Sao Paulo Med. J. vol.117 número2

Marilda Mazzali Maria Almerinda Vieira Fernandes Ribeiro-Alves Gentil Alves Filho

Original Article

INTRODUCTION

Renal allo g raft bio psies have been used as a g o o d metho d fo r mo nito ring the evo lutio n o f kid ne y tra nsp la nts fo r a t le a st 2 0 ye a rs.1 Histo lo gical analysis permits differential diagno sis o f the causes o f allo g raft dysfunctio n to be made. Such an evaluatio n can lead to the avo idance o f the use o f additio nal immuno suppressive drug s, thereby reducing the incidence o f co mplicatio ns.1 ,2 The usual po sitio n o f an allo g raft in the iliac fo ssa renders it easily palpable and accessible to safe needle bio psy.1 Ho wever, the risk o f accidents leading to lo ss o f the allo g rafts is still aro und 1 %.3 Sufficient material fo r histo lo g ical evaluatio n is g enerally o btained in abo ut 9 0 % o f the cases.3

In the pre se nt study, we a na lyz e d 3 3 9 percutaneo us needle allo g raft bio psies fro m 1 3 5 pa tients a nd c o mpa red these results with the c linic a l p re se nta tio n a nd la b o ra to ry d a ta o btained befo re the bio psy as well as with the incidence o f co mplicatio ns.

METHODS

Fro m N o vember 1 9 8 6 to December 1 9 9 1 , 3 3 9 percutaneo us bio psies were o btained fro m 1 3 5 renal transplant patients.

Pe rcutane ous re nal graft biopsy:

a clinical, laboratory and pathological analysis

Disciplina de Nefrologia, Departamento de Clínica Médica, Faculdade de Ciências

Médicas-Universidade Estadual de Campinas, Campinas, Brazil

ABSTRACT

Contex t: Renal allo g raft bio psies have been used as a g o o d metho d fo r mo nito ring the evo lutio n o f kidney transplants fo r at least 2 0 years.1 Histo lo g ical analysis permits differential diag no sis o f the causes o f allo g raft dysfunctio n to be made.

O bjectives: To co rrelate the data o f urinalysis and serum creatinine with histo lo g ical diag no sis o f renal g raft in a g ro up o f renal transplant patients.

Design: Accuracy study, retro spective analysis.

Setting: A university terciary referral center.

Sa m ple: 3 3 9 percutaneo us allo g raft bio psies o btained fro m 1 5 3 patients. Blo o d and urine samples were o btained befo re the g raft bio psy.

M a in M ea surem ents: Labo rato ry evaluatio n and hysto lo g ical analysis (lig ht micro sco py, imuno fluo rescent eletro nic micro sco py).

Results: Mo st o f the bio psies (5 8 .9 %) were perfo rmed during the first mo nth po st-transplant. An increase in serum creatinine was asso ciated with acute tubular and/ o r co rtical necro sis. Pro teinuria and no rmal serum creatinine were asso ciated with g lo merular lesio ns. N o n-nephro tic rang e pro teinuria and an increase in serum creatinine were asso ciated with chro nic rejectio n.

Conclusion: Evaluatio n o f serum creatinine and urinalysis can be useful in sug g esting the histo lo g ical g raft diag no sis.

The usua l immuno sup p re ssive p ro to c o l inc lud e d a z a thio p rine (2 mg / kg / d a y) a nd predniso ne (2 mg / kg / day) fo r recipients o f a tra nspla nt fro m a living rela ted HLA-identic a l sibling do no r, and cyclo spo rine (7 mg / kg / day) fo r recipients o f a transplant fro m a living related no n-identical o r cadaver do no r. Predniso ne was pro g ressively reduced to 1 0 mg / day at the third mo nth po st-transplant, and the cyclo spo rine do se was adjusted to maintain blo o d levels aro und 1 0 0 to 2 0 0 ng / d l a s d e te rmine d b y a mo no clo nal antibo dy radio immuno assay.

Acute rejectio n episo des were treated with a pulse o f methylpredniso lo ne (5 0 0 mg / day, IV), fo r three days.

La b o ra to ry eva lua tio n. Blo o d a nd urine samples were co llected befo re renal bio psy. The urina ry a na ly sis invo lve d se d ime nt a nd bio chemical tests. W hen pro teinuria was po sitive, 2 4 ho ur urine samples were co llected fo r the quantificatio n o f pro tein. The blo o d samples were analyz ed fo r their creatinine (Jaffé metho d) and c yc lo spo rine levels a s well a s their a b ility to co ag ulate.

