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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 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.
• 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 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.
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.
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/min
BP – 170/100 mm Hg right arm supine
Well hydrated , no pallor , mild edema feet.
Systemic examination – Normal
No graft edema or tenderness
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
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
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 6.8
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
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 REJECTION
TRANSPLANT 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 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%
Transplant  glomerulopathy
Transplant  glomerulopathy

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Transplant glomerulopathy

  • 1.
  • 2. 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
  • 3. • 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.
  • 4. • 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.
  • 5. 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.
  • 6. 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.
  • 7. Differentials • Acute kidney injury • d/t Acute gastroenteritis • To r/o Chronic allograft failure /nephropathy • To r/o associated TACROLIMUS toxicity
  • 8. 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
  • 9. 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
  • 10. 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
  • 11. 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
  • 12. What were we dealing with? Post transplant renal dysfunction + nephrotic range proteinuria + low complements A)Chronic allograft failure B)De- Novo graft glomerulopathy
  • 13. 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
  • 14. 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.
  • 15. Kidney biopsy report Light microscopy- a)Glomeruli – • 14 (one sclerosed, 13 viable) • Enlarged, with ill defined lobularity • Marked thickening of GBM
  • 16. 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
  • 17. 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
  • 18. Immunoperoxiadases • C4d is strongly +ve (++) along the glomeruli and peritubular capillaries Final Impression on biopsy – CHRONIC HUMORAL REJECTION TRANSPLANT GLOMERULOPATHY
  • 19. Diagnosis • Chronic allograft failure • Chronic humoral rejection+ Transplant glomerulopathy
  • 20. What next ??? • PLASMA EXCHANGES • RITUXIMAB • BORTEZOMIB • IMMUNOGLOBULIN
  • 21. 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%