Renal pathology in other solid organ and bone marrow transplants

1
Renal pathology in other solid organ and bone
marrow transplants
Anke Schwarz, Deptm. of Nephrology Verena
Bröcker, Inst. for Pathology
2
NHL 1997 BMT 1997 Lung Tx 2001 ESRD 2011 37 yrs
old
3
Changes in reciprocal s-creatinine (GFR)in
cardiac-transplant recipients
Myers et al, NEJM 1984
4
Evolution of GFR in heart-transplanted patients
(n151)
Lindelöw et al, JASN 2000
5
Seriel creatinine clearances in patients after
lung or lung-heart transplantation (n115)
Filled boxeslater ESRD
Kunst et al, J Heart Lung Transplant 2004
6
Survival at dialysis after lung
transplantationcompared with expected survival
(n40)
Mason et al, J Heart Lung Transplant 2007
7
Renal biopsies after non-renal transplantation

• 105 renal biopsies in 101 patients 2000 2009
  (Hannover)
• 14 after bone marrow transplantation
• 41 after liver transplantation
• 30 after lung transplantation
• 20 after heart transplantation

8
Renal biopsies after non-renal transplantation

• 105 renal biopsies in 101 patients 2000 2009
  (Hannover)
• 14 after bone marrow transplantation
• 41 after liver transplantation
• 30 after lung transplantation
• 20 after heart transplantation
• 34 renal biopsies in 34 patients 1987 2000
  (Basel)
• 20 after bone marrow transplantation
• 14 after heart transplantation

9
Renal biopsies after non-renal transplantation

• Indication for renal biopsy in Hannover
• non-recovery after ARF at transplant. 9
• creatinine increase 83
• rapid creatinine increase 22
• proteinuria 22
• nephrotic syndrome 13
• evaluation of renal prognosis before
• re-transplantation of an extrarenal organ
  9

10
Renal biopsies after non-renal transplantation

• End stage renal disease in Hannover
• BM 1 out of 1375 patients (0.07)
• Liver 32 out of 2016 patients (1.6)
• Lung 35 out of 725 patients (4.8)
• Heart 41 out of 505 patients (8.1)

11
101 patients with renal biopsies after non-renal
transplantation
BM (14) Liver (39) Lung (28) Heart (20)
Age (yrs) 4012 4415 4911 5614
Gender (?) 64 74 82 85
BMI 254 223 234 275
Hypertens. 57 62 86 90
Diabetes 7 36 39 35
12
101 patients with renal biopsies after non-renal
transplantation
BM (14) Liver (39) Lung (28) Heart (20)
Age (yrs) 4012 4415 4911 5614
Gender (?) 64 74 82 85
BMI 254 223 234 275
Hypertens. 57 62 86 90
Diabetes 7 36 39 35
13
105 renal biopsies after non-renal
transplantation
BM (14) Liver (41) Lung (30) Heart (20)
Time post-tx (mos) 4542 6265 3640 8673
GFR (CG, mL/min)) 4828 3822 3011 2916
14
34 renal biopsies after heart transplantation
Heart n14 Basel 1987-2000 Heart n20 Hannover 2000-2009
Time post-Tx (mos) 2015 8673
S-Creatinine µmol/L 28117 380252
Prevalence CNI-toxicity 55 50
P0.01
NS
NS
15
Main histopathological lesions in kidney biopsies

(n101)
Interlobular/ arcuata-arteries
16
Acute tubular injury in organ groups
n.s.
17
Glomerulosclerosis and fibrosis in organ groups
(GS)
(IF/TA)
18
Chronic vascular lesions in organ groups
(AH)
(AS)
p0.006
19
Glomerulonephritis and TMA in organ groups
Bone marrow SLE, MGN, fibrillary GN Liver IgA,
MPGN Heart IgA, Shunt-Nephritis
20
Interstitial fibrosis/ tubular atrophy and kidney
outcome
gt/ 3 years follow up
21
Impact of age and time after tx on chronic changes
Multivariate regression Multivariate regression Multivariate regression Multivariate regression
Age at biopsy (mo) Age at biopsy (mo) Time after tx (mo) Time after tx (mo)
regress. coeff. ß p regress. coeff. ß p
GS () n.s. 0.259 0.000
IFTA () n.s. 0.055 0.033
AH (0-3) 1.63 x 10-3 0.014 6.72 x 10-3 0.000
Arteriosclerosis (0-3) 1.98 x 10-3 0.000 5.33 x 10-3 0.001
22
Impact of age and time after tx on chronic changes
Age Time after tx
GS (1-point increase) 4 months
IFTA (1-point increase) 18 months
AH (1 grade increase) 51 years 12 years
AS (1 grade increase) 42 years 16 years
23
Main histopathological diagnosis
(n101)
24
Main histopathological diagnosis

• NOS
• No reason for impaired renal function
• IFTAgt20 and GS and nephrosclerosis without
  obvious reason

(n101)

• Other
• Bone marrow Nephrocalcinosis, Minimal Change,
  Cast-Nephropathy
• Heart Nephrocalcinosis/ interstitial Nephritis
• Liver Diabetic NP, Iron-overload, Minimal Change
• Lung Polyoma-Virus NP, Nephrocalcinosis

