- Email: [email protected]
Severe glomerular sclerosis is not associated with poor outcome after kidney transplantation
Severe Glomerular Sclerosis Is Not Associated with Poor Outcome after Kidney Transplantation Amy D. Lu, MD, MPH, Dev Desai, MD, PhD, Bryan D. Myers, MD, Donald C. Dafoe, MD, Edward J. Alfrey, MD, Stanford, California
BACKGROUND: The increased utilization of expanded criteria kidney donors has necessitated the reevaluation of multiple donor risk factors to insure the best outcome from this valuable resource. Reports of decreased graft survival in recipients of kidneys from donors with ≥20% glomerular sclerosis (GS) have led many transplant centers to refuse these donor kidneys. The purpose of this study is to compare outcome in recipients of cadaveric donor kidneys with ≥20% GS versus those with <20% or no GS at our center. METHODS: We retrospectively reviewed 18 donor and 19 recipient and outcome variables in 89 recipients of kidneys, which were biopsied at the time of transplantation, between February 1995 and November 1998. We evaluated outcome based upon the percent of GS and the degree of vasculopathy. RESULTS: Donors with ≥20% GS were older and had more hypertension. Recipients of kidneys with ≥20% GS were older, had higher serum creatinine values at 1 and 2 years, but similar rates of delayed graft function and 2-year graft survival. Vasculopathy did not correlate to any important donor criteria except the percent GS. However, serum creatinine was significantly higher in recipients of kidneys with moderate vasculopathy versus none, up to 2 years after transplantation. There was no significant difference in graft loss based upon vasculopathy. CONCLUSIONS: Kidneys from donors with ≥20% GS provide excellent outcome similar to kidneys from donors with no GS. Am J Surg. 2000;180: 470 – 474. © 2001 by Excerpta Medica, Inc.
From the Departments of Surgery (ADL, DD, DCD, EJA) and Medicine (BDM, EJA), Stanford University School of Medicine, Stanford, California. Requests for reprints should be addressed to Edward J. Alfrey, 500 University Drive, PO Box 850, MC H062, Hershey, Pennsylvania 17033. Presented at the 52nd Annual Meeting of the Southwestern Surgical Congress, Colorado Springs, Colorado, April 9 –12, 2000.
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© 2001 by Excerpta Medica, Inc. All rights reserved.
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ggressive use of expanded criteria donors ([ECDs], donor kidneys that would not meet normal acceptance criteria) has encouraged some centers to develop algorithms for the utilization of kidneys with specific donor criteria based upon outcome associated with these criteria. A recent study suggested that poor outcome can be expected when kidneys with ⱖ20% glomerular sclerosis (severe GS) are transplanted1 Patients who received kidneys with severe GS had an unacceptably high incidence of delayed graft function (DGF) and graft loss, 88% and 38%, respectively. Some centers discard kidneys when there is ⬎20% GS.2 We have not used the biopsy results alone as a reason to discard kidneys and have been able to achieve excellent outcome in recipients of ECD kidneys.3–5 Most experts would agree that this degree of GS may have a significant impact on outcome if the GS accurately reflects the functioning parenchyma of the transplanted kidney. As patients age, the glomeruli near the capsule are more likely to be sclerosed. Therefore, the percent of sclerosed glomeruli may not be an accurate reflection of the functional potential. We prefer to use functional data, eg, the calculated admission creatinine clearance (Ccr),6 – 8 and rarely exclude kidneys based upon a single criterion except viral or malignant comorbidities. Many studies have evaluated the effect of donor age on outcome; frequently, increasing age has been associated with an increase in DGF and decreased graft survival.9 –24 In this study we evaluated our database for recipients of cadaveric only kidney transplants who underwent a biopsy at the time of transplant and compared outcome based upon the percent of glomerular sclerosis and vascular changes.
PATIENTS AND METHODS A retrospective review was performed in 89 patients who were transplanted between February 1995 and November 1998 who had a biopsy at the time of the transplant. All patients consented and were enrolled into an Institutional Review Board-approved study of delayed graft function after kidney transplantation. Data were entered into a relational database. A deep wedge or core biopsy was performed at the time of the transplant in all patients. The biopsies were reviewed for the presence of glomerular sclerosis and vasculopathy. The number of sclerosed glomeruli were counted, compared with the total number of glomeruli and reported as a percentage. Vasculopathy was reported as none, mild, or moderate intimal thickening. All biopsy specimens contained more than 10 glomeruli. The patients were classified into three groups: no GS, ⬍20% 0002-9610/00/$–see front matter PII S0002-9610(00)00502-X
GLOMERULAR SCLEROSIS AFTER KIDNEY TRANSPLANTATION/LU ET AL
TABLE I Comparison of Donor Variables
Donor age (yrs) Donor history of hypertension Donor lowest recorded systolic blood pressure Donor average urine output (mL/hr) Donor calculated admission creatinine clearance (mL/min) Donor peak creatinine (mg/dL) Mean percent glomerular sclerosis on transplant biopsy
No GS (n ⴝ 50)
<20% GS (n ⴝ 26)
