The initiation and progression of sickle cell nephropathy

Abstract

renal failure might shed light on general mechanismsthat can be applied to other diseases. I will focus this dis-cussion on homozygous (SS) SCD, not on the manyvariants of this disease in which SS hemoglobin is com-bined with other hemoglobin subtypes.The major pathologies in SCD-associated renal failureare papillary necrosis (PN), focal segmental glomerulo-sclerosis (FSGS), and type 1 membranoproliferative glo-merulonephritis (MPGN) [7]. A frequent complicationof SCD, PN was documented in 15% to 40% of patientswith SCD undergoing urography to work up symptomsor urinary abnormalities, usually gross hematuria [8, 9].Moreover, the frequency of PN among asymptomaticSCD patients who systematically underwent urographywas 67% [10]. When PN is detected incidentally in SCD,it seldom is associated with a measurable decline in GFR[10], but we will look at how PN might set the stage forsubsequent renal failure in SCD. By contrast, renal biop-sies in patients [5, 7, 11, 12] and autopsy studies [13]suggest that FSGS is the most common cause of renalfailureinSCD.Moreover,clinicopathologicstudiesshowthat the early lesion of most forms of SCD nephropathyisglomerularenlargement withprogressivedevelopmentof perihilar FSGS [7, 11]. These data support FSGS asthe major cause of SCD nephropathy (Fig. 1). AlthoughMPGN in SCD is morphologically similar to the classicvariety of this disease, few cases have the characteristicimmune deposits, particularly in the early stages [7, 11].The etiology of MPGN in SCD is poorly understood,but it is not the major cause of renal failure in SCD [7].Consequently, the focus of this discussion will be onFSGS as the major cause of SCD nephropathy and onPN as the possible prodrome for the subsequent appear-ance of FSGS.