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ADULT UROLOGY

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EXPERIENCE WITH MARGINAL LIVING RELATED KIDNEYDONORS: ARE THEY BECOMING ROUTINE OR ARE THERE

STILL ANY DOUBTS?

ANAND SRIVASTAVA, TAPAN SINHA, P. P. VARMA, S. C. KARAN, A. S. SANDHU, G. S. SETHI,R. KHANNA, R. TALWAR, AND V. NARANG

ABSTRACTbjectives. To analyze donor and recipient outcome of grafts from marginal kidney donors (ie, elderly or

uffering from some anomaly).ethods. We had 81 marginal donors from July 1996 to July 2004; 46 were older than 60 years, and 39

ad renal or nonrenal anomaly. The donors and recipients were evaluated for morbidity, graft and recipienturvival, and the number of rejection episodes.esults. The mean (� standard deviation) age of elderly donors was 62.2 � 3.1 years. Follow-up ranged

rom 6 months to 50 months (mean 21.15 � 0.9 months). Actuarial 1-year and 3-year graft survival ratesere 95% and 81%, respectively. Twenty-six percent of recipients maintained serum creatinine levels less

han 1.4 mg/dL. The mean age of hypertensive donors was 46.2 years, and blood pressure was controlledith one drug. Serum creatinine levels in the recipients were less than 1.4 mg/dL in 10 and less than 2.5g/dL in the rest. Eleven percent of hypertensive donors required an increase in their antihypertensiveedication. All donors showed a 15% to 20% increase in their glomerular filtration rate. Donors underwent

imultaneous surgery when indicated.onclusions. Criteria to reject donors need to be reviewed periodically. The elderly and donors with othernomalies are consistently showing acceptable results. Hypertensive donors require assessment with awakembulatory blood pressure monitoring. UROLOGY 66: 971–975, 2005. © 2005 Elsevier Inc.

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he number of patients with end stage renaldisease is rising. In India alone approximately

0,000 such patients are added annually.1 Trans-lantation offers advantages related to longevitynd quality of life.2 Recent reports from Italy,3 Bra-il,4 and India1 admit the growing imbalance betweenvailable kidneys and potential recipients. Cadavericransplantation has not really become common de-pite legal sanction in India. The use of living donorsaries among different countries from less than 1 do-or per 1 million population in Spain and Finland tolmost 20 in Norway.4 To bridge this gap several cen-ers are expanding their living related donor pool bysing marginal donors.1–3 Though these marginalidneys once were supposed to have higher failure

rom the Department of Urology, Army Hospital (Research &eferral), Delhi Cantt, Delhi, IndiaReprint requests: Anand Srivastava, M.S., Army Hospital (Re-

earch & Referral), Department of Urology, Delhi Cantt, Delhi10010, India. E-mail: annand_srivastava@yahoo.comSubmitted: February 21, 2005, accepted (with revisions): May

w, 2005

2005 ELSEVIER INC.LL RIGHTS RESERVED

ates, many reports now have shown acceptable do-or morbidity and comparable graft and recipienturvival.1,5–7 The use of marginal kidneys might beore common today, but they accounted for less

han 2% of all organ transplants in 1999, the mostecent year for which the United Network for Organharing (UNOS) has data.8 The UNOS registryhows that marginal cadaveric kidney transplanta-ion is associated with significant reduction inortality when compared with transplant candi-

ates who remained on maintenance dialysis.9 Ex-rapolating this conclusion to living marginalidneys is logical. However, their use has beenontroversial.10,11 We report our experience witharginal donors and the feasibility of their use in

iving related donor transplantation (LRDT).

