Accurate assessment of kidney function by measurement of glomerular filtration rate (GFR) is essential to the risk assessment of prospective living kidney donors. We evaluated the performance of various estimating equations for creatinine clearance (Cockcroft-Gault), GFR (Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration), and 24-hour urine collections for creatinine clearance in obese potential kidney donors. We evaluated 164 potential kidney donors including 49 with a BMI of 30–35 and 32 with a BMI >35 that have completed a routine living donor evaluation with a measured GFR. All the estimating equations performed poorly in obese donors. While 24-hour urine collections performed better, only 15% had an adequate 24-hour urine collection. Since obese kidney donors may be at higher than average risk for kidney failure, accurate assessment of kidney function in these donors is crucial to ensure their long-term health postdonation.
Kidney transplantation is considered the treatment of choice for selected patients with end-stage kidney disease. Successful transplantation not only provides a better quality of life but also survival advantage to these patients [
Prospective living donors undergo extensive medical and psychosocial evaluation to ensure that donation is safe for both recipient and donor. Most transplant programs have used a glomerular filtration rate (GFR) cut-off of 80 mL/min/1.73 m2 to define optimal live kidney donors [
During the last two decades, there has been a dramatic rise in obesity in the United States with one-third of adults classified as obese. Not surprisingly, therefore, the proportion of donors with obesity is also rising, with 19.5% of living donors having body mass index (BMI) >30 kg/m2 in 2008 [
Individuals 18 years and older, who were evaluated as possible live kidney donors from September 1, 2009 to December 31, 2010 at the University of Illinois at Chicago were included if they had a measured glomerular filtration rate (mGFR) completed as part of their workup. The study protocol was approved by the Institutional Review Board at the University of Illinois at Chicago.
Serum creatinine levels were measured during the initial evaluation of prospective donors. Per institutional protocol, individuals that had a BMI > 30 kg/m2 or an inadequate 24-hour urine collection underwent a measured GFR to assess kidney function. The estimated glomerular filtration rate (eGFR) was calculated using the 4-variable Modification of Diet in Renal Disease study equation (MDRD) [
The creatinine clearance was calculated using a 24-hour urine collection and estimated by the Cockcroft-Gault equation based on ideal body weight [
Measured GFR (mGFR) was obtained using Technetium 99 m-mercaptoacetyltriglycine (99 mTc-MAG3) renal scan. Briefly, individuals were given 7 mCi of Technetium 99 m-mercaptoacetyltriglycine while in the supine position. Dynamic images of the kidneys were obtained for 21 minutes and were read by a radiologist. Absolute GFR was reported and corrected for body surface area using the Dubois and Dubois formula [
Differences between continuous and categorical variables were compared using the one-way analysis of variance and Chi-square test, respectively. Continuous variables were reported as mean ± standard deviation. We evaluated bias that represented the average difference between measured and estimated values. A positive bias indicated that the measured value was higher than the estimated value. Precision was measured by the interquartile range (IQR) of the difference between measured and estimated values. Finally, we assessed accuracy by looking at the percentage of estimated values within 30% of measured values (P30).
During the study period, 164 individuals completed a 99 mTc-MAG3 scan as part of their living donor evaluation. Of these individuals, 83 had a BMI < 30 kg/m2 (Normal group), 49 with a BMI between 30–35 kg/m2 (Class I Obesity group), and 32 with a BMI > 35 kg/m2 (Class II/III Obesity group). The characteristics of each group are shown in Table
Characteristics of potential kidney donors with measured glomerular filtration rate.
Normal (BMI < 30) | Class I Obesity (BMI 30–35) | Class II/III Obesity (BMI > 35) | ||
---|---|---|---|---|
Age (yrs) | 0.30 | |||
Weight (kg) | <0.001 | |||
BMI | <0.001 | |||
Male | 42 (51%) | 25 (51%) | 5 (16%) | 0.002 |
Ethnicity | 0.14 | |||
White | 24 (29%) | 9 (18%) | 5 (16%) | |
Black | 30 (36%) | 21 (43%) | 20 (62%) | |
Hispanic | 24 (29%) | 13 (27%) | 6 (19%) | |
Other | 5 (6%) | 6 (12%) | 1 (3%) |
Abbreviations: BMI—body mass index (kg/m2).
Table
Performance of estimating equations.
Bias (mL/min/1.73 m2) | IQR (mL/min/1.73 m2) | P30 | |
---|---|---|---|
Normal (BMI < 30) ( | |||
Cockcroft-Gault CrCl | 35.3 | 64% | |
MDRD eGFR | 35.6 | 71% | |
CKD-EPI eGFR | 35.3 | 76% | |
Class I Obesity (BMI 30–35) ( | |||
Cockcroft-Gault CrCl | 36.5 | 61% | |
MDRD eGFR | 36.0 | 69% | |
CKD-EPI eGFR | 37.9 | 69% | |
Class II/III Obesity ( | |||
Cockcroft-Gault CrCl | 31.9 | 66% | |
MDRD eGFR | 37.3 | 62% | |
CKD-EPI eGFR | 35.7 | 56% |
Abbreviations: Bias—(measured GF-estimated GFR); IQR—interquartile range; BMI—body mass index (kg/m2); P30—percentage of estimated readings within 30 percent of measured reading; CrCl—creatinine clearance; MDRD—modification of diet in renal disease; CKD-EPI—chronic kidney disease epidemiology collaboration; eGFR—estimated glomerular filtration rate.
In the Class II/III Obesity group, the equations did not perform as well. The bias for MDRD and CKD-EPI eGFR suggests that the equations overestimate mGFR compared to the Normal and Class I Obesity groups. The precision was more variable between equations in this group and the accuracy was lower, especially for the MDRD and CKD-EPI equations.
All potential kidney donors also provided a 24-hour collection of urine for protein excretion and creatinine clearance. In our group of 164 individuals, 84 (51%) had overcollection, 56 (34%) had undercollection, and only 24 individuals (15%) had adequate urine collection by assessing creatinine excretion. Of these 24, the performance of the 24-hour urine collection improved for individuals with higher BMI (Table
Performance of 24-hour creatinine clearance.
Bias (mL/min/1.73 m2) | IQR (mL/min/1.73 m2) | P30 | |
---|---|---|---|
Normal | 38.8 | 22% | |
Class I Obesity (BMI 30–35) ( | 23.9 | 75% | |
Class II/III Obesity (BMI > 35) ( | 10.0 | 86% |
Abbreviations: Bias—(measured GF-estimated GFR); IQR—interquartile range; BMI—body mass index (kg/m2); P30—percentage of estimated readings within 30 percent of measured readings.
Finally, we evaluated the sensitivity and specificity of the three estimating equations in selecting mGFR of 80 mL/min/1.73 m2 (Table
Sensitivity and specificity of estimating equations.
mGFR > 80 mL/min/1.73 m2 | ||
SENS | SPEC | |
Normal | ||
CG-CrCl | 51% | 67% |
MDRD eGFR | 74% | 47% |
CKD-EPI eGFR | 81% | 40% |
Class I Obesity | ||
CG-CrCl | 47% | 69% |
MDRD eGFR | 81% | 46% |
CKD-EPI eGFR | 86% | 23% |
Class II/III Obesity | ||
CG-CrCl | 45% | 92% |
MDRD eGFR | 100% | 17% |
CKD-EPI eGFR | 100% | 17% |
Abbreviations: mGFR—measured glomerular filtration rate; SENS—sensitivity; SPEC—specificity; CG-Cockcroft-Gault equation; CrCl—creatinine clearance; MDRD—modification of diet in renal disease; CKD-EPI—chronic kidney disease epidemiology collaboration; eGFR—estimated glomerular filtration rate.
The primary goal of the extensive medical evaluation for living kidney donors is to protect the well-being of the prospective donor. Central to the donor evaluation is the assessment of predonation kidney function and factors that may affect it postdonation. Reports of long-term followup after uninephrectomy suggest that kidney donation is safe and does not adversely affect the survival or kidney function of a healthy donor [
There is increasing evidence that obese individuals are at a higher risk of developing kidney disease [
Measured GFR using urinary or plasma clearance of exogenous filtration markers is the present gold standard for the evaluation of donor kidney function [
An interesting finding in our donor cohort was the negative bias seen with the MDRD and CKD-EPI equations in Class II/III obesity indicating an overestimation of GFR compared to the measured GFR. In healthy individuals, the MDRD equation is known to underestimate measured GFR [
One limitation of this study is the use of 99 mTc-MAG3 scanning. Measured GFR using exogenous filtration markers (125I-iothalamate, iohexol, diethylenetriaminopenta-acetic acid) provides potentially greater accuracy of GFR assessment [
Potential concerns for transplant centers are that GFR measurement using 99 mTc-MAG3 (or another type of radioisotope scan) introduces radiation exposure to the donor, cost to the evaluation process, and requires personnel familiar with the testing procedure. However, less invasive and less expensive methods may not be adequate to accurately measure kidney function in obese donors.
Although the focus of this discussion has been on the importance of accurate predonation GFR estimation for the donor, donor GFR estimation is certainly a variable of importance for the recipient as well. Lower levels of donor GFR are associated with graft dysfunction and graft loss [
Accurate determination of GFR is essential to the risk assessment of prospective kidney donors. Creatinine-based GFR estimation equations are unreliable for the evaluation of obese donors. 24-hour urine collection is not only cumbersome but also fraught with errors due to inadequate collection in such donors. Further studies are required to develop better methods of GFR estimation in obese individuals with normal kidney function. Until then, measured GFR should be used as a confirmatory test to enhance clinical decision making in these circumstances.
Sanjeev K. Akkina was supported by Grant Number K23DK084121 from the National Institute of Diabetes and Digestive and Kidney Diseases. Anna C. Porter was supported by Grant no. KM1CA156717, University of Chicago/University of Illinois at Chicago KM1 Career Development Award in Comparative Effectiveness Research funded by the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases, National Cancer Institute, or the National Institutes of Health.