Eleven years of chronic hemodialysis in Uruguay: Mortality time course

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1 Kidney Interntionl, Vol. 47 (1995), pp Eleven yers of chronic hemodilysis in Uruguy: Mortlity time course Ju M. FERNANDEZ, EMI!vIA SHWEDT, PABLO AMBROSONI, FRANISO GONZALEZ, nd NELSON MAZZUHI Registiy ommittee, Uruguyn Society of Nephrology, Montevideo, UnLguy Eleven yers of chronic hemodilysis in Uruguy: Modlity time course. Uruguy is developing country with 3.1 million inhbitnts. hronic dilysis tretment (DT) begn to spred fter the cretion of the Ntionl Fund of Resources (NFR) in 198. This Fund receives contribution from ll inhbitnts to finnce, mong others, the high cost tretment, dilysis nd renl trnsplnttion (RT). We nlyzed the dt bse from 1981 to 1991 of the Hemodilysis Ntionl Registry to find the mortlity time course. To compre with other popultions, indirect stndriztion methods were used. Two thousnd nd seventy-one ptients received chronic hemodilysis tretment (HT) during the period cited. Incidence nd prevlence of end-stge renl disese (ESRD) incresed from 32 to 9 nd from 38 to 39 ptients per millon popultion, respectively. Annul gross mortlity decresed from 21 to 9% in spite of simultneouse increse in the percentge of high risk ptients. According to the ge-mtched ntionl generl mortlity, the rtio between observed nd expected deths ws 21 in 1981 nd 4 in The stndrdized deth rte ws deths/1 ptient-yers t risk when the USA ESRD 1987 to 1989 mortlity rte by ge, rce nd dignosis ws used s stndrd. These results point out tht it is possible to provide ESRD tretment in developing ountries to chieve pproprite omprtive results in delying mortlity. Uruguy hs stble, predominntly white popultion round 3.1 million inhbitnts, 1.7% of whom re older thn 65 yers (census 1985) [1]. For 199 the gross ntionl product (GNP) per person ws U $262 nd the humn development index.881 [2]. For the sme yer the nnul mortlity ws 1%, the infnt mortlity rte 21 per 1 live births, nd life expectncy ws 72 yers [3]. There were only spordic cses of chronic dilysis tretment (DT) before DT begn to spred rpidly fter the cretion by the Uruguyn government of the Ntionl Fund of Resources (NFR) in 198. The NFR supports the tretment by hemodilysis (HD), chronic mbultory peritonel dilysis (APD) nd renl trnsplnttion (RT) for ll persons with end-stge renl disese (ESRD). The Uruguyn Society of Nephrology hs hd ntionl registry since This registry hs ccumulted dt from the entire popultion from the strt of DT in the country. The gol of the present study ws to describe mortlity time trends in Uruguyn chronic HD ptients nd compre it with Received for publiction September 6, 1994 nd in revised form Jnury 13, 1995 Accepted for publiction Jnury 13, by the Interntionl Society of Nephrology 1721 other popultions. The Uruguyn generl popultion ws used s the ge stndrd. Recently, Wolfe et l [4] suggested tht foreign countries could compre their ESRD mortlity rtes to the USA rtes using dequte methodology. Therefore the USA ESRD 1987 to 1989 mortlity by ge, rce nd dignosis ws used s nother stndrd popultion for comprison. Methods Ptients All ptients were included on the registry t the onset of chronic hemodilysis tretment (HT). Dt were obtined yerly through the collbortion of ll physicins in chrge of dilysis units in the entire country. In this study the dt bse of the period 1981 to 1991 ws considered. At the end of the period (1991), there were 28 HT centers nd 8 nephrologists. Before 1985 ll fcilities were in the cpitl city, Montevideo. By 1991 there were 1 centers spred over the rest of the country. The generl chrcteristic of HT chnged in Uruguy during the intervl [5]: before 