Ind ic a tio ns fo r p e rc uta ne o us ne e d le allo g raft bio psy. Percutaneo us needle allo g raft bio psy was indicated when at least o ne o f the fo llo wing criteria was present:

1 . An increase in the serum creatinine level to mo re than 2 5 % abo ve basal.

2 . Sig ns a nd symp to ms o f a c ute re je c tio n, including fever, edema, arterial hypertensio n, renal pain, bo dy weig ht g ain, eo sinphilia, o lig uria a nd eleva tio n o f serum c rea tinine levels.

3 . Cadaver kidney recipients with o lig uria o r

anuria and/ o r stable serum creatinine levels abo ve no rmal values (> 2 mg %).

4 . Unsuccessful treatment o f the acute rejectio n with methylpredniso lo ne.

5 . A b no rma l urina ly sis w ith g lo me rula r hema turia , pro teinuria in iso la ted sa mples and/ o r hematic o r leuko cytic casts.

6 . Twenty-fo ur ho ur pro teinuria abo ve 1 g / day. Bio psy Pro cedure. Prio r to renal bio psy, the patients had their blo o d pressure co ntro lled and their blo o d co ag ulatio n parameters determined. In additio n, the allo grafts were evaluated by renal ultraso und. If o ther causes o f renal dysfunctio n such as vascular o r ureteral o bstructio n were co nclusively discarded, the renal bio psy was perfo rmed. Vin-Silverman-Franklin o r discardable Tru-Cut Traveno l needles were used. Usually the ne e dle wa s po sitio ne d in the c o nve x la te ra l b o rde r in the supe rio r po le a nd, a fte r lo c a l anesthesia, was intro duced in a perpendicular po sitio n, fo llo wed by the remo val o f o ne o r two tissue fra g me nts. Po st-b io psy he ma turia w a s mo nito re d b y the visua l insp e c tio n o f urine samples o n three separate o ccasio ns.

Histo lo g ic a l A na ly sis. Re na l b io p sy fra g me nts we re c o nside re d a de q ua te if the y co ntained co rtical o r co rtical/ medullar junctio n tissue. Samples co ntaining o nly medullar tissue were ina deq ua te fo r dia g no sis, a nd a no ther bio psy was perfo rmed. The bio psy material was p ro c e sse d in the Unive rsity De p a rtme nt o f Pa tho lo g ic a l A na to my. Fra g me nts w e re examined by lig ht micro sco py fo llo wing HE, PAS and Masso n staining . Immuno fluo rescent staining was do ne with antiserum to Ig M, Ig G , Ig A, C3 , C1 q, kappa and lambda. So me samples were examined by electro n micro sco py.

Statistical Metho ds. Statistical analysis was carried o ut using the chi-square test and unpaired Student’s t test.

RESULTS

Fro m N o vember 1 9 8 6 to December 1 9 9 1 , 3 3 9 needle allo graft bio psies were o btained fro m 1 3 5 renal transplant patients (9 5 M, 4 0 F), o ut o f a to tal o f 2 4 7 such transplants perfo rmed during

Ta ble 1 - N umber of percuta neous gra ft biopsies performed per pa tient during study period

donor patients number o f relationship

graft biopsies biopsy/ patient

identical HLA 1 4 2 6 1 .8 5

non-identical HLA 5 7 1 1 9 2 .0 8

cadaver 6 4 1 9 4 3 .0 3 *

Total 135 339 2.51

this perio d. The number o f bio psies per patient (Table 1 ) was sig nificantly g reater in individuals receiving a kidney fro m cadaver do no rs (p < 0 .0 5 ). In 6 4 such recipients, 1 9 4 bio psies were do ne, co mpared to 1 4 5 bio psies in 7 1 patients receiving a kidney fro m related living do no rs (1 4 HLA-identical and 5 7 no n-identical).