MATERIAL AND METHODS

We reviewed our LRDT data for the 8-year period from July996 to July 2004. A total of 81 donors were considered mar-inal (Table I). Marginal donors were defined as those who

ere not ideal in terms of age and glomerular filtration rate

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GFR) or who had a renal or nonrenal anomaly.1 Forty-sixonors were older than 60 years, and 39 had renal or nonrenalnomaly. Among the elderly donors, 1 each also had hyper-ension, a solitary simple renal cyst, and incisional hernia, andhad low GFR (less than 65 mL/min).In all cases, kidneys with lower GFR were taken for trans-

lant regardless of renal or vascular anomalies.All hypertensive donors were controlled with one antihy-

ertensive medication (blood pressure less than 140/90 mm Hg)nd had a normal GFR for age. One of these was 63 years old andad been diagnosed with hypertension approximately 6 monthsarlier. All hypertensive donors had normal echocardiographynd treadmill stress test (TMT) results.

Grafts with renal cysts were evaluated radiologically (ultra-ound, contrast-enhanced computed tomography scan) andonfirmed to have Bosniak grade 1 cysts. Cysts were unroofed.

Two donor kidneys had one renal calculus each (8 mm and.2 cm); these were removed through a small pyelotomy afterarvesting. One ureteric calculus was delivered from the cutreteric end, and the other was removed through a small ure-erotomy. These donors had a normal simplified stone meta-olic workup, as advocated by Rivers et al.12

Adequate ureteral length was obtained by dissection ofhe retrocaval ureter posterior to the inferior vena cava, andhe terminal unhealthy portion was excised before trans-lantation.Of the 2 donors with adrenal tumors, 1 had a 1.5-cm adrenal

yst, which was detected preoperatively and excised duringonor nephrectomy. The other patient had a normal preoper-tive workup; however, during nephrectomy he had markedypertensive episodes and was found to have a small adrenalumor. The tumor was removed and the kidney harvested. Theumor was later reported as a pheochromocytoma. The patientnderwent metaiodobenzyl guanidine scan postoperativelynd did not harbor any other lesion.

One left lumbar kidney was accepted for transplantation. Itad three arteries and two veins. This kidney was approachedith a low lumbar incision. Two arteries were fashioned into a

ommon stem and anastomosed end to side to the externalliac artery, whereas the third artery was anastomosed to thenternal iliac artery.

The patient with cholelithiasis and choledocholithiasis wassymptomatic and underwent endoscopic sphincterotomynd extraction of common bile duct stones 2 months afterephrectomy. Mesh hernioplasty of the incisional hernia waserformed under the same anesthesia.Preoperative donor evaluation included physical examina-

TABLE I. Marginal donorsonor Group No. of Patients

lderly donors 46enal anomaly or disease 19Low GFR 8Renal cyst 3Renal calculi 2Ureteral calculi 2Retrocaval ureter 1Adrenal tumors 2Ectopic kidneys 1onrenal anomalies 20Hypertension 18Cholelithiasis and choledocholithiasis 1Incisional hernia 1

EY: GFR � glomerular filtration rate.

ion, hematologic and biochemical screening, urine micros- t

72

opy and culture, 24-hour estimation of urinary protein andicroalbumin, chest x-ray, electrocardiogram (ECG), renal

onogram, excretory urogram, 99mtechnetium diethylene tri-mine pentaacetic acid (99mTc DTPA) scan, angiogram, andissue typing and matching. Fundoscopy, echocardiography,nd TMT were done in all elderly and hypertensive donors andhen otherwise indicated.All donors underwent nephrectomy through a flank incision.Donors were followed with clinical evaluation, blood pres-

ure (BP) measurement, urinalysis, 24-hour urinary protein,emogram, blood urea nitrogen (BUN), and serum creati-ine measurement, and 99mTc DTPA renal scan at 3 monthsnd yearly after that. All donor complications were re-orded. Donors with stones and benign diseases were eval-ated for recurrence.Patient and graft survival were assessed with Kaplan-Meier

urves. Serum creatinine and urinary protein excretion wereecorded every 3 months in the recipient. A 99mTc DTPA renalcan was performed at 3 months and yearly thereafter. Theumber of rejection episodes was recorded.Immunosuppression was achieved with cyclosporine A,

rednisolone, and azathioprine. In 2001 we started using my-ophenolate mofetil in high-risk and unrelated donations.

