CASE HISTORY• Mr. KM• 25 male , software professional from

Bangalore• Live related ABO compatible kidney transplant

recipient – 2008 • Mother to son, cross match – 4%• Native kidney disease- Vesicoureteric reflex

with secondary Chronic Tubulo Interstitial Disease.

• On MHD since 2007 from left arm AV Fistula

• Induction agents were –a)Antithymocyte globulinb)Methyl prednisolone

• Maintainance drugs were – a) Tacrolimusb) Mycophenolate mofetilc) Prednisolone

• Peritransplant period was uneventful with normal renal function on follow up till Sept-2011.

• In Sept 2011, he had worsening renal function with increased creatinine to 4 mg% on follow up in OPD.

• He was treated with iv Methylprednisolone 500 mg 3 doses and hydration on presumption of chronic rejection. Kidney biopsy was not done.

• Following this his creatinine stabilised to 2 mg% on discharge . But he lost to follow up

since then till date.

This time he presented in Sept 2013

1)Loose motions 4-6 times/ day since 2monthsOn and off Semisolid in consistency, Not associated with blood or mucus.

2) Severe nausea with occasional non bilious vomitting since past one week.

There was no history of fever, dysuria or oligoanuria.

There was h/o poor compliance for the immunosupressive medications with intermittent self ommission of the drugs.

He had taken treatment for the same froma general practitioner , details not available.

Differentials

• Acute kidney injury

• d/t Acute gastroenteritis

• To r/o Chronic allograft failure /nephropathy

• To r/o associated TACROLIMUS toxicity

On examination

Young male,Pulse- 80/minBP – 170/100 mm Hg right arm supineWell hydrated , no pallor , mild edema feet.Systemic examination – NormalNo graft edema or tenderness

Investigations • CBC- Hb- 10.4 gm%WBC- 8450/mm3Platelet- 3.26 lacs

• PBS - No fragmented cells

• RFT -BUN- 54.4 mg%Sr. Creat- 4.8 mg%Sodium – 138 mg%Potassium- 3.8 mg%Bicarb- 18.4

Tacrolimus Level – 6.8 on 4 mg, 5 yr post Tx

Investigations Urinalysis-3+ AlbuminNo RBC, WBC, EC, Cast

Urine spot Protein Creatine Ratio -9.7 gm/mg%

Stool examination-Plenty of pus cells,Ocassional RBCs GNBNo opportunistic Organism

Stool culture, CDTA -Negative

USG abdomen and transplant kidney with doppler- was within normal limits

C3 – 55 (88-165)C4- 21.4 (10-40)

CMV IgM/IgG – were negative

He was started on i.v ciprofloxacin and Metronidazole with oral and i.v hydration

What were we dealing with?

Post transplant renal dysfunction + nephrotic range proteinuria + low complements

A)Chronic allograft failure

B)De- Novo graft glomerulopathy

On Admn

Day 1 Day 2 Day 3 Day 4

Creat 4.9 5 5 5.7 6.8K 3.8 3.6 3.6 3.5 3.7UO 1400 1320 1250 950 400

Patient underwent kidney biopsy

Started oninj.MPS 500 mg for 3 days

??REJECTION

He was dialysed (Heparin Free) on day 7 with a creatinine of 8.9 mg% from the functional AV fistula.

Tacrolimus dose was reduced to 3 mg/day

Oral prednisolone was increased to 30 mg and tapered gradually.

Kidney biopsy report

Light microscopy-

a)Glomeruli – • 14 (one sclerosed, 13 viable)• Enlarged, with ill defined lobularity• Marked thickening of GBM

b) Interstitium – • Edematous ,• Single cluster of subcapsular lymphocytes

c) Tubules –• 10% show atrophy• 60 % reveal foci of necrosis• Rest have hydropic changes

d) Vasculature - • Marked luminal narrowing in small sized vessels due to prominent hyaline change

Immunofluorescence-

• C3 +ve – irregular deposits along capillary loop

• C4d is strongly +ve (++) along the glomeruli and peritubular capillaries

• IgG/M/A, C1q and fibrinogen are negative

Immunoperoxiadases

• C4d is strongly +ve (++) along the glomeruli and peritubular capillaries

Final Impression on biopsy – CHRONIC HUMORAL REJECTIONTRANSPLANT GLOMERULOPATHY

Diagnosis

• Chronic allograft failure

• Chronic humoral rejection+ Transplant glomerulopathy

What next ???

• PLASMA EXCHANGES• RITUXIMAB• BORTEZOMIB• IMMUNOGLOBULIN

Patient was given 6 cycles of PLEX, single volumestarting from day 9 every alternate day.

Hemodialysis was continued every 3rd day.

HD stopped 5 days before discharge on day 20.

Creatinine stabilised in the range of – 4.5 to 5 mg % with urine output 1800-2000 ml/day

Patient following up in OPD with creatinine – 3.2 mg%