Publications (95) View all
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Article: Prevalence of and risk factors for chronic kidney disease in rural Nicaragua.
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ABSTRACT: Mostly anecdotal reports describe a high prevalence of chronic kidney disease in northwestern Nicaragua, predominantly among younger men, resulting in substantial morbidity and mortality. The true prevalence, nature and aetiology of kidney disease in this region remain unknown. We performed a population-based prevalence study in Quezalguaque, Nicaragua to assess the frequency of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2), and compared the prevalence of reduced eGFR in Quezalguaque with the USA using the NHANES 1999-2006 data. We also conducted an embedded case-control study in a subset of participants to assess kidney disease risk factors. From 1882 eligible households, 771 individuals from 300 households participated in the prevalence study, 98 (13%) of whom had reduced eGFR. Reduced eGFR was more common among older participants, men and participants living at lower altitudes. Among 18-29-year-old participants, 2.6% had reduced eGFR, and among 30-41-year-old participants, 7.4% had reduced eGFR; this compares with 0.2% and 0.8%, respectively, in NHANES. No individuals in these age groups were diabetic. Among cases, only 27% had dipstick proteinuria of 1+ or greater, compared with 7% of controls. Haematuria did not significantly differ between cases and controls (24% versus 18%). In age- and sex-adjusted models, hypertension and residence at lower altitude were independently associated with reduced eGFR, while occupational history was not associated with reduced eGFR. Kidney disease appears common in residents of Quezalguaque, Nicaragua, particularly in younger men, with features most consistent with tubulointerstitial disease. Further research is needed to elucidate the causes of kidney disease in this region.Nephrology Dialysis Transplantation 09/2011; 26(9):2798-805. · 3.40 Impact Factor -
Article: Performance of MDRD study and CKD-EPI equations for long-term follow-up of nondiabetic patients with chronic kidney disease.
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ABSTRACT: BACKGROUND: Chronic kidney disease (CKD) typically extends over decades. Longitudinal monitoring of kidney function in CKD is thus of great importance. Here, we retrospectively evaluate use of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to monitor long-term course of kidney function and to identify individuals with progressive kidney function loss. METHODS: Patients were selected from our outpatient clinic for having four glomerular filtration rate measurements (mGFR, (125)I-iothalamate) and at least ≥ 4 years of follow-up. Renal function slopes were obtained by within-individual linear regression. RESULTS: Sixty-five nondiabetic CKD patients (40 male, mean baseline age 44 ± 12 years) with a median (range) of 9 (4-16) mGFR measurements and a median follow-up of 11 (4-33) years were included. Both equations significantly underestimated mGFR/(BSA) at baseline and at the end of follow-up. mGFR slope was significantly underestimated by the MDRD study but not by CKD-EPI equation (slopes -1.41 ± 2.06, -1.07 ± 1.72 and -1.39 ± 1.77 mL/min/1.73m(2)/year, respectively). Sensitivity and specificity to identify progressive kidney function loss (mGFR/(BSA) slope > 1.5 mL/min/1.73m(2)/ year, n = 23) were 78 and 88% for the MDRD study and 91 and 80% for CKD-EPI equation. In the subgroup of progressors, both MDRD study and CKD-EPI equation underestimated the rate of mGFR loss (P < 0.05) CONCLUSIONS: Long-term course of mGFR is reasonably well estimated by CKD-EPI and slightly underestimated by MDRD study equation. Patients with progressive kidney function loss may, however, not be reliably identified, so caution is warranted when using these equations in clinical practice.Nephrology Dialysis Transplantation 05/2011; · 3.40 Impact Factor -
Article: A predictive model for progression of chronic kidney disease to kidney failure.