≥20% GS (n ⴝ 13)
P Value*
37 ⫾ 161vs3 17%1vs3 75 ⫾ 22 236 ⫾ 157 100 ⫾ 26 1.4 ⫾ 0.6 01vs2,3
51 ⫾ 11 29% 77 ⫾ 16 221 ⫾ 113 96 ⫾ 24 1.3 ⫾ 0.6 8 ⫾ 42vs3
56 ⫾ 123 62%3 83 ⫾ 20 272 ⫾ 170 86 ⫾ 25 1.4 ⫾ 0.5 26 ⫾ 73
⬍0.03 ⬍0.006 NS NS NS NS ⬍0.0001
Donor (D) variables were compared between recipients of kidneys grouped based upon the percent of glomerular sclerosis (GS) on a biopsy at the time of the transplant: none, ⬍20%, and ⱖ20%. * Unpaired Student’s t test or chi square as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
TABLE II Recipient and Outcome Variables No GS (n ⴝ 50) Recipient age (yrs) Human leukocyte antigen match Cold storage time (hrs) Delayed graft function, dialysis in the first week after transplant Serum creatinine in mg/dL at 1 month Serum creatinine in mg/dL at 3 months Serum creatinine in mg/dL at 1 year Serum creatinine in mg/dL at 2 years Best recorded serum creatinine after transplant Percent of patients with at least one rejection episode One-year patient survival One-year graft survival Two-year patient survival Two-year graft survival
<20% GS (n ⴝ 26)
≥20% GS (n ⴝ 13)
P Value*
48 ⫾ 101vs3 1.3 ⫾ 1.6 22 ⫾ 71vs2,3
52 ⫾ 14 1.1 ⫾ 1.5 19 ⫾ 72vs3
56 ⫾ 123 0.6 ⫾ 0.7 14 ⫾ 43
0.012 NS 0.004
36% 1.9 ⫾ 1.31vs3 1.6 ⫾ 0.9 1.8 ⫾ 0.9 1.7 ⫾ 0.8 1.5 ⫾ 0.8 28% 100% 94% 98% 89%
27% 2.1 ⫾ 1.3 1.8 ⫾ 0.7 1.5 ⫾ 0.52vs3 1.3 ⫾ 0.12vs3 1.6 ⫾ 0.9 11% 92% 80% 92% 80%
15% 2.8 ⫾ 2.03 2.0 ⫾ 1.1 2.3 ⫾ 1.03 1.9 ⫾ 0.33 1.7 ⫾ 0.9 10% 100% 100% 100% 92%
NS 0.04 NS 0.007 0.005 NS NS NS NS NS NS
Recipient and outcome variables were compared between recipients of kidneys grouped based upon the percent of glomerular sclerosis (GS) on a biopsy at the time of the transplant: none, ⬍20%, and ⱖ20%. There were 4 recipients of dual transplants in the group with no GS, 7 in the group with ⬍20% GS, and 4 in the group with ⱖ20% GS. * Unpaired Student’s t test or chi-square test as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
GS, ⱖ20% (severe) GS. We evaluated 18 donor variables, and 19 recipient and outcome variables. The donor variables included age; any history of hypertension; the number of hours in the intensive care unit prior to the procurement procedure; the lowest recorded systolic blood pressure; the total time the blood pressure was below 90 mm Hg; the lowest, average and highest hourly urine outputs; the lowest 4-hour period of urine output; the lowest hematocrit; the admission, peak and terminal serum creatinine; the admission and terminal Ccr6; the amount of time CPR was performed if applicable; and the percent of GS and severity of vasculopathy on the biopsy specimen. Recipient data included age; the waiting time prior to transplantation; the human leukocyte antigen match; the cold storage time; the incidence of DGF, defined as dialysis in the first week after the transplant; the serum creatinine at 1 week, 3 and 6 months, and 1 and 2 years; the CCr at 3 months; the best serum creatinine; the length of stay; the mean number of rejections per patient, and the number of patients with at
least one rejection episode; the peak and transplant panel reactive antibody level; the donor to recipient weight ratio; the incidence of graft loss, defined as a permanent return to dialysis; and the 1-year and 2-year actuarial patient and graft survival. We then divided the patients into three groups based upon vasculopathy. The analyses were then repeated. There were 15 recipients of dual transplants in this series where the recipient received both kidneys from an ECD. The decision to use kidneys as a dual was not based upon the biopsy result. There were 4 dual kidney transplant recipients in the group with no GS, 7 in the group with ⬍20% GS, and 4 in the group with severe GS. The immunosuppressive protocol was identical for all three groups; the strategy was triple therapy consisting of prednisolone, cyclosporine emulsion, and azathioprine until 1997 when azathioprine was replaced with mycophenolate mofetil, initiated at 1 g twice daily. Cyclosporine levels were monitored and kept between 350 and 450 ng/mL by
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TABLE III Comparison of Donor, Recipient, and Outcome Variables by Degree of Vasculopathy
Donor age (yrs) Donor history of hypertension Percent GS on biopsy Recipient age Cold storage time (hrs) Delayed graft function, dialysis in the first week after transplant Serum creatinine in mg/dL at 1 month Serum creatinine in mg/dL at 1 year Serum creatinine in mg/dL at 2 years Best recorded serum creatinine after transplant Percent of patients with at least one rejection episode
No Vasculopathy (n ⴝ 55)
Mild Vasculopathy (n ⴝ 26)
Moderate Vasculopathy (n ⴝ 8)
P Value*
40 ⫾ 16 16%1vs2,3 4 ⫾ 81vs3 49 ⫾ 12 20 ⫾ 8
54 ⫾ 11 44%2vs3 8 ⫾ 12 52 ⫾ 11 19 ⫾ 6
47 ⫾ 17 50%3 12 ⫾ 93 55 ⫾ 12 24 ⫾ 6
NS 0.01 0.01 NS NS
31% 2.0 ⫾ 1.3 1.7 ⫾ 0.8 1.5 ⫾ 0.5
31% 1.9 ⫾ 1.3 1.7 ⫾ 0.8 1.6 ⫾ 0.3
25% 3.5 ⫾ 2.1 2.5 ⫾ 1.1 2.9 ⫾ 2.1
NS 0.01 0.04 0.02
1.5 ⫾ 0.9
1.5 ⫾ 1.0
1.8 ⫾ 0.5
NS
20%
25%
NS
19%
Donor (D), and recipient (R) and outcome variables were compared between recipients of kidneys grouped based upon the degree of vasculopathy on a biopsy at the time of transplant: none, mild, and moderate. * Unpaired Student’s t test or chi-square test as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
TDX for the first 6 months and then 250 to 350 ng/mL thereafter. Chi-square and unpaired Student’s t tests were performed when appropriate with significance defined at P ⬍0.05.
