One- and five-year follow-ups on blood pressure and renal function in kidney donors

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1 Trasplat Iteratioal ISSN ORIGINAL ARTICLE Oe- ad five-year follow-ups o blood pressure ad real fuctio i kidey doors Geir Mjoe, 1 Karste Midtvedt, 1 Igar Holme, 2 Ole Øye, 3 Per Fauchald, 4 Herik Bergrem 1 ad Hallvard Holdaas 1 1 Medical Departmet, Oslo Uiversity Hospital, Rikshospitalet, Norway 2 Departmet of Prevetive Cardiology ad Cetre for Cliical Research, Oslo Uiversity Hospital Ullevaal, Oslo, Norway 3 Surgical Departmet, Oslo Uiversity Hospital, Oslo, Norway 4 Norwegia Directorate for Health, Oslo, Oslo, Norway Keywords hypertesio, live kidey door, ephrectomy, real fuctio. Correspodece Geir Mjoe MD, Medical Departmet, Oslo Uiversity Hospital, N-0027 Oslo, Norway. Tel.: ; fax: ; geir.mjoe@oslouiversitetssykehus.o Received: 19 April 2010 Revisio requested: 23 May 2010 Accepted: 12 July 2010 Published olie: 16 August 2010 doi: /j x Summary It is cosidered safe to doate a kidey if iteratioally accepted medical criteria are fulfilled. However, some doors have ecoutered hypertesio, proteiuria ad impaired real fuctio after doatio. The study was based o retrospective data o 908 doors, doatig i the period Preoperative ad follow-up data were collected from patiet files ad the Norwegia Livig Door Registry. Follow-up data were available for 665 doors at 1 year after doatio, ad 256 doors at 5 years after doatio. We calculated the estimated glomerular filtratio rate (egfr) usig the four variable Modificatio of Diet i Real Disease equatio. At 1 ad 5 years after doatio, the prevalece of hypertesio was 11.7% ad 27.1% respectively compared to 2.6% before doatio. Proteiuria was preset i 3.3% ad 1.6% at 1 ad 5 years. Mea egfr was 56.1 ± 10.8 ml/mi/1.73 m 2 at 1 year ad 61.0 ± 11.8 ml/mi/1.73 m 2 at 5 years. Mea blood pressure was ± 10.6/ 76.2 ± 7.5 mmhg at doatio ( = 908), ± 14.2/77.9 ± 8.2 mmhg at 1-year ( = 649) ad ± 15.4/78.8 ± 8.3 mmhg at 5-year follow-ups ( = 247). We foud o evidece of further declie i real fuctio beyod the iitial decremet followig ephrectomy. Itroductio Despite its advatages, livig kidey doatio remais a complex ethical, moral ad medical issue. Iteratioal cosesus exists o evaluatios ad screeig of potetial doors prior to doatio [1]. For reasos of icreased demad for orgas, some trasplat cetres ow are willig to accept margial livig doors with older age, obesity, well-cotrolled hypertesio or low-ormal glomerular filtratio rate (GFR). Sice the 1970s, follow-up studies o previous kidey doors have bee performed with geerally reassurig results [2 9]. However, there have bee cocers about methodological weakesses with some of these studies [3,4,10,11]. Regular ad log-term follow-up of all kidey doors is recommeded [1,12]. Previous doors i geeral are cosidered healthy ad thus regular follow-up visits may be difficult to accomplish. There are curretly o established guidelies detailig follow-up duratio ad itervals, ad follow-up routies vary cosiderably amog differet cetres [13]. The mai purpose of this study was to describe the prevalece of hypertesio, proteiuria ad real fuctio i livig kidey doors at 1 ad 5 years after kidey doatio. Materials ad methods I Norway, all kidey trasplatatios are performed at oe cetre. Predoatio work-up ad postdoatio followup of recipiets ad doors are performed i each couty by the local ephrology departmet i cooperatio with Joural compilatio ª 2010 Europea Society for Orga Trasplatatio 24 (2011)

2 Livig kidey doatio Mjoe et al. the trasplat cetre. Data of all livig kidey doors i Norway have sice 1997 bee etered i a livig door registry [14]. Each data registratio icludes a basic medical examiatio with blood ad uriary samples. Preoperative ad follow-up data were collected from patiet files ad the Norwegia Livig Door Registry. The study was approved by the regioal ethics committee. Hypertesio was defied as blood pressure above 140/ 90 mmhg ad/or use of blood pressure lowerig medicatio. Proteiuria was examied by dipstick, 24-h urie collectio or albumi/protei-creatiie ratio, ad was reported as preset (>300 mg/day) or ot. Creatiie