Focal segmental glomerulosclerosis (FSGS) recurs in 30% of patients with FSGS receiving a first renal transplant and in over 80% of patients receiving a second transplant after a recurrence. Recurrence often leads to graft failure. The pathogenesis remains unknown and may involve a circulating permeability factor that initiates injury to the glomerular capillary. There are anecdotal reports of pediatric patients with posttransplant lymphoproliferative disorder (PTLD) and recurrent FSGS who have had remission of proteinuria after treatment with rituximab. These observations have prompted speculation that B cells may play a role in the pathogenesis of recurrent FSGS. We report four consecutive adult patients with early recurrent FSGS refractory or dependent on plasmapheresis who received rituximab (total dose 2000-4200 mg). None of the patients treated with rituximab achieved remission in proteinuria, and one patient experienced early graft loss. In these four adult renal transplant patients with recurrent FSGS, rituximab failed to diminish proteinuria.
We examined the magnitude of adaptive hyperfiltration in the remaining kidney of 16 aging (Ͼ57 yr) and 16 youthful (Ͻ55 yr) individuals who had undergone a contralateral nephrectomy. Healthy volunteers who were youthful (n ϭ 143) or aging (n ϭ 37) provided control values for the binephric condition. One-kidney glomerular filtration rate (GFR; ϩ42%), renal plasma flow (ϩ38%), plasma oncotic pressure (ϩ2.8 mmHg), and mean arterial pressure (ϩ7.0 mmHg) were all higher in youthful uninephric vs. binephric subjects. Corresponding excesses in aging uninephric vs. binephric subjects were by 38 and 36% and 1.4 and 14.0 mmHg, respectively. Modeling of these data revealed that an isolated increase in either the glomerular ultrafiltration coefficient (Kf) by 110% or in the transcapillary hydraulic pressure gradient (⌬P) by 7 mmHg, could account for the observed level of hyperfiltration in youthful uninephric subjects. Corresponding increases for aging uninephric subjects were 61% for Kf and 5 mmHg for ⌬P. We conclude that the magnitude of adaptive hyperfiltration is similar in aging to that in youthful uninephric subjects, albeit at a lower absolute GFR level. Isolated increases in either Kf or ⌬P or a combination of smaller increases in both can account for the hyperfiltration. Greater adaptive arterial hypertension in aging than youthful uninephric subjects raises the possibility of a disproportionate role for glomerular hypertension and ⌬P elevation in aging compared with youthful uninephric subjects. Glomerular hypertension could exacerbate the sclerosing glomerulopathy of senescence and lead to renal insufficiency. We recommend that living donors of a kidney transplantation in or beyond the seventh decade be used with caution.living kidney donor; uninephrectomy; glomerular filtration A SHORTAGE OF KIDNEYS FOR transplantation (Tx) in the United States has resulted in a recipient waiting list in excess of 50,000 and a median waiting time of 1,131 days (38). One measure adopted to lower the donor deficit has been the increasing use of unrelated, living donor transplants (35,36,38). Another recent source of additional donors has been deceased donors who meet the so-called "expanded" criteria for donation, the most prominent of which is a donor age in the seventh or even eighth decade (38). Although the expanded criteria have been recommended for deceased donors, the use of living donors over 60 yr of age has, in fact, more than doubled during the past decade (38), suggesting a possible trend toward the increasing use of aging donors, be they deceased or living.A large body of evidence indicates that both the short-term and long-term risks of living kidney donation are minimal and that the ensuing uninephric state is safe for the living donor (9,22,25,26). Donors above age 60 yr at the time of nephrectomy have been few, however, and a comparison between their course and outcome and those of younger donors has not been reported. A relative paucity of aging donors reflects an inverse relationship between graft survival and d...
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