Nephrotic Syndrome After Allogeneic Hematopoietic Cell Transplantation: Incidence And Outcomes (2010)

The NIH Consensus recognizes nephrotic syndrome (NS) as part of the chronic GVHD symptomatology, however the incidence and outcomes of this manifestation have not been well-defined. To characterize this complication, we conducted an IRB-approved retrospective review of 626 consecutive patients (age>16 yrs: [MRD], n=352; [MUD], n=274) who underwent allogeneic hematopoietic cell transplantation (HCT) between October 2000 and December 2007 at the University of Michigan. Conditioning regimens included full intensity (FIC) in 470 patients and reduced intensity (RIC) in 156 patients. Nephrotic range proteinuria was identified in 17 patients. Renal biopsy confirmed the diagnosis in seven of these patients. The median time to onset of NS was 7.3 months following 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 MRD and 3.7% MUD 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 11 patients (65%). Prior history of acute GVHD was seen in 11 patients (65%). Interestingly, history of symptomatic cystitis was seen in 9 patients (53%), eight of whom had BK virus detected in the urine. 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. 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 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 risk factors may limit the potential morbidity and mortality associated with NS.Tabled 1Patients characteristicPatientMUD/MRDAge at TransplantDXProteinuria estimate (g/24 h)GenderGVHD RegimenKidney Biopsy1MUD53MPD5.5FTacro/MTXMinimal cange GN2MUD56MM14MTacro/MTXMemberanous GN3MRD57MDS14MTacro/MTXMemberanous GN4MUD55AML3.4MTacro/MTXN/A5MRD30NHL3.74MTacro/MTXMemberanous GN6MRD47AML10MTacro/MTXMemberanous GN7MUD49NHL6.9MTacro/MMFN/A8MUD38AML8.7FTacro/MMFN/A9MUD18Aplastic Anemia4.22FTacro/MTXN/A10MRD34AML5.96FTacro/MTXN/A11MUD61MDS13.27MTacro/MTXN/A12MRD26CMML3.58FTacro/MMFN/A13MRD63NHL4.54FTacro/MMF/MTXN/A14MUD55AML22.57MTacro/MTX/EtanerceptMinimal Change GN15MRD59NHL3.37MTacro/MMFN/A16MRD62AML5.47FTacro/MMF/MTXMemberanous GN17MUD46AML7.96FTacro/MTX/EtanerceptN/AMUD=matched unrelated donor; MRD=matched related donor; GN=glomerulonephritis; NA=non applicable; MTX=methotrexate; MMF=mycophenolate mofrtil; Open table in a new tab MUD=matched unrelated donor; MRD=matched related donor; GN=glomerulonephritis; NA=non applicable; MTX=methotrexate; MMF=mycophenolate mofrtil;