25
Kidney biopsies of heart transplanted patients
Hannover and Basel
26
Kidney biopsies of heart transplanted patients
Hannover and Basel
27
Thrombotic microangiopathy

• Hannover 2000 2009 n10/101 (10)
• TMA after BM-Tx n1
• TMA after liver-Tx n5
• TMA after lung-Tx n4
• TMA after heart-Tx n0
• Basel 1987 2000 n8/34 (24)
• TMA after BM-Tx n5
• TMA after heart-Tx n3

28
TMA

• TMA in 428 renal transplant patients 1.2
• TMA in 4203 native kidneys 1.1
• TMA in 101 native kidneys after non-renal
  transplantation in Hannover 2000-2009 10
• TMA in 14 native kidneys after non-renal
  transplantation in Basel 1987-2000 24

29
TMA after non-renal transplantation

• Shulman et al 1981 BM 3 autopsy cases
• Bonser et al 1984 liver case report
• Dische et al 1988 liver case report
• Nizze et al 1988 BM, heart 167 autopsies,
  15
• Griffiths et al 1996 heart, lung 22
  histologies, 14
• Pillebout et al 2005 liver 15 histologies,
  50
• Lefaucheur et al 2008 liver 26 histologies, 47

30
Thrombotic microangiopathy

• Complement mutation-associated
• de novo Thrombotic Microangiopathy
• following kidney transplantation

M. Le Quintrec et al AJT 2008
TMA with HUS after RTX n24 Mutations in genes
encoding complement abnormalities 29
31
Thrombotic microangiopathy

• Immunosuppression with TMA in Hannover
• cyclosporine-based n5
• tacrolimus-based n2
• cyclosporine and everolimus n3

32
arteriolar lesion 3
glomerular lesion 5
(glomerular arteriolar lesion 3)
33
Thrombotic microangiopathy

• Symptoms of TMA in Hannover n10
• hemolytic uremic syndrome 5
• severe hypertensive episode 6
• lung edema 1
• retinal bleeding 1
• creatinine increase 8
• (proteinuria 4g/day 1)

34
6 month kidney survival after biopsy
TMA p0.01
35
Renal biopsies after non-renal transplantation

• most often signs of acute renal failure,
  pre-existing hypertension and CNI-toxicity
• high number of patients with glomerulonephritis
• high number of patients with TMA

Conclusion 1
36
Renal biopsies after non-renal transplantation

• mostly signs of acute renal failure,
  pre-existing hypertension and CNI-toxicity
• high number of patients with glomerulonephritis
• high number of patients with TMA

Conclusion 1
37
Renal biopsies after non-renal transplantation

• mostly signs of acute renal failure,
  pre-existing hypertension and CNI-toxicity
• high number of patients with glomerulonephritis
• high number of patients with TMA

Conclusion 1
38
Renal biopsies after non-renal transplantation

• find early specific lesions
• in the advanced stage the extent of IFTA
  determines renal outcome
• extrarenal transplantation may accelerate the
  process of aging by multifactorial causes

Conclusion 2
39
Renal biopsies after non-renal transplantation

• find early specific lesions
• in the advanced stage the extent of IFTA
  determines renal outcome
• extrarenal transplantation may accelerate the
  process of aging by multifactorial causes

Conclusion 2
40
Renal biopsies after non-renal transplantation

• find early specific lesions
• in the advanced stage the extent of IFTA
  determines renal outcome
• extrarenal transplantation may accelerate the
  process of aging by multifactorial causes

Conclusion 2
41
Therapeutic consequences

• Reduce CNI as much as possible
• Finish CNI - mTOR inhibitor combination
• Agressive blood pressure control
• Plasmapheresis in TMA with HUS
• Renal replacement planning

42
Renal transplantation by LIVING DONATION
1997-2010 9 patients 106 years Liver-Tx
2006-2011 6 patients 84 years Lung-Tx
2009 1 patient 15 years Heart-Tx
43
Thank you for your attention

• Department of Nephrology
• Hermann Haller
• Anke Schwarz

• Institute for Pathology
• Hans Kreipe
• Jan U. Becker
• Verena Bröcker

• Hemato-Oncology
• Gastro-Enterology
• Pulmonology
• Thoracic Surgery
• Christian Koenecke
• Jens Gottlieb
• Christian Strassburg
• Christoph Bara
• Frank Lehner

AJT 2010
44
Thank you for your attention

• Department of Nephrology
• Hermann Haller
• Anke Schwarz

• Institute for Pathology
• Hans Kreipe
• Jan U. Becker
• Verena Bröcker

• Hemato-Oncology
• Gastro-Enterology
• Pulmonology
• Thoracic Surgery
• Christian Koenecke
• Jens Gottlieb
• Christian Strassburg
• Christoph Bara
• Frank Lehner

• Institute for Pathology
• Michael Mihatsch, Basel

AJT 2010
45
Thank you for your attention

• Department of Nephrology
• Hermann Haller
• Anke Schwarz

• Institute for Pathology
• Hans Kreipe
• Jan U. Becker
• Verena Bröcker

• Hemato-Oncology
• Gastro-Enterology
• Pulmonology
• Thoracic Surgery
• Christian Koenecke
• Jens Gottlieb
• Christian Strassburg
• Christoph Bara
• Frank Lehner

• Institute for Pathology
• Michael Mihatsch, Basel

AJT 2010