Chronic renal failure following liver transplantation: a retrospective analysis.
BACKGROUND
Liver transplant recipients are at risk of chronic renal disease, principally as a result of nephrotoxicity of the commonly used immunosuppressive agents cyclosporine and tacrolimus. We have investigated the incidence of chronic renal failure and its risk factors in our transplant population, which was treated predominantly with cyclosporine.


METHODS
A single-center retrospective study was done of 883 consecutive adult patients receiving a first liver transplant between 1982 and 1996. Potential risk factors for the development of chronic renal failure were recorded, including serial measurements of cyclosporine therapy and renal function.


RESULTS
Severe chronic renal failure (serum creatinine level >250 microM/L for at least 6 months) developed in 25 patients, representing 4% of patients surviving 1 year or more. Twelve of these patients developed end-stage renal failure and mortality was 44%. The predominant cause of renal failure was cyclosporine nephrotoxicity. Serum creatinine as early as 3 months after surgery was strongly associated with the eventual development of severe chronic renal failure (P=0.001), and this group could be further subdivided into two groups with differing risk factors. The first group had early (<1 year) renal dysfunction, with older age (P=0.03), cytomegalovirus infection (P=0.03), need for perioperative renal replacement therapy (P=0.06), and regrafting (P=0.06) as risk factors for eventual renal failure; the second group had late-onset (>1 year) renal dysfunction, with cyclosporine levels at 1 month after surgery (P=0.007) and daily and cumulative cyclosporine dosage at 5 years (P=0.01 for both) as risk factors.


CONCLUSIONS
With improved survival of liver transplant recipients, chronic renal failure has become an important cause of morbidity and is associated with a high mortality. Many patients at risk of severe chronic renal failure may be identified at an early stage. Treatment regimens that avoid or prevent cyclosporine-induced nephrotoxicity are urgently required for this population.
Liver Unit, Queen Elizabeth Medical Centre, Birmingham, United Kingdom.
N C
NC
Fisher
P G
PG
Nightingale
B K
BK
Gunson
G W
GW
Lipkin
J M
JM
Neuberger
D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus