ARTIcle
Risk Factors for Steroid-Resistant T-Cell–Mediated Acute
Cellular Rejection and Their Effect on Kidney Graft and
Patient Outcome
Waleed Awadain,
1
Osama Gheith,
1
Ahmed Hassan,
2
Nabil Hassan,
1
Salem El-Deeb,
2
Amjad el-Agroudy,
1
Ashraf Fouda,
1
Mohamed Ahmed Ghoneim
1
Abstract
Objectives: Acute rejection in renal transplant is
considered a risk factor for short-term and long-term
allograft survival. The expected reversal rate for the
first acute cellular rejection, by steroid pulse, ranges
between 60% and 100%, and lack of improvement
within 1 week of treatment is defined as steroid-
resistant rejection. This work sought to evaluate
factors that lead to steroid-resistant acute cellular
rejection among patients with first live-donor renal
allotransplant and its effect on graft and patient
survival.
Materials and Methods: Patients with an
improvement in serum creatinine levels were
considered controls (group 1; n=100); while the
others were considered an early steroid-resistant
group (group 2; n=99). Both groups were matched
demographically.
Results: Patients with a target cyclosporine level
below accepted therapeutic levels were
significantly higher in group 2 (P = .02). We found
no significant differences between the groups
regarding posttransplant complications (P > .05).
Mean hospital stay was longer in group 2 (P = .021).
Living patients with functioning graft were more
prevalent in group 1, while those alive on dialysis
were more prevalent in group 2. The groups were
comparable regarding long-term patient and graft
survival despite significantly lower creatinine values
in patients of group 1 at 6 months’ follow-up
(P ≤ .001).
Conclusions: Prebiopsy low cyclosporine trough
levels and associated chronic changes among patients
who were maintained on calcineurin inhibitor-based
regimens represented the most-important risk factors
for the early steroid-resistant group. Rescue therapies
improve short-term graft outcome; however, they did
not affect either patient or long-term graft survival
after 5 years’ follow-up.
Key words: Steroid resistant, Acute rejection, Long-term
graft outcome, Risk factors
Introduction
Renal transplant is the criterion standard for
treating-end stage renal disease and has the greatest
potential for restoring a healthy and productive life.
1
Immunologic rejection is one of the most-important
complications affecting a transplanted kidney. Three
major forms of rejection are recognized: hyperacute,
acute, and chronic. Each had its own distinctive
changes.
2
The most-common form of immunologic
rejection in the early posttransplant period is acute
cellular rejection, which is mediated predominantly
by host lymphocytes responding to the allogeneic
donor kidney. Acute rejection typically occurs 5 to 7
days after the transplant, but it could occur at
virtually anytime afterwards, with the highest
incidence in the first 3 months. Overall rates of
rejection varied from 10% to 50% within the first 6
months depending on human leukocyte antigen
(HLA) matching and immunosuppressive protocol.
3
Acute rejection in renal transplant is considered a
risk factor for short-term and long-term allograft
survival. Since the introduction of new
immunosuppressive agents, progressive decrease in
the incidence of rejection episodes, and subsequent
Copyright © Başkent University 2012
Printed in Turkey. All Rights Reserved.
From the
1
Urology and Nephrology Center, Mansoura University, Mansoura, Egypt; and the
2
Faculty of Medicine, Zagazeg University, Egypt
Corresponding author: Osama A Gheith, MD, Urology & Nephrology Center, Mansoura,
Egypt
Phone: +965 66641967 Fax: +965 2488815 E-mail: ogheith@yahoo.com
Experimental and Clinical Transplantation (2012) 5: 446-453
DOI: 10.6002/ect.2011.0202