Faculty Bibliography

BACKGROUND: One of the less well-defined complications of familial dysautonomia (FD) is chronic kidney disease (CKD). The goal of this report is to better define the prevalence and severity of kidney disease in this population and identify associated risk factors. METHODS: We conducted a retrospective analysis of the database of the Dysautonomia Treatment and Evaluation Center at New York University School of Medicine for patients with FD who were seen at ages 15, 20, 25, 30, 35, and 40 years. Estimated glomerular filtration rate (GFR) was compared with that of the general population. Changes in mean blood pressure from supine to erect at ages 15 and 20 years were analyzed for patients who eventually required dialysis therapy and compared with those of the other patients with FD. Percentage of patients requiring dialysis and duration of treatment also were analyzed. RESULTS: Mean estimated GFR of each predefined age group was considerably less than that of the general population starting at age 15 years (P < 0.001). Patients with FD were more likely to develop stage 3, 4, or 5 CKD than the general population. Of patients who remained alive at age 25 years, 19% eventually required dialysis. Those who required dialysis therapy were less likely to have had a feeding gastrostomy tube placed (P < 0.001) and had much more pronounced postural changes in blood pressure (P < 0.0001) by age 15 years. For those requiring dialysis therapy, average duration of treatment was 9 months. CONCLUSION: Patients with FD are far more likely than the general population to develop CKD. Patients with FD who eventually required dialysis showed a greater degree of orthostatic hypotension and were significantly less likely to have had a feeding gastrostomy tube placed for hydration before the age of 15 years. Dialysis therapy is not well tolerated in this population

AIMS: Primary focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease in both children and adults. Our current treatments are suboptimal, and a significant percentage of cases are resistant to current therapy. PATIENTS AND METHODS: We performed an open-label, 6-month trial of the new immunosuppressive agent mycophenolate mofetil (MMF) in 18 biopsy-proven patients resistant to a course of corticosteroids therapy. Seventy-five percent had also failed to respond to a cytotoxic agent and/or a calcineurin inhibitor. RESULTS: A substantial improvement in proteinuria was seen in 44% (8/18) of the patients by 6 months. This was sustained for up to 1 year post treatment in 50% (4/8) of this group. No patient had a complete remission. No deterioration in renal function was observed in any patient over the treatment period, but 3 progressed to chronic kidney failure during follow-up. Adverse effects were mild. Only 1 patient required a dose reduction due to an intercurrent infection. CONCLUSIONS: MMF appears safe to use in this group of patients and did lower proteinuria in 44% of this cohort resistant to other forms of treatment. Relapses were common, suggesting more prolonged or combination therapy may be required. More rigorous trials utilizing this medication should be considered to further assess the risk-benefit ratio of treatment with MMF in patients with FSGS

Plasmapheresis (PP) is often employed in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the renal allograft, where it appears to be effective in the pediatric population. The efficacy of PP in adults and predictors of response are not well documented. We analyzed the records of 13 adult patients from three transplant centers who underwent PP for recurrent FSGS between 1993 and 1999. One patient (8%) had a complete response, one (8%) had a partial response, and 3 (23%) partially responded but remain PP-dependent. All 5 responders were started on PP within 30 days of recurrence, while 7 of the 8 non-responders initiated PP after a delay of at least 42 days (p = 0.0047). FSGS recurred within 30 days of transplantation in all 5 responders, while 4 of 8 non-responders had no evidence of recurrence until 42-150 days after transplantation (p = 0.098). Post-transplant biopsies were examined in 10 patients and revealed either cellular (6) or collapsing (4) variants of FSGS. We conclude PP is less effective in adults than in children as a treatment for recurrent FSGS in the renal allograft. Predictors of response to PP include early initiation of treatment after recurrence and possibly an early recurrence of disease

Focal segmental glomerulosclerosis (FSGS) has been increasing in incidence over the past 2 decades and may currently be the most common form of primary nephrotic syndrome in the United States. Nephrotic patients with FSGS who do not achieve a remission in proteinuria usually advance to end-stage renal disease within 5 to 10 years. Although initially felt to be a steroid-resistant disease, especially in adults, studies show significant responsiveness to more prolonged courses of steroids. For patients with steroid-resistant or steroid-dependent FSGS, cyclosporine A and cytotoxic agents have shown efficacy in clinical trials. Other agents used include pulse methylprednisolone, azathioprine, tacrolimus, mycophenolate mofetil, and combination therapy. For recurrent FSGS after renal transplantation, plasmapheresis is often used but appears not to be as efficacious in adults as in the pediatric population