1985, 8% of the centers hd no wter tretments; in 1991 ll hd inverse osmosis or deionizers. The weekly frequency of HD ws thrice for 8% of the ptients before 1984, 85% between 1984 nd 1986, nd more thn 9% of the ptients fter The durtion of HD sessions ws four hours in most cses. Acette dilyste nd cuprophne membrnes were minly used. Since 1981 ll centers hve reused the dilyzers. Reuse incresed progressively; in 1991 the men ws seven hemodiyses per dilyzer. In 199 erythropoietin ws used for the first time in Uruguy, nd during this yer 2 ESRD ptients were treted with the drug. During the period of 1981 to 1991, 271 ESRD ptients were hemodilyzed (236 whites nd 35 blcks). Forty-one ptients were dmitted before Jnury 1, Seven hundred nd seventeen ptients died nd 179 received RT. Twenty-six ptients were trnsferred to DPA due to difficulties with the vsculr ccess for HD. Eight ptients trnsferred to other countries for personl resons nd were lost to follow-up. The popultion dt to clculte the incidence nd prevlence of ESRD ws tken from the 1985 Ntionl ensus [1]. The nnul gross mortlity rte (GMR) ws clculted s the number of deths divided by one hlf the number of those who were live on Jnury 1 plus one hlf the number live on December 31 of ech yer. The deth rte ws computed s the

2 1722 Fernández et l: hronic hemodilysis in Urnguy Tble 1. hronic hemodilysis in Uruguy (1981 to 1991) New ptients Yer N Dibetes Age > 65 Deths GM ptient-yers Deths/ Number of new ptients, number of dibetics nd those ged more thn 65 yers (>65) mong new ptients, number of deths, gross mortlity percentge (GM), nd deths/1 ptient-yers t risk. A totl of 717 ptients died during the period of 1981 to Among them, it ws impossible to know the precise yer of deth of five ptients, nd this is the reson for not including them in this Tble. totl number of deths per 1 ptient-yers t risk by determining the exct time t risk for ech ptient. The survivl curve ws drwn using the Kpln-Meier method. The indirect stndrdiztion method ws used to djust the mortlity results [6]. The bsis for such nlysis is the rtio of the observed to the expected number of deths: the stndrdized mortlity rtio (SMR). The stndrdized deth rte (SDR) in the study popultion ws computed multiplying the overll deth rte in the stndrd popultion by SMR. Two stndrd popultions were used: (1) the nnul mortlity by ge in the Uruguyn generl popultion, ccording the 1985 census dt nd the officil report of the government [7]. The SMR ws clled SMR1. (2) The ESRD USA deth rtes during 1987 to 1989 per 1 ptient-yers t risk [41 ws used s the ge, primry disese nd rce stndrd. The SMR ws clled SMR2 nd the corresponding stndrdized deth rte, SDR2. In ech yer the strt dte for ptient ws Jnury 1 nd the stop dte ws one of the following: the lst dy of the yer (December 31), the dte of deth, the dte of RT, or the lst dy of follow-up, whichever occurred first. For this nlysis we dhered to the inclusion nd follow-up criteri described by Wolfe et l [4]: ptients with prior filed RT nd ptients who recovered renl function during follow-up were excluded from nlysis. Ptients who were trnsferred to other fcilities were followed with regrd to RT nd mortlity sttus until the study stop dte. Only ptients who strted therpy more thn 9 dys before the study strt dte were included. Only those dys of ptient follow-up fter the strt dte were included in the computtions. Due to this inclusion nd follow-up criteri, the number of ptients considered in this nlysis ws 1665, of whom 574 died. Results Demogrphic detils nd mortlity of the Uruguyn chronic HD popultion is sumrized in Tble 1. Figure 1 shows the time course of incidence nd prevlence. Figure 2 shows the probbility of