protein casts , nodular glomerulosclerosis in a graft biopsy sample s
DESCRIPTION
Protein casts , nodular glomerulosclerosis in a graft biopsy sample s. Agnieszka Perkowska-Ptasinska Transplantation Institute, Medical University of Warsaw, Poland. Case 1. 55 year s old male with end-stage native kidneys insufficiency of unknown reason, - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/1.jpg)
Protein casts,
nodular
glomerulosclerosis
in a graft biopsy
samples Agnieszka Perkowska-Ptasinska
Transplantation Institute, Medical University of Warsaw, Poland
![Page 2: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/2.jpg)
• 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
![Page 3: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/3.jpg)
• 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
![Page 4: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/4.jpg)
Case 1 – graft biopsy
![Page 5: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/5.jpg)
Case 1 – graft biopsy
![Page 6: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/6.jpg)
Case 1 – graft biopsy
![Page 7: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/7.jpg)
Case 1 – graft biopsy
Light chain kappa Light chain
lambda
![Page 8: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/8.jpg)
•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
![Page 9: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/9.jpg)
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
![Page 10: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/10.jpg)
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
![Page 11: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/11.jpg)
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)
![Page 12: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/12.jpg)
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
![Page 13: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/13.jpg)
Case 2 – native kidney biopsy
![Page 14: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/14.jpg)
Case 2 – native kidney biopsy
IFL: negative for Ig, C3, C1q and light chains
![Page 15: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/15.jpg)
Case 2 – native kidney biopsy
![Page 16: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/16.jpg)
Case 2 – native kidney biopsy
Morphological picture:nodular glomerulosclerosissevere arteriolar hyalinistaioninterstitial fibrosis and tubular atrophy
Diagnosis: Diabetic nephropathyLCDD?
![Page 17: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/17.jpg)
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
![Page 18: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/18.jpg)
Case 2
July 2012:serum crea conc. 1,6 mg/dlproteinuria: 100 mg/dl
Serum FLC: marked excess of kappa LC
Kidney transplant biopsy
![Page 19: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/19.jpg)
Case 2 – transplant kidney biopsy
![Page 20: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/20.jpg)
Case 2 – transplant kidney biopsy
![Page 21: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/21.jpg)
Case 2 – transplant kidney biopsy
IFL: kappa light chain
C4d
![Page 22: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/22.jpg)
Case 2 – transplant kidney biopsy
![Page 23: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/23.jpg)
Case 2 – transplant kidney biopsyMorphological picture:
nodular glomerulosclerosisinterstitial fibrosis and tubular atrophy
Diagnosis: LCDD
![Page 24: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/24.jpg)
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
![Page 25: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/25.jpg)
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
![Page 26: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/26.jpg)
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
![Page 27: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/27.jpg)
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
![Page 28: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/28.jpg)
AL amyloidosis
• Small series of patients subjected to KTX
• No patient lost the graft because of transplant
amyloidosis
![Page 29: Protein casts , nodular glomerulosclerosis in a graft biopsy sample s](https://reader035.vdocuments.site/reader035/viewer/2022062520/56815827550346895dc58a21/html5/thumbnails/29.jpg)
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.