RESULTS

There were 46 elderly donors, with a mean age of2.2 � 3.1 years. The oldest donor was 71 years old.he male/female ratio was 0.7:1. Follow-up ranged

rom 6 months to 50 months (mean 21.15 � 0.9onths). The average increase in the donors’ GFR at

-year follow-up was 14 � 4 mL/min. Actuarial-year and 3-year graft survival rates were 95% and1%, respectively, and patient survival rates were8% and 74%, respectively. Twenty-six percent ofecipients maintained serum creatinine levels lesshan 1.4 mg/dL, 41% between 1.4 and 2.5 mg/dL,nd 33% greater than 2.5 mg/dL. Fifteen recipients33%) had acute rejection episodes during the firstmonths. One patient had three episodes of rejec-

ion in the first 6 months.Eight elderly donors had a mean total GFR of 53 �

.5 mL/min and a mean single kidney GFR of 26.3 �

.1 mL/min. Lowest GFR accepted for transplanta-ion was 24 mL/min. The average increase in theFR was 13 � 2 mL/min in recipients, with fol-

ow-up ranging from 6 months to 26 monthsmean 14.4 � 7 months). Serum creatinine levelas less than 2 mg/dL in 2 recipients and greater

han 2 mg/dL in the rest for the same period.The average duration of treatment in the hyper-

ensive donors was 3.5 years (range, 6 months to 5ears). Their mean age was 46.2 years, and bloodressure was controlled with nonpharmacologicanagement and a single antihypertensive drug.

erum creatinine levels in the recipients were lesshan 1.4 mg/dL in 10 and less than 2.5 mg/dL in theest (including the elderly donor) at a median fol-ow-up of 30 months. Two donors required an ad-itional antihypertensive medication at follow-upsf 2 and 3.5 years, respectively. Ten of the hyper-

ensive donors have had 2 years of follow-up. The

UROLOGY 66 (5), 2005

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ean increase in their serum creatinine has been.5 � 0.2 mg/dL, and their GFR has increased by aean of 18 � 2.4 mL/min over this period. Noneas developed proteinuria.The two kidneys with cysts have had 2 and 2.5

ears of follow-up. The GFR has increased by 15L/min, and there has been no cyst recurrence.The patient with an incidental adrenal cyst has

ad no recurrence at 6.5 years’ follow-up. The do-or with pheochromocytoma had postoperativeypotension and required ionotropic support for6 hours. The graft is functioning well at 3 years’ollow-up.

The GFR of the kidney with the retrocaval ureteras increased from 47 mL/min to 66 mL/min.mong the donors and recipients of kidneys with

enal and ureteral calculi, there has been no recur-ence at follow-ups ranging from 13 months to 28onths. A minimum of 3 L of fluid intake has been

dvised to both.The ectopic kidney has done well at 6 months,

nd its GFR has increased by 13 mL/min. The do-ors with cholelithiasis and choledocholithiasisnd incisional hernia are doing well. Thirteen do-ors (16%) had minor and 1 had a severe wound

nfection. All donors have shown a 15% to 20%ncrease in the GFR of their remaining kidney.

COMMENT

In older series, mortality and morbidity of liveonor nephrectomy has been 0.03% and 0.23%,espectively.13 Better surgical techniques and anes-hesia have brought the mortality down to nil inurs and other more recent series.1,3 The donorith pheochromocytoma required intensive care

or 36 hours.There is a reluctance to use elderly donors, owing

o age-related structural and functional changes inheir kidneys. In the UNOS-approved transplantenters, age is not a limiting factor for donation innly 25% of centers. Thirty-seven percent of cen-ers exclude donors more than 65 years of age and5% exclude those aged more than 70 years.14