was measured preoperatively at the trasplatatio cetre, ad at follow-up at the door s local hospital. Durig the study period, creatiie assays throughout Norway were stadardized to accommodate cliical use of the Modificatio of Diet i Real Disease (MDRD) formula [15]. Creatiie clearace was measured before doatio, but was ot available at follow-up. Usig the MDRD formula [16], we calculated the estimated glomerular filtratio rate (egfr) at 1 ad 5 years after doatio [17 20]. For reasos of cocers regardig imprecisio ad tedecy to uderestimate true GFR, we did ot calculate preephrectomy egfr. Preoperative data cosisted of height, weight, body mass idex (BMI), age, geder, curret smokig, systolic ad diastolic blood pressure, creatiie, cholesterol ad fastig glucose. Whe the blood pressure measured the day before surgery differed from the measuremet obtaied durig door evaluatio, the lowest value was chose. Follow-up data cosisted of creatiie, egfr, presece of proteiuria (>300 mg/day), systolic ad diastolic blood pressure, ad use of blood pressure lowerig medicatio. Data were reported as mea ± SD. Paired t-test ad McNemar s test were performed as appropriate. Whe performig multiple comparisos, the Boferroi correctio was applied. Statistical aalyses were performed usig spss versio 16 (SPSS Ic., Chicago, IL, USA). Results At our cetre, a total of 908 livig kidey doatios were performed durig Preoperative door characteristics were available for all doors, ad are show i Table 1. Follow-up data (Table 2) were available for 665 doors at 1 year after doatio, ad 256 doors at 5 years after doatio. At 1-year follow-up, 11.7% ( = 76/649) of doors were hypertesive based o blood pressure >140/ 90 mmhg or use of atihypertesive medicatio, a sigificat (P < 0.001) icrease compared with the prevalece prior to doatio. Mea blood pressure was ± 14.2/77.9 ± 8.2 mmhg. Sixtee doors were usig Table 1. Baselie data = 908. Total ( = 908) Oe-year data ( = 665) Five-year data ( = 251) Variable Meas (SD), Meas (SD), Meas (SD), Height, cm (9.1) (9.2) (9.0) Weight, kg (13.0) (13.0) (12.7) BMI, kg/m (3.3) (3.2) (3.1) Age, years (11.7) (11.8) (11.7) Male (41.1) (41.5) (38.3) Smokig (34.9) (32.6) (37.3) Creatiie clearace, ml/mi (29.0) (29.0) (31.6) Preoperative creatiie, lmol/l (13.0) (13.1) (9.7) Creatiie first postoperative day, lmol/l (20.6) (20.8) (18.7) Creatiie at discharge*, lmol/l (20.7) (20.6) (19.0) Postoperative egfr, ml/mi/ (8.7) (9.0) (8.5) egfr at discharge*, ml/mi/ (9.4) (9.4) (8.6) S-cholesterol, mmol/l (1.0) (1.1) (1.1) S-glucose, mmol/l (0.5) (0.5) (0.5) Systolic blood pressure, mmhg (10.6) (10.4) (10.1) Diastolic blood pressure, mmhg (7.5) (7.3) (6.8) Hypertesio (2.5) (2.6) (2.7) P-value calculated by chi-square or t-test. *Mea hospital stay was 7 days. Estimated glomerular filtratio rate by MDRD equatio. Hypertesio defied as BP over 140/90 or use of medicatio. 74 Joural compilatio ª 2010 Europea Society for Orga Trasplatatio 24 (2011) 73 77

3 Mjoe et al. Livig kidey doatio Table 2. Follow-up data o 703 kidey doors. Variable Oe-year follow-up ( = 665) Mea (SD), Five-year follow-up ( = 256) Mea (SD), Systolic bp, mmhg (14.2) (15.4) Diastolic bp, mmhg (8.2) (8.3) Hypertesio* (11.7) (27.1) Bp medicatio (2.5) (17.4) Creatiie, lmol/l (17.8) (16.7) egfr, ml/mi/1.73 m (10.8) (11.8) Proteiuria >300 mg/day (3.3) (1.6) BMI, kg/m (5.4) (4.0) Bp, blood pressure; BMI, body mass idex. *Hypertesio was defied as systolic blood pressure >140, or diastolic blood pressure >90, or use of blood pressure medicatio. Estimated glomerular filtratio rate by MDRD equatio. atihypertesive drugs. Ucomplicated hypertesio was preset before doatio i 17 (2.6%) doors with available data at 1 year after doatio; three of these used oe blood pressure lowerig medicatio ad oe used two. At 1 year, six were ow ormotesive ad altogether six were usig blood pressure medicatio. The remaiig ie doors were still characterized as hypertesive, although they were ot o atihypertesive therapy. At 5-year follow-up, 27.1% were hypertesive, a sigificat (P < 0.001) icrease from 1-year follow-up. Mea blood pressure was ± 15.4/78.8 ± 8.3 mmhg. Forty-three doors used