasma clearance of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA), calculated using the slope-intercept method, with body surface area normalization (du Bois) and Brochner-Mortensen correction. RESULTS Overall, the CKD-EPI equation is more accurate than the MDRD Study equation throughout the GFR range, with improved bias (median difference of estimated GFR - measured GFR) and root mean square error (P <0.001). CKD-EPI versus MDRD Study equation: bias, 1.1 ± 13.8 vs -1.0 ± 15.2 mL/min/1.73 m(2); precision, 12.1 vs 12.2 mL/min/1.73 m(2). Ethnic coefficients did not improve estimates of GFR significantly. The correctness of staging was improved using the CKD-EPI equation. LIMITATIONS All participants had CKD, but few were of European descent. The reference GFR technique was different from the original studies. CONCLUSIONS The CKD-EPI is more accurate than the MDRD Study equation, particularly at higher GFRs. Therefore, we recommend adopting the CKD-EPI equation without ethnic adjustment for estimating GFR in multiethnic Asian patients with CKD.

Estimating Glomerular Filtration Rates by Use of Both Cystatin C and Standardized Serum Creatinine Avoids Ethnicity Coefficients in Asian Patients with Chronic Kidney Disease

BACKGROUND The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is most accurate for estimating glomerular filtration rate (GFR) but requires an adjustment for African-American patients. Estimation equations are also improved with the use of serum cystatin C combined with standardized creatinine. Combination equations have been derived by the CKD-EPI and Chinese investigators. We investigated whether these cystatin C-based equations improve estimation adequately, so that adjustments for ethnicity are not required in a multiethnic Asian population with chronic kidney disease (CKD). METHODS This was a cross-sectional study of 232 stable CKD patients who underwent GFR measurements using 3-sample plasma clearances of (99m)Tc-DTPA, and for whom serum cystatin C and creatinine were quantified. RESULTS For all patients, the median biases with cystatin C equations were generally greater than with the CKD-EPI equation, and precision and root mean square error (RMSE) were not significantly better. However, the combination serum creatinine and cystatin C equation improved the precision, RMSE, and percentage of estimated GFR to within 15% and 30% of the measured GFR (57.3% vs 50.0%, 88.4% vs 82.8%, respectively). The derived ethnicity coefficients for the combination equation were all >1 (1.009-1.082) but small, suggesting that coefficients are not required. The Chinese-specific equations were more biased and performed more poorly than the CKD-EPI equation. CONCLUSIONS The use of a cystatin C and creatinine combination equation for estimating GFR in a multiethnic Asian population with CKD does not require ethnicity coefficients because the derived coefficients are very close to each other.

The clinical course of rapidly growing nontuberculous mycobacterial peritoneal dialysis infections in Asians: A case series and literature review

Introduction:  Peritoneal dialysis (PD)‐related infections due to rapidly growing nontuberculous mycobacterium (RGNTM) are rare in Asians and have variable clinical outcomes.

Comparative outcomes of primary autogenous fistulas in elderly, multiethnic Asian hemodialysis patients

