• 64yo M - ESRD due to DMN. RRT 2003. PD → HD

• Diabetes mellitus. X >30 yr. Insulin management. • Diabetic retinopathy.• CAD. 3V-CABG 1996. MIBI Oct/05 ~EF 57%, no risk territories. • Hyperlipidemia. • Hypertension.• Legionnaire’s disease, 1991.• Buschke’s scleroderma of the neck.• Remote smoker- quit over 15 years ago.• Autonomic and peripheral neuropathy• GERD.

• Functional ability high

Transplant history

• Extended Criteria Donor August 10th • Low immunologic risk: Neg PRA &

cross-match• Cold Ischemic time 9hr• BENEFIT trial: CsA, MMF & pred.

+CsA arm.• DGF: HD on POD #2. • Cr 220umol/L @ d/c POD #7.

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• Donor kidney biopsy

DiagnosisRenal Biopsy:• Hypertensive nephropathy with mild parenchymal

atrophy and scarring and less than 20% glomerulosclerosis

• Marked tubular degenerative changes.

Comment: to have a glomerulus with segmental sclerosis is somewhat more than one would expect to see in the spectrum of hypertensive nephropathy. Whether this could be a sign of primary glomerular disease (early secondary FSGS) should be evaluated clinically.

Transplant history

• Early BK rise resulted in progressive reduction in immunosuppression

• By Jan/07: MMF 500 bid, Target CsA ~100

Date 29/09/06 6/10/06 23/10/06 11/11/06 5/12/06 05/01/07

Blood 5,100 1, 678 9,525

Urine 58 x 106 620 x106 2135 x106 349 x106

Meds Level

MMF 1g2

CsA 200

MMF 1g2

CsA 100–150 ug/L (actual 150-190)

MMF 0.5mg2

CsA ~100 ug/L

• 1st Xplant Biopsy Oct 6th. Cr @ 304umol/L. No rejection or BKN.• ?Xplant obstruction –Lymphocele marsupilized Oct 18th. Transient Cr

drop to 275umol/L • 2nd Xplant Biopsy Nov 9th for Cr rise 256 → 315umol/L. Rx’d as acute

rejection with 3d IV solumedrol –no pred taper. Creatinine 262 umol/L by end November. No BKN

• 3rd Xplant Biospy Jan 18th 2007. Creatinine 335 Jan 11, 2007

Bx 2Bx 1 Bx 3

marsupilization

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• Renal Tx 10 Aug 06

• Increase serum creatinine

• R/O rejection

IF

• C4d- Section is folded and hard to interpret. Peritubular capillaries appear negative. The one glomerulus shows some irregular staining which appears to be in the mesangium and around one capillary, interpreted as negative.

DiagnosisRenal Biopsy (2 months post-Tx):• Negative for rejection

• Banff scores: – G0 I1 T0 V0 AH1

• Mild to moderate arteriosclerotic small vessel disease, including arteriolar hyalinosis (presumably of donor origin)

• 1st Xplant Biopsy Oct 6th. Cr @ 304umol/L. No rejection or BKN.• ?Xplant obstruction –Lymphocele marsupilized Oct 18th. Transient Cr

drop to 275umol/L • 2nd Xplant Biopsy Nov 9th for Cr rise 256 → 315umol/L. Rx’d as acute

rejection with 3d IV solumedrol –no pred taper. Creatinine 262 umol/L by end November. No BKN

• 3rd Xplant Biospy Jan 18th 2007. Creatinine 335 Jan 11, 2007

Bx 2Bx 1 Bx 3

marsupilization

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• CAD Tx 3 months ago

• Recent surgery to correct urinary obstruction

• Recent increase in creatinine

• Rejection?

IF

• IgG- Negative.• IgA- Negative.• IgM- Negative.• C3- Moderate staining in a small vessel.• C1q- Negative.• Kappa- Negative.• Lambda- Negative.• Fibrinogen- Moderate to strong interstitial staining. • Albumin- Mild non specific background.• C4d- Peritubular capillaries negative. Minimal glomerular

staining with a focal and segmental character, mostly in a wispy mesangial distribution.

C3

Fibrin

Albumin

C4d

BK virus ISH

• negative

DiagnosisRenal Biopsy (3 months post-transplantation):

• Mild tubulo-interstitial rejection

• Severe arteriosclerotic vascular disease apparently of donor origin

• Banff score: – G0, I2, T2, V0, AH1

• 1st Xplant Biopsy Oct 6th. Cr @ 304umol/L. No rejection or BKN.• ?Xplant obstruction –Lymphocele marsupilized Oct 18th. Transient Cr

drop to 275umol/L • 2nd Xplant Biopsy Nov 9th for Cr rise 256 → 315umol/L. Rx’d as acute

rejection with 3d IV solumedrol –no pred taper. Creatinine 262 umol/L by end November. No BKN

• 3rd Xplant Biospy Jan 18th 2007. Creatinine 335 Jan 11, 2007

Bx 2Bx 1 Bx 3

marsupilization

U07-1117#622858320• Transplant in Aug/06• Lowest creat 220• Now 330• BK plasma ++• Prior biopsy – for BK• +/- rejection on last Nov – 3d steroid – no benefit• D6F• Immunosupp CsA- low levels, cellcept, prednisone

IF• IgG- Negative.• IgA- Negative.• IgM- interstitial plasma cells and lymphocytes.• C3- minimal non specific TBM• C1q- Negative.• Kappa- Occasional interstitial plasma cells. Glomerulus

negative.• Lambda- Numerous interstitial lymphocytes or plasma cells.• Fibrinogen- Moderate interstitial staining. • Albumin- Moderate background with some prominence of

basement membranes.• C4d- Negative.

IgM

C3

Kappa

Lambda

fibrinogen

albumin

IH

• EBER negative

• Slight predominance of lambda over kappa

DiagnosisRenal Biopsy (5 months post-Tx):• Plasma cell rich acute cellular rejection

(tubulointerstitial pattern with a minimal vascular component)

• Banff scores– G0 CG0 I3 CI2 T3 CT2 V1 CV2 AH0 MM2

Comment

• The obvious feature is tubulointerstitial rejection.• Accompanying vasculitic lesion is minimal and

barely sufficient for diagnosis.• Unusual IF: lymphocytes/plasma cells expressing

predominantly lambda light chain + IgM• Special studies are not in favor of PTLD• EBV serology (IgM) should be verified