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Renal Transplantation and Renovascular Hypertension
Urological Survey
Renal Transplantation and Renovascular Hypertension A Risk Prediction Model for Delayed Graft Function in the Current Era of Deceased Donor Renal Transplantation W. D. Irish, J. N. Ilsley, M. A. Schnitzler, S. Feng and D. C. Brennan Biostatistics and Health Outcomes Research, CTI Clinical Trial and Consulting Services, Cincinnati, Ohio Am J Transplant 2010; 10: 2279 –2286.
Delayed graft function (DGF) impacts short- and long-term outcomes. We present a model for predicting DGF after renal transplantation. A multivariable logistic regression analysis of 24,337 deceased donor renal transplant recipients (2003–2006) was performed. We developed a nomogram, depicting relative contribution of risk factors, and a novel web-based calculator (http:// www.transplantcalculator.com/DGF) as an easily accessible tool for predicting DGF. Risk factors in the modern era were compared with their relative impact in an earlier era (1995–1998). Although the impact of many risk factors remained similar over time, weight of immunological factors attenuated, while impact of donor renal function increased by 2-fold. This may reflect advances in immunosuppression and increased utilization of kidneys from expanded criteria donors (ECDs) in the modern era. The most significant factors associated with DGF were cold ischemia time, donor creatinine, body mass index, donation after cardiac death and donor age. In addition to predicting DGF, the model predicted graft failure. A 25–50% probability of DGF was associated with a 50% increased risk of graft failure relative to a DGF risk ⬍ 25%, whereas a ⬎ 50% DGF risk was associated with a 2-fold increased risk of graft failure. This tool is useful for predicting DGF and long-term outcomes at the time of transplant. Editorial Comment: This is an update and improvement on a prior nomogram published by the same authors in 2003.1 This current version is based on a more contemporary cohort of recipients and deceased donors. Additional factors now known to affect DGF are also considered in the current model, including warm ischemic time, duration of dialysis, donor weight and recipient body mass index. Some cases unlikely to inform the model were excluded, such as multiorgan recipients and preemptive transplants. The authors also excluded machine perfused kidneys. The nomogram is available online, accessible to all without cost. The new nomogram was externally validated with a cohort of patients from 2007 (not used to create the model) with the c-index at 0.704. The authors noted improvement in accuracy over the prior model. The use of such a model will remain under discussion. A c-index of 0.7, while improved over the prior model, suggests a fair amount of outcome prediction is not explained by the nomogram. In other health domains, such as stroke or acute myocardial infarction, models have been developed that predict outcomes with a c-statistic at 0.85—much better. How should the nomogram be used? The authors suggest stratifying DGF risk for research purposes or for allocation. It could be used to compare predicted to observed incidence of DGF under various management strategies. In an accompanying editorial Bartlett et al assert that without a robust c-statistic it could be used qualitatively to inform a patient of risk but it should not be used for any regulatory purposes.2 They have suggested that it may be used to help identify best practices for management and prevention of DGF. David A. Goldfarb, M.D. 0022-5347/11/1855-1826/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
1826
www.jurology.com
AND
RESEARCH, INC.
Vol. 185, 1826-1827, May 2011 Printed in U.S.A. DOI:10.1016/j.juro.2010.12.075
RENAL TRANSPLANTATION AND RENOVASCULAR HYPERTENSION
1. Irish WD, McCollum DA, Tesi RJ et al: Nomogram for predicting the likelihood of delayed graft function in adult cadaveric renal transplant recipients. J Am Soc Nephrol 2003; 14: 2967. 2. Bartlett ST, Schweitzer EJ and Cooper M: Prediction model for delayed kidney transplant function: no need for new regulation. Am J Transplant 2010; 10: 2191.
A Study of Renal Outcomes in Obese Living Kidney Donors J. M. Nogueira, M. R. Weir, S. Jacobs, D. Breault, D. Klassen, D. A. Evans, S. T. Bartlett and M. Cooper Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland Transplantation 2010; 90: 993–999.
