M Samhan

Induction immunosuppression with interleukin-2 receptor antibodies (basiliximab and daclizumab) in renal transplant recipients

KIDNEY transplantation is the treatment of choice for patients with end-stage renal disease. Acute rejection (AR) episodes are still a major problem in renal transplant recipients (RTR), predisposing them for chronic allograft dysfunction and graft loss. The search for more specific immunosuppressive agents to prolong graft survival has recently led us to focus on anti-interleukin (IL)-2 receptor antibodies (anti-IL-2Rab) in induction therapy. Two anti-IL-2 Rab are now approved for clinical use. They are biologically engineered to contain more human gene regions and fewer murine-derived regions. These are basiliximab (Simulect; Novartis, Basel, Switzerland) and daclizumab (Zenapax; Hoffman-La Roche, Switzerland). Reports of successful clinical trials of these agents in induction treatment of RTR is already available in the literature. These authors found anti IL-2 Rab useful for prevention of AR episodes and reported good tolerability. This paper reports on a prospective study of use of basiliximab (Simulect) and daclizumab (Zenapax) in induction immunosuppression in mismatched first renal transplants in our unit.

High incidence of post-transplant diabetes mellitus in Kuwait

Post-transplant diabetes mellitus (PTDM) has been reported to occur in 5-15% of non-diabetic renal transplant recipients. During a 15-year period (January 1983-January 1998), 631 renal transplant recipients (TxR) were followed-up in our Centre of whom 79 (12.5%) had pre-transplant diabetes mellitus. Among the 552 TxR who were non-diabetic at pre-transplantation, 117 (21.2%) developed PTDM. The gender, native renal disease and the mode of pre-transplant dialysis did not differ in those with and without PTDM. Of the 117 TxR who developed PTDM, 63 (53.8%) were above the age of 45 years where as only 90 (20.7%) of the 435 who remained non-diabetic (NDM) were above this age (P<0.05). PTDM occurred in 115 (29.6%) recipients of Arab origin (Kuwaitis and non-Kuwaitis) where as only two (1.7%) non-Arabs developed it. There was no difference in the incidence of PTDM when prednisone and azathioprine (two drug regime) were used or with cyclosporine (triple drug regime). The incidence of acute rejection episodes did not differ among PTDM and NDM groups. The over all incidence of infections requiring hospitalisation was higher in PTDM group (1.8 episodes per patient) compared to NDM group (one episode per patient) during the study period (P<0.001). Coronary heart disease was also more frequent in PTDM (15 vs. 6%, P<0.05). The cumulative graft survival at 1, 5, 10 and 14 years in the PTDM (97, 92, 74 and 67%, respectively) and NDM groups (97, 91, 80 and 73%, respectively) was similar. However, an important cause of graft loss was death of the recipient in PTDM compared to NDM (10.7 vs. 3.6%). Similarly, the patient survival up to 14 years did not differ between PTDM and NDM groups (80 and 82%, respectively), although infection related deaths were more frequent in the PTDM group (65 vs. 49%) although not statistically significant. In conclusion, there is a high incidence of PTDM in Kuwait; age and race being the two important contributory factors. The overall patient and graft survival are not adversely affected by PTDM although infections and coronary heart disease are more frequently encountered in this group.

Cytomegalovirus infection in kidney transplant recipients: early diagnosis and monitoring of antiviral therapy by the antigenemia assay.

CYTOMEGALOVIRUS (CMV) is one of the most frequent infections in renal transplant recipients. After primary infection the virus remains dormant in various cells/organs for years. There are many factors that may reactivate virus replication; among them, organ transplantation certainly is the most important one, often causing serious disease and often associated with decreased graft survival. Though treatment is available, its timing and dosage should be tailored according to the ongoing CMV disease. There are different approaches for the diagnosis of CMV infections. The “gold standard” is cell culture in which the virus can be isolated. However, it is a timeconsuming and expensive procedure. Though combining virus isolation with immunofluorescence technique reduces the time from weeks to days, it is still not enough to meet the demand of a rapid diagnosis. Polymerase chain reaction (PCR) may have a strong impact on the diagnosis of CMV infection, but there is a need for further standardization and simplification. Many of the kidney transplant recipients fail to produce antibodies due to immunosuppressive therapy, making serological diagnosis undependable in CMV infections. Recently, detection of a specific CMV replication-related antigen (CMV antigen pp65) directly in leukocytes of patients has shown a good correlation with the clinical condition of the patient. This, CMV antigenemia assay (AA) seems to provide not only a reliable, specific, and sensitive diagnostic tool, but also facilitates monitoring the effectiveness of antiviral therapy.

It Takes Time After Bilateral Nephrectomy for Better Control of Resistant Hypertension in Renal Transplant Patients

UNLABELLED Severe resistant hypertension in end-stage renal disease patients has traditionally been an indication for bilateral nephrectomy (BN) before kidney transplantation. Nevertheless the influence of BN on successful control of hypertension has not been well documented. We sought to clarify the effect of BN on blood pressure patterns and control in renal transplant patients. MATERIALS AND METHODS We retrospectively reviewed 28 patients who underwent BN between November 2003 and May 2009 before or after kidney transplantation. Nineteen of them were under treatment with 4 or 5 antihypertensives according to the international guide lines; they had BN for resistant hypertension. They were considered as group 1 (G1). Nine patients operated for indications other than resistant hypertension; they constitute group 2 (G2) and considered as a control group. All patients received triple immunosuppression according to our local protocol. BN was done either before, simultaneously or after transplantation. Antihypertensives were recorded before and after BN. We evaluated our patients at 3 months, 1 year, and 3 years. Acute rejection episodes and calcinurein nephrotoxicity were reported. RESULTS In G1, the mean age was 30.2 years (range, 10-62). In G2, the mean age was 33.6 years (range, 11-61). Before BN, G1 patients used antihypertensive drugs (3.6 +/- 1.05 drugs per day; mean +/- SD), which was significantly higher than in G2 patients (2.0 +/- 1.65 drugs per day; P = .02). Three months after BN, G1 patients used 2.6 + 0.9 drugs per day, with gradual reduction in number of antihypertensives to 1.4 +/- 1.3 drugs per day at 3 years (P = .008). In G2, there was reduction in antihypertensive drug number per day, which was insignificant during the follow-up period. No difference was noted between G1 and G2 drug administered after BN. We conclude that BN is effective to help blood pressure control, in resistant hypertension in renal transplant patients, but it starts to show up 3 months after surgery, and continues to work for a year and more.