RESULTS Donor Variables and Glomerular Sclerosis As expected, the donor age and patients with hypertension increased as the percent GS increased (Table I). There were no significant differences in any other donor variables between the three groups. Specifically, none of the preprocurement parameters, which measure donor stability including systolic blood pressure and urine output, were different. Additionally, none of the donor’s functional parameters including serum creatinines and creatinine clearances (CCr) were different. These data suggest that there were no preprocurement donor issues that would affect outcome. Recipient and Outcome Variables and Glomerular Sclerosis Recipients of kidneys from donors with no GS were significantly younger versus recipients of kidneys from donors with severe GS (see Table II). Additionally, the cold storage time was significantly shorter in those with severe GS versus ⬍20% or none. The incidence of DGF was not different between the groups. In fact, DGF was lowest in the recipients of kidneys with severe GS, although the differences were not statistically significant. The serum creatinine at 1 and 2 years was significantly lower in recipients of kidneys with ⬍20% GS versus severe GS. The 1-year and 2-year actuarial graft survival was not different between the groups. Importantly, recipients of kidneys with severe GS had a 100% and 92% 1-year and 2-year graft survival, respectively. 472
Vasculopathy and Outcome Donors of kidneys with moderate vasculopathy had characteristics similar to those with mild or no vascular changes (see Table III). There was significantly more GS in kidneys with moderate glomerulopathy versus none (12 ⫾ 9% versus 4 ⫾ 8%, respectively; P ⫽ 0.01). The only significantly different recipient or outcome variable between the groups based upon vasculopathy was that recipients of kidneys with moderate changes had higher serum creatinine at 1 and 2 years versus those with no vascular changes. Dual Transplants There were no significant differences in recipient DGF in recipients of dual kidney transplants with no, ⬍20%, or ⱖ20% GS (0%, 0 of 4; 29%, 2 of 7; 0%, 0 of 4, respectively; P ⫽ not significant). The serum creatinines were also similar at 1 year (1.3 ⫾ 0.3, 1.6 ⫾ 0.9, and 1.8 ⫾ 1.2 mg/dL, respectively). Graft loss was 25% (1 of 4), 14% (1 of 7), and 0% (0 of 4), respectively (P ⫽ not significant). We also repeated the analysis excluding recipients of dual kidneys to determine if the use of dual kidneys was responsible for the improvement in DGF and graft survival. The differences persisted despite excluding recipients of dual transplants (see Table IV). Multiple Regression Analysis We used multiple regression analysis to evaluate predictors of elevated creatinine at posttransplant day 7, an indirect measure of DGF. Donor age, percent GS on biopsy, recipient age, and cold storage did not significantly affect creatinine at day 7, although cold storage approached significance (P ⫽ 0.06).
COMMENTS
This study is different from the analysis by Gaber et al1 in that we evaluated only recipients of kidneys from cadaveric
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TABLE IV Donor, Recipient, and Outcome Variables by Percent of Glomerular Sclerosis No GS (n ⴝ 46) Donor age (yrs) Recipient age (yrs) Human leukocyte antigen match Cold storage time (hrs) Delayed graft function, dialysis in the first week after transplant Serum creatinine in mg/dL at 1 year Serum creatinine in mg/dL at 2 years Best recorded serum creatinine after transplant Percent of patients with at least one rejection episode Graft loss at any time during the study period
<20% GS (n ⴝ 19)
≥20% GS (n ⴝ 9)
P Value*
37 ⫾ 161vs2,3 47 ⫾ 10 1.4 ⫾ 1.6 22 ⫾ 71vs2,3
49 ⫾ 122 49 ⫾ 14 1.2 ⫾ 1.4 18 ⫾ 62
52 ⫾ 123 54 ⫾ 14 0.4 ⫾ 0.7 14 ⫾ 53
0.005 NS NS 0.03
39% 1.8 ⫾ 0.9 1.7 ⫾ 0.8 1.5 ⫾ 0.9 23% 5%
26% 1.5 ⫾ 0.32vs3 1.3 ⫾ 0.12vs3 1.7 ⫾ 0.9 22% 15%
20% 2.5 ⫾ 0.93 2.0 ⫾ 0.43 1.9 ⫾ 0.9 11% 0%
NS 0.04 0.008 NS NS NS
Donor (D), recipient (R) and outcome variables were compared between recipients of kidneys grouped based upon the percent of glomerular sclerosis (GS) on a biopsy at the time of the transplant: none, ⬍20%, and ⱖ20%. Recipients of dual transplants were excluded from the analysis. * Unpaired Student’s t test or chi-square test as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
donors. Additionally, we evaluated 18 donor variables that may have an impact on outcome. We found that there were no donor differences that would affect long-term outcome between the recipients of kidneys from donors with no or ⬍20% GS and those with severe (ⱖ20%) GS. The donors in the severe GS group were older and had more hypertension, which is what we expected. There were no differences in DGF between the groups based upon percent GS; in fact, the lowest incidence of DGF was in the group of recipients from kidneys with severe GS, although they also had significantly shorter cold storage times. The serum creatinines at 1 and 2 years was higher in recipients of kidneys with severe GS, but the graft survival was excellent, 100% at 1 year. Donors of kidneys with moderate or no vasculopathy had significantly more hypertension similar to donors with more GS. The incidence of DGF was similar between the groups. Also, the serum creatinine levels at 1 and 2 years were higher in the group with moderate vasculopathy, similar to the group with severe GS. However, the severity of vasculopathy did not parallel the extent of GS. An important factor in the group with severe GS was the shorter cold storage time, which should decrease the incidence of DGF. The decreased outcome in recipients of kidneys from older donors has been attributed to a number of age-related changes including a decline in renal mass associated with concomitant cortical atrophy; glomerular atrophy, mesangial proliferation, and basement membrane thickening with mild hyalinization of arterioles. Additionally, muscular arteries undergo intimal and medial collagenization, although intimal proliferation and medial hypertrophy are relatively rare in older kidneys in the absence of hypertension.25 This does not preclude the use of these kidneys but suggests that care should be taken when making decisions about utilization. There were several recipients of dual kidney transplants in all three groups. We do not believe that the markedly different outcome in this study compared with other studies relates to the use of dual kidneys. When we repeated the analysis excluding recipients of dual transplants, the excel-
lent results persisted in recipients of kidneys from donors with severe GS. The purpose of this report is to demonstrate that kidneys from donors with severe GS can be used. At our institution, we will use these kidneys as dual transplants in some situations; we have previously described our algorithm for using dual transplants.4 There was a 100% graft survival in single and dual kidney recipients from donors with severe GS. The recipients of dual kidneys with severe GS had serum creatinine values at 1 year that were identical to recipients of single kidneys with ⬍20% GS or no GS. Although excellent outcome in terms of graft survival at 1 year was achieved in recipients of single kidneys with severe GS, it may be that optimal long-term outcome will be realized in the recipients of dual transplants. Another recent report also provided analysis that suggests that excellent outcome can be achieved despite severe GS on a biopsy at the time of transplantation.26 These data and ours do not support the policies of some centers that refuse a donor kidney when the procurement biopsy demonstrates ⱖ20% GS. A more extensive review of donor history and a better understanding of functional potential is more useful than relying on the biopsy results alone. In conclusion, recipients of kidneys with ⱖ20% GS or moderate vasculopathy on biopsy have low rates of DGF and excellent graft survival at 2 years. We believe kidneys should not be declined for transplantation based upon the degree of glomerular sclerosis or vasculopathy alone. Judicious use of these kidneys can provide excellent outcome.
