Accuracy of the MDRD (Modification of Diet in Renal Disease) study and CKD-EPI (CKD Epidemiology Collaboration) equations for estimation of GFR in the elderly.

BACKGROUND: Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI(cr)) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m(2). Newer equations have been reported using cystatin C concentration either alone (CKD-EPI(cys)) or in combination with creatinine concentration (CKD-EPI(cr-cys)). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. STUDY DESIGN: Diagnostic test evaluation in a prospective cohort. SETTING & PARTICIPANTS: Participants (n = 394; median age, 80 [range, 74-97] years) recruited from nephrology clinics and the community. INDEX TEST: GFR estimated using the MDRD Study, CKD-EPI(cr), CKD-EPI(cys) and CKD-EPI(cr-cys) equations. REFERENCE TEST: GFR measured using an iohexol clearance method. RESULTS: Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m(2). MDRD Study-, CKD-EPI(cr)-, and CKD-EPI(cr-cys)-estimated GFRs overestimated GFR (median differences of 3.5 [P< 0.001], 1.7 [P < 0.001], and 0.8 [P = 0.02] mL/min/1.73 m(2), respectively); the CKD-EPI(cys) equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P(30)]) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPI(cr), CKD-EPI(cys), and CKD-EPI(cr-cys) equations, respectively. Accuracy of the MDRD Study equation was inferior (P = 0.004) to the CKD-EPI(cr) equation at GFR >60 mL/min/1.73 m(2). LIMITATIONS: Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. CONCLUSIONS: The CKD-EPI(cr) equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P(30) in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.

Bone mineral metabolism and its relationship to kidney disease in a residential care home population: a cross-sectional study.

BACKGROUND: Institutionalized older people have a high risk of bone fractures due to osteoporosis. In addition, chronic kidney disease (CKD) is highly prevalent in older people living in residential homes. Secondary hyperparathyroidism, poor calcium intake and deficiency of 1,25-dihydroxyvitamin D may lead to decreased bone mass in people with CKD. The present cross-sectional study assessed the relationship between markers of bone mineral metabolism and kidney function in a residential care home population. METHODS: Older subjects were recruited from residential care homes and kidney function stratified by the estimated glomerular filtration rate (GFR). Parathyroid hormone (PTH), 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 188 residents not receiving vitamin D/calcium treatment [mean age 85 (range 68- 100) years, 75% female] and in 52 residents receiving vitamin D/calcium supplementation. RESULTS: Amongst those not receiving vitamin D/calcium, median PTH increased with declining GFR (P < 0.0001), particularly as GFR (mL/min/1.73 m(2)) fell below 45. PTH concentration was suppressed by increasing 25-hydroxyvitamin D (P < 0.0001), but not 1,25-dihydroxyvitamin D (P > 0.05) concentration. Nearly all residents (92%) had 25-hydroxyvitamin D deficiency or insufficiency and this was uninfluenced by kidney function (P > 0.05). Concentration of 1,25-dihydroxyvitamin D declined with worsening renal function (P < 0.0004) but 1,25-dihydroxyvitamin D deficiency was prevalent at all stages of kidney disease, including amongst residents receiving vitamin D/calcium supplementation. CONCLUSION: Vitamin D deficiency and secondary hyperparathyroidism are common in this population irrespective of renal function. However, as GFR falls below 45, the prevalence of secondary hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency increases. Unidentified CKD appears to exacerbate secondary hyperparathyroidism in this at risk population.

Chronic kidney disease prevalence in a UK residential care home population.

BACKGROUND: Chronic kidney disease (CKD) is common ( approximately 30%) in non-institutionalized older people but little is known about the prevalence of CKD amongst older people living in residential care. METHODS: An observational study of older subjects [n = 250, median age 86 (range 67-100) years, 79% female, 100% Caucasian, 16% diabetic, 48% hypertensive, 5% known renal disease, mean number of medications 7] who were recruited over a 9-month period from 155 residential care homes in east Kent (total population 3811) using a randomization process. The estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) was calculated using the Cockcroft and Gault equation corrected for the body surface area and the simplified Modification of Diet in Renal Disease (MDRD) Study equation. Serum cystatin C concentration was also measured. RESULTS: Using the MDRD equation 18% had eGFR >/=60, 39% stage 3A CKD (eGFR 45-59), 34% stage 3B CKD (eGFR 30-44) and 10% stage 4 CKD (eGFR 15-29). By the Cockcroft-Gault equation the equivalent figures were 3%, 18%, 48% and 31%, respectively. Agreement between the equations for staging of CKD was poor (kappa = 0.07). However, >80% of residents were categorized as having stage 3 CKD (>40% stage 3B) or worse whichever equation was used. Serum cystatin C concentration was increased in 92% of the population. Increasing age and higher body mass index were predictive of decreased renal function. CONCLUSION: Significant CKD is prevalent and unrecognized in this population. This may have important management implications particularly for treatment with renally excreted drugs, fracture prevention or managing cardiovascular risk.

Susceptibility of glomerular filtration rate estimations to variations in creatinine methodology: a study in older patients.