Microdissection techniques have revealed thicken-ng of the arterial media and intima, glomerular scle-osis and hyalinization, and tubular degeneration andtrophy.15,16 Both graft survival and donor morbidityere considered to be adversely affected.17,18 More

ecent studies, however, have shown acceptable re-ults.7,11,19 Kumar et al. retrospectively reviewedhe long-term outcome of 112 elderly live relatedonors compared with 87 patients whose kidneyonors were younger than 45 years. No addedorbidity for elderly compared to younger donorsas observed. None of the donors had deteriora-

ion in the preoperative status of BP, BUN, and

erum creatinine at 3 months.19 Velosa et al.20 con- k

ROLOGY 66 (5), 2005

luded that kidneys from older living donors up to0 years of age are safe if the prenephrectomy GFRs greater than 70 mL/min/m2. We might suggestere that this issue is not so important. Ojo et al.9ave confirmed that even the use of marginal ca-averic kidneys provides a definite survival and eco-omic advantage over continued dialysis. Moreover,lthough older cadaveric kidneys might have re-uced graft survival compared with their youngerounterparts, this effect is negligible in LRDT.5,6 Kerrt al.21 supported the use of kidneys from older livingonors, having reviewed retrospectively 1126 con-ecutive cyclosporine-treated primary kidney trans-lants, of which 598 were from living donors (74rom donors older than 55 years) and 528 from ca-aver donors (54 from donors older than 55 years).he use of kidneys from cadaver donors older than5 years was associated with a significantly de-reased long-term graft survival, but no such asso-iation existed for recipients of kidneys from livingonors older than 55 years.21 Our own study hashown graft and patient survival to be 81% and4%, respectively, at 3 years.Serum creatinine levels stabilized at greater than

.4 mg/dL in 74% of recipients of kidneys fromlderly donors in our series. Many investigatorsave documented higher creatinine levels in suchecipients.10,11 Graft and patient survival has beenomparable with those in whom the creatinine lev-ls were less than 1.4 mg/dL in our and other se-ies.6,7,11,22 Sumrani et al.11 retrospectively studied69 LRDT and found that the mean serum creati-ine level in the early (first 2 months) and later (5ears) follow-up was significantly greater in recip-ents of older donors (older than 55 years versusess than 55 years). Velosa et al.,20 in their study of5 elderly donors, reported that though the abso-ute GFR values are lower in older donors, the per-entage increase in GFR in both the donors andecipients of these kidneys is not different fromhat in younger donors. This was borne out by ourtudy as well. None of the donors with low GFReveloped proteinuria or showed an increase inheir serum creatinine. Their GFR increased at anverage of 20%. This is in agreement with similarata from Kumar et al.1 We accepted kidneys withow GFR only from elderly donors. Elderly parentsre among the most common donors at our center,wing to a sense of responsibility to their childrennd grandchildren. Some parents suffer depressionf donation is refused.6 In India hemodialysis is aery costly undertaking and sometimes not readilyvailable. These constraints have obligated us toccept these donors. There are, however, no stud-es assessing the long-term fate of these donors andheir kidneys.With respect to acute rejection episodes among

idneys from elderly donors, our series had 15%

973

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cute rejection episodes, which is well within theate for younger donors.11 Kuo et al.23 retrospec-ively examined the outcome for recipients ofRDT from donors older than 60 years (n � 7)ith those for recipients with donors aged less

han 50 years (n � 20) and found no significantifference in acute rejection rates, rate of delayedraft function, or in recipient or graft survival at 1ear. Although Kumar et al.1 found a significantlyreater incidence of acute rejection in kidneysrom older donors as compared with those fromounger donors (42% versus 19%, P �0.05), thisas not borne out by our study. Sumrani et al.11

etrospectively studied 169 LRDTs and found thathe incidence of acute rejection and graft survivalt 1 and 5 years was independent of donor age.Accepted exclusion criteria for donors have in-

luded hypertension, and as definitions of hyper-ension have fallen over the years the cutoff BPevels have also fallen, from 160/95 in the 1970s to40/90 today. There are three reasons for applyinghis exclusion. These are (a) that hypertension be-omes more prevalent after nephrectomy,24 (b)hat the hypertensive donor might face increasedisks to kidney function after nephrectomy,25 andc) the uncertainty of graft outcome from theseonors. A meta-analysis of 48 studies with 3124atients and 1703 controls found that unilateralephrectomy did not affect the prevalence of hy-ertension.26 Several studies conclude that moder-te hypertension alone does not pose a significantazard to the kidney if GFR and urine protein areormal.2,27,28 In general, mildly hypertensive do-ors with normal renal function without protein-ria and microalbuminuria and aged more than 40ears have been accepted as donors.14 However,here is a varied approach among transplantingnits as to the acceptability of hypertensive do-ors. A survey of 173 U.S. transplant centers in995 found that 64% of centers exclude donorsaking an antihypertensive agent, 54% excludehose with persistent borderline hypertension, and% had no policy.14 There is consensus in all guide-