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ABSTRACT: Chronic kidney disease (CKD) is common. Kidney disease severity can be classified by estimated glomerular filtration rate (GFR) and albuminuria, but more accurate information regarding risk for progression to kidney failure is required for clinical decisions about testing, treatment, and referral. To develop and validate predictive models for progression of CKD. Development and validation of prediction models using demographic, clinical, and laboratory data from 2 independent Canadian cohorts of patients with CKD stages 3 to 5 (estimated GFR, 10-59 mL/min/1.73 m(2)) who were referred to nephrologists between April 1, 2001, and December 31, 2008. Models were developed using Cox proportional hazards regression methods and evaluated using C statistics and integrated discrimination improvement for discrimination, calibration plots and Akaike Information Criterion for goodness of fit, and net reclassification improvement (NRI) at 1, 3, and 5 years. Kidney failure, defined as need for dialysis or preemptive kidney transplantation. The development and validation cohorts included 3449 patients (386 with kidney failure [11%]) and 4942 patients (1177 with kidney failure [24%]), respectively. The most accurate model included age, sex, estimated GFR, albuminuria, serum calcium, serum phosphate, serum bicarbonate, and serum albumin (C statistic, 0.917; 95% confidence interval [CI], 0.901-0.933 in the development cohort and 0.841; 95% CI, 0.825-0.857 in the validation cohort). In the validation cohort, this model was more accurate than a simpler model that included age, sex, estimated GFR, and albuminuria (integrated discrimination improvement, 3.2%; 95% CI, 2.4%-4.2%; calibration [Nam and D'Agostino χ(2) statistic, 19 vs 32]; and reclassification for CKD stage 3 [NRI, 8.0%; 95% CI, 2.1%-13.9%] and for CKD stage 4 [NRI, 4.1%; 95% CI, -0.5% to 8.8%]). A model using routinely obtained laboratory tests can accurately predict progression to kidney failure in patients with CKD stages 3 to 5.JAMA The Journal of the American Medical Association 04/2011; 305(15):1553-9. · 30.03 Impact Factor -
Article: Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities.
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ABSTRACT: An equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provides more accurate estimates of the glomerular filtration rate (eGFR) than that from the modification of diet in renal disease (MDRD) Study, although both include a two-level variable for race (Black and White and other). Since creatinine generation differs among ethnic groups, it is possible that a multilevel ethnic variable would allow more accurate estimates across all groups. To evaluate this, we developed an equation to calculate eGFR that includes a four-level race variable (Black, Asian, Native American and Hispanic, and White and other) using a database of 8254 patients pooled from 10 studies. This equation was then validated in 4014 patients using 17 additional studies from the United States and Europe (validation database), and in 1022 patients from China (675), Japan (248), and South Africa (99). Coefficients for the Black, Asian, and Native American and Hispanic groups resulted in 15, 5, and 1% higher levels of eGFR, respectively, compared with the White and other group. In the validation database, the two-level race equation had minimal bias in Black, Native American and Hispanic, and White and other cohorts. The four-level ethnicity equation significantly improved bias in Asians of the validation data set and in Chinese. Both equations had a large bias in Japanese and South African patients. Thus, heterogeneity in performance among the ethnic and geographic groups precludes use of the four-level race equation. The CKD-EPI two-level race equation can be used in the United States and Europe across a wide range of ethnicity.Kidney International 03/2011; 79(5):555-62. · 6.61 Impact Factor -
Article: Early change in proteinuria as a surrogate outcome in kidney disease progression: a systematic review of previous analyses and creation of a patient-level pooled dataset.
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ABSTRACT: Proteinuria is a candidate surrogate end point for randomized controlled trials (RCTs) in chronic kidney disease (CKD). There is a reasonably sound biological basis for this hypothesis, but only preliminary empirical evidence currently exists. A systematic review and creation of a patient-level dataset of randomized controlled trials (RCTs) in CKD that reported changes in proteinuria and assessed progression of kidney disease as defined by dialysis, transplantation, death, or changes in GFR or creatinine were performed. Systematic review. Seventy RCTs met the eligibility criteria; 17 eligible RCTs contained analyses of proteinuria as a predictor of outcomes; 15 RCTs concluded that greater proteinuria was associated with adverse outcomes. A majority were studies of diabetic or hypertensive kidney disease and tested renin-angiotensin system blockade. Definitions of predictor and outcome variables were too variable to conduct a meta-analysis of group data. Database creation. Over 4 years was required to create the patient-level dataset. The final dataset included 34 studies and > 9000 patients with a variety of CKD types and interventions. There are a relatively small number of RCTs designed to rigorously test therapies for kidney disease progression. Current analyses of change in proteinuria as a predictor of CKD progression are heterogeneous and incomplete, indicating further evaluation in a pooled individual patient-level database is necessary to advance knowledge in this field.Nephrology Dialysis Transplantation 03/2011; 26(3):848-57. · 3.40 Impact Factor