REFERENCES 1. Gaber LW, Moore LW, Alloway RR, et al. Glomerular sclerosis as a determinant of posttransplant function of older donor renal allografts. Transplantation. 1995;60:334. 2. Karpinski J, Lajoie G, Cattran D, et al. Outcome of kidney transplantation from high risk donors is determined by both structure and function. Transplantation. 1999;67:1162–1167. 3. Lee CM, Scandling JD, Pavalakis M, et al. A review of the kidneys that nobody wanted: determinants of optimal outcome. Transplantation. 1998;65:213–219. 4. Lu AD, Carter JT, Weinstein RJ, et al. Excellent outcome in
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recipients of dual kidney transplants: a report of the first fifty dual transplants at Stanford University. Arch Surg. 1999;134:971–976. 5. Lee CM, Carter JT, Weinstein R, et al. Dual kidney transplantation: older donors for older recipients. J Am Coll Surg. 1999;189:82–92. 6. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31– 41. 7. Guilliauseau PJ, Fontbonne A, Cahen-Varsaux J, et al. Creatinine clearance evaluation in routine diabetes practice. Diabetes Res. 1988;7:145–148. 8. Robert S, Zarowitz BJ, Peterson EL, Dumler F. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med. 1993;10:1487–1495. 9. Alexander JW, Bennett LE, Breen TJ. Effect of donor age on outcome of kidney transplantation. Transplantation. 1994;57:871– 876. 10. Cecka JM, Terasaki PI. Optimal use for older donor kidneys: older recipients. Transplant Proc. 1995;27:801– 802. 11. Lloveras J. The elderly donor. Transplant Proc. 1991;23:2592– 2595. 12. Kuo PC, Johnson LB, Schweitzer EJ, et al. Utilization of the older donor for renal transplantation. Am J Surg. 1996;172:551– 557. 13. Blumke M, Keller J, Elbe F, et al. Donor age is a risk factor in cadaver kidney transplantation. Transplant Proc. 1992;24:2728. 14. Busson M, Benoit G, N’Doye P, Hors J. Analysis of cadaver donor criteria on the kidney transplant survival rate in 5,129 transplantations. J Urol. 1995;154:356 –360. 15. Rao KV, Kasiske BL, Odlund MD, et al. Influence of cadaver donor age on posttransplant renal function and graft outcome. Transplantation. 1990;49:91–95.
16. Sautner T, Gotzinger P, Wamser P, et al. Impact of donor age on graft function in 1180 consecutive kidney recipients. Transplant Proc. 1991;23:2598 –2601. 17. Koning OH, Ploeg RJ, van Bockel JH, et al. Risk factors for delayed graft function in cadaveric kidney transplantation. Transplantation. 1997;63:1620 –1628. 18. Segoloni GP, Messina M, Triolo G, et al. Impact of donor age in kidney transplantation. Transplant Proc. 1991;23:2620 –2621. 19. Kumar MAS, Stephan R, Chui J, et al. Effect of donor age on graft function and graft survival in cadaver renal transplantation. Transplant Proc. 1993;25:2183–2184. 20. Lloveras J, Arias M, Puig JM, et al. Five-year follow-up of 250 recipients of cadaveric kidney allografts from donors older than 55 years of age. Transplant Proc. 1995;27:981–983. 21. Nghiem DD, Cottington EM, Hsia S. Transplantation of the extreme age donor kidneys. Transplant Proc. 1993;25:1567. 22. Ablaza V, Morris M, Badosa F, et al. Kidneys from cadaveric donors over 60 years of age. Transplant Proc. 1993;25:1554 –1555. 23. Roels L, Vanrenterghem Y, Waer M, et al. The aging kidney donor: another answer to organ shortage? Transplant Proc. 1990;22: 368 –370. 24. Roodnat JI, Zietse R, Mulder PGH, et al. The vanishing importance of age in renal transplantation. Transplantation. 1999; 67:576 –580. 25. Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950;29:496 –507. 26. Pokorna E, Vitko S, Chadimova M, et al. Proportion of glomerulosclerosis in the procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation. 2000;69:36 – 43.
DISCUSSION
did you not choose to show the creatinine clearance as an outcome variable? This measurement and its decline over time, might be a better predictor of graph longevity. Although I’m very encouraged by this two-year data, I’m more interested in whether this marginal donor pool can come close to achieving the average 8 to 9 year graph survival rates that are currently enjoyed by a typical cadaveric recipient.
Dr. Ronald A. Squires (Oklahoma City, OK): This study is, indeed, a very interesting one, and I think very helpful, because this is a popular topic, as all of us in the transplant community try to begin to expand the donor organ pool, using many different diverse strategies. The study suggests that Glomerular Sclerosis may not be as strong a marker for adverse outcome, as we had been taught to believe. After looking at the manuscript, I have three questions. First, I noticed that your recipients of severely sclerotic kidneys, were statistically significantly older than your recipients of less sclerotic or non-sclerotic kidneys. Is this random, or do you selectively exclude marginal donor organs, from your younger recipients? Secondly, do you do anything special or different when utilizing a marginal donor? For example, do you pump these kidneys prior to implanting them to help ensure that they’re good? Or, do you look at donor recipient’s distance from your facility in choosing to accept a marginal donor? I noticed that your cold ischemia times are significantly shorter in your greater than 20 percent sclerosis group, than in your non-sclerosis group. And, as was clearly shown, the serum creatinines are significantly higher in your highly sclerotic group. You didn’t choose to show creatinine clearance, however, in your manuscript. Why
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CLOSING Dr. A. D. Lu: There was a statistical difference in the recipient age. There was no distribution change protocol whereby the expanded crietiaon donors were placed selectively into aged recipients. However, we do place dual kidneys into aged, smaller recipients. The percent of patients receiving dual kidneys was higher in the group with severe GS vs. no GS (31% vs. 8%) and this probably accounted for the difference seen in recipient age. We do not pump kidneys in our region. Finally, in terms of creatinine clearance, we looked at our creatinine clearance at the 3-month mark, and there was no statistical difference among the 3 groups. It approached 60 mL per minute in all groups. We agree that following this parameter will be important over time.
