Sin ttulo de diapositiva

1
Utility of morphometry in the study of donor and
protocol biopsies
D. Serón Servicio de Nefrología Hospital
Bellvitge Barcelona
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Morphometry
Disadvantages
Advantages
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When is morphometry redundant?When may it be
useful?When is it necessary?
4
Topics
Redundant Morphometry applied to the study of
donor biopsies Potential utility Mophometric
evaluation of protocol biopsies in clinical
trials Necessary Glomerular adaptation after
renal transplantation
5
Topics
Redundant Morphometry applied to the study of
donor biopsies Potential utility Mophometric
evaluation of protocol biopsies in clinical
trials Necessary Glomerular adaptation after
renal transplantation
6
Preexisting donor damage and outcome
year parameter ____________________________
________________________________ Leunissen Transpl
antation 1989 sum of scores Serón NDT
1993 Vvint/cortex Wang NDT 1998 ah,
GS Gaber L Transplantation 1995 GS Abdi
R Transplantation 1998 glomerular
size Karpinski Transplantation 1999 donor
vasculopathy Parmjeet R Transplantation
2000 ci, GS Escofet X Transplantation
2003 GS _________________________________
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Is there any advantage in the morphometric
evaluation of donor biopsies?
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Evaluation of donor biopsies (June 2000-Dec
2001, N 77 (?10 glom, ?1 art)
Banff criteria cg ci ct cv ah mm
Quantitative parameters glomerulosclerosis Vvi
nt/c () Vvglom/c () Vg x 106 m3 Vvintima/artery
Lopes JA et al. Kidney Int 2005 67 1595
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Results (1)
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Results (2)
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Results (3)
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Results (4)
Multivariate analysis histologic lesions and 3m
CrCl
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Conclusions
Morphometric evaluation of donor biopsies does
not improve the prediction of outcome
14
Topics
Redundant Morphometry applied to the study of
donor biopsies Potential utility Mophometric
evaluation of protocol biopsies in clinical
trials Necessary Glomerular adaptation after
renal transplantation
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CAN and sequential protocol biopsies
Donor biopsies 15 4th month protocol bx 42
1st year protocol bx 52
CAN
50 25 0
0 3 6 9 12 m
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Prevention trial and protocol biopsies
Donor Bx
Protocol Bx
?Fibrosis ?CAN ?cv ?Vvinterstitium/c
?Vvintima/artery
placebo
treatment
0 1 2 3 4 5 6 m
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Minimum sample size (50 reduction) (?0.05,
?0.20)
Variable Patients per group __________________
__________________ ?CAN 300 ?Transplant vasc
(cv) 1200 ?Vvint/cortex 63 ?Vvintima/artery
49 ____________________________________
Serón, Transplantation 2000 69(9) 1849
Moreso et al. Am J Transplantation 2001 1(1) 82
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Conclusions
Morphometric evaluation of protocol biopsies in
trials aimed to prevent CAN may allow to reduce
minimum sample size
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Topics
Redundant Morphometry applied to the study of
donor biopsies Potential utility Mophometric
evaluation of protocol biopsies in clinical
trials Necessary Glomerular adaptation after
renal transplantation
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Glomerular number (Ng)Disector /fraccionator
(n56)
0.23-1.82 x 106
Hughson M et al Kidney Int 2003 63 2113
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Ng and Vg in humans