The indicatio ns fo r renal bio psy were g raft dysfunctio n in 2 7 2 instances (8 0 .2 %), anuria in 3 4 (1 0 . 0 %) a nd a b no rma l urina lysis in 3 3 (9 . 8 % ). G ra ft d ysfunc tio n (n = 2 7 2 ) w a s asso ciated with o lig uria in 7 4 instances (2 7 .2 %) and no respo nse to rejectio n treatment in 1 5 (5 .5 %). In the patients fo r who m allo g raft bio psy was indicated by abno rmal urinalysis, the mo st fre q ue nt a b no rma lity o b se rve d wa s iso la te d p ro te inuria (in 2 0 b io p sie s) fo llo w e d b y p ro te inuria in a sso c ia tio n w ith g lo me rula r hematuria in six bio psies. Iso lated g lo merular hematuria was the cause o f renal bio psy o n seven o ccasio ns (Table 2 ). O ne hundred and eig hty-three bio psies (5 3 .9 %) were do ne during the first mo nth po st-transplant, with a g radual reductio n in the number thereafter. In the first year after the re na l tra nsp la nt, 3 0 2 b io p sie s (8 9 %) w e re p e rfo rme d (Ta b le 3 ). Ad e q ua te ma te ria l fo r analysis was o btained in 3 0 6 fragments (9 1 .1 %). Severe hemo rragic co mplicatio ns o ccurred in fo ur cases, and led to g raft lo ss in two .

A c ute re je c tio n w a s o b se rve d in 1 3 6 frag ments (4 0 .1 %), 1 0 6 o f them during the first two mo nths po st-transplant and fo ur after the first year. In this g ro up, renal dysfunctio n was the main indicato r o f renal bio psy in 1 2 7 instances, fo llo w e d b y a nuria in se ve n a nd a b no rma l urinalysis in two . Acute cellular rejectio n (ACR) witho ut a vascular co mpo nent o r acute tubular ne c ro sis wa s o b se rve d in 5 7 b io psie s. AC R asso ciated with acute tubular necro sis was seen in 4 7 instances and was asso ciated with vascular rejectio n in 3 2 frag ments. N o difference in the inc id e nc e o f A C R w a s o b se rve d b e tw e e n re c ipie nts o f c a da ve r o r living -re la te d do no r o rg ans.

A c ute tub ula r ne c ro sis (ATN ) w a s the seco nd mo st frequent diag no sis (6 6 bio psies, 1 9 .4 %). As with ACR, acute tubular necro sis was

o bserved mainly during the first two mo nths po st-transplant (6 2 cases). The histo lo g ical diag no sis o f ATN was mo re frequent in cadaver do no r recipients. In individuals with ATN , the indicatio n fo r bio psy was renal dysfunctio n in 5 2 instances, anuria in 1 2 and abno rmal urinalysis in two .

C hro nic re je c tio n w a s o b se rve d in 4 0 frag ments (1 1 .7 %). This diag no sis became mo re fre q ue nt a fte r the sixth mo nth po st-tra nspla nt (Table 3 ). Renal dysfunctio n was ag ain the majo r ind ic a to r o f the ne e d fo r a b io p sy. In 2 6 frag ments, a g lo merular lesio n was detected.

G lo merulo nephritis (G N ) was diag no sed in 2 7 b io psies (7 .9 %). Fo c a l a nd seg menta l g lo me rulo sc le ro sis w a s the mo st fre q ue nt diag no sis, o ccurring in ten bio psies fro m eig ht p a tie nts. Me sa ng io c a p illa ry typ e I G N w a s o bserved in seven bio psies fro m fo ur patients, and type III in two bio psies fro m two patients. Membrano us G N o ccurred in two frag ments fro m two patients. In o ne patient, the diag no sis was me sa ng ia l p ro life ra tive G N . In this g ro up , pro teinuria (7 .7 1 g , SD 8 .8 2 ) was g reater than in o thers, while serum creatinine (2 .3 6 mg / dl, SD 1 .9 9 ) wa s the lo west a mo ng the va rio us g ro ups. In living do no r recipients, the diag no sis o f G N was mo re frequent than in cadaver o nes. Acute vascular rejectio n was o bserved in 1 4 frag ments (4 .1 %) fro m 1 1 patients. G raft lo ss o ccurred in all patients within two mo nths after diag no sis. All bio psy indicatio ns were based o n re na l dysfunc tio n. The urina lysis (pro te inuria belo w 1 g/ l, hematuria < 5 0 RBC per high po wer field) and serum creatinine levels (6 .4 5 mg / dl) were similar to ACR g ro up.

Table 2 - Indications for percutaneous graft biopsies

Indicatio ns number (%)

G raft dysfunction 272 (80.2%)

- with oliguria 7 4

- no response to anti-rejection treatment 1 5

Anuria 3 4 (1 0 .0 %)

Abnormal urinalysis 3 3 (9 .8 %)

- isolated proteinuria 2 0

- proteinuria + glomerular hematuria 6

Co rtical necro sis was the diag no sis in 1 3 fra g me nts (3 . 8 % ), a nd in 1 2 o f the m the ind ic a tio n fo r re na l b io p sy w a s a nuria . All b io p sie s w e re d o ne in the first mo nth p o st-transplant. A to tal o f seven patients were included in this g ro up and all the g rafts were remo ved.