Background: Little is known about the long–term outcomes of obese living kidney donors (OLKDs). We undertook this study to describe renal outcomes of OLKDs several years after donation. Methods: We invited 101 OLKDs for follow-up health evaluation. Results: Thirty-six subjects (35.6%) completed evaluation at 6.8 ⫾ 1.5 years postdonation. The mean estimated glomerular filtration rate (eGFR) using the abbreviated modification of diet in renal disease (MDRD) equation (MDRD-eGFR) at follow-up was 72.1 ⫾ 16.3 (range: 42–106) mL/min per 1.73 m, and 47.2% of subjects had an MDRD-eGFR of 30 to 59. The absolute decrease in MDRD-eGFR from the time of donation to follow-up was 27.2 ⫾ 13.1 mL/min per 1.73 m (p ⬍0.001 on paired t test), which represents a 29.2% drop in the serial MDRD-eGFRs. Seven subjects (19.4%) had microalbuminuria (30 –300 g/mg creatinine). Subjects with microabuminuria were more likely to have MDRD-eGFR of less than 60 mL/min per 1.73 m (p ⫽ 0.021). Subjects whose body mass index was greater than or equal to 35 kg/m (n ⫽ 14) were found to have an absolute decrement in MDRD-eGFR similar to those with body mass index less than 35 kg/m (31.5 ⫾ 15.6 and 24.7 ⫾ 11.0 mL/min/1.73 m, respectively; p ⫽ not significant). Fifteen (41.6%) were hypertensive at follow-up. Conclusions: On medium-term follow-up, a large proportion of OLKDs will have a MDRD-eGFR of less than 60 mL/min per 1.73 m, and the likelihood increases markedly among those who develop microalbuninuria. This raises concern for hyperfiltration injury. Furthermore, OLKDs experience a substantial incidence of hypertension. Caution is advised in selecting OLKDs pending further data on long-term outcomes. Editorial Comment: The increasing disparity between transplant candidates and the number of organs available has placed pressure on the transplant community to be aggressive regarding the limits of eligibility for organ donation. There may be features of a living donor that raise concern over the potential for long-term renal or other morbidity after donation. However, at the time the decision is made to donate there might be no definitive evidence available to preclude it. Obesity is such an example, as it now may be considered a risk factor for chronic kidney disease. Studies from 5 years ago suggested that nephrectomy for obese donors had few adverse short-term sequelae. At 1 year residual renal function was appropriate without development of hypertension or microalbuminuria. These authors provide a descriptive study of a cohort of obese donors followed out to nearly 7 years. Average eGFR was 72 and 47% of patients had an eGFR of less than 60. Of the patients 19% had microalbuminuria and this finding was more likely with an eGFR of less than 60 ml/min/1.73 m2. Hypertension was reported in 42% of the cohort. The story at 7 years of followup looks different than the 1-year results. The authors sound a word of caution in pursuing the practice of using obese donors, noting the high percentage who had an eGFR of less than 60 ml/min/1.73 m2, microalbuminuria and new onset hypertension. This center now proceeds with great caution in recommending donation for those with a body mass index greater than 35. This study underscores the need to maintain appropriate body weight and regular followup for the long term after donor nephrectomy. David A. Goldfarb, M.D.
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Renal Transplantation and Renovascular Hypertension A Risk Prediction Model for Delayed Graft Function in the Current Era of Deceased Donor Renal Transplantation W. D. Irish, J. N. Ilsley, M. A. Schnitzler, S. Feng and D. C. Brennan Biostatistics and Health Outcomes Research, CTI Clinical Trial and Consulting Services, Cincinnati, Ohio Am J Transplant 2010; 10: 2279 –2286.
Delayed graft function (DGF) impacts short- and long-term outcomes. We present a model for predicting DGF after renal transplantation. A multivariable logistic regression analysis of 24,337 deceased donor renal transplant recipients (2003–2006) was performed. We developed a nomogram, depicting relative contribution of risk factors, and a novel web-based calculator (http:// www.transplantcalculator.com/DGF) as an easily accessible tool for predicting DGF. Risk factors in the modern era were compared with their relative impact in an earlier era (1995–1998). Although the impact of many risk factors remained similar over time, weight of immunological factors attenuated, while impact of donor renal function increased by 2-fold. This may reflect advances in immunosuppression and increased utilization of kidneys from expanded criteria donors (ECDs) in the modern era. The most significant factors associated with DGF were cold ischemia time, donor creatinine, body mass index, donation after cardiac death and donor age. In addition to predicting DGF, the model predicted graft failure. A 25–50% probability of DGF was associated with a 50% increased risk of graft failure relative to a DGF risk ⬍ 25%, whereas a ⬎ 50% DGF risk was associated with a 2-fold increased risk of graft failure. This tool is useful for predicting DGF and long-term outcomes at the time of transplant. Editorial Comment: This is an update and improvement on a prior nomogram published by the same authors in 2003.1 This current version is based on a more contemporary cohort of recipients and deceased donors. Additional factors now known to affect DGF are also considered in the current model, including warm ischemic time, duration of dialysis, donor weight and recipient body mass index. Some cases unlikely to inform the model were excluded, such as multiorgan recipients and preemptive transplants. The authors also excluded machine perfused kidneys. The nomogram is available online, accessible to all without cost. The new nomogram was externally validated with a cohort of patients from 2007 (not used to create the model) with the c-index at 0.704. The authors noted improvement in accuracy over the prior model. The use of such a model will remain under discussion. A c-index of 0.7, while improved over the prior model, suggests a fair amount of outcome prediction is not explained by the nomogram. In other health domains, such as stroke or acute myocardial infarction, models have been developed that predict outcomes with a c-statistic at 0.85—much better. How should the nomogram be used? The authors suggest stratifying DGF risk for research purposes or for allocation. It could be used to compare predicted to observed incidence of DGF under various management strategies. In an accompanying editorial Bartlett et al assert that without a robust c-statistic it could be used qualitatively to inform a patient of risk but it should not be used for any regulatory purposes.2 They have suggested that it may be used to help identify best practices for management and prevention of DGF. David A. Goldfarb, M.D. 0022-5347/11/1855-1826/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
1826
www.jurology.com
AND
RESEARCH, INC.
