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Factors predicting donor renal function after donor nephrectomy: Does age matter?
Indian Journal of Transplantation 2011 October–December Volume 5, Number 4; pp. 162–164
Review Article
Factors predicting donor renal function after donor nephrectomy: Does age matter? Aneesh Srivastava1, Jatinder Kumar2, Rakesh Kapoor1 1
Professor, 2Senior Resident, Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow – 226014, UP, India.
INTRODUCTION Approximately 4.5 million of people are affected by the end-stage renal disease.1 For these patients, kidney transplant is now established as the best option. There is a large gap between the demand and availability of the kidneys for this purpose. Therefore, the acceptance criterion has been expanded to include older patients which may have suboptimal organs. Compared with cadaver donor renal transplantation, living donor transplantation has clear benefits for the recipient, including shorter waiting time, better renal function and longer patient and graft survival. However, there is no potential physical benefit to the donor, but there are inherent risks.2 Donor nephrectomy may lead to surgical as well as medical complications in donors including decreased renal function reported in 0.14% donors who developed end-stage renal failure.3 A great number of experiments using renal ablation models have established that after a critical reduction in the number of functioning nephrons, hemodynamic changes, with an increase in the glomerular plasma flow and capillary hydraulic pressure, and glomerular hypertrophy take place in the remaining nephrons.4 These maladaptive hemodynamic and hypertrophic changes, together with an increased production of vasoactive and profibrinogenic substances by the remaining nephrons, collaborate in the appearance of structural and functional abnormalities; this if untreated lead to end-stage renal failure.5 The clinical course and risk factors for developing endstage renal disease after donor nephrectomy in living related donors have scarcely been investigated. Various formulae have been described and utilized to calculate creatinine clearance following donor nephrectomy, e.g. modified modification of diet in renal disease (MDRD), Cockcroft-Gault (CG) formula, and chronic kidney disease epidemiology
Correspondence: Dr. Aneesh Srivastava, email: [email protected] doi: 10.1016/S2212-0017(11)60032-4
collaboration (CKD–EPI) equation. Creatinine clearance and cystatin-C clearance have shown progressive decline in the renal function with increasing age. Age-related decline in the glomerular filtration rate is generally believed to be <1 mL/min/1.73 m2 each year. The search for an ideal method is still ongoing. Elderly donor may have an increased risk in peri- and post-transplant period. Kidneys procured from elderly patients undergo several changes that decrease their nephron mass and reduce the glomerular filtration rate, associated with adverse conditions of diabetes mellitus, hypertension, and arteriosclerosis. This observation implies that kidney grafts from elderly donors cannot be regarded as optimal and are not suitable for younger patients. Because of the ever-growing waiting lists and the paucity of available organs, increasingly, kidneys from extended criteria, deceased donors are being used specially for older patients where the use of optimal organs might not be advisable. In this article, we have reviewed the literature to predict the factors affecting the renal function after donor nephrectomy, and attempt to evaluate the impact of donor age on the outcome in terms of renal parameters in the donor itself and the recipient.