THE AMERICAN JOURNAL OF SURGERY® VOLUME 180 DECEMBER 2000
BACKGROUND: The increased utilization of expanded criteria kidney donors has necessitated the reevaluation of multiple donor risk factors to insure the best outcome from this valuable resource. Reports of decreased graft survival in recipients of kidneys from donors with ≥20% glomerular sclerosis (GS) have led many transplant centers to refuse these donor kidneys. The purpose of this study is to compare outcome in recipients of cadaveric donor kidneys with ≥20% GS versus those with <20% or no GS at our center. METHODS: We retrospectively reviewed 18 donor and 19 recipient and outcome variables in 89 recipients of kidneys, which were biopsied at the time of transplantation, between February 1995 and November 1998. We evaluated outcome based upon the percent of GS and the degree of vasculopathy. RESULTS: Donors with ≥20% GS were older and had more hypertension. Recipients of kidneys with ≥20% GS were older, had higher serum creatinine values at 1 and 2 years, but similar rates of delayed graft function and 2-year graft survival. Vasculopathy did not correlate to any important donor criteria except the percent GS. However, serum creatinine was significantly higher in recipients of kidneys with moderate vasculopathy versus none, up to 2 years after transplantation. There was no significant difference in graft loss based upon vasculopathy. CONCLUSIONS: Kidneys from donors with ≥20% GS provide excellent outcome similar to kidneys from donors with no GS. Am J Surg. 2000;180: 470 – 474. © 2001 by Excerpta Medica, Inc.
From the Departments of Surgery (ADL, DD, DCD, EJA) and Medicine (BDM, EJA), Stanford University School of Medicine, Stanford, California. Requests for reprints should be addressed to Edward J. Alfrey, 500 University Drive, PO Box 850, MC H062, Hershey, Pennsylvania 17033. Presented at the 52nd Annual Meeting of the Southwestern Surgical Congress, Colorado Springs, Colorado, April 9 –12, 2000.
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© 2001 by Excerpta Medica, Inc. All rights reserved.
A
ggressive use of expanded criteria donors ([ECDs], donor kidneys that would not meet normal acceptance criteria) has encouraged some centers to develop algorithms for the utilization of kidneys with specific donor criteria based upon outcome associated with these criteria. A recent study suggested that poor outcome can be expected when kidneys with ⱖ20% glomerular sclerosis (severe GS) are transplanted1 Patients who received kidneys with severe GS had an unacceptably high incidence of delayed graft function (DGF) and graft loss, 88% and 38%, respectively. Some centers discard kidneys when there is ⬎20% GS.2 We have not used the biopsy results alone as a reason to discard kidneys and have been able to achieve excellent outcome in recipients of ECD kidneys.3–5 Most experts would agree that this degree of GS may have a significant impact on outcome if the GS accurately reflects the functioning parenchyma of the transplanted kidney. As patients age, the glomeruli near the capsule are more likely to be sclerosed. Therefore, the percent of sclerosed glomeruli may not be an accurate reflection of the functional potential. We prefer to use functional data, eg, the calculated admission creatinine clearance (Ccr),6 – 8 and rarely exclude kidneys based upon a single criterion except viral or malignant comorbidities. Many studies have evaluated the effect of donor age on outcome; frequently, increasing age has been associated with an increase in DGF and decreased graft survival.9 –24 In this study we evaluated our database for recipients of cadaveric only kidney transplants who underwent a biopsy at the time of transplant and compared outcome based upon the percent of glomerular sclerosis and vascular changes.
PATIENTS AND METHODS A retrospective review was performed in 89 patients who were transplanted between February 1995 and November 1998 who had a biopsy at the time of the transplant. All patients consented and were enrolled into an Institutional Review Board-approved study of delayed graft function after kidney transplantation. Data were entered into a relational database. A deep wedge or core biopsy was performed at the time of the transplant in all patients. The biopsies were reviewed for the presence of glomerular sclerosis and vasculopathy. The number of sclerosed glomeruli were counted, compared with the total number of glomeruli and reported as a percentage. Vasculopathy was reported as none, mild, or moderate intimal thickening. All biopsy specimens contained more than 10 glomeruli. The patients were classified into three groups: no GS, ⬍20% 0002-9610/00/$–see front matter PII S0002-9610(00)00502-X
GLOMERULAR SCLEROSIS AFTER KIDNEY TRANSPLANTATION/LU ET AL
TABLE I Comparison of Donor Variables
Donor age (yrs) Donor history of hypertension Donor lowest recorded systolic blood pressure Donor average urine output (mL/hr) Donor calculated admission creatinine clearance (mL/min) Donor peak creatinine (mg/dL) Mean percent glomerular sclerosis on transplant biopsy
No GS (n ⴝ 50)
<20% GS (n ⴝ 26)
≥20% GS (n ⴝ 13)
P Value*
37 ⫾ 161vs3 17%1vs3 75 ⫾ 22 236 ⫾ 157 100 ⫾ 26 1.4 ⫾ 0.6 01vs2,3
51 ⫾ 11 29% 77 ⫾ 16 221 ⫾ 113 96 ⫾ 24 1.3 ⫾ 0.6 8 ⫾ 42vs3