ines however, that the presence of end organ damagehypertensive retinopathy, abnormal ECG/echocar-iography or chest x-ray results, impaired renalunction, or proteinuria) constitutes a contraindi-ation to donation. We accepted patients withoderate recent-onset hypertension with BP less

han 140/90 mm Hg and taking one drug, withreserved GFR and no urinary abnormalities ornd organ damage. In their study of hypertensiveiving donors, Textor et al.2 reported an increase inerum creatinine levels of 0.41 � 0.04 mg/dL at 1ear after donation and recommended awake BPonitoring rather than casual office BP measure-ent to better assess BP control. Awake BP moni-

oring indicated less complete achievement of tar- t

74

et BP levels in 56% of their hypertensive donors.he increase in serum creatinine levels was larger

n our study (0.5 � 0.2 mg/dL). Because we usednly casual office BP measurement, some of ouronors might not be as tightly controlled as weould like to think. Two of our hypertensive do-ors (11%) required a step-up of their medica-ion. Torres et al.24 followed 24 donors who hadorderline hypertension for 10 years. Nine de-eloped definite hypertension. The investigatorsuggested that donation of one kidney might ac-elerate the development of hypertension in pa-ients with predisposition and recommended thatndividuals with borderline or treated hyperten-ion should be advised not to donate.Most centers would accept kidneys with a single

yst.14 We confirmed their benign nature radiolog-cally and unroofed them before transplanting.here has been no recurrence.The donor with adrenal cyst has not had any

ecurrence. The finding of pheochromocytomaas incidental at surgery. To our knowledge thereas been no such reported case.The recipients of the ectopic kidney and retroca-

al ureter are doing well. We do not have a fixedolicy about excluding donors with anatomical ab-ormalities and deal with each case on its merits.Graft lithiasis does not affect long-term func-

ion.29 Use of such kidneys is only tempered by theact that lithiasis might reoccur in both donor andecipient. The likelihood of recurrence is quite lowith asymptomatic stones of less than 1 cm.30 Re-

urrences in the recipient can be treated with ex-racorporeal shock wave lithotripsy in the proneosition.29,30 Therefore donors with small (lesshan 1 cm) nonobstructive stones with normalimplified metabolic workup can be considered foronation.Donors with gallstones, incisional hernia, or

ther surgically treatable diseases might be takenor donation and this disease treated under theame anesthesia, with advantage to the donor.

CONCLUSIONS

In view of the increasing demand for kidneys, theransplant community is obligated to continuouslyeevaluate the criteria used to reject donors. In theuture more marginal donors will have to be ac-epted. From our results it is apparent that most ofhese marginal kidneys have comparable results,nd the living donor pool might thus be expanded.lderly donors should not be refused on the basisf chronological age alone. However, certain cate-ories of donors (hypertensive donors or thoseith low GFR) need longer follow-up to support

heir use irrefutably. Hypertensive donors need

UROLOGY 66 (5), 2005

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igorous pre- and postoperative assessment of theirP, preferably with ambulatory BP monitoring.

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iving related donor pool in renal transplantation: use of mar-inal donors. J Urol 163: 33–38, 2000.

2. Textor CS, Taler JS, Driscoll N, et al: Blood pressure andenal function after kidney donation from hypertensive livingonors. Transplantation 78: 276–283, 2004.

3. Veroux P, Veroux M, Pulliati C, et al: Living kidneyransplantation: a starting experience. Transpl Proc 36: 475–78, 2004.

