Nephrotic Syndrome After Allogeneic Hematopoietic Cell Transplantation: Incidence and Outcomes.

Abstract 3324

Poster Board III-212

The NIH Consensus recognizes nephrotic syndrome (NS) as part of the chronic GVHD symptomatology, but this manifestation is rare and the incidence and outcomes have not been well-defined. To characterize this complication, we conducted an IRB-approved retrospective review of 626 consecutive patients (age > 16 yrs: related donor [RD], n=352; unrelated donor [URD], n=274) who underwent allogeneic hematopoietic cell transplantation (HCT) between October 2000 and December 2007 at the University of Michigan. Data abstraction was facilitated by the use of an electronic medical record search engine (EMERSE) that allowed for efficient identification of key concepts based on a specified set of key words and phrases (e.g. “GVHD,” “proteinuria,” and “nephrotic syndrome”). Conditioning regimens included full intensity (FIC) in 470 patients and reduced intensity (RIC) in 156 patients. Nephrotic range proteinuria was identified in 17 of the patients, which is the largest cohort reported to date following allogeneic HCT. Renal biopsy confirmed the diagnosis in seven of these patients. The median time to onset of NS was 7.3 months (range 1.4 – 40.6 months) following allogeneic HCT. Clinical manifestations included hypoalbuminemia (100%), hypercholesterolemia (82%), edema (76%), renal impairment (65%), and thrombosis (29%). The overall cumulative incidence of NS was 2.9%: 2.4% in FIC and 4.6% in RIC HCT recipients; and 2.3% in RD and 3.7% URD HCT recipients. Of note, in patients who received irradiation-based conditioning regimens, there was an increased cumulative incidence of NS compared to those who did not, 4.8% versus 2.1%, respectively.

Diagnostic symptoms of chronic GVHD based upon the NIH Consensus was seen in 65% (n=11) of the patients, all of whom were on immunosuppressive therapy at the time of diagnosis of NS. Prior history of acute GVHD was seen in 65% (n=11) of the patients. Interestingly, history of symptomatic cystitis was seen in 53% (n=9) of the patients, eight of whom had BK virus detected in the urine. The management and treatment for NS was variable. All of the patients received systemic steroids (0.25 mg/kg – 2 mg/kg), with or without mycophenolate mofetil and a calcineurin inhibitor. Additional therapy with rituximab was administered in nine patients. Durable remission with no further recurrence of proteinuria was observed in 47% of the patients (n=8). The median time to response was 4.8 months (range 0.3 – 13.5 months). Recurrence of proteinuria was seen in 29% of the patients (n=5), and primary refractory proteinuria was observed in 23% of the patients (n=4). Overall survival for the cohort was 49.5% at 4 years (confidence interval 24% - 75%) with median follow up of 5.1 years. The median survival from diagnosis of NS was 2.5 years. As of May 2009, eight patients are alive and nine have died. The causes of death include GVHD (n=6), relapse (n=2) and unknown (n=1). NS is a rare but important complication following allogeneic HCT. Early recognition of the clinical presentations and identification of high-risk groups may limit the potential morbidity and mortality associated with NS.