transplant glomerulopathy

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  • 1.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

2. Induction agents were a)Antithymocyte globulin b)Methyl prednisolone Maintainance drugs were a) Tacrolimus b) Mycophenolate mofetil c) Prednisolone Peritransplant period was uneventful with normal renal function on follow up till Sept-2011. 3. 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. 4. This time he presented in Sept 2013 1)Loose motions 4-6 times/ day since 2months On and off Semisolid in consistency, Not associated with blood or mucus. 2) Severe nausea with occasional non bilious vomitting since past one week. 5. 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 from a general practitioner , details not available. 6. Differentials Acute kidney injury d/t Acute gastroenteritis To r/o Chronic allograft failure /nephropathy To r/o associated TACROLIMUS toxicity 7. On examination Young male, Pulse- 80/min BP 170/100 mm Hg right arm supine Well hydrated , no pallor , mild edema feet. Systemic examination Normal No graft edema or tenderness 8. Investigations CBC- Hb- 10.4 gm% WBC- 8450/mm3 Platelet- 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 9. Investigations Urinalysis- 3+ Albumin No RBC, WBC, EC, Cast Urine spot Protein Creatine Ratio - 9.7 gm/mg% Stool examination- Plenty of pus cells, Ocassional RBCs GNB No opportunistic Organism Stool culture, CDTA - Negative 10. 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 11. What were we dealing with? Post transplant renal dysfunction + nephrotic range proteinuria + low complements A)Chronic allograft failure B)De- Novo graft glomerulopathy 12. On Admn Day 1 Day 2 Day 3 Day 4 Creat 4.9 5 5 5.7 6.8 K 3.8 3.6 3.6 3.5 3.7 UO 1400 1320 1250 950 400 Patient underwent kidney biopsy Started on inj.MPS 500 mg for 3 days ??REJECTION 13. 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. 14. Kidney biopsy report Light microscopy- a)Glomeruli 14 (one sclerosed, 13 viable) Enlarged, with ill defined lobularity Marked thickening of GBM 15. 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 16. 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 17. Immunoperoxiadases C4d is strongly +ve (++) along the glomeruli and peritubular capillaries Final Impression on biopsy CHRONIC HUMORAL REJECTION TRANSPLANT GLOMERULOPATHY 18. Diagnosis Chronic allograft failure Chronic humoral rejection+ Transplant glomerulopathy 19. What next ??? PLASMA EXCHANGES RITUXIMAB BORTEZOMIB IMMUNOGLOBULIN 20. Patient was given 6 cycles of PLEX, single volume starting 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%