survivl for dibetic nd non-dibetic ptients. Gross mortlity decresed (Tble 1) from 21 to 9%, despite the lrge increse in high risk MD popultion rte (dibetics nd elders older thn 65 yers; Fig. 3). SMR1 time course is independent of the ge chnges, so it llows n pproch to the true mortlity time course (Fig. 4). It decresed from 27 in 1981 to 4 in The overll SMR1 ws 7. The SMR2 ws clculted s 574/12 =.57, which indictes tht the number of deths in the Uruguyn ESRD popultion during the period considered ws lower thn the USA ESRD norm. Thus, while the USA ESRD overll mortlity ws 25.6 deths/1 ptient-yers t risk, the SDR2 ws.57*25.6 = The P vlue from the chi-squre sttistic indictes tht the difference in rtes is sttisticlly significnt. Figure 5 shows the nnul deths/1 ptients t risk nd SDR2 trend course. Discussion Dilysis is high cost tretment nywhere in the world. The worldwide men cost of mintining ptient in HD or APD is round U $3, per yer. This is greter thn the GNP of the world's welthiest countries (U $18, to U $2, per person). Third world countries hve gret difficulties in finncing this type of tretment [8]. During 1991 in Uruguy, the nnul cost of HD (U $13,3 per ptient) represented bout 4 times the 1991 per cpit GNP level (hospitliztion nd outptient drugs not included). In Uruguy MD begn in 1958 s tretment protocol for cute renl filure [9], nd in 1965 ws instituted s the tretment regimen for ESRD [1]. Owing to the high cost, there were only spordic cses of HT before the cretion of the NFR. Since 198, the NFR hs received contributions from ll inhbitnts of the country to finnce, mong others, the high cost of tretment, dilysis nd RT. Thnks to this orgniztion nd to liberl cceptnce policy there ws rpid expnsion of l-it. The incidence nd prevlence (Fig. 1) were, in the lst few yers, similr to the rtes found in developed countries [11, 12]. The yerly contribution to the NFR ws bout U $12 per inhbitnt in 1991; forty percent were for HT expenses. DPA hd limited development in Uruguy during the period nlyzed; only 48 ptients were treted with this modlity until There hs been ntionl progrm nd n experienced clinicl group working in RT in Uruguy since The number of cdveric nd living-relted renl donors ws low, which explins the limited number of RT done during this period. Mortlity is higher in ESRD ptients thn in the ge-mtched generl popultion [12 14]. This my be relted to comorbid differences between ESRD ptients nd the generl popultion [15] nd to tretment relted fctors such s blood pressure control, HD dose, nutritionl sttus, etc. [16, 17]. SMR1 showed how mny times Uruguyn ESRD ptients die in comprison to the ntionl generl popultion. During the first yers of HT in Uruguy some elderly nd complicted ptients (who my lso be dignosed with rteriosclerotic hert disese, peripherl vsculr disese, cerebrl stroke, cirrhosis, or cncer mlignncy) were not referred by the internists. Afterwords, owing to the ccumulted experience nd good results, more t risk ptients were referred nd ccepted. Therefore, comorbid conditions were probbly worse in the lst yers of this study. In spite of this, SMR1 decresed from 21 to 4. In our opinion this could be explined by better qulity of tretment. As elucidted in the Methods section, severl tretment relted technologies improved during this period. Mortlity in ESRD ptients disclosed strong geogrphicl