BACKGROUND The number of elderly (≥65 years) end-stage renal disease (ESRD) patients on hemodialysis is rapidly increasing. Vascular access outcomes remain contradictory and understudied across different elderly populations. We hypothesized age might influence primary autogenous fistula use and outcomes in a predominantly diabetic multiethnic Asian ESRD population. METHODS Demographic and clinical factors affecting fistula patency and maturation were retrospectively compared among patients with incident ESRD aged <65 and ≥65 years at a single center. Fistula patency was estimated by Kaplan-Meier curves with log-rank test comparison. RESULTS We analyzed 280 primary fistulas (59% radiocephalic, 33% brachiocephalic, and 8% brachiobasilic) in this cohort consisting of 31.8% aged ≥65 years, 50% Chinese, 39% Malay, 42% women, and 70% diabetic. One- and 2-year primary and secondary patency in patients aged <65 vs ≥65 years were comparable: 41.3% vs 36.7% and 28.7% vs 24.4% (P = .547) and 57.7% vs 56.8% and 47.1% vs 47.2% (P = .990). On multivariate analysis, only non-Chinese, dialysis initiation with tunneled catheters, and surgical/endovascular interventions affected fistula survival hazard ratios (HR): 0.622 (95% confidence interval [CI], 0.43-1.00), 0.549 (95% CI, 0.297-0.841), and 2.503 (95% CI, 1.695-3.697), respectively. Nonmaturation and intervention rates were also similar at 56.7% vs 61.8% and 34% vs 32.2% at 3 and 6 months and 0.31 vs 0.36 per access year, respectively (P > .05). Females and tunneled catheters were the only risk factors for nonmaturation (HR, 1.568; 95% CI, 1.148-1.608, and HR, 1.623; 95% CI, 1.400-1.881, respectively). CONCLUSIONS A primary fistula strategy in incident elderly ESRD is feasible and does not result in inferior outcomes. Age should therefore not be a determinant for primary fistula creation.

Global evolutionary trend of the prevalence of primary glomerulonephritis over the past three decades.

Objective: The prevalence of primary glomerulonephritis in Singapore is compared with that of 28 other countries to review changing trends in the evolution of primary glomerulonephritis in Asia and other countries. Method: 2,586 renal biopsies in Singapore over the past 3 decades were reviewed and compared with data from 28 other countries. Results: In the 1st decade most Asian countries have mesangial proliferative glomerulonephritis as the most common form of primary glomerulonephritis, and in the 3rd decade there has been a dramatic increase in focal and segmental glomerulosclerosis reflecting aging and obesity in keeping with more developed countries. IgA nephritis remains the commonest glomerulonephritis in many countries. Membranous glomerulonephritis continues to be more prevalent in Western countries while mesangial proliferative glomerulonephritis remains prevalent in many Asian countries. Conclusion: Apart from geographical and genetic influences, socioeconomic factors may play a role in the evolution of the biopsy pattern in some countries. Worldwide, the prevalence of focal segmental glomerulosclerosis continues to increase. In third world countries some of the commoner forms of glomerulonephritis are related to infections, in contrast to developed countries where the antigenic exposure may be related to diet, allergens and other industrial agents.

Report of the Asian Forum of Chronic Kidney Disease Initiative (AFCKDI) 2007. ''Current status and perspective of CKD in Asia'': diversity and specificity among Asian countries

The Japanese Society of Nephrology (JSN) sponsored the Asian Forum of CKD Initiative (AFCKDI) 2007 with the support of the International Society of Nephrology-Commission for Global Advancement in Nephrology (ISN-COMGAN), Asian Pacific Society of Nephrology (APSN), the Kidney Disease: Improving Global Outcome (KDIGO) and other national societies of nephrology in the Asian Pacific region on 27–28 May 2007 in Hamamatsu City, Japan. An international organising committee was established by leading experts of the CKD initiative. The main objective of this forum was to clarify the current status and perspectives of CKD and to promote coordination, collaboration and integration of initiatives in the Asian Pacific region. The forum received 56 papers from 16 countries; it began with the symposium “A Challenge to CKD in the world” and was followed by the ISN-COMGAN affiliated workshop “Current status and perspective of CKD in Asia”. The second day was dedicated to discussion on the evaluation, surveillance and intervention in CKD in this area. At the end of the forum, we decided on the future plan as follows: (1) The AFCKDI will provide opportunities annually or biannually for every person who promotes CKD initiatives in the Asian Pacific region to join together and build consensus for action; (2) the second forum will be held in Kuala Lumpur on 4 May 2008 at the time of the 11th Asian Pacific Congress of Nephrology (APCN). Zaki Morad, President of the 11th APCN, will host the second forum; (3) the International Organising Committee (IOC) of the 1st AFCKDI will continue its function by adding other experts, including the organisers of the APCN; (4) the AFCKDI is not an organisation by itself, nor does it belong to any society, but is organised by each host national society of nephrology. The IOC will assist the domestic committee for the success of the forum and will assure the continuation of the mission; (5) in order to organise the forum and promote CKD initiatives in the Asia Pacific region, the AFCKDI will look for support by both national and international societies. The AFCKDI will keep an intimate and mutual relation with the ISN, APSN and KDIGO.

