Transcript Recurrence of LCAT deficiency in renal graft (PPT / 5720.5 KB)

Native and transplant kidney pathology
Case 8
Erik Heyerdahl Strøm
Dept. of Pathology
Oslo University Hospital Rikshospitalet
Oslo, Norway
ECP Helsinki 30 August 2011
Clinical history
Caucasian male 22 years.
•
•
•
•
•
mild edema of lower extremities
hematuria
proteinuria, increasing to nephrotic level
moderate hypertension
slightly reduced renal function
Suspicion of chronic glomerulonephritis
Kidney biopsy was performed
PAS
Silver staining
Silver staining
Biopsy diagnosis
Glomerular lipid-containing deposits
suggestive of
Lecithin:cholesterol acyltransferase
(LCAT) deficiency
Clinical follow-up
• Lipid metabolism:
– Very low HDL, low LDL, elevated cholesterol
and triglycerides
• Corneal opacities
Genetic testing
Compound heterozygous:
Two mutations
(R244H and M252K)
in exon 6 of the LCAT-gene, located on
chromosome 16.
Final diagnosis: Familial LCAT-deficiency
Familial LCAT deficiency
Familial LCAT deficiency
• autosomal recessive disease
• due to a defect in esterification of plasma
cholesterol
– severe reduction of HDL
– elevation of free cholesterol, triglycerides and
phospholipids
Familial LCAT deficiency
lipid-containing depositions within several organs:
• kidney
– proteinuria, renal failure
• cornea
– decreased vision
• erythrocytes
– anemia due to defect of cytoplasmic membrane
• aorta and muscular arteries
– premature atherosclerotic vascular disease?
Familial LCAT deficiency
Genetics
>70 different mutations described
 Familial LCAT deficiency
 Milder disease (”Fish-eye disease”)
Kluivenhoven JA: J Lipid Res 2004
”Fish eye”
Corneal opacities:
* multiple small greyish spots  “foggy” discoloration;
band-like at the periphery
* impaired vision
* present from early childhood in LCAT deficiency
Cornea in LCAT disease
Cornea in LCAT disease
Pathogenesis of renal lesion
• Heterogeneous lesions may be due to
several mechanisms of disease
– deposition of different types of lipid containing
molecules, incl. abnormal lipoproteins: Lipoprotein X
(Lp-X)
– capillary wall impairment
– complement activation?
Differential diagnosis
• renal lesions in chronic liver diseases
– ”hepatic glomerulosclerosis” (Sagaguchi H 1965)
– Alagilles’s syndrome (hypoplasia of intrahepatic
bile ducts)
• other lipidoses
Case history
• Transplanted at 28 yrs, 6 yrs after initial
diagnosis
• Received kidney from his father, who was
heterozygous for LCAT mutation
Two days after transplantation
Biopsy proven acute rejection Banff IA
Biopsy two days after transplantation
Protocol biopsy 6 weeks after transplantation
Protocol biopsy one year after transplantation
CD 68
Recurrence of LCAT deficiency in
renal graft
• Documented in graft
- 7 weeks after transplantation
- more than 5 years graft survival
What is the significance of the changes in the
2 days post transplant biopsy?
1)
Unspecific changes?
- probably not
2)
Donor derived changes?
- probably not
3)
Recurrence of disease?
- most likely
Why present this case?
Ultrastructural morphology is quite suggestive of
LCAT-deficiency
Early recurrence in transplant
Coworkers:
Dr. Ståle Sund, Dept. of Pathology, Førde Central
Hospital, Norway
Dr. Morten Reier-Nilsen, Dept. of Medicine, Drammen
Hospital, Norway
Dr. Christina Dørje, Dept. of Nephrology, Oslo University
Hospital, Norway
Dr. Trond P. Leren, Dept. of Medical Genetics, Oslo
University Hospital, Norway
Ultrastruct Pathol 2011:35: 139–45