DISCUSSION

Percutaneo us needle allo g raft bio psy may b e pe rfo rme d in o rde r to e va lua te the re na l functio n o f kidney transplant patients. The po sitio n o f the allo g raft in the iliac fo ssa permits easy access fo r the bio psy pro cedure. The kidney can b e lo c a liz e d b y b ima nua l p a lp a tio n a nd he mo sta sis is fa c ilita te d b y the use o f a co mpressive technique.3 Adequate material fo r histo lo g ic a l a na lysis, c o nta ining c o rtic a l a nd co rtical/ medullar junctio n material is o btained in 8 0 % to 1 0 0 % o f renal bio psies. Renal bio psy a c c idents tha t result in kidney lo ss a re ra re, o ccurring in abo ut 1 % o f the cases. In the present stud y, the inc id e nc e o f a llo g ra ft lo ss a fte r percutaneo us needle bio psy was 1 .5 % (2 g raft lo sses fo r 1 3 5 patients).

The majo r indicatio n fo r kidney transplant bio psy was the differential diag no sis o f acute rejectio n and renal dysfunctio n. This indicatio n was based o n the increase in serum creatinine levels. Pro bable differential diag no ses included acute vascular rejectio n, chro nic rejectio n, acute tubular necro sis and cyclo spo rine nephro to xicity. Matas1 suggested that 4 0 % o f renal transplant patients presented no changes in their immuno suppressive

therapy after renal allo graft bio psy. In the present stud y, unc ha ng e d immuno sup p re ssio n w a s o bserved in 3 8 % o f the cases.

The usefulness o f urinalysis as an indicato r fo r allo g raft bio psy is co ntro versial. Hematuria has no value either as an indicato r fo r renal b io psy o r in the pro g no sis o f rena l func tio n. Pro teinuria is an impo rtant marker and has been extensively studied.4 ,5 ,6 ,7 Massive pro teinuria after transplant is frequent during the first three mo nths, with spo ntaneo us remissio n during evo lutio n.4 Persistent pro teinuria o ccurs in abo ut 3 0 % o f transplants, and is po sitively co rrelated with the p re se nc e o f g lo me rula r le sio ns, w hic h is ind ic a tive o f c hro nic re je c tio n o r g lo merulo nephritis. Persistent pro teinuria is o ne o f the mo st frequent indicato rs fo r renal bio psy. In the present study, pro teinuria was used as an indicato r fo r allo graft bio psy in 7 .6 % o f the cases, and was present in 2 1 .6 % o f the renal bio psies. A b no rma l urina lysis w a s ind ic a tive o f allo g raft bio psy in 1 0 % o f the cases, especially a fte r the third mo nth p o st-tra nsp la nt. The histo lo gical diagno ses were chro nic rejectio n and g lo merular disease.

Ac ute tub ula r ne c ro sis (ATN ) o c c urs in abo ut 3 0 to 6 0 % o f cadaver kidney recipients a nd in a b o ut 1 0 % o f re c ip ie nts fro m living do no rs.8 The fo rmer incidence may be asso ciated with extended perio ds o f co ld o rg an sto rag e that can pro mo te tissue ischemia and acute tubular necro sis. The hemo dynamic status o f the do no r c a n a lso influenc e the o nset o f a c ute tub ula r necro sis.8 ,9 In o ur study, ATN o ccurred in 2 9 .3 %

Ta ble 3 - Time post-tra nspla nt w hen gra ft biopsies w ere performed

Days ACR AVR ATN CR G N o ther to tal

1

||

3 1

||

6 1

||

1 8 1

||

after 1 st year 4 0 0 2 0 9 4 3 7

Tota l 1 3 6 1 4 6 6 4 0 2 7 5 6 3 3 9

ACR = acute cellular rejectio n, AVR = acute vascular rejectio n, ATN = acute tubular necro sis, CR = chro nic rejectio n, G N =

g lo merulo nephritis. * o ther: medullar (n=3 3 ), co rtical necro sis (n=1 3 ), hemo lytic uremic syndro me (n=3 ), Cyclo spo rine nephro to

o f the patients (7 4 .3 % received a kidney fro m a cadaver do no r and 2 5 .6 % fro m a living do no r). Urinalysis was no t impo rtant in this g ro up, since the presence o f no n-g lo merular hematuria and leuko cyturia co uld have been seco ndary to the po st-o perato ry perio d o r to the presence o f a bladder catheter.