BACKGROUND: It is recommended that measurement of serum creatinine should be supplemented with a creatinine-based estimation of glomerular filtration rate (GFR). The influence of creatinine methodology on these estimates is not always appreciated. We have studied differences in creatinine methods and their influence on GFR estimation specifically in older people. METHODS: In all, 46 older patients (mean age 80 y, range 69-92 y) with predominantly mild or moderate kidney disease were studied. Serum creatinine was measured using a rate Jaffe method and two different enzymatic methods. Isotope dilution mass spectrometry served as the reference creatinine method. GFR was estimated using both the Modification of Diet in Renal Disease (MDRD) and Cockcroft and Gault formulae: a 51Cr-EDTA GFR estimation served as the reference GFR method. RESULTS: Both enzymatic methods produced creatinine results that were significantly different (P<0.001) from the reference method. The Jaffe method over- and underestimated creatinine at low and high concentrations, respectively. The most likely explanation for these differences relates to standardization of the assays. Irrespective of creatinine method, the Cockroft and Gault formula tended to underestimate GFR, and the MDRD formula to overestimate GFR. Use of the differing creatinine methods to estimate GFR produced predictable biases of the estimate, with mean GFR estimates varying by 14% across the creatinine methods. CONCLUSION: Estimates of GFR depend critically upon the accuracy and precision of the creatinine measurement used in their calculation.

Estimation of glomerular filtration rate in older patients with chronic renal insufficiency: is the modification of diet in renal disease formula an improvement?

OBJECTIVES: To evaluate a new formula for glomerular filtration rate (GFR), derived from the Modification of Diet in Renal Disease (MDRD) study in older people. DESIGN: An observational study of the performance of the MDRD formula compared with other formulae and creatinine clearance (ClCr) as measures of the GFR. SETTING: Volunteers were recruited via outpatient clinics. PARTICIPANTS: Fifty-two patients (27 men, 25 women: mean age 80, range 69-92) with a variety of medical diagnoses. Mean GFR was 53.3 mL/min/1.73 m2 (range 15.9-100.2). Exclusion criteria included renal replacement therapy/renal transplantation and cognitive impairment. MEASUREMENTS: 51Chromium ethylenediaminetetraacetic acid (51Cr EDTA) was used as the reference method against which the formulaic estimates of GFR were compared using bias plot and regression analyses. RESULTS: The MDRD and Cockcroft and Gault formulae (both coefficient of determination (R2) = 0.84) gave the best fit with GFR, followed by the Jelliffe formula (R2 = 0.81), ClCr (R2 = 0.73) and the Baracskay formula (R2 = 0.56). ClCr (-1.2%) demonstrated minimal bias compared with the MDRD (8.0%) and Cockcroft and Gault (-10.4%) formulae. However, imprecision compared with 51Cr EDTA was lowest for the Cockcroft and Gault formula, with 50% of estimates lying between -9.5 and -0.5 mL/min/1.73 m2 of measured 51Cr EDTA clearance. This compares with -6.7 and 10.1 mL/min/1.73 m2 for ClCr and 0.0 and 12.7 mL/min/1.73 m2 for the MDRD formula. CONCLUSION: Calculated estimates of GFR are an improvement over ClCr estimation. On balance, the MDRD formula does not improve the estimate of GFR compared with the Cockcroft and Gault formula in older Caucasian patients with chronic renal insufficiency.

Kidney function in older people: pathology, assessment and management.

It is commonly not appreciated that kidney failure is predominantly a disease of older people and that the use of renal replacement therapy (RRT) amongst these patients is increasing rapidly. It is still unclear whether the decline in kidney function with increasing age represents pathology or is part of the normal ageing process. Conventional laboratory approaches to the assessment of kidney function in older people are inadequate, but the use of calculated clearance formulae and serum cystatin C can enable the earlier detection of chronic kidney disease (CKD) in this population. This could facilitate treatment aimed at reducing the progression of kidney disease in older people and improved management of its secondary complications.

Cystatin C improves the detection of mild renal dysfunction in older patients.

BACKGROUND: Conventional estimates of glomerular dysfunction, including serum creatinine and creatinine clearance, are inadequate in older people. In this study we have compared the diagnostic accuracy of a novel test of kidney disease, cystatin C, against these markers in older patients with a range of renal function. METHODS: Fifty-three patients (mean age 79.6 years, range 69-92 years) with a variety of medical diagnoses were recruited via outpatient clinics. Exclusion criteria included active rheumatoid disease, known current malignancy, renal replacement therapy/renal transplantation and cognitive impairment. (51)Cr-EDTA was used as the reference method against which the other markers of glomerular filtration rate were compared using regression analyses. RESULTS: The best fit with glomerular filtration rate was given by Cockcroft and Gault calculated clearance (R(2) = 0.83), followed by serum cystatin C (R(2) = 0.79), serum creatinine (R(2) = 0.76) and creatinine clearance (R(2) = 0.73). The accuracy for glomerular filtration rate prediction was poor for all markers. Serum cystatin C detected nearly all patients with mild renal impairment whereas serum creatinine only detected half of these cases. Regression modelling predicted that the upper limit of normal for serum cystatin C would be exceeded as glomerular filtration rate fell below 64 mL/min/1.73 m(2), compared with 44 mL/min/1.73 m(2) for serum creatinine. CONCLUSION: Serum cystatin C is a simple and sensitive screening test for kidney dysfunction in older people.