DISCUSSION Chien and Wang in their study included 51 living donors of renal transplant between March 2002 and December 2008, calculated 24-hour creatinine clearance and functional ratio by dimercaptosuccinic acid (DMSA) scan pre- and post-donation. They found an increase in the mean creatinine clearance of preserved kidney from 58.2 mL/min to 79.6 mL/min on day 2 post-nephrectomy. The function of the preserved kidney increased on average by 36.9%. Better
Factors predicting donor renal function
initial function of the preserved kidney was associated with higher creatinine clearance. Ten percent of donors demonstrated a decrease in renal function on postoperative day 2. Old age was significantly associated with lower creatinine clearance after nephrectomy. The percentage increase on the renal function was lower in older donors.6 Nozaki and Ishida from Tokyo Women Medical University, Japan, did a study on 68 donors and found that pre- and postoperative serum creatinine and uric acid were significantly higher in male donors. They also found that the ratio of glomerular sclerosis, systolic blood pressure, and diastolic blood pressure positively correlated with donor age on simple regression analysis. Deterioration of renal function after donor nephrectomy correlated negatively with body mass index (BMI), and positively with the severity of arteriosclerosis in the interlobar arteries. They concluded that preventing the progression of arteriosclerosis and selecting an optimal BMI before donor nephrectomy helped to avoid impaired renal function among live kidney donors.7 Renal function parameters such as serum creatinine, cystatin-C, urinary total protein, urine Immunoglobulin G (IgG), urine transferring, urine albumin, urine retinol binding protein, urine a1 and b2 microglobulin, and urine N-acetyl beta-glucosaminidase were studied in 83 transplant patients by Hamza et al. They found that these markers showed a relevant increase between 12 and 18 hours after donor nephrectomy. The time to increase differed slightly between individual parameters. At day 4, there was no significant difference between the initial and final values, except urine a1 microglobulin, which indicates an impaired tubular function.8 In a study conducted from March 1976 to March 2005 on 146 old-aged (>50 years) donors by El Agroudy et al., 30.8% donors became hypertensive and most of them received one drug only. Five donors became diabetic and five developed proteinuria. The rate of diabetic and hypertensive was similar to the age-matched general population.9 Recipient survival after elderly donor kidney transplantation was directly related to donor age and creatinine levels at 1 month. The use of protective immunotherapy (cyclosporinefree) has been identified as a protective factor. Regarding graft survival, donor age (>70 years) was an independent risk factor. This result is consistent with findings in other series, although some studies have donor age as an independent risk factor. Moreover, other independent risk factors identified in their review include the presence of acute tuber necrosis (ATN) and serum creatinine levels above 2.5 mg/dL at 1 month after surgery. Hwang et al. in their study of 222 patients estimated kidney volume before and 6 months after surgery using voxel count method utilizing 64-section helical computed
Review Article
163
tomography scanners and found it to be valid and accurate option to calculate the actual kidney weight and its correlation with donor characteristics and kidney function. Donors of younger ages and with lower pre-operative kidney volume tend to have a higher volume increase in the remaining kidney after donor nephrectomy. Pre-operative kidney volume measurement could be used to predict the delayed kidney function recovery.10 The study by Barry et al. examines the short-term (3 months) effect of donor nephrectomy on glomerular filtration rate (GFR) and the occurrence of stage-3 chronic kidney disease (CKD) post donor nephrectomy, and observed that stage-3 CKD was commonly observed in older donors and eGFR is a poor predictor of true GFR in kidney donors.11 Galeano et al. in their study categorized donors into three groups based on the age, as <50 years, 50–70 years, and >70 years. When these groups were compared, no difference was observed in the time bound dialysis, the prevalence of delayed graft function, or rejection episodes or in the initial immunosuppression. They have reported an increased incidence of rejection episodes among kidney from older donors, which are more immunogenic than the kidney from younger donors. Graft function at 3 and 12 months was significantly worse among recipients transplanted from older donors.12 Another study of 52 elderly donors by Kumar et al. highlighted the fact that actuarial 2- and 5-year survival was 96% and 74%, respectively, and was comparable to the graft survival of the recipient of kidneys from the young donors. These donors also did not had any complication on a 6-year follow-up, and therefore healthy donors should not be rejected based on chronological age only.13 The above fact was reiterated by a study on larger population in 2003 by Kumar et al.14
CONCLUSION Elderly donors can be safely used as donors if other comorbidities are not present. The graft survival in the recipient is also comparable to the graft survival in kidney from young donors.
REFERENCES 1.
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplant, and recipient of a first cadaveric transplant. N Engl J Med 1999;341:1725.
164
2.
3.
4.
5. 6.
7.
8.