Acute rejectio n is co nsidered to be the mo st fre q ue nt c a use o f a llo g ra ft d ysfunc tio n a nd usually o ccurs during the first three mo nths po st-transplant.1 ,2 In the present study, we o bserved acute rejectio n in 4 0 .1 % o f the bio psies. The incidence o f acute rejectio n was similar between recipients fro m cadaver o r living related do no rs. Ac ute re je c tio n a sso c ia te d w ith ATN w a s a frequent histo lo g ical o bservatio n in o ur patients. This asso ciatio n may reflect antig en presentatio n by necro tic tubule cells which results in a rejectio n pro cess.8

Acute vascular rejectio n can be seco ndary to the presence o f humo ral facto rs.1 0 Vascular re je c tio n is c o nsid e re d a p o o r p ro g no stic indicato r, because the intimal infiltrate can lead to o cclusive arterio lo pathy and tissue ischemia.1 1 Individuals in this g ro up had sho rt survival since the ag g ressive immuno suppressive therapy can pro mo te infectio us co mplicatio ns and death o f the patient. In o ur series, acute vascular rejectio n was asso ciated with lo ng -term g raft lo ss in 1 0 0 % o f the cases. The histo lo g ical analysis sho wed re na l c o rtic a l isc he mia a nd o b lite ra tive a rte rio lo pa thy, se c o nda ry to intima l g ro wth, sug g estive o f endo thelial disease.

Chro nic rejectio n o ccurs frequently after the sixth mo nth po st-tra nspla nt a nd pro g resses to chro nic renal failure.1 2 The co nditio n o ccurs in abo ut 1 7 % o f renal transplants, altho ug h in o ur series the inc idenc e o f c hro nic rejec tio n wa s 1 1 .8 % (4 0 histo lo g ical diag no ses in 2 1 patients). The clinical diag no sis was based o n an increase in serum creatinine levels, usually in the presence o f no rmal urinalysis. The averag e level o f iso lated p ro te inuria w a s a b o ut 1 . 3 1 g . Histo lo g ic a l evaluatio n sho wed tubular atro phy, interstitial fibro sis and thickening o f vascular walls, all o f which sug g est ischemic disease. Varying deg rees o f g lo merular sclero sis were also present. The

d iffe re ntia l d ia g no sis b e tw e e n tra nsp la nt g lo merulo pathy, chro nic rejectio n and seg mental g lo me rulo sc le ro sis c a n b e d iffic ult. Immuno fluo resc enc e a nd elec tro n mic ro sc o py can be helpful in such cases.

Po st-tra nsp la nt g lo me rulo ne p hritis is frequent, but classificatio n as de no vo , recurrent o r indeterminate is difficult since the primary renal d ise a se is ra re ly d ia g no se d . Suc h g lo me rulo ne p hritis c a n b e d ue to p e rsiste nt systemic facto rs,1 3 do no r g lo merular disease,1 4 ischemic lesio ns, hypertensio n o r seco ndary to a c ute re je c tio n e p iso d e s.8 Fo llo w ing its intro ductio n, cyclo spo rine has been fo und to be a further facto r causing g lo merular lesio ns1 5 ,1 6

Histo lo g ically, g lo merular lesio ns can be superpo sed since, as with ischemia, hypertensio n a nd immuno lo g ic a l o r to x ic fa c to rs, the patho g enic mechanisms can lead to endo thelial injury1 7 w hic h in turn p ro d uc e s fo c a l a nd se g me nta l g lo me rulo sc le ro sis, usua lly in the va sc ula r p o le o f the g lo me rulus. The se mechanisms can pro mo te thickening o f the basal membrane. In sho rt, the histo lo g ical analysis o f bio psy frag ments by o ptical micro sco py alo ne, alo ng with imprecise diag no sis o f the primary renal disease, do es no t permit co rrect diag no sis o f po st-transplant g lo merular disease.

The d iffe re ntia l d ia g no sis o f c hro nic rejectio n, cyclo spo rine-mediated nephro to xicity a nd fo c a l a nd se g me nta l g lo me rulo sc le ro sis re q uire s immuno fluo re sc e nc e a nd e le c tro n micro sco py. The serum levels o f cyclo spo rine may also be useful in such diag no ses.1 7 ,1 8

In summary, percutaneo us needle allo g raft bio psy is an useful pro cedure in the fo llo w-up o f kidney transplants. Since such bio psies permit a differentiatio n between rejectio n and any o ther causes o f allo g raft dysfunctio n, they sho uld pro ve to b e use ful in d e te rmining a d e q ua te immuno suppressive therapy and in reducing the risk o f co mplicatio ns.

g lo merular lesio ns, usually after the sixth mo nth p o st-tra nsp la nt. La te p ro te inuria in the no n-ne p hro tic ra ng e a sso c ia te d w ith inc re a se d creatinine levels may be indicative o f chro nic rejectio n.