Beta-2-Microglobulin in the Assessment of Renal Function of the Transplanted Kidney

Plasma and urine beta-2-microglobulin (B2m) were measured in 37 renal transplant recipients and 34 healthy subjects. Serum B2m was found to be a more sensitive index of renal function than serum creatinine. Renal transplant recipients had significantly higher urine B2m when compared with normal controls. Normal subjects had a higher serum to urine B2m ratio (SUR) while those with renal impairment had a lower SUR. Serum B2m used alone or together with urine B2m and SUR appears a useful index for assessment of renal allograft function as well as detection of potential renal damage.

Predicting First-Year Mortality in Incident Dialysis Patients with End-Stage Renal Disease - The UREA5 Study

We aimed to develop a risk prediction model for first-year mortality (FYM) in incident dialysis patients with end-stage renal disease. We retrospectively examined patient comorbidities and biochemistry, prior to dialysis initiation, using a single-center, prospectively maintained database from 2005-2010, and analyzed these variables in relation to FYM. A total of 983 patients were studied. 22% had left ventricular ejection fraction (LVEF) <45%. FYM was 17%, and independent predictors included URate <500 or >600 μmol/l, LVEF <45% (higher odds ratio if <30%), Age >70 years, Arteriopathies (cerebrovascular and/or peripheral-vascular diseases), serum Albumin <30 g/l, and Alkaline phosphatase >80 U/l (p < 0.05, C-statistic 0.74), and these constitute the acronym UREA5. Using linear modeling, risk weightage/integer of 3 was assigned to LVEF <30%, 2 to age >70 years, and 1 to each remaining variable. Cumulative UREA5 scores of ≤1, 2, 3, 4, and ≥5 were associated with FYM of 6, 8, 22, 31, and 46%, respectively (p < 0.0001). Increasing UREA5 scores were strongly associated with stepwise worsening of FYM after dialysis initiation.

Transplant renal artery stenosis presenting with recurrent acute pulmonary edema.

Renal artery stenosis of the transplant kidney occurs in approximately 6% of renal allograft recipients. Severe bilateral renal artery stenosis and unilateral renal artery stenosis to a single functioning kidney have been described as causes of recurrent pulmonary edema in nontransplant patients with normal cardiac function. We report 2 patients with severe transplant renal artery stenosis who presented with recurrent episodes of acute pulmonary edema. Successful revascularization in 1 patient prevented the recurrence of pulmonary edema. In renal allograft recipients who present with unexplained recurrent episodes of acute pulmonary edema, who do not have an obvious cardiac cause, transplant renal artery stenosis should be considered as a possible etiology.

Acute cyclosporine a nephrotoxicity in a renal allograft recipient with hypothyroidism

Cyclosporine A (CsA) is an important immunosuppressant in kidney transplantation. Acute CsA nephrotoxicity secondary to high drug levels is a well-recognized complication in the immediate posttransplant period. Cyclosporine A is metabolized in the body by the hepatic cytochrome P-450 enzyme system. We present a case of a hypothyroid patient who developed toxic blood CsA levels and acute nephrotoxicity with standard doses of CsA. A reduction of CsA levels led to an improvement of allograft function. Correction of the hypothyroid state resulted in the normalization of CsA requirements, but overcorrection led to an increased requirement of CsA. Thyroid dysfunction should be considered as an interacting factor in the metabolism of CsA.