Indian Journal of Transplantation 2011 October–December; Vol. 5, No. 4
Chin EH, Hazzan D, Herron DMG, et al. Laparoscopic donor nephrectomy/intraoperative safety, immediate morbidity, and delayed complication with 500 cases. Surg Endosc 2007; 21:521. El Agroudy AE, Sabry AA, Wafa EW, et al. Long term followup of living kidney donor: a longitudinal study. BJU Int 2007;100:1351. Brenner BM. Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 1983; 23:647–55. Remuzzi G, Bektani T. Pathophysiology of progressive nephropathies. N Engl J Med 1998;339:1448–56. Chien CH, Chiang YJ, Wang HH, et al. Change in renal function after laparoscopic donor nephrectomy for kidney transplantation. Transpl Proc 2010;42:692–5. Nozaki T, Ishida H, Tokumoto T, et al. Risk factor for deterioration of renal function after donor nephrectomy. Transpl Proc 2010;42:1476–8. Hamza A, Wagner S, Weigand K, et al. Transperitoneal, hand assisted laparoscopic donor nephrectomy: surveillance of
9.
10.
11.
12.
13.
14.
Srivastava et al.
renal function by immune monitoring. Transpl Proc 2008;40: 895–901. El Agroudy AE, Wafa EW, Sabry AA, et al. The health of elderly living donors after donation. Ann Transplant 2009; 14:13–9. Jeon HG, Lee SR, Joo DJ, et al. Predictors of kidney volume change and delayed kidney function recovery after donor nephrectomy. J Urol 2010;184:1057–63. Barry YM, Parker T 3rd, Daoud Y, et al. Definition of chronic kidney disease after uninephrectomy in living donors: what are the implications? Transplantation 2010;90:575–80. Galeano C, Marcén R, Jimenez S, et al. Utilization of elderly kidney donors does not affect graft survival in medium term. Transpl Proc 2010;42:3935–7. Kumar A, Mandhani A, Srivastava A, et al. Expanding the living related donor pool in renal transplantation: use of marginal donors. J Urol 2000;163:33–6. Kumar A, Das SK, Srivastava A. Expanding the living related donor pool in renal transplantation: use of marginal donors. Transpl Proc 2003;35:28–9.
Review Article
Factors predicting donor renal function after donor nephrectomy: Does age matter? Aneesh Srivastava1, Jatinder Kumar2, Rakesh Kapoor1 1
Professor, 2Senior Resident, Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow – 226014, UP, India.
INTRODUCTION Approximately 4.5 million of people are affected by the end-stage renal disease.1 For these patients, kidney transplant is now established as the best option. There is a large gap between the demand and availability of the kidneys for this purpose. Therefore, the acceptance criterion has been expanded to include older patients which may have suboptimal organs. Compared with cadaver donor renal transplantation, living donor transplantation has clear benefits for the recipient, including shorter waiting time, better renal function and longer patient and graft survival. However, there is no potential physical benefit to the donor, but there are inherent risks.2 Donor nephrectomy may lead to surgical as well as medical complications in donors including decreased renal function reported in 0.14% donors who developed end-stage renal failure.3 A great number of experiments using renal ablation models have established that after a critical reduction in the number of functioning nephrons, hemodynamic changes, with an increase in the glomerular plasma flow and capillary hydraulic pressure, and glomerular hypertrophy take place in the remaining nephrons.4 These maladaptive hemodynamic and hypertrophic changes, together with an increased production of vasoactive and profibrinogenic substances by the remaining nephrons, collaborate in the appearance of structural and functional abnormalities; this if untreated lead to end-stage renal failure.5 The clinical course and risk factors for developing endstage renal disease after donor nephrectomy in living related donors have scarcely been investigated. Various formulae have been described and utilized to calculate creatinine clearance following donor nephrectomy, e.g. modified modification of diet in renal disease (MDRD), Cockcroft-Gault (CG) formula, and chronic kidney disease epidemiology
Correspondence: Dr. Aneesh Srivastava, email: [email protected] doi: 10.1016/S2212-0017(11)60032-4
collaboration (CKD–EPI) equation. Creatinine clearance and cystatin-C clearance have shown progressive decline in the renal function with increasing age. Age-related decline in the glomerular filtration rate is generally believed to be <1 mL/min/1.73 m2 each year. The search for an ideal method is still ongoing. Elderly donor may have an increased risk in peri- and post-transplant period. Kidneys procured from elderly patients undergo several changes that decrease their nephron mass and reduce the glomerular filtration rate, associated with adverse conditions of diabetes mellitus, hypertension, and arteriosclerosis. This observation implies that kidney grafts from elderly donors cannot be regarded as optimal and are not suitable for younger patients. Because of the ever-growing waiting lists and the paucity of available organs, increasingly, kidneys from extended criteria, deceased donors are being used specially for older patients where the use of optimal organs might not be advisable. In this article, we have reviewed the literature to predict the factors affecting the renal function after donor nephrectomy, and attempt to evaluate the impact of donor age on the outcome in terms of renal parameters in the donor itself and the recipient.