REFERENCES

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2. Matas AJ, Tellis VA, Sablay L, Quinn T, So bberman R, Veith FJ. The value o f needle allo graft bio psy. III: A pro spective study. Surgery 1985;98:922-5.

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4. Camero n JS. Glo merulo nephritis in renal transplant. Transplanta-tio n 1982;34:237-45.

5. Cheigh JS, Stenzel KH, Susin M, Rubin AL, Riggio RR, Withel JC. Kidney transplant nephro tic syndro me. Am J Med 1974;57:730-40.

6. Cheigh JS, Mo uradian J, Susin M et al. Kidney transplant nephro tic syndro me: relatio nship between allo graft histo patho lo gy and natu-ral co urse. Kidney Int 1990;18:358

7. Shapiro RS, Deshmukl A, Kro pp K. Massive po sttransplant pro -teinuria. Transplantatio n 1976;22:489-92.

8. Bro phy D, Najarian JS, Kjelstrand CM. Acute tubular necro sis after renal transplantatio n. Transplantatio n 1980;29:245.

9. Kjellstrand CM, Casall RE, Simmo ns RL, Shiderman JR, Buselmeier TJ, Najarian JS. Etio lo gy and pro gno sis in acute po st-transplant re-nal failure. Am J Med 1976;61:190

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11. Schro eder TJ, Weiss MA, Smith RD, Stephens GW, Carey M, First MR. The use o f OKT3 in the treatment o f acute vascular rejectio n. Transpl.Pro c 1991;23:1043.

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RESUMO

Contex to: Bió psia percutânea do rim transplantado tem representado um bo m méto do para mo nito riz ação da evo lução funcio nal do enxerto há pelo meno s 2 0 ano s. A análise histo ló g ica no s permite o diag nó stico deferencial entre as várias causas de disfunção do enxerto . O bjetivos: Co rrelacio nar, em pacientes transplantado s renais, o exame simples de urina e a creatinina sérica co m achado s histo ló g ico s do enxerto renal. Tipo de Estudo: Estudo da acurácia, análise retro spectiva.

Loca l: Ho spital das Clínicas da UN ICAMP. Am ostra : 3 3 9 bio psias renais percutâneas (de 1 3 5 pacientes transplantado s) no perío do de janeiro de 1 9 8 4 a dez embro de 1 9 9 1 . Amo stras de sang ue e de urina fo ram co letadas antes da bio psia renal.

Va riá veis estuda da s: Avaliação labo rato rial e análise histo ló g ica. Resulta dos: Em 9 4 ,1 % das indicaçõ es de bio psia fo i o btido material para análise histo ló g ica. Em 5 8 ,9 % das bio psias a indicação o co rreu no primeiro mês de transplante. Elevação da creatinina sérica asso cio u-se a necro se tubular ag uda e/ o u necro se co rtical. Pro teinúria co m níveis de creatinina sérica dentro da no rmalidade asso cio u-se a do enças g lo merulares. Pro teinúria (níveis não nefró tico s) e aumento da creatinina estiveram asso ciado s a rejeição crô nica do transplante. Conclusã o: A análise da creatinina sérica e do exame de urina em pacientes transplantado s renais po de sug erir o padrão histo ló g ico diferenciado de aco metimento .

M a rilda M a zza li - Assistent Pro fesso r - N ephro lo g y Unit - DCM/ FCM UN ICAMP

M a ria Almerinda Vieira Ferna ndes RibeiroAlves

-Assistent Pro fesso r - N ephro lo g y Unit - DCM/ FCM UN ICAMP

Gentil Alves Filho - Assistent Pro fesso r - N ephro lo g y Unit - DCM/ FCM UN ICAMP

Sources of Funding: N o t declared

Conflict of interest: N o t declared

La st received: 1 4 July 1 9 9 8

Accepted: 1 3 O cto ber 1 9 9 8

Address for correspondence:

Marilda Maz z ali

Disciplina de N efro lo g ia - DCM/ FCM UN ICAMP Universidade Estadual de Campinas