protein casts , nodular glomerulosclerosis in a graft biopsy sample s
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Protein casts,
nodular
glomerulosclerosis
in a graft biopsy
samples Agnieszka Perkowska-Ptasinska
Transplantation Institute, Medical University of Warsaw, Poland
• 55 years old male with end-stage native kidneys insufficiency of unknown reason,
• renal transplant from 3 HLA mismatched, cadaveric, 57 years old female donor,
• the donor and recipient: HIV (-), HCV (-), HBV (-),
• at the time of Tx: mild anemia,
• the initial immunosuppression: cyclosporine, mycophenolan-mofetil and prednisone in typical doses.
Case 1
• Three weeks after transplantation the patient was
still oliguric, and dialysis-dependant,
• the urine protein content was 25 mg/dl,
• on the day 21 the graft biopsy was performed.
Case 1
Case 1 – graft biopsy
Case 1 – graft biopsy
Case 1 – graft biopsy
Case 1 – graft biopsy
Light chain kappa Light chain
lambda
•The initial diagnosis: cast nephropathy due to light chain gammapathy accompanied by mild thrombotic microangiopathy,
•trepanobiopsy, blood, and urine immunofixation tests: findings consistent with the diagnosis of myeloma multiplex IIB.
•INR, APTT, LDH, bilirubin concentration - within normal limits,
•Pt received chemioterapy, but the graft function remained very poor.
Case 1
Procoagulant factors myloma-related:
Acute thrombotic microangiopathy
- an impaired fibrinolysis (mostly secondary to increased PAI-1 activity),
- the influence of monoclonal proteins with fibrin structure,
- a procoagulant antibody production,
- the impact of the inflammatory cytokines on the endothelium.
Transplantation-related :
-rejection
-acute CNI toxicity
6 weeks after transplantation patient was still
dialysis-dependant, on the 51 post transplant
day the graft was removed due to it’s constant
dysfunction.
Case 1
Protein casts in kidney transplant
Recipients treated with rapamycin: quite common DGF due to acute tubular injury associated with casts indistinguishable from myeloma casts.
Casts composition:
•Smith et al.: degenerating renal tubular epithelial cells (JASN 14: 1037–1045, 2003)
•Pelletier et al.: myoglobin (Transplantation 2006 15;82(5):645-50)
Male, born in 1953
medical problems: • diabetes type 2, insulinotherapy
(retinopathy? no data)
• monoclonal gammapathy (no detailed information, patient received chemiotherapy with leukeran, azatiophryne and prednisone)
2007: proteinuria 9g/d, crea: 2,7mg/dl native kidney biopsy
Case 2
Case 2 – native kidney biopsy
Case 2 – native kidney biopsy
IFL: negative for Ig, C3, C1q and light chains
Case 2 – native kidney biopsy
Case 2 – native kidney biopsy
Morphological picture:nodular glomerulosclerosissevere arteriolar hyalinistaioninterstitial fibrosis and tubular atrophy
Diagnosis: Diabetic nephropathyLCDD?
Case 2
2010: •Serum free light chains ratio within normal limits •preemptive kidney transplantation, kidney graft received from patient’s younger brother (no HLA match)
the donor and recipient: HIV (-), HCV (-), HBV (-),
the initial immunosuppression: tacrolimus, mycophenolan-mofetil and prednisone in typical doses.
the lowest serum crea conc. 1,2 mg/dl
Case 2
July 2012:serum crea conc. 1,6 mg/dlproteinuria: 100 mg/dl
Serum FLC: marked excess of kappa LC
Kidney transplant biopsy
Case 2 – transplant kidney biopsy
Case 2 – transplant kidney biopsy
Case 2 – transplant kidney biopsy
IFL: kappa light chain
C4d
Case 2 – transplant kidney biopsy
Case 2 – transplant kidney biopsyMorphological picture:
nodular glomerulosclerosisinterstitial fibrosis and tubular atrophy
Diagnosis: LCDD
Plasma cell dyscrasias
A spectrum of diseases that
include:• MGUS (monoclonal gammapathy of uncertain
significance) (2% - 4% of all individuals > 50 years)
• multiple myeloma (MM) (10% of all hematologic
malignancies)
• solitary plasmacytoma,
• AL amyloidosis
Often associated with monoclonal immunoglobulin-
dependant kidney injury
three distinct morphological forms:- cast nephropathy (abnormal Ig obstructing tubular casts), - monoclonal immunoglobulin deposition disease (MIDD), (light chains, heavy chains, or both deposit along glomerularand tubular basement membranes)- AL amyloidosis (monoclonal Ig associates with other serum proteins form insoluble fibril deposits)
Plasma cell dyscrasias
ESRD and KTX in patients with plasma cell
dyscrasias
ERA-EDTA Registry study:
• 1,54% ESRD cases due to MM or LCDD
KTX for pts with plasma cell dyscrasias is rare
(case reports, small series)
• 1.4% of patients with MM-related ESRD receives
kidney transplant
• In majority of cases MM-related kidney disease
reoccurs in the transplant
L(H)CDD• may manifest as:
mesangial proliferationMPGN-like patterncrescentic GN-like nodular glomerulosclerosis (most common)
• in majority of cases there is a recurrence of light chain deposition disease (LCDD) with the same pattern of injury as in native kidney
• early, severe recurrence in the allograft more common in crescentic, and MPGN-like types of LCDD
AL amyloidosis
• Small series of patients subjected to KTX
• No patient lost the graft because of transplant
amyloidosis
Plasma cell dyscrasias
• Patients with plasma cell dyscrasias and end-stage renal disease (ESRD) may be candidates for kidney transplantation if their monoclonal Ig has been adequately controlled.
• allograft outcomes are determined by:- the type of plasma cell dyscrasia- the histology of the native renal disease- the responsiveness of the underlying plasma cell
disorders to chemotherapy - the inherent toxicity of the monoclonal Ig.
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