56 ⫾ 123 62%3 83 ⫾ 20 272 ⫾ 170 86 ⫾ 25 1.4 ⫾ 0.5 26 ⫾ 73
⬍0.03 ⬍0.006 NS NS NS NS ⬍0.0001
Donor (D) variables were compared between recipients of kidneys grouped based upon the percent of glomerular sclerosis (GS) on a biopsy at the time of the transplant: none, ⬍20%, and ⱖ20%. * Unpaired Student’s t test or chi square as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
TABLE II Recipient and Outcome Variables No GS (n ⴝ 50) Recipient age (yrs) Human leukocyte antigen match Cold storage time (hrs) Delayed graft function, dialysis in the first week after transplant Serum creatinine in mg/dL at 1 month Serum creatinine in mg/dL at 3 months Serum creatinine in mg/dL at 1 year Serum creatinine in mg/dL at 2 years Best recorded serum creatinine after transplant Percent of patients with at least one rejection episode One-year patient survival One-year graft survival Two-year patient survival Two-year graft survival
<20% GS (n ⴝ 26)
≥20% GS (n ⴝ 13)
P Value*
48 ⫾ 101vs3 1.3 ⫾ 1.6 22 ⫾ 71vs2,3
52 ⫾ 14 1.1 ⫾ 1.5 19 ⫾ 72vs3
56 ⫾ 123 0.6 ⫾ 0.7 14 ⫾ 43
0.012 NS 0.004
36% 1.9 ⫾ 1.31vs3 1.6 ⫾ 0.9 1.8 ⫾ 0.9 1.7 ⫾ 0.8 1.5 ⫾ 0.8 28% 100% 94% 98% 89%
27% 2.1 ⫾ 1.3 1.8 ⫾ 0.7 1.5 ⫾ 0.52vs3 1.3 ⫾ 0.12vs3 1.6 ⫾ 0.9 11% 92% 80% 92% 80%
15% 2.8 ⫾ 2.03 2.0 ⫾ 1.1 2.3 ⫾ 1.03 1.9 ⫾ 0.33 1.7 ⫾ 0.9 10% 100% 100% 100% 92%
NS 0.04 NS 0.007 0.005 NS NS NS NS NS NS
Recipient and outcome variables were compared between recipients of kidneys grouped based upon the percent of glomerular sclerosis (GS) on a biopsy at the time of the transplant: none, ⬍20%, and ⱖ20%. There were 4 recipients of dual transplants in the group with no GS, 7 in the group with ⬍20% GS, and 4 in the group with ⱖ20% GS. * Unpaired Student’s t test or chi-square test as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
GS, ⱖ20% (severe) GS. We evaluated 18 donor variables, and 19 recipient and outcome variables. The donor variables included age; any history of hypertension; the number of hours in the intensive care unit prior to the procurement procedure; the lowest recorded systolic blood pressure; the total time the blood pressure was below 90 mm Hg; the lowest, average and highest hourly urine outputs; the lowest 4-hour period of urine output; the lowest hematocrit; the admission, peak and terminal serum creatinine; the admission and terminal Ccr6; the amount of time CPR was performed if applicable; and the percent of GS and severity of vasculopathy on the biopsy specimen. Recipient data included age; the waiting time prior to transplantation; the human leukocyte antigen match; the cold storage time; the incidence of DGF, defined as dialysis in the first week after the transplant; the serum creatinine at 1 week, 3 and 6 months, and 1 and 2 years; the CCr at 3 months; the best serum creatinine; the length of stay; the mean number of rejections per patient, and the number of patients with at
least one rejection episode; the peak and transplant panel reactive antibody level; the donor to recipient weight ratio; the incidence of graft loss, defined as a permanent return to dialysis; and the 1-year and 2-year actuarial patient and graft survival. We then divided the patients into three groups based upon vasculopathy. The analyses were then repeated. There were 15 recipients of dual transplants in this series where the recipient received both kidneys from an ECD. The decision to use kidneys as a dual was not based upon the biopsy result. There were 4 dual kidney transplant recipients in the group with no GS, 7 in the group with ⬍20% GS, and 4 in the group with severe GS. The immunosuppressive protocol was identical for all three groups; the strategy was triple therapy consisting of prednisolone, cyclosporine emulsion, and azathioprine until 1997 when azathioprine was replaced with mycophenolate mofetil, initiated at 1 g twice daily. Cyclosporine levels were monitored and kept between 350 and 450 ng/mL by
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TABLE III Comparison of Donor, Recipient, and Outcome Variables by Degree of Vasculopathy
Donor age (yrs) Donor history of hypertension Percent GS on biopsy Recipient age Cold storage time (hrs) Delayed graft function, dialysis in the first week after transplant Serum creatinine in mg/dL at 1 month Serum creatinine in mg/dL at 1 year Serum creatinine in mg/dL at 2 years Best recorded serum creatinine after transplant Percent of patients with at least one rejection episode
No Vasculopathy (n ⴝ 55)
Mild Vasculopathy (n ⴝ 26)
Moderate Vasculopathy (n ⴝ 8)
P Value*
40 ⫾ 16 16%1vs2,3 4 ⫾ 81vs3 49 ⫾ 12 20 ⫾ 8
54 ⫾ 11 44%2vs3 8 ⫾ 12 52 ⫾ 11 19 ⫾ 6
47 ⫾ 17 50%3 12 ⫾ 93 55 ⫾ 12 24 ⫾ 6
NS 0.01 0.01 NS NS
31% 2.0 ⫾ 1.3 1.7 ⫾ 0.8 1.5 ⫾ 0.5
31% 1.9 ⫾ 1.3 1.7 ⫾ 0.8 1.6 ⫾ 0.3
25% 3.5 ⫾ 2.1 2.5 ⫾ 1.1 2.9 ⫾ 2.1
NS 0.01 0.04 0.02
1.5 ⫾ 0.9
1.5 ⫾ 1.0
1.8 ⫾ 0.5
NS
20%
25%
NS
19%
Donor (D), and recipient (R) and outcome variables were compared between recipients of kidneys grouped based upon the degree of vasculopathy on a biopsy at the time of transplant: none, mild, and moderate. * Unpaired Student’s t test or chi-square test as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
TDX for the first 6 months and then 250 to 350 ng/mL thereafter. Chi-square and unpaired Student’s t tests were performed when appropriate with significance defined at P ⬍0.05.