DISCUSSION Chien and Wang in their study included 51 living donors of renal transplant between March 2002 and December 2008, calculated 24-hour creatinine clearance and functional ratio by dimercaptosuccinic acid (DMSA) scan pre- and post-donation. They found an increase in the mean creatinine clearance of preserved kidney from 58.2 mL/min to 79.6 mL/min on day 2 post-nephrectomy. The function of the preserved kidney increased on average by 36.9%. Better
Factors predicting donor renal function
initial function of the preserved kidney was associated with higher creatinine clearance. Ten percent of donors demonstrated a decrease in renal function on postoperative day 2. Old age was significantly associated with lower creatinine clearance after nephrectomy. The percentage increase on the renal function was lower in older donors.6 Nozaki and Ishida from Tokyo Women Medical University, Japan, did a study on 68 donors and found that pre- and postoperative serum creatinine and uric acid were significantly higher in male donors. They also found that the ratio of glomerular sclerosis, systolic blood pressure, and diastolic blood pressure positively correlated with donor age on simple regression analysis. Deterioration of renal function after donor nephrectomy correlated negatively with body mass index (BMI), and positively with the severity of arteriosclerosis in the interlobar arteries. They concluded that preventing the progression of arteriosclerosis and selecting an optimal BMI before donor nephrectomy helped to avoid impaired renal function among live kidney donors.7 Renal function parameters such as serum creatinine, cystatin-C, urinary total protein, urine Immunoglobulin G (IgG), urine transferring, urine albumin, urine retinol binding protein, urine a1 and b2 microglobulin, and urine N-acetyl beta-glucosaminidase were studied in 83 transplant patients by Hamza et al. They found that these markers showed a relevant increase between 12 and 18 hours after donor nephrectomy. The time to increase differed slightly between individual parameters. At day 4, there was no significant difference between the initial and final values, except urine a1 microglobulin, which indicates an impaired tubular function.8 In a study conducted from March 1976 to March 2005 on 146 old-aged (>50 years) donors by El Agroudy et al., 30.8% donors became hypertensive and most of them received one drug only. Five donors became diabetic and five developed proteinuria. The rate of diabetic and hypertensive was similar to the age-matched general population.9 Recipient survival after elderly donor kidney transplantation was directly related to donor age and creatinine levels at 1 month. The use of protective immunotherapy (cyclosporinefree) has been identified as a protective factor. Regarding graft survival, donor age (>70 years) was an independent risk factor. This result is consistent with findings in other series, although some studies have donor age as an independent risk factor. Moreover, other independent risk factors identified in their review include the presence of acute tuber necrosis (ATN) and serum creatinine levels above 2.5 mg/dL at 1 month after surgery. Hwang et al. in their study of 222 patients estimated kidney volume before and 6 months after surgery using voxel count method utilizing 64-section helical computed
Review Article
163