atihypertesive drugs. Seve doors who were hypertesive before doatio had follow-up data at 5 years. Four were usig oe blood pressure medicatio, two were usig two ad oe had become ormotesive. Blood pressure icreased i doors with measuremets both at doatio ad at 1-year follow-up ( = 649, ± 10.5/76.3 ± 7.4 mmhg vs ± 14.2/77.9 ± 8.2 mmhg, P = 0.002/P < 0.001), as well as i doors with measuremets both at 1- ad 5-year follow-ups ( = 205, ± 14.4/77.8 ± 8.3 mmhg vs ± 15.5/78.6 ± 8.2 mmhg, P = 0.02/P = 0.4). Proteiuria 1 year after doatio was preset i 3.3% ( = 20/598) of doors (oe before doatio). At 5-year follow-up, 1.6% ( = 4/244) had proteiuria. Of the 20 doors with proteiuria at 1-year follow-up, eight had become egative, ad 12 had missig data. Doors with proteiuria had a mea BMI of 25.4 kg/m 2 at baselie, similar to those without. Oe year after doatio, mea creatiie was ± 17.8 lmol/l, egfr was 56.1 ± 10.8 ml/mi/ 1.73 m 2 ad 68.8% of doors had egfr <60 ml/mi/ 1.73 m 2. At 5-year follow-up, mea creatiie was 96.7 ± 16.7 lmol/l, egfr was 61.0 ± 11.8 ml/mi/1.73 m 2 ad 48.8% had egfr <60 ml/mi/1.73 m 2. The egfr at discharge from the hospital was sigificatly correlated with both egfr at 1- (r = 0.68) ad 5-year (r = 0.66) follow-ups. Betwee 1- ad 5-year follow-ups ( = 211), there was a icrease i egfr of 1.7 ml/mi/1.73 m 2 per year (53.7 ± 10.3 ml/mi/1.73 m 2 vs ± 11.6 ml/mi/1.73 m 2, P < 0.001). Creatiie values declied throughout the study period, with a correspodig icrease i egfr. The creatiie values obtaied at 5 years after doatio were obtaied at the ed of the period, with more laboratories havig chaged their creatiie assays causig a possible bias. Therefore, we also calculated mea egfr from 1-year follow-ups performed at similar time poits (year) to the 5-year follow-ups. This showed a higher mea egfr at 58.1 ± 10.9 ml/mi/1.73 m 2, however, still lower tha the mea egfr at 5-year follow-up. Discussio The mai fidig i this study is a icrease i blood pressure after doatio. After a iitial decremet followig ephrectomy, egfr did ot show ay further declie betwee 1- ad 5-year follow-ups. Elevated blood pressure is a exclusio criterio for acceptig a potetial door [21]. I our study populatio, 26 doors with hypertesio were allowed to doate, reflectig curret iteratioal treds allowig doors with ucomplicated hypertesio to doate, provided adequate follow-up is available [1,22]. At 1 ad 5 years after doatio, we foud a sigificat icrease i the prevalece of hypertesio. However, six of 17 doors with hypertesio before doatio were ormotesive after 1 year, suggestig some degree of white coat hypertesio durig evaluatio. We also foud a sigificat icrease i both systolic blood pressure ad diastolic blood pressure at 1 year compared with predoatio values. At 5 years, there was a further icrease i systolic blood pressure from 1-year follow-up. The log-term cosequeces of developig hypertesio after kidey doatio might be associated with a icreased risk of cardiovascular disease ad progressive declie i real fuctio [23]. Several studies examiig the risk of hypertesio after kidey doatio have bee retrospective, without or with appropriate cotrol groups, ad with substatial loss of doors durig follow-up [3,10]. Some log-term studies have demostrated o icrease i hypertesio [5,7], whereas others have suggested door ephrectomy to be associated with a icrease i blood pressure [2,3,10,24]. There are some limitatios to the iterpretatio of results o blood pressure i our study. Although our Joural compilatio ª 2010 Europea Society for Orga Trasplatatio 24 (2011)