RESULTS Donor Variables and Glomerular Sclerosis As expected, the donor age and patients with hypertension increased as the percent GS increased (Table I). There were no significant differences in any other donor variables between the three groups. Specifically, none of the preprocurement parameters, which measure donor stability including systolic blood pressure and urine output, were different. Additionally, none of the donor’s functional parameters including serum creatinines and creatinine clearances (CCr) were different. These data suggest that there were no preprocurement donor issues that would affect outcome. Recipient and Outcome Variables and Glomerular Sclerosis Recipients of kidneys from donors with no GS were significantly younger versus recipients of kidneys from donors with severe GS (see Table II). Additionally, the cold storage time was significantly shorter in those with severe GS versus ⬍20% or none. The incidence of DGF was not different between the groups. In fact, DGF was lowest in the recipients of kidneys with severe GS, although the differences were not statistically significant. The serum creatinine at 1 and 2 years was significantly lower in recipients of kidneys with ⬍20% GS versus severe GS. The 1-year and 2-year actuarial graft survival was not different between the groups. Importantly, recipients of kidneys with severe GS had a 100% and 92% 1-year and 2-year graft survival, respectively. 472
Vasculopathy and Outcome Donors of kidneys with moderate vasculopathy had characteristics similar to those with mild or no vascular changes (see Table III). There was significantly more GS in kidneys with moderate glomerulopathy versus none (12 ⫾ 9% versus 4 ⫾ 8%, respectively; P ⫽ 0.01). The only significantly different recipient or outcome variable between the groups based upon vasculopathy was that recipients of kidneys with moderate changes had higher serum creatinine at 1 and 2 years versus those with no vascular changes. Dual Transplants There were no significant differences in recipient DGF in recipients of dual kidney transplants with no, ⬍20%, or ⱖ20% GS (0%, 0 of 4; 29%, 2 of 7; 0%, 0 of 4, respectively; P ⫽ not significant). The serum creatinines were also similar at 1 year (1.3 ⫾ 0.3, 1.6 ⫾ 0.9, and 1.8 ⫾ 1.2 mg/dL, respectively). Graft loss was 25% (1 of 4), 14% (1 of 7), and 0% (0 of 4), respectively (P ⫽ not significant). We also repeated the analysis excluding recipients of dual kidneys to determine if the use of dual kidneys was responsible for the improvement in DGF and graft survival. The differences persisted despite excluding recipients of dual transplants (see Table IV). Multiple Regression Analysis We used multiple regression analysis to evaluate predictors of elevated creatinine at posttransplant day 7, an indirect measure of DGF. Donor age, percent GS on biopsy, recipient age, and cold storage did not significantly affect creatinine at day 7, although cold storage approached significance (P ⫽ 0.06).
COMMENTS
This study is different from the analysis by Gaber et al1 in that we evaluated only recipients of kidneys from cadaveric
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TABLE IV Donor, Recipient, and Outcome Variables by Percent of Glomerular Sclerosis No GS (n ⴝ 46) Donor age (yrs) Recipient age (yrs) Human leukocyte antigen match Cold storage time (hrs) Delayed graft function, dialysis in the first week after transplant Serum creatinine in mg/dL at 1 year Serum creatinine in mg/dL at 2 years Best recorded serum creatinine after transplant Percent of patients with at least one rejection episode Graft loss at any time during the study period
<20% GS (n ⴝ 19)
≥20% GS (n ⴝ 9)
P Value*
37 ⫾ 161vs2,3 47 ⫾ 10 1.4 ⫾ 1.6 22 ⫾ 71vs2,3
49 ⫾ 122 49 ⫾ 14 1.2 ⫾ 1.4 18 ⫾ 62
52 ⫾ 123 54 ⫾ 14 0.4 ⫾ 0.7 14 ⫾ 53
0.005 NS NS 0.03
39% 1.8 ⫾ 0.9 1.7 ⫾ 0.8 1.5 ⫾ 0.9 23% 5%
26% 1.5 ⫾ 0.32vs3 1.3 ⫾ 0.12vs3 1.7 ⫾ 0.9 22% 15%
20% 2.5 ⫾ 0.93 2.0 ⫾ 0.43 1.9 ⫾ 0.9 11% 0%
NS 0.04 0.008 NS NS NS
Donor (D), recipient (R) and outcome variables were compared between recipients of kidneys grouped based upon the percent of glomerular sclerosis (GS) on a biopsy at the time of the transplant: none, ⬍20%, and ⱖ20%. Recipients of dual transplants were excluded from the analysis. * Unpaired Student’s t test or chi-square test as appropriate; superscripted numbers denote groups compared that are significantly different. NS ⫽ not significant.
donors. Additionally, we evaluated 18 donor variables that may have an impact on outcome. We found that there were no donor differences that would affect long-term outcome between the recipients of kidneys from donors with no or ⬍20% GS and those with severe (ⱖ20%) GS. The donors in the severe GS group were older and had more hypertension, which is what we expected. There were no differences in DGF between the groups based upon percent GS; in fact, the lowest incidence of DGF was in the group of recipients from kidneys with severe GS, although they also had significantly shorter cold storage times. The serum creatinines at 1 and 2 years was higher in recipients of kidneys with severe GS, but the graft survival was excellent, 100% at 1 year. Donors of kidneys with moderate or no vasculopathy had significantly more hypertension similar to donors with more GS. The incidence of DGF was similar between the groups. Also, the serum creatinine levels at 1 and 2 years were higher in the group with moderate vasculopathy, similar to the group with severe GS. However, the severity of vasculopathy did not parallel the extent of GS. An important factor in the group with severe GS was the shorter cold storage time, which should decrease the incidence of DGF. The decreased outcome in recipients of kidneys from older donors has been attributed to a number of age-related changes including a decline in renal mass associated with concomitant cortical atrophy; glomerular atrophy, mesangial proliferation, and basement membrane thickening with mild hyalinization of arterioles. Additionally, muscular arteries undergo intimal and medial collagenization, although intimal proliferation and medial hypertrophy are relatively rare in older kidneys in the absence of hypertension.25 This does not preclude the use of these kidneys but suggests that care should be taken when making decisions about utilization. There were several recipients of dual kidney transplants in all three groups. We do not believe that the markedly different outcome in this study compared with other studies relates to the use of dual kidneys. When we repeated the analysis excluding recipients of dual transplants, the excel-
lent results persisted in recipients of kidneys from donors with severe GS. The purpose of this report is to demonstrate that kidneys from donors with severe GS can be used. At our institution, we will use these kidneys as dual transplants in some situations; we have previously described our algorithm for using dual transplants.4 There was a 100% graft survival in single and dual kidney recipients from donors with severe GS. The recipients of dual kidneys with severe GS had serum creatinine values at 1 year that were identical to recipients of single kidneys with ⬍20% GS or no GS. Although excellent outcome in terms of graft survival at 1 year was achieved in recipients of single kidneys with severe GS, it may be that optimal long-term outcome will be realized in the recipients of dual transplants. Another recent report also provided analysis that suggests that excellent outcome can be achieved despite severe GS on a biopsy at the time of transplantation.26 These data and ours do not support the policies of some centers that refuse a donor kidney when the procurement biopsy demonstrates ⱖ20% GS. A more extensive review of donor history and a better understanding of functional potential is more useful than relying on the biopsy results alone. In conclusion, recipients of kidneys with ⱖ20% GS or moderate vasculopathy on biopsy have low rates of DGF and excellent graft survival at 2 years. We believe kidneys should not be declined for transplantation based upon the degree of glomerular sclerosis or vasculopathy alone. Judicious use of these kidneys can provide excellent outcome.