3 Fernández et l: hronic hemodilysis in Uruguy E. (.3 (n Yer Fig. 1. Annul chnges in incidence I) nd point prevlence t December 31 (. P) of ESRD ptients in Uruguy. I nd P were expressed s the number per million popultion Time, yers since onset of ESRD Fig. 2. Kpln-Meier hemodilysis ptient survivl curves in non-dibetic (non D) nd dibetic (D) ptients. Dibetic ptients hd significntly worse survivl thn non-dibetic ptients # Yer Fig. 3. Percentge of ptients older thn 65 yers () nd dibetics () mong ptients live t Jnu,y 1, from 1981 to differences. Lower vlues were reported by Jpn nd the EDTA Registry. Gross mortlity in Jpn rnged from 8.8% in 198 to 9.2% in 1988 [18]. In the EDTA Registry the deth rte rnged from 12 in 198 to 111 deths per 1 ptient-yers in 1987 [19]. In 1986 in the USA mortlity ws deths per 1 ptientyers nd in 199 [12]. The Ltin Americn Dilysis Registry showed gross mortlity of 16.7% in 1991 [14]. To mke n interntionl comprision of mortlity in ESRD ptients is difficult due to different methods of tretment nd time periods considered for nlysis. The recent publiction of mortlity tbles by ge, rce nd renl disese by Wolfe et l [4] offers the possibility to mke suitble comprision. The overl deth rte in USRDS 1987 to 1989 ws 25.6 per 1, ptient-yers t risk. Since 1985, the SDR2 vlues were lower thn tht number (Fig. 5). This is difficult to explin. ountries with gressive trnsplnt policies my hve incresed mortlity in chronic dilysis progrms becuse younger nd helthier ptients re selected to receive trnsplnts [2]. onsidering tht renl trnsplnt ctivity in Uruguy ws lower, these fctors could prtilly explin SMR1 -s N 1 i i -'I N) NJ ) ci =1 Yer Fig. 4. The rtio between the number of observed nd expected deths (SMR1) mong chronic hemodilysis ptients during the period of 1981 to 1991, ccording to the ge-mtched generl popultion in Uruguy. In 1981 chronic hemodilysis ptients died 27 times more thn generl popultion nd in 1991 this rtio ws 4. During the period, 717 ptients died; expected deths were 12. Overll SMR1 ws 717/12 =

4 1724 Fernández et l: hronic /iemodilysis in Uruguy Deths/i ptient yers t risk r o ui o o ( " Yer D D o Fig. 5. Overll mortlity rte for the 1665 ptients considered (selected using Woift et l criteri [4]) ws 119 deth/1 ptient-yers t risk; in 1981 it ws 236 decresing to 79 in 1991 ). When the USA ESRD 1987 to 1989 mortlity rte by ge, rce nd dignosis ws used s stndrd, the stndrized deth rte ws 143 deths/1 ptient-yers, rnging from 516 in 1981 to 83 in 1991 (). the mortlity differences. omorbid conditions upon entrnce is n ccepted mortlity fctor [211. In our nlysis the role of this fctor on the deth rte differences ws not considered. The prescription for dilysis therpy nd the reuse of dilyzers hve received incresing recognition s ffecting overll progrm survivl results. Shorter dilysis is ssocited with higher mortlity [22]. In Uruguy most ptients hve been dilyzed for 12 hours per week since Dilysis time ppers to be shorter in the United Sttes [23], nd this could be nother fctor to explin the mortlity differences. It hs been proposed tht reuse could ply role in the mortlity differences mong Europen, Jpnese nd USA ptient popultions [24]. In fct, mortlity is lower in Europe where only 1% of centers reuse dilyzers nd in Jpn where there is no reuse t ll. In Uruguy, like in the USA, it is wide-spred prctice, so the mortlity difference could not stem from reuse. These overll results point out tht, with suitble ntionl funding strtegies, it is possible to properly undertke ESRD tretment in developing countries. Efforts of the Uruguyn Society of Nephrology to keep the ntionl register updted hs llowed yerly knowledge of the incidence, prevlence nd mortlity rtes, nd to directly improve tretment outcomes. Acknowledgments The utors thnk those doctors who hve completed questionnires. Without their collbortion, this work could not hve been prepred. We grtefully cknowledge the collbortion of the NFR stff, specilly its Technicl Director, Dr. Victor Zerbino, M.D. nd the Socil Workers, An