4 Livig kidey doatio Mjoe et al. health care system offers life-log follow-up free of charge, we also experiece doors lost to follow-up. I cotrast to predoatio measuremets, a slightly elevated blood pressure after doatio will ot ecessarily lead to more frequet cotrols. More frequet visits to health care providers durig follow-up may result i a higher frequecy of diagosed hypertesio [24]. I the geeral populatio, every 10-mmHg icrease i systolic blood pressure ad 5-mmHg icrease i diastolic blood pressure is associated with a 1.5-fold icrease i death from ischaemic heart disease ad stroke [25]. Whether a icrease i blood pressure followig kidey doatio is similarly progostic requires future cosideratio. Closer surveillace ad early itervetio i otherwise healthy adults could offset such risks ad is a strog argumet for madatory life-log follow-up of kidey doors. Several studies have demostrated varyig levels of icreased proteiuria followig kidey doatio [6,26 29],ad some have also suggested a icrease i proteiuria with time after doatio [4,6,30]. Meta-aalyses support the otio that kidey doatio icreases proteiuria [2,4]. Commo risk factors for proteiuria i the geeral populatio are hypertesio, diabetes ad obesity [31]. Oe report suggested a associatio betwee obesity ad proteiuria after door ephrectomy [32]. We did ot fid this associatio i our material. Reassurigly, as i previous studies [2,4,30,33], we foud o evidece of further declie i real fuctio after the iitial decremet due to ephrectomy. Differeces i creatiie assays ad ethicity make absolute values of egfr from differet populatios of previous kidey doors difficult to compare. A recet study based o registry data [34] foud a postdoatio mea egfr of 56.1 ml/mi/1.73 m 2 i Caucasias withi 1-year postdoatio, similar to our fidig. Other studies have show differet values for egfr [4,33,35] after doatio. As the MDRD equatio may uderestimate real fuctio i previous kidey doors, true GFR may be slightly higher [17,19,20]. As egfr at discharge is highly correlated with the value after 1 ad 5 years, this parameter may be useful i decidig whether a door may eed more frequet follow-up visits. The stregth of this study is preoperative ad followup data from a relatively large ad represetative sample of kidey doors with early complete baselie data. Limitatios iclude blood pressure measuremets, aalysis of creatiie ad doors lost to follow-up. It is difficult to estimate the possible impact of loss to follow-up i a sigle study. Two meta-aalyses [3,4] have idicated that doors lost to follow-up are healthier tha doors attedig timed cotrol visits. I coclusio, we report a icrease i blood pressure ad icreased frequecy of hypertesio after kidey doatio. From 1 to 5 years post doatio, there was o evidece of declie i real fuctio. Our fidigs support a coscietious follow-up of live kidey doors. Authorship GM: collected data, performed statistical aalysis ad participated i writig of the mauscript. IH ad HB: participated i writig of the mauscript ad statistical aalysis. OØ, PF, KM ad HH: participated i writig of the mauscript. Fudig Geir Mjøe is supported by a PhD scholarship sposored by the foudatio for health ad rehabilitatio. Ackowledgemets This project has bee fiaced with fuds from the Norwegia Foudatio for Health ad Rehabilitatio. Refereces 1. Delmoico F. A report of the Amsterdam forum o the care of the live kidey door: data ad medical guidelies. Trasplatatio 2005; 79: S Kasiske BL, Ma JZ, Louis TA, Swa SK. Log-term effects of reduced real mass i humas. Kidey It 1995; 48: Boudville N, Prasad GV, Koll G, et al. Meta-aalysis: risk for hypertesio i livig kidey doors. A Iter Med 2006; 145: Garg AX, Muirhead N, Koll G, et al. Proteiuria ad reduced kidey fuctio i livig kidey doors: a systematic review, meta-aalysis, ad meta-regressio. Kidey It 2006; 70: Narku-Burgess DM, Nola CR, Norma JE, Page WF, Miller PL, Meyer TW. Forty-five year follow-up after uiephrectomy. Kidey It 1993; 43: Talseth T, Fauchald P, Skrede S, et al. Log-term blood pressure ad real fuctio i kidey doors. Kidey It 1986; 29: Najaria JS, Chavers BM, McHugh LE, Matas AJ. 20 years or more of follow-up of livig kidey doors. Lacet 1992; 340: Boer G, Shelp WD, Newto M, Rieselbach RE. Factors ifluecig the icrease i glomerular filtratio rate i the remaiig kidey of trasplat doors. Am J Med 1973; 55: Eger E, Skjorte F. Sigificace of uriary microscopy ad real biopsy i the evaluatio of livig doors before trasplatatio. Scad J Urol Nephrol 1972; 6: Omme ES, Wisto JA, Murphy B. Medical risks i livig kidey doors: absece of proof is ot proof of absece. Cli J Am Soc Nephrol 2006; 1: Joural compilatio ª 2010 Europea Society for Orga Trasplatatio 24 (2011) 73 77

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