International Journal of Urology

(2003)

10,

607–609

Blackwell Science, LtdOxford, UKIJUInternational Journal of Urology0919-81722003 Blackwell Publishing Asia Pty LtdNovember 20031011607609Case Report

Renal following liver transplantationT Kobayashi

et al.

Correspondence: Osamu Ogawa

MD

PhD

, Professor andChairman, Department of Urology, Kyoto University,Graduate School of Medicine, Shogoin Kawahara-cho 54,Sakyo-ku, Kyoto 606-8507, Japan. Email: ogawao@kuhp.kyoto-u.ac.jp

Received 12 December 2001; accepted 16 May 2003.

Case Report

Living related renal transplantation for end-stagerenal disease after liver transplantation from abrain-dead donor

TAKASHI KOBAYASHI,

1

HIROSHI OKUNO,

1

MITSUHIRO TACHIBANA,

2

NORIKO MORI,

3

HIROSHI YOSHIDA,

1

SHINGO YAMAMOTO,

1

TOSHIYUKI KAMOTO,

1

AKITO TERAI

1

AND OSAMU OGAWA

1

Departments of

1

Urology and

2

Clinical Pathology, Graduate School of Medicine, Kyoto University, Kyoto and

3

Division of Nephrology, Department of Medicine, Shizuoka General Hospital, Shizuoka, Japan

Abstract

We report a case in which a living related renal transplantation was successfully performed for end-stage renal disease that had progressed after a liver transplantation from a brain-dead donor for livercirrhosis associated with type C hepatitis. Because the transplanted liver function had been excellentwith the use of tacrolimus and mycophenolate mofetil, the same immunosuppressive agents withprednisolone were employed for the renal transplantation. Both grafts are functioning well withoutrecurrence of hepatitis at 10 months after the renal transplantation. From our experience, renaltransplantation should not be contraindicated even if the patient has undergone liver transplantationor has hepatitis C viral infection.

Introduction

Although simultaneous hepatorenal transplantationhas become a relatively common therapeutic modalityfor some diseases such as hyperoxaluria, only a fewcases of metachronous double transplantation havebeen reported. Herein we report a case in which aliving-related renal transplantation was successfullyperformed for end-stage renal disease (ESRD) that pro-gressed 3 years after a successful brain-death livertransplantation.

Case report

A 59-year-old man presented with ESRD and hoped fora living renal transplantation donated by his 55-year-oldsister. Three years earlier, the patient underwent trans-plantation of a liver from a brain-dead donor for liver

cirrhosis associated with type C viral chronic hepatitis.Creatinine serum (s-Cr.) level was 1.5 mg/dL just beforethe liver transplantation (Fig. 1a). The transplantationwas carried out successfully with administration of tac-rolimus (TAC) and mycophenolate mofetil (MMF) forimmunosuppression. One year later, the patient devel-oped mild renal insufficiency (s-Cr., 1.8 mg/dL) andrenal needle biopsy (first biopsy) revealed nephroscle-rosis with striped interstitial fibrosis and arteriolar hyali-nosis (Fig. 2a). The immunosuppressive agents were notconverted and eventually the patient developed ESRD3 years after the liver transplantation. During this time,the liver graft had functioned well. Serum level of hep-atitis C virus ribonucleic acid (HCV-RNA) was less than5

¥

10

6

equivalent/mL (

<

5 M eq/mL) by quantitativereverse transcription–polymerase chain reaction (RT-PCR) assay.

A living renal transplantation from the patient’s sisterwas planned. As well as blood type, 8 of 10 loci (A, B,BW, DR, and DQ) of the human lymphocyte antigens(HLA) were matched between the donor and recipient,with just one locus mismatched. Both the donor andrecipient had normotensive blood pressure. In additionto TAC and MMF, prednisolone was employed accord-ing to immunosuppression protocols for kidney

608 T Kobayashi

et al.

transplantation. Because the liver graft function wasnormal at the time of kidney transplantation, no specificattention was paid, and the usual kidney transplantationprocedures were followed. Anesthesia was introducedwith an intravenous injection of 300 mg (4 mg/kg) thi-opental sodium and 10 mg (0.1 mg/kg) vecuronium bro-mide, and was maintained with inhalation of isoflurane.Serum creatinine level decreased to 1.3 mg/dL immedi-ately after the transplantation. Postoperative course wasuneventful (Fig. 1b) and the recipient was discharged4 weeks after surgery. Intraoperative routine needlebiopsy of the transplanted kidney after reperfusion (1-hbiopsy) revealed mesangioproliferative non-IgA glom-erulonephritis and normal arteriolae (Figs 2b,c).

