chronic transplant glomerulopathy - clinical and histological characteristics
DESCRIPTION
CHRONIC TRANSPLANT GLOMERULOPATHY - clinical and histological characteristics. Agnieszka Perkowska-Ptasinska 1 , M. Ciszek, A.L. Urbanowicz, L. Paczek, M. Glyda, A. Debska-Slizien, A. Rydzewski, K. Dziewanowski, M. Myslak and M. Durlik - PowerPoint PPT PresentationTRANSCRIPT
CHRONIC TRANSPLANT
GLOMERULOPATHY
- clinical and histological
characteristics
Agnieszka Perkowska-Ptasinska1, M. Ciszek, A.L. Urbanowicz, L. Paczek,
M. Glyda, A. Debska-Slizien, A. Rydzewski, K. Dziewanowski, M. Myslak
and M. Durlik
1Transplantation Institute, Warsaw Medical University, Poland
CHRONIC TRANSPLANT
GLOMERULOPATHY
CLINICALLY: proteinuria, hypertension, declining graft function and graft loss
MORPHOLOGY:double contours of glomerular capillaries, no IF/EM deposits
Habib 1993;Regele J Am Soc Nephrol 2002; Sijpkens Ki 2004;Gloor AJT 2006;Sis AJT 2007; Gloor AJT 2007; Cosio AJT 2008;
CHRONIC TRANSPLANT GLOMERULOPATHY
• rare before 6 months after Tx,
• the incidence rises from 1.0-4.0% at 1 year to 20% at 5 years
• more common in patients with:- historical or ongoing acute rejection
- DSA (especially against HLA II Ag )
- ABO incompatibility with a donor
- non-HLA reactive Ab (MICA, anti-endothelial cell Ab,
anti-angiotensin type 1 receptor Ab) Dinavahii J AM Soc Nephrol 2011WillicombeTransplantation 2012Dragun Curr Opin Organ Transplant. 2012
Lesions that accompany TG: PTCitis, glomerulitis C4d in PTCs
,
CHRONIC TRANSPLANT GLOMERULOPATHY
what about the morphology of the interstitium, tubules, arteries,
arterioles?
Regele J AM Soc Nephrol 2002; Shimizu KI 2002;Aita Clin Transplant 2005; Gloor AJT 2007; Sis AJT 2007, Perkowska Trans Proc 2009
The retrospective study of:159 patients with TG and 85 recipients without TG, but with other
chronic changes in the graft biopsy (IF/TA and/or chronic vascular
lesions)
median observational time: 118 months (range 39-270 months)
median time from Tx to biopsy: 55 months (range 0.4-243 months)
F:102, M:142
AIM:
to give a detailed morphological characteristics of TG
to search for potential impact of each of studied lesions on graft survival
Methods:
the analysis of clinical and histological (LM) data
including C4d deposition in PTCs and glomeruli (IHC on paraffin sections)
Methods
Light microscopical evaluation based on Banff classification
Compartment
additional parameters (added to Banff criterias)
glomeruli •linear C4d in glomerular capillaries,
•thrombi,
•mesangiolysis,
•globally and segmentally sclerosed glomeruli (%)
arteries arteriosclerosis without the multiplication of elastic lamina
arterioles •subendothelial sclerotization,
•smooth muscle cells hyperplasia,
•thrombi
interstitium• PTCs’ dilatation
TG vs non-TG caseslight microscopical evaluation
Banff criteria + additional parametersTG Non-TG p
C4d in PTCs 42.9% 1,3% <0.0001
C4d in PTCs and glomerular capillaries 6.5% 0 0.03
C4d only in glomerular capillaries 0 0 NS
PTC-itis 40.9% 11.8% <0.0001
PTCs’ dilatation 35.9% 10.6% <0.0001
Acute interstitial inflammation („i”) 30.8% 10.6% <0.0001
Total interstitial inflammation („ti”) 81.8% 68.2% 0.03
The percantage of globally/segmentally sclerosed glomeruli
30.2 ± 21.7 19.6 ± 21.2 <0.0001
Mesangiolysis 39% 11.8% <0.0001
Increase in mesangial celullarity 39% 8.2% <0.0001
Increase in mesangial matrix volume 48.4% 27.1% 0.002
Glomerulitis 61% 7.1% <0.0001
Tubulitis 31.5% 10.6% 0.0002
Endarteritis 9.8% 0 0.003
Arteriosclerosis without the multiplication of elastic lamina
18.9% 3.6% 0.001
Arteriosclerosis with the multiplication of elastic lamina 28.7% 22.9% NS
Arteriolar sclerotization 47.2% 18.8% <0.0001
Arteriolar SMCs hyperplasia/hypertrophy 39.6% 11.8% <0.0001
Arteriolar wall hyalinisation 86.8% 77.7% NS
Correlation between TG and other morphological lesions
TGrs (p)
C4d in PTCs 0.37 (<0.0001)
increase in mesangial matrix 0.32 (<0.0001)
increase in mesangial cellularity 0.4 (<0.0001)
segmentally and globally sclerosed glomeruli (%) 0.31 (<0.0001)
arteriolosclerosis 0.33 (<0,0001)
PTC-itis 0.27 (<0.0001)
PTCs’ dilatation 0.26 (<0.0001)