Ng/Vg/BSA
Hoy WE et al, Kidney Int Suppl 2003 83, S31
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Renal adaptation after transplantation
Ng Vg
adaptation
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Ng
Morfometry
Radiology
Histology
New parameters
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Ng in vivo
Vcortex MRI
Vvglom/cortex Vg
Biopsy
Fulladosa X et al J Am Soc Nephrol 2003 14 2662
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Vren and Vcortex by means of a MRI
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Volumen renal VrenVolumen cortical Vcort
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Vglom/cortex y Vg
Fulladosa X et al J Am Soc Nephrol 2003
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Estimación del número de
Vcortex Vvglom/cortex Ng
__________________ Vg
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Characteristics of patientsSCr lt 200 mmol/l and
proteinuria lt 1g/24h 4m protocol biopsy (n39)
Mean ? SD ________________________________
______   N 39   Donor age 38 ?
18 Donor sex (male / female) 26 /
13 Recipient age 46 ? 14 Recipient sex
(male / female) 24 / 15 Recipient BSAa
(sqm) 1.74 ? 0.19 Cold ischemia time
(hours) 20 ? 5 Delayed graft function (no /
yes) 37 / 2 Serum Creatinine (?mol/l) 123?30 Prot
einuria g/day 0.38 ? 0.47 _____________________
_________________
Fulladosa X et al J Am Soc Nephrol 2003 14 2662
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Relationship between Ng and GFR
Fulladosa X et al J Am Soc Nephrol 2003 51 310
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Ng is a major determinant of GFR2GFR 9 Ng
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Glomerular enlargement after transplantation(n41
)
?Vg
Recipient biopsy
Donor biopsy
0
4
Alperovich G et al, AJT 2004 4 650
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Vg after transplantationVg
Donor Biopsy Recipient Biopsy p _______________
________________________________ Ah 0.15?0.42 0.2
9?0.56 NS cg 0.10?0.30 0.15 ?0.36 NS ci 0.19?0.
45 0.49 ?0.64 0.0006 ct 0.15 ?0.42 0.49 ?
0.67 0.0002 cv 0.02 ?0.16 0.19
?0.60 0.087 Vg 4.1 ?1.4 5.1 ?2.4 0.021 _______
________________________________________
Alperovich G et al, AJT 2004 4 650
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Vg y FG a los 4m
CrClml/min
R0.38, p0.01
Vg (x106?3)
Alperovich G et al, AJT 2004 4 650
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Glomerular enlargement may be a necessary
condition to achieve a good renal function
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Epidemiological paradox
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?GFR
?Graft Survival
? Vg
?Graft Survival
?Glomerulosclerosis
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Vg, GFR and graft survivaln144 patients,
protocol biopsy at 4m
Donor age (years) 37 ? 16 (12 76) Donor
gender (male/female) 101 / 43 Patient age
(years) 47 ? 13 (15 72) Patient gender
(male/female) 95 / 49 Panel reactive antibodies
() 7 ? 18 (0 100) DR mismatches 0.6 ?
0.6 (0 2) Cold ischemia time (hours) 22 ?
5 (7 38) Delayed graft function (no/yes) 121
/ 23 Acute rejection (no/yes) 114 / 30 Time of
protocol biopsy (days) 125 ? 52 (25
261) Serum creatinine (?mol/l) 140 ? 44 (72
298) Proteinuria (g/day) 0.34 ? 0.28 (0.03
1.00)

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Vg, FG y Sup injn144 patients protocol biopsy
at 4m
RR IC p ________________________________ Vg
gt 5 x 106?3 2.4 1.0-5.6 0.04 CrCl lt60 ml/min
3.5 1.0-11.9 0.04 ______________________________
__
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Vg, CrCl and Graft survivaln144
biopsia de protocolo 6m gt 10 glom
? 60 ml/min/1.73m2 lt 60 ml/min/1.73m2
High Low
CrCl (Cockroft Gault
? 5 x 106?3 lt 5 x 106?3
Large Small
Vg (Weibel Gomez)
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Vg, FG, GS
Cum. Survival
1
,8
,6
,4
,2
0
Time (months)
0
25
50
75
100
125
150
175
200
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Conclusion
Glomerular volume and renal function are
independent predictors of graft survival
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Summary
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Acknoledgements
Francesc Moreso Xavier Fulladosa Miguel
Hueso José Antonio Lopes Meritxell
Ibernon Gabriela Alperovich Montserrat Gomà Marta
Carrera Josep Maria Cruzado Salvador
Gil-Vernet Josep Maria Grinyó

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Vg small CrCl high n24 (17) Vg small CrCl
low n60 (42) Vg large CrCl high n20 (20) Vg
large CrCl low n31 (21)