Routine biopsy of the graft kidney performed on the94th postoperative day (3-month biopsy) showed nor-mal glomeruli and recurrence of striped fibrosis with

hyalinized arteriolae (Fig. 2d), and was limited to withinvery small areas. Trough level of serum TAC was11.2 ng/mL in this setting and the dose of TAC wasreduced according to the planned protocol. Predniso-lone was ceased at 21 months after the renal transplan-tation, and at the setting of 27 post-transplantationmonth, the level of s-Cr. was controlled at 1.4 mg/dLwith the administration of 3 mg TAC and 1 g MMF.

Discussion

The most common cause of chronic renal insufficiencyafter organ transplantation is renal toxicity of the cal-cineurin inhibitor.

1,2

Indeed, the first biopsy after the livertransplantation in the present case revealed nephroscle-rosis with striped interstitial fibrosis and arteriolar hyali-nosis, which were compatible with typical findings inchronic renal toxicity from a calcineurin inhibitor.

3

How-ever, because the serum creatinine (s-Cr.) level beforethe liver transplantation was moderately high (1.5 mg/dL), it was suspected that another unknown coexistingcause of renal insufficiency was suspected; the histo-pathological findings observed in the first biopsy maybe a result of a vaso-occlusive process such as transplantvasculopathy or renal artery stenosis.

3

To decide whichimmunosuppressive agents to use for the renal transplan-tation, two concepts were employed. First, renal toxicityof the calcineurin inhibitor would not necessarily occurin the graft kidney even though it had happened in thenatural kidneys. Second, minimal change of the immu-nosuppressive protocol was required, as it had success-fully controlled liver graft function and HCV replication

Fig. 1

(a) Serum creatinine (s-Cr.) and administrationdose of tacrolimus (TAC) after liver transplantation froma brain-dead donor. (b) Level of s-Cr. decreased immedi-ately after renal transplantation and trough concentrationof TAC was stabilized according to the scheduled dosereduction.

s-C

r(m

g/d

L)

Tro

ug

h c

on

cen

trat

ion

(n

g/m

L)

Post–transplant (ng/mL)

(b)

(a)

TAC

(mg

/day

)s-

Cr

(mg

/dL

)TA

C(m

g/d

ay)

Fig. 2

Microphotographs in periodic acid-Schiff (PAS)stain of the first biopsy (A:

¥

200; B:

¥

400), 1-h biopsy(C:

¥

400), and 3-month biopsy (D:

¥

200). There was asimilarity between the specimens of the first and 3-monthbiopsies with striped fibrosis and hyalinized arteriolae(arrow in B), which was not detected in the specimen ofthe 1-h biopsy.

Renal following liver transplantation 609

after the earlier liver transplantation, leading to contin-uation of TAC after renal transplantation. In fact, in a 3-month biopsy specimen, abnormal findings indicatingnephrotoxicity of TAC was limited to within very smallareas and both grafts were functioning well 27 monthsafter the second surgery.

The impact of HCV infection in renal allograft recip-ients is not yet fully understood. Roth

et al

. demon-strated the short-term safety of transplanting HCV-infected ESRD patients in their prospective study thatincluded quantitative assay of HCV replication andserial liver biopsy.

4

Molmenti

et al

. followed 17 patientswith HCV infections who underwent kidney transplan-tation after liver transplantation and documented rea-sonable patient and graft survivals, though a transientrise of liver function tests were observed in somepatients. They concluded that the presence of liverallograft with HCV infection should not preclude kid-ney transplantation, provided there was no sign ofhepatic decompensation.

5

Although the utility of quan-titative assay of HCV is still unclear, repeated monitor-ing of serum viral titer as well as conventional liverenzyme tests should be carried out. In the present case,serum level of HCV-RNA increased after renal trans-plantation, transaminases had been within normal limitswithout antiviral treatment including rivabirin orinterferon.

Successful liver transplantation is associated withESRD in up to 5% of recipients who are followedbeyond 5 years.

1,5

Although some investigators havereported that the survival prognosis of patients whodeveloped ESRD after organ transplantation waspoor,

6

some recent reports have demonstrated fair out-comes of renal transplantation for ESRD following aprior solid organ transplantation.

2,5

These recentreports strongly supported our decision to indicate

renal transplantation for our patient with HCVinfection who had undergone an earlier livertransplantation.

However, it is reported that survival of renal graftrecipients who have undergone solid organ transplanta-tion is worse than the overall survival rate after kidneytransplantation.

2

Moreover, previous studies on suc-cessful renal transplantation following other organtransplantation showed have shown only short-termfollow-ups of small size samples. The present patient isregarded as a high-risk patient and is being carefullyobserved.

References

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