tomography scanners and found it to be valid and accurate option to calculate the actual kidney weight and its correlation with donor characteristics and kidney function. Donors of younger ages and with lower pre-operative kidney volume tend to have a higher volume increase in the remaining kidney after donor nephrectomy. Pre-operative kidney volume measurement could be used to predict the delayed kidney function recovery.10 The study by Barry et al. examines the short-term (3 months) effect of donor nephrectomy on glomerular filtration rate (GFR) and the occurrence of stage-3 chronic kidney disease (CKD) post donor nephrectomy, and observed that stage-3 CKD was commonly observed in older donors and eGFR is a poor predictor of true GFR in kidney donors.11 Galeano et al. in their study categorized donors into three groups based on the age, as <50 years, 50–70 years, and >70 years. When these groups were compared, no difference was observed in the time bound dialysis, the prevalence of delayed graft function, or rejection episodes or in the initial immunosuppression. They have reported an increased incidence of rejection episodes among kidney from older donors, which are more immunogenic than the kidney from younger donors. Graft function at 3 and 12 months was significantly worse among recipients transplanted from older donors.12 Another study of 52 elderly donors by Kumar et al. highlighted the fact that actuarial 2- and 5-year survival was 96% and 74%, respectively, and was comparable to the graft survival of the recipient of kidneys from the young donors. These donors also did not had any complication on a 6-year follow-up, and therefore healthy donors should not be rejected based on chronological age only.13 The above fact was reiterated by a study on larger population in 2003 by Kumar et al.14
CONCLUSION Elderly donors can be safely used as donors if other comorbidities are not present. The graft survival in the recipient is also comparable to the graft survival in kidney from young donors.
REFERENCES 1.
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplant, and recipient of a first cadaveric transplant. N Engl J Med 1999;341:1725.
164
2.
3.
4.
5. 6.
7.
8.
Indian Journal of Transplantation 2011 October–December; Vol. 5, No. 4
Chin EH, Hazzan D, Herron DMG, et al. Laparoscopic donor nephrectomy/intraoperative safety, immediate morbidity, and delayed complication with 500 cases. Surg Endosc 2007; 21:521. El Agroudy AE, Sabry AA, Wafa EW, et al. Long term followup of living kidney donor: a longitudinal study. BJU Int 2007;100:1351. Brenner BM. Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 1983; 23:647–55. Remuzzi G, Bektani T. Pathophysiology of progressive nephropathies. N Engl J Med 1998;339:1448–56. Chien CH, Chiang YJ, Wang HH, et al. Change in renal function after laparoscopic donor nephrectomy for kidney transplantation. Transpl Proc 2010;42:692–5. Nozaki T, Ishida H, Tokumoto T, et al. Risk factor for deterioration of renal function after donor nephrectomy. Transpl Proc 2010;42:1476–8. Hamza A, Wagner S, Weigand K, et al. Transperitoneal, hand assisted laparoscopic donor nephrectomy: surveillance of
9.
10.
11.
12.
13.
14.
Srivastava et al.
renal function by immune monitoring. Transpl Proc 2008;40: 895–901. El Agroudy AE, Wafa EW, Sabry AA, et al. The health of elderly living donors after donation. Ann Transplant 2009; 14:13–9. Jeon HG, Lee SR, Joo DJ, et al. Predictors of kidney volume change and delayed kidney function recovery after donor nephrectomy. J Urol 2010;184:1057–63. Barry YM, Parker T 3rd, Daoud Y, et al. Definition of chronic kidney disease after uninephrectomy in living donors: what are the implications? Transplantation 2010;90:575–80. Galeano C, Marcén R, Jimenez S, et al. Utilization of elderly kidney donors does not affect graft survival in medium term. Transpl Proc 2010;42:3935–7. Kumar A, Mandhani A, Srivastava A, et al. Expanding the living related donor pool in renal transplantation: use of marginal donors. J Urol 2000;163:33–6. Kumar A, Das SK, Srivastava A. Expanding the living related donor pool in renal transplantation: use of marginal donors. Transpl Proc 2003;35:28–9.