Vol. 185, 1826-1827, May 2011 Printed in U.S.A. DOI:10.1016/j.juro.2010.12.075
RENAL TRANSPLANTATION AND RENOVASCULAR HYPERTENSION
1. Irish WD, McCollum DA, Tesi RJ et al: Nomogram for predicting the likelihood of delayed graft function in adult cadaveric renal transplant recipients. J Am Soc Nephrol 2003; 14: 2967. 2. Bartlett ST, Schweitzer EJ and Cooper M: Prediction model for delayed kidney transplant function: no need for new regulation. Am J Transplant 2010; 10: 2191.
A Study of Renal Outcomes in Obese Living Kidney Donors J. M. Nogueira, M. R. Weir, S. Jacobs, D. Breault, D. Klassen, D. A. Evans, S. T. Bartlett and M. Cooper Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland Transplantation 2010; 90: 993–999.
Background: Little is known about the long–term outcomes of obese living kidney donors (OLKDs). We undertook this study to describe renal outcomes of OLKDs several years after donation. Methods: We invited 101 OLKDs for follow-up health evaluation. Results: Thirty-six subjects (35.6%) completed evaluation at 6.8 ⫾ 1.5 years postdonation. The mean estimated glomerular filtration rate (eGFR) using the abbreviated modification of diet in renal disease (MDRD) equation (MDRD-eGFR) at follow-up was 72.1 ⫾ 16.3 (range: 42–106) mL/min per 1.73 m, and 47.2% of subjects had an MDRD-eGFR of 30 to 59. The absolute decrease in MDRD-eGFR from the time of donation to follow-up was 27.2 ⫾ 13.1 mL/min per 1.73 m (p ⬍0.001 on paired t test), which represents a 29.2% drop in the serial MDRD-eGFRs. Seven subjects (19.4%) had microalbuminuria (30 –300 g/mg creatinine). Subjects with microabuminuria were more likely to have MDRD-eGFR of less than 60 mL/min per 1.73 m (p ⫽ 0.021). Subjects whose body mass index was greater than or equal to 35 kg/m (n ⫽ 14) were found to have an absolute decrement in MDRD-eGFR similar to those with body mass index less than 35 kg/m (31.5 ⫾ 15.6 and 24.7 ⫾ 11.0 mL/min/1.73 m, respectively; p ⫽ not significant). Fifteen (41.6%) were hypertensive at follow-up. Conclusions: On medium-term follow-up, a large proportion of OLKDs will have a MDRD-eGFR of less than 60 mL/min per 1.73 m, and the likelihood increases markedly among those who develop microalbuninuria. This raises concern for hyperfiltration injury. Furthermore, OLKDs experience a substantial incidence of hypertension. Caution is advised in selecting OLKDs pending further data on long-term outcomes. Editorial Comment: The increasing disparity between transplant candidates and the number of organs available has placed pressure on the transplant community to be aggressive regarding the limits of eligibility for organ donation. There may be features of a living donor that raise concern over the potential for long-term renal or other morbidity after donation. However, at the time the decision is made to donate there might be no definitive evidence available to preclude it. Obesity is such an example, as it now may be considered a risk factor for chronic kidney disease. Studies from 5 years ago suggested that nephrectomy for obese donors had few adverse short-term sequelae. At 1 year residual renal function was appropriate without development of hypertension or microalbuminuria. These authors provide a descriptive study of a cohort of obese donors followed out to nearly 7 years. Average eGFR was 72 and 47% of patients had an eGFR of less than 60. Of the patients 19% had microalbuminuria and this finding was more likely with an eGFR of less than 60 ml/min/1.73 m2. Hypertension was reported in 42% of the cohort. The story at 7 years of followup looks different than the 1-year results. The authors sound a word of caution in pursuing the practice of using obese donors, noting the high percentage who had an eGFR of less than 60 ml/min/1.73 m2, microalbuminuria and new onset hypertension. This center now proceeds with great caution in recommending donation for those with a body mass index greater than 35. This study underscores the need to maintain appropriate body weight and regular followup for the long term after donor nephrectomy. David A. Goldfarb, M.D.
1827