Debenedetti nd Inés Mrtinez. We lso cknowledge the ssistnce of Mrs. T. Forster. Reprint requests to Sociedd Uruguy de Nefrologl, Jime ibils, 2824 bis P 116, Box 16217, Montevideo, Uruguy. References 1. World Helth Sttistics Annul Genève, World Helth Orgniztion, Progrm de ls Nciones Unids pr el Desrrollo (PNUD). Informe sobre desrrollo humno, entro de omuniccion, Investigción y Documentción entre Europ, Espn y Americ Ltin (IDEAL), 1993 (in Spnish) 3. LATIN AMERIAN DEMOGRAPHI ENTER: Ltin Americn Life Tbles Demogrphic Bulletin Yer XXII, No 44, WOLFE RA, GAYLIN DS, PORT FK, HELD PJ, Woon L: Using USRDS generted tbles to compre locl ESRD mortlity rtes to ntionl rtes. Kidney mt 42: , SHEWDT E, GONZALEZ F, FERNANDEZ J, AMBROSONI F, MAzzUcHI N: Diez ños de hemodiálisis en el Uruguy: ondiciones de ingreso, crcteristics del trtmiento y resultdos. NefrologI 13 (Suppl 4):2 29, 1993 (in Spnish) 6. ARMITAGE F: Sttisticl Methods in Medicl Reserch. Boston, Blckwell Scientific Publictions, 1971, pp Bioestdistics Vitles. Repflblic Orientl del Uruguy, Direccibn Generl de EstdIstic y enso, 1988 (in Spnish) 8. GURLAND HJ, LYSAGHT MJ: Future trends in renl replcement therpy. Artif Orgns 17: , FERNANDEZ A, ESPASANDIN W, PETRUELLI D: Trtmiento de l Insuficienci Renl Agud. El Riñón Artificil. Fcultd de Medicin de Montevideo, 1962 (in Spnish) 1. PETRUELLI D, AMI'ALANS LA, LOMBARDI R, LLOPART T, orlo F: Hemodiálisis crónic intermitente en I insuficienci renl crónic. El DI Medico Uruguyo 444:65 653, 197 (in Spnish) 11. Report on Mngement of Renl Filure in Europe, XXIII, Nephrol Dil Trnsplnt 7 (Suppl 2), U.S. Renl Dt System: USRDS 1991 Annul Dt Report. Bethesd, Ntionl Institutes of Helth, Ntionl Institutes of Dibetes nd Digestive nd Kidney Diseses, Am J Kidney Dis 22 (Suppl 2), DEGOULET P, REAH I, ROZEMBAUM W, AIME F, DEVRIES, BERGER, ROJAS P, JAOBS, LEGRAIN M: Progrmme Dilyse Informtique. VI-Survie et fcteurs de risque. J Urol Nephrol 85:99 962, 1979 (in French) 14. MAZZUHI N, FERNANDEZ JM, SHWEDT E, ELIA F, USUMANO AM, STO-RIs K, SILVA-ANAO M, POBLETE H, ESPINOSA NR, ASTILLO H, MILANES L, ARDILA M, ARIZA M: Ltin Americn Registry of Dilysis nd Renl Trnsplnttion. Dilysis Report for 1991 from Argentin, Bolivi, Brsil, hile, Pnm, Peru, Uruguy nd Venezuel. Nefrologi Ltinomericn 1:89 99, 1994 (in Spnish) 15. PARFREY PS, FAtNrr JD: rdic disese in chronic uremi. Pthophysiology nd clinicl epidemiology. ASAIO J , MAILLOUX LU, BELLUI AG, NAPOLITANO B, MOSSEY RT: The contribution of hypertension to dilysis ptient outcomes. Point of view. ASAIO J , 1994

5 Fernández et l: hronic hemodilysis in Uruguy VANFIOLDER R, RINGOIR SM: Adequcy of dilysis: A criticl nlysis. (Editoril Review) Kidney mt 42:54 558, OoA1c M: Mortlity in chronic dilysis ptients in Jpn.AmfKidney Dis 15:41 413, BRUNNER FP, SELW NH: Results of renl replcement therpy in Europe, 198 to Am J Kidney Dis 15: , KJELLSTRAND M, HYLANDER B, OLLINS A: Mortlity on dilysis On the influence of erly strt, ptient chrcteristics, nd trnsplnttion nd cceptnce rtes. Am J Kidney Dis 15:483 49, OLLINS AJ, HANSON G, UMEN A, KJELLSTRAND, KESHAVIA}{ P: hnging risk fctor demogrphics in end-stge renl disese ptients entering hemodilysis nd the impct on long-term mortlity. Am J Kidney Dis 15: , LOWRIE EG, LEW NL: Deth risk in hemodilysis ptients: The predictive vlue of commonly mesured vribles nd n evlution of deth rte differences between fcilities. Am JKidney Dis 15: , HELD PJ, BIGG R, LrSI DW, PORT FK, HJuM R, LEVIN N: The dose of hemodilysis ccording to dilysis prescription in Europe nd the United Sttes. Kidney mt 42 (Suppl 38):S16 S21, SHA.LDON S: Unnswered questions pertining to dilysis dequcy in Kidney mt 43(Suppl 41):S274 S277, 1993