Chronic Graft Versus Host Disease Presenting As Nephrotic Syndrome

Chronic graft versus host disease presenting as Nephrotic syndrome

Binod Dhakal, Eric P Cohen, Jeanne Palmer, Parameswaran, Hari

Department of Medicine, Medical College of Wisconsin.

Background:

Proteinuria after allogeneic hematopoietic cell transplantation (allo-HCT) can be multifactorial.  Renal dysfunction and ESRD are more frequent after allo-HCT but the reports of chronic graft versus host disease affecting the kidney are rare.

Methods:

We report the clinical and natural history of 7 patients presenting with nephrotic range proteinuria (NRP) defined as >=3g/24hrs after allo-HCT.

Results:

Median age at transplant was 50 years (range 42-58) years. Four of seven patients had well matched unrelated donor and three had fully matched sibling grafts (all blood stem cells, PBSC). The development of NRP was a late event occurring at a median of +682 d of allo-HSCT (range 342-880days). All but one of seven patients had evidence of other chronic GVHD at the time of diagnosis of NRP.  Median serum creatinine at diagnosis was 1.17mg/dl.

Renal biopsy was performed in all cases. Histologic patterns were variable with membranous glomerulonephritis (n=4); minimal change disease (n=1), focal segmental glomerulosclerosis (n=1) and tubulitis (n=1) observed. At the onset of NRP 3 out of 7 patients were off all immunosuppressants and four were still on tapering doses of immunosuppression. Indication for allo-HCT was AML (n=3), CLL (n=2), Multiple myeloma (n=1) and MDS (n=1) and in all cases in remission at the time NRP diagnosis.

Treatment: All patients were initially started on Prednisone (>0.5mg/kg) but only one had complete remission with single agent prednisone. Other immunosuppressant including Rituximab, Tacrolimus, Sirolimus, Cyclosporine, MMF and Rituxan were used for non-responders to prednisone. Time and response to resolution to proteinuria was variable as shown in the table below. No patients progressed to ESRD and two patients had died as of the last follow up.

Case number	Proteinuria g/d	S creat at diagnosis, mg/dl	cGVHD yes/no	Biopsy result	Treatment	Rx result
1	10.20	0.98	Yes	MGN	PDN,Tacro,MMF	CR
2	1.67	1.17	No	MGN	PDN,Tacro	CR
3	5.02	1.26	Yes	MCD	PDN,Tacro	CR
4	2.04	2.96	Yes	Tubulitis	PDN	CR
5	8.48	0.89	Yes	MGN	PDN,Tacro,Siro	NR
6	1.57	2.6	Yes	MGN	PDN,MMF	NR
7	0.61	0.8	Yes	FSGS	PDN,CsA	CR

Conclusions:

Our data confirm the association of NRP with chronic GVHD. Monitoring for proteinuria and timely recognition of this entity may avoid the need for sustained immunosuppression and nephronal loss.