4. Garcia VD, Garcia CD, Keitel E, et al: Expanding crite-ia for the use of living donors: what are the limits? Transplroc 36: 808–810, 2004.

5. Langle F, Sautner T, Grunberger T, et al: Impact ofonor age in graft function on living related kidney transplant.ranspl Proc 24: 2725–2727, 1992.

6. Kumar A, Kumar RV, Shrinadh ES, et al: Should elderlyonors be accepted in a live related renal transplant program?lin Transpl 8: 523–526, 1994.

7. Kostakis AJ, Kyriakidis S, Garbis S, et al: The fate ofenal transplant from elderly living related donors. Transplroc 22: 1432–1433, 1990.

8. The United Network Of Organ Sharing: Policies, sec-ion 3.5.1. Organ distribution: allocation of cadaveric kid-eys. Definition of expanded criteria donor and standardonor. Available at: http://www.unos.org/policiesandbylaws/olicies.asp? resources�true. Accessed July 24, 2004.

9. Ojo AO, Hanson JA, Meier-Kriesche HU, et al: Survivaln recipients of marginal cadaveric donor kidneys comparedith other recipients and waitlisted transplant candidates.Am Soc Nephrol 12: 589–597, 2001.10. Hayashi T, Koga S, Higashi Y, et al: Living related renal

ransplantation from elderly donor (older than 66 years ofge). Transpl Proc 27: 984–985, 1995.

11. Sumrani N, Delaney V, Ding ZK, et al: Renal transplantrom elderly living donors. Transplantation 51: 305–309,991.12. Rivers K, Sughand S, and Menon M: When and how to

valuate a patient with nephrolithiasis. Urol Clin North Am7: 203–213, 2002.13. Johnson EM, Remucal MJ, Gillingham KJ, et al: Com-

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ar and glomerular changes in the ageing kidney. J Pathol 121:5–78, 1977.17. Korb SM, Pustay M, Kolovich R, et al: Renal transplan-

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elated kidney donors over 60 years old. Transpl Int 9: 109–14, 1992.19. Kumar A, Verma BS, Srivastava A, et al: Long-term fol-

ow up of elderly donors in a live related renal transplantrogram. J Urol 163: 1654–1658, 2000.20. Velosa AJ, Offord PK, and Schroeder RD: Effect of age,

ex and glomerular filtration rate on renal function outcome ofiving kidney donors. Transplantation 60: 1618–1621, 1995.

21. Kerr SR, Gillingham KJ, Johnson EM, et al: Living do-ors �55 years: to use or not to use? Transplantation 67:99–1004, 1999.22. Gaber LW, Moore LW, Alloway RR, et al: Glomerulo-

clerosis as a determinant of posttransplant function of olderonor renal allografts. Transplantation 60: 334–339, 1995.23. Kuo PC, Johnson LB, Schweitzer EJ, et al: Utilization of

he older donor for renal transplantation. Am J Surg 172: 551–57, 1996.24. Torres VE, Offord KP, Anderson CF, et al: Blood pres-

ure determinants in living related renal allograft donors andheir recipients. Kidney Int 31: 1383–1390, 1987.

25. Novick AC, Gephardt G, Guz B, et al: Long term followp after partial nephrectomy of a solitary kidney. New EnglMed 325: 1058–1062, 1991.26. Kasiske BL, Ravenscraft M, Ramos E, et al: The evalua-

ion of living renal transplant donors: clinical practice guide-ines. J Am Soc Nephrol 7: 2288–2313, 1996.

27. Beevers DG, and Lip GY: Does non-malignant essentialypertension cause renal damage? A clinician’s view. J Humypertens 10: 695–699, 1996.28. Perry HM, Miller JP, Fornoff JR, et al: Early predictors

f 15-year end-stage renal disease in hypertensive patients.ypertension 25: 587–594, 1995.29. Wheatley M, Ohl D, Sonda DP, et al: Treatment of renal

ransplant stones by extra corporeal shock wave lithotripsy inhe prone position. Urology 37: 57–60, 1991.

30. William RE: Long term survey of 538 patients with

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