Patient developed acute and chronic renal failure in 1999 associated with a renal stone. History, and a diagnosis of chronic pyelonephritis. She was started.

•Patient developed acute and chronic renal failure in 1999 associated with a renal stone. History, and a diagnosis of chronic pyelonephritis. She was started on peritoneal dialysis.

•Laparoscopic left nephrectomy was performed in June 2000 for retained stones.

#428207110

S00-45788

Left kidney, fragmentary removal:

• End-stage kidney– Chronic tubulointerstitial inflammation and

scarring, consistent with obstruction and/or pyelonephritis.

– Marked parenchymal crystal deposits, probably secondary oxalate deposition.

« The findings here are probably secondary oxalosis on the basis of chronic renal failure, although I concede that the degree of crystal deposition is exceptional. I should add that there are congenital metabolic errors which usually lead to massive levels of oxalate retention in tissues, but these usually lead to end-stage renal disease before the age of 20. »

• LRD kidney transplant was performed October 25, 2000.

• Rising creatinine about 2 months later lead to transplant biopsy

• Demonstration of crystals which lead to investigations resulting in diagnosis of primary oxaluria (type I)

• Creatinine continue to rise.

Renal biopsies after 1st Tx

Indication Banff Deposits

U00-14101 time of Tx G0 I0 T0 V0 AH2 -

U00-14762 (~ 2 weeks post-Tx)

creat 120 G0 I0 T0 V0 AH2 Focal tubular calcifications

U00-15830 (~ 1 month post-Tx)

creat 160 G0 I0 T0 V0 AH2 Acute tubular injury with calcium oxalate deposition

U01-253 (~ 2 months post-Tx)

creat 280 G0 I0 T0 V0 AH2 Extensive tubular deposition of calcium oxalate consistent with oxalosis

Scanned slide

• Combined liver/kidney transplant June 21, 2003 with initial serum creatinine of 80 µmol/L.

• First post transplant biopsy done when creatinine rose to 120 µmol/L

Renal biopsies after 2nd Tx

Indication Banff Deposits

U03-9704 time of Tx G0 I0 T0 V0 AH1 -

U03-12130

(~ 6 weeks post-Tx)

creat 120 with proteinuria

N.S. findings

G0 CG0 I1 CI1 T0 CT1 V0 CV1 AH0 MM0

tubular calcium phosphate deposition

U03-12130

• Ureteral stenosis diagnosed in September 2003 (stent ?)

• Second biopsy when 170 µmol/L (At time of surgical incision of ureter post-stent changes)

Renal biopsies after 2nd Tx

Indication Banff Deposits

U03-9704 time of Tx G0 I0 T0 V0 AH1 -

U03-12130

(~ 6 weeks post-Tx)

creat 120 with proteinuria

N.S. findings

G0 CG0 I1 CI1 T0 CT1 V0 CV1 AH0 MM0

tubular calcium phosphate deposition

U03-15919

(~ 4 months post-Tx)

creat 180

post stent change

acute bacterial interstitial nephritis

G0 CG0 I3 CI2 T1 CT2 AH2 MM0

extensive calcium phosphate and calcium oxalate deposition

U03-15919

IF

• Cytoplasmic staining of plasma cells for IgG, kappa, lambda

DiagnosisRenal Biopsy:• Acute bacterial interstitial nephritis with pus

casts probably on the basis of partial ureteral obstruction by calcium oxalate debris.

• Tubular deposition of calcific debris, both calcium phosphate and calcium oxalate.

• Possible subclinical immune complex glomerulonephritis.

• No evidence of rejection.• (G0 CG0 I3 CI2 T1 CT2 V- CV- AH2

MM0)

April 2004

• Obstructed renal transplant secondary to ischemic ureter ?

• Portions of transplant ureter (proximal ureter) surgically removed + transplant biopsy.

Renal biopsies after 2nd TxIndication Banff Deposits

U03-9704 time of Tx G0 I0 T0 V0 AH1 -

U03-12130

(~ 6 weeks post-Tx)

creat 120 with proteinuria

N.S. findings

G0 CG0 I1 CI1 T0 CT1 V0 CV1 AH0 MM0

tubular calcium phosphate deposition

U03-15919

(~ 4 months post-Tx)

creat 180

post stent change

acute bacterial interstitial nephritis

G0 CG0 I3 CI2 T1 CT2 AH2 MM0

extensive calcium phosphate and calcium oxalate deposition

U04-6303

(~ 10 months post-Tx)

ureteral obstruction

acute rejection IA

G0 CG0 I3 CI2 T2 CT2V0 CV0 AH1 MM0

no crystals in kidney but present in ureter

DiagnosisRenal Biopsy:Kidney allograft biopsy (10 months post-transplantation):Active chronic tubulointerstitial nephritis A) Changes consisted with chronic obstruction B) Banff Score G0 CG0 I3 CI2 T2 CT2 V0 CV0 AH1 MM0C) No deposits by EM

Proximal right ureter: A) Focal granulation tissue consistent with ischemic damageB) Granulomatous reaction to crystalline material, consistent with oxalate deposits

• Following her biopsy in April 2004 (with imaging studies documenting ureteral obstruction despite stent) at the time of surgical ureteral repair, she returned home and serum creatinine settled to the 130-140 mol/L range.

• On prednisone 5 mg daily, cellcept 500 mg bid, tacrolimus 3 mg bid, and other meds.

• When serum creatinine rose to 160-170 in late September 2006 and 200 in early October 2006 with no change in medications or acute medical illness, concern lead to imaging studies (generally normal) and renal transplant biopsy (November 6).

• Subsequently serum creatinine seems to have fallen 190 155.

U06-21176

#428207110

• Systemic oxalosis

• Liver-kidney transplant 3 yrs ago

• Base creat ~ 130

• Recent increase to 180-210 range

• ?rejection

• ?recurrent disease

IF• IgG- Negative.• IgA- Negative.• IgM- Negative.• C3- Moderate vascular staining. • C1q- Negative.• Kappa- Negative.• Lambda- Negative.• Fibrinogen- Mild interstitial staining. • Albumin- Negative.• C4d- Negative.

C3

Fibrin

EM

• Will be ready in the coming weeks

DiagnosisRenal Biopsy:• Chronic pyelonephritis with medullary

calcium oxalate deposition related to systemic oxalosis

• No evidence of rejection

• Banff scores:– G0 CG1 I1 CI1 T0 CT1 V0 CV1 AH0 MM0