Living-related donor transplants should be performed with caution in patients with focal segmental glomerulosclerosis

The success rates of living-related donor (LRD) transplants are clearly superior to those obtained with cadaver donors. However, caution should be exercised when considering LRD transplantation for a condition which has an increased chance of recurring after transplantation and causing ultimate graft failure. The recurrence rate of focal segmental glomerulosclerosis (FSGS) in the allograft is 20%–40%, with graft failure resulting in 40%–50% of these cases. However, these figures may be an underestimation of the true rate of recurrence of FSGS. Once a first transplant fails due to recurrent disease, the risk of recurrence in the second transplant approaches 80%. Subgroups of patients at high risk for recurrence have been identified. In patients not at high risk for recurrent FSGS, the use of a LRD should be considered, provided that the donor and recipient and their families have been informed that the disease may recur and lead to graft failure. In patients at high risk for recurrence, a LRD transplant should be avoided. Hopefully, future development of a simple and reliable test to predict the likelihood of recurrence will enable us to counsel and advise our patients with FSGS about the wisdom or dangers of proceeding with a LRD transplant.     

Phenotypic heterogeneity associated with defective apolipoprotein B-100 and occurrence of the familial hypercholesterolemia phenotype in the absence of an LDL-receptor defect within a Canadian kindred

Of 163 individuals with a diagnosis of heterozygous familial hypercholesterolemia (FH), only one subject was found to be positive for familial defective apo B-100 (FDB). The eight-member kindred ascertained through this subject who presented with both a clinical phenotype of FH and the FDB apo B-100 (Arg₃₅₀₀→-Gln) mutation was studied. Plasma lipid and lipoprotein profiles, apo E phenotypes, apo B gene markers at the 3′ hypervariable region and LDL-receptor haplotypes (ApaLI, PvuII, NcoI), were determined, together with LDL-receptor activity on freshly isolated blood lymphocytes. The FDB mutation, present in four relatives, was associated with three different phenotypes: FH and severe hypercholesterolemia, moderate hypercholesterolemia and normolipidemia. The FH phenotype occurred in the absence of any functional LDL-receptor defect. In homozygotes for the absence of the PvuII cutting site who had the apo B mutation, LDL-cholesterol levels were low in the presence of the apo E3/2 phenotype and high in the presence of the apo E4/4 phenotype. None of the major known environmental influences accounted for the wide range of variation in LDL-cholesterol among the affected members. Further observations in the spouse and offspring of the normolipidemic FDB subject confirmed the association of apo E4, the FDB mutation and the PvuH(-/-) genotype with high cholesterol levels. It is concluded that the phenotypic expression of the FDB mutation may vary widely as a function of the genetic environment within a family. The presence of phenotypic heterogeneity among individuals with the same apo B mutation may result from epistatic interaction of the apo B locus with genetic factors regulating cholesterol homeostasis, including possible involvement of the apo E and the LDL-receptor gene loci. This study also confirms that the clinical diagnosis of FH is not necessarily associated with an LDL-receptor defect.     

Increased recognition of IgA nephropathy in African-American children

Based upon the percentage of cases of IgA nephropathy (IgAN) in biopsy series, a lower prevalence has been assumed for African-Americans compared with Americans of European descent. This may be due to a racial difference in the basic underlying pathology of IgAN or to racial differences in patterns of referral and biopsy selection practices. Over the past decade (1985 – 1994), we have found similar incidences of IgAN in Caucasian and African-American children from Shelby County, Tennessee. The incidence was 3.0 cases per million per year for Caucasian and 5.7 cases per million per year for African-American children. IgAN may be more common in African-American children than previously appreciated. Population-based incidence studies will be necessary to determine whether or not our experience has become a more widespread phenomenon. Received August 21, 1996; received in revised form and accepted December 18, 1996