linear C4d deposition in glomerular capillaries 0.09 (0.2)
arteriolar SMCs hyperplasia/hypertrophy 0.26 (<0.0001)
„ti” lesion 0.2 (0.002)
tubulitis 0.2 (0.002)
arteriosclerosis without the multiplication of elastic lamina
0.21 (0.002)
„t” lesion 0.15 (0.03)
glomerulitis 0.15 (0.02)
graft survival in TG vs non-TG group
Non-TG group
TG group
months
pro
bab
ility
Patients’ survival
non-TG group
TG group
pro
bab
ility
months months
pro
bab
ility
without graft losswith graft loss
TG group - graft survival
PARAMETER
univariate analysis,
Weibull regression model
HR 95% CI p
>1 Tx 1.5 1.1-2.2 0.02
recipient’s age at the time of Tx >30y 5.3 0.4-0.9 0.02
donor’s age at the time of Tx >30y 2.0 1.3-3.3 0.003
TG recognition before 44th month after Tx 6.4 4.6-9.0 <0.001
TG recognition between 44-89th month after Tx 2.6 1.8-3.6 <0.001
PTCs’ dilatation 1.5 1.0-2.2 0.05
Acute interstitial inflammation („i”) 1.7 1.1-2.5 0.02
AS without the multiplication of elastica 1.7 1.1-2.7 0.04
Thrombi in glomerular capillaries 3.7 1.7-8.0 0.001
C4d in PTCs 0.9 0.6-1.3 NS
C4d in glomerular capillaries (linear deposits) 1.4 0.6-3.3 NS
TG group - graft survival
PARAMETERS included in the
BEST multivariate regression model
multivariate analysis,
Weibull regression
model
HR 95% CI p
C4d in PTCs 1.1 0.8-1.4 0.68
AS without multiplication of elastica
1.5 1.1-2.1 0.02
TG recognition before 44th month after Tx vs base level
5.3 3.8-7.4
<0.01
TG recognition between 44-89th month after Tx vs base level
1.9 1.4-2.6
<0.01
At least moderate interstitial inflammation (Banff ti2+3)
1.2 0.8-1.7 0.47
Mild interstitial inflammation (Banff ti1)
0.7 0.5-1.0 0.06
Recipient’s age at the time of Tx >30y 1.7 1.3-
2.3<0.0
1
Thrombi in glomerular capillaries 2.2 1.1-
4.2 0.02
TG C4d (+) vs TG C4d (-)
clinical variables TG C4d (-) TG C4d (+) p
recipient’s sexF: 50%
M: 50%
F: 27.27%
M: 72.73% 0.005
recipient’s age
at the time of Tx40.1 ± 12.0 34.0 ± 10.7 0.002
No significant difference in the:- level of proteinuria,
- number of current transplantation,- number of HLA mismatches,- percentage of highly (>50%) immunized recipients,- level of immunosupression,- time interval between Tx and recognition of TG.- donor’s age and sex,
histological parameters TG C4d (+) TG C4d (-) p
PTC’s dilatation 60.61% 17.05% <0.0001
PTC-itis 60.61% 26.14% <0.0001
PTC-itis
with neutrophils
10% 0 0.01
pathologial recognitions
TG C4d (+) TG C4d (-) p OR (95%CI)
acute T-cell mediated rejection (type I,II) 27.66% 10.77% 0.03 3.17 (1.15-
8.71)
TG C4d (+) vs TG C4d (-)
clinicallyTG exerts a negative impact on both recipients’ and grafts’ survivalThe earlier TG development is associated with worse prognosis as for the graft survival
morphologicallyTG is associated with a spectrum of both acute and chronic inflammatory as well as structural changes in glomeruli, tubules, arteries and arterioles. Among these lesions AS without elastica multiplication and glomerular thrombi are independent risk factors for the graft loss PTC-itis, the presence of neutrophils in PTCs and PTCs’ dilatation are more common in C4d(+) TG cases
CONCLUSIONS: TG vs non-TG group differ
ARTERIOLAR SUBENDOTHELIAL SCLEROTIZATION AND ARTERIOLAR WALL SMCs HYPERTROPHY/HYPERPLASIA
- very few publications, - documented as a feature of thrombotic microangiopathies in native kidneys
(antiphospholipid syndrome,LN,
malignant hypertension, scleroderma,HUS)
Caetano Hypertension 2001Nochy J Am Soc Nephrol 1999Ruggenenti Am J Kidn Dis
1996
CONCLUSIONS:
Chronic VASCULAR lesions associated with
TG
ARTERIOSCLEROSIS WITHOUT THE
MULTIPLICATION OF ELASTIC LAMINA (proliferative arteriopathy)
Characteristic for dynamic fibrotic tissue proliferation in the intima typical of inflammatory and thrombotic vasculopathies
in renal transplants: one study??? Wieczorek AJT 2006
CONCLUSIONS:
Chronic VASCULAR lesions associated with
TG
EXERTS NEGATIVE IMPACT ON GRAFT SURVIVAL
TG is commonly associated with arterial and arteriolar lesions that share the same pathogenesis, evolve on the background of chronic endothelial injury,
most probable Ab-mediated and/or TMA related
CONCLUSIONS