REFERENCES 1. Gaber LW, Moore LW, Alloway RR, et al. Glomerular sclerosis as a determinant of posttransplant function of older donor renal allografts. Transplantation. 1995;60:334. 2. Karpinski J, Lajoie G, Cattran D, et al. Outcome of kidney transplantation from high risk donors is determined by both structure and function. Transplantation. 1999;67:1162–1167. 3. Lee CM, Scandling JD, Pavalakis M, et al. A review of the kidneys that nobody wanted: determinants of optimal outcome. Transplantation. 1998;65:213–219. 4. Lu AD, Carter JT, Weinstein RJ, et al. Excellent outcome in
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recipients of dual kidney transplants: a report of the first fifty dual transplants at Stanford University. Arch Surg. 1999;134:971–976. 5. Lee CM, Carter JT, Weinstein R, et al. Dual kidney transplantation: older donors for older recipients. J Am Coll Surg. 1999;189:82–92. 6. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31– 41. 7. Guilliauseau PJ, Fontbonne A, Cahen-Varsaux J, et al. Creatinine clearance evaluation in routine diabetes practice. Diabetes Res. 1988;7:145–148. 8. Robert S, Zarowitz BJ, Peterson EL, Dumler F. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med. 1993;10:1487–1495. 9. Alexander JW, Bennett LE, Breen TJ. Effect of donor age on outcome of kidney transplantation. Transplantation. 1994;57:871– 876. 10. Cecka JM, Terasaki PI. Optimal use for older donor kidneys: older recipients. Transplant Proc. 1995;27:801– 802. 11. Lloveras J. The elderly donor. Transplant Proc. 1991;23:2592– 2595. 12. Kuo PC, Johnson LB, Schweitzer EJ, et al. Utilization of the older donor for renal transplantation. Am J Surg. 1996;172:551– 557. 13. Blumke M, Keller J, Elbe F, et al. Donor age is a risk factor in cadaver kidney transplantation. Transplant Proc. 1992;24:2728. 14. Busson M, Benoit G, N’Doye P, Hors J. Analysis of cadaver donor criteria on the kidney transplant survival rate in 5,129 transplantations. J Urol. 1995;154:356 –360. 15. Rao KV, Kasiske BL, Odlund MD, et al. Influence of cadaver donor age on posttransplant renal function and graft outcome. Transplantation. 1990;49:91–95.
16. Sautner T, Gotzinger P, Wamser P, et al. Impact of donor age on graft function in 1180 consecutive kidney recipients. Transplant Proc. 1991;23:2598 –2601. 17. Koning OH, Ploeg RJ, van Bockel JH, et al. Risk factors for delayed graft function in cadaveric kidney transplantation. Transplantation. 1997;63:1620 –1628. 18. Segoloni GP, Messina M, Triolo G, et al. Impact of donor age in kidney transplantation. Transplant Proc. 1991;23:2620 –2621. 19. Kumar MAS, Stephan R, Chui J, et al. Effect of donor age on graft function and graft survival in cadaver renal transplantation. Transplant Proc. 1993;25:2183–2184. 20. Lloveras J, Arias M, Puig JM, et al. Five-year follow-up of 250 recipients of cadaveric kidney allografts from donors older than 55 years of age. Transplant Proc. 1995;27:981–983. 21. Nghiem DD, Cottington EM, Hsia S. Transplantation of the extreme age donor kidneys. Transplant Proc. 1993;25:1567. 22. Ablaza V, Morris M, Badosa F, et al. Kidneys from cadaveric donors over 60 years of age. Transplant Proc. 1993;25:1554 –1555. 23. Roels L, Vanrenterghem Y, Waer M, et al. The aging kidney donor: another answer to organ shortage? Transplant Proc. 1990;22: 368 –370. 24. Roodnat JI, Zietse R, Mulder PGH, et al. The vanishing importance of age in renal transplantation. Transplantation. 1999; 67:576 –580. 25. Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950;29:496 –507. 26. Pokorna E, Vitko S, Chadimova M, et al. Proportion of glomerulosclerosis in the procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation. 2000;69:36 – 43.
DISCUSSION
did you not choose to show the creatinine clearance as an outcome variable? This measurement and its decline over time, might be a better predictor of graph longevity. Although I’m very encouraged by this two-year data, I’m more interested in whether this marginal donor pool can come close to achieving the average 8 to 9 year graph survival rates that are currently enjoyed by a typical cadaveric recipient.
Dr. Ronald A. Squires (Oklahoma City, OK): This study is, indeed, a very interesting one, and I think very helpful, because this is a popular topic, as all of us in the transplant community try to begin to expand the donor organ pool, using many different diverse strategies. The study suggests that Glomerular Sclerosis may not be as strong a marker for adverse outcome, as we had been taught to believe. After looking at the manuscript, I have three questions. First, I noticed that your recipients of severely sclerotic kidneys, were statistically significantly older than your recipients of less sclerotic or non-sclerotic kidneys. Is this random, or do you selectively exclude marginal donor organs, from your younger recipients? Secondly, do you do anything special or different when utilizing a marginal donor? For example, do you pump these kidneys prior to implanting them to help ensure that they’re good? Or, do you look at donor recipient’s distance from your facility in choosing to accept a marginal donor? I noticed that your cold ischemia times are significantly shorter in your greater than 20 percent sclerosis group, than in your non-sclerosis group. And, as was clearly shown, the serum creatinines are significantly higher in your highly sclerotic group. You didn’t choose to show creatinine clearance, however, in your manuscript. Why
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CLOSING Dr. A. D. Lu: There was a statistical difference in the recipient age. There was no distribution change protocol whereby the expanded crietiaon donors were placed selectively into aged recipients. However, we do place dual kidneys into aged, smaller recipients. The percent of patients receiving dual kidneys was higher in the group with severe GS vs. no GS (31% vs. 8%) and this probably accounted for the difference seen in recipient age. We do not pump kidneys in our region. Finally, in terms of creatinine clearance, we looked at our creatinine clearance at the 3-month mark, and there was no statistical difference among the 3 groups. It approached 60 mL per minute in all groups. We agree that following this parameter will be important over time.
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