Should early renal transplantation be deemed necessary among patients with end-stage sickle cell nephropathy who are receiving hemodialytic therapy?

Abstract

The presence of chronic renal failure (CRF) significantly shortens the survival of patients with sickle cell disease (SCD); the outcomes of patients with end-stage sickle cell nephropathy (ESSCN) who are receiving long-term hemodialysis (HD) do not seem to be encouraging either. In view of the significantly superior survival rates of renal transplant recipients, patients with ESSCN who are receiving HD may be encouraged to undergo renal transplantation at an earlier stage, perhaps with precedence over patients without SCD. CRF, which occurs in 4% to 20% of renal transplant recipients, is a key predictor of the poor outcome of patients with SCD (1,2). The presence of CRF significantly shortens the survival of patients with SCD, who have a median life expectancy of 27 years as opposed to 51 years for those without renal failure (2). Although renal replacement therapy, in the form of HD and renal transplantation, generally remains the standard management, little is known about the long-term outcome of patients with ESSCN. A retrospective cohort study was performed at the HD facility of our Tertiary Care Center in the Eastern Province of Saudi Arabia (where Asian β-globin haplotype, a local mutation independent of the West African or Central African origin, is prevalent among patients with SCD) from January 1992 to January 1999. There were two groups (n=203): Group 1 was composed of 11 patients with ESSCN, and group 2 was composed of 192 patients with end-stage renal disease as the result of diverse causes. Factors frequently affecting morbidity and mortality (e.g., age, gender, dialytic age, blood transfusion, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and episodes of vascular access-related septicemia) were matched between these two groups. Group 1 demonstrated a higher requirement of blood transfusion (13.7±6 vs. 8.2±3.3 units, P <0.05) and a higher prevalence of HBV (18.2% vs. 4.64%, P <0.002) and anti-HCV positivity (63.6% vs. 44.3%, P <0.004) compared with group 2. A higher incidence of vascular-related septicemia was noted in group 1 compared with group 2 (2.59 vs. 1.19 episodes/100 patient months, P <0.0001). Significantly higher mortality was observed in group 1 compared with group 2 (11.59% vs. 5.87%/year, P <0.001) at a relatively younger age (31±8.2 vs. 47.8±18 years, P <0.0.021) and shorter dialytic age (27±5.6 vs. 44.2±12.3 months, P <0.008). Patients with ESSCN clearly revealed a higher mortality at a significantly younger age and shorter dialytic age in comparison with patients without SCD who are receiving long-term HD. An early onset of end-stage renal disease, a higher prevalence of HBV and HCV virus infections, and a significantly elevated incidence of VRS seem to be the potential determinants of the suboptimal survival of patients with ESSCN who are receiving long-term HD. Poor survival rates are largely related to the bacterial and viral infections in this asplenic population, which may also be attributable to hepatic failure related to iron overload and chronic hepatitis (HBV and HCV) because HD creates a high-risk environment for the transmission of HCV in association with the obligatory need for vascular access sites and extracorporeal blood circulation (1–3). Oxidative stress caused by HD filters adversely affects cell-mediated immunity in the already immunocompromised HD population. Studies on renal allograft survival in patients with SCD with the Asian β-globin haplotype (predominant in the Eastern Province of Saudi Arabia and Central India) are not available to match with the survival of Afro-American transplant recipients (>65% of whom are known to have Benin β-globin haplotype, with its origin in West Africa). Nevertheless, in the registry data from 1984 to 1996, 1-year allograft survival in patients with SCD was similar to that of the age-matched Afro-American transplant recipients (using identical criteria for the selection of the patient from both the groups), although the 3-year survival rate of 48% was significantly less than that of the control population (60%) (4,5). Furthermore, there was a trend toward better patient survival with renal transplantation in relation to dialysis in end-stage renal disease (6). In light of the superior survival rates of renal transplant recipients compared with patients who are receiving HD, patients with ESSCN who are receiving HD may be encouraged to undergo renal transplantation at an earlier stage, perhaps with precedence over patients without SCD. Anil K. Saxena B. R. Panhotra Ali M. Al-Arabi Al-Ghamdi