Glomerular volume, %GSG and %ischemic glomeruli on a 5-year biopsy as predictors of overall graft failure and death in unadjusted analysis

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Table of contents:

Page 2. Supplemental Table 1. Demographics of 835 kidney transplant recipients who were included, and 630 kidney transplant recipients who were not included in this study because of missing or inadequate 5-year biopsy.

Page 3. Supplemental Table 2. A summary of microstructural biopsy characteristics at 3 time points.

Page 4. SupplementalTable 3. Glomerular volume, %GSG and %ischemic glomeruli on a 5-year biopsy as predictors of overall graft failure and death in unadjusted analysis.

Page 5. SupplementalTable 4. Banff scores and morphometry measures of GSG and ischemia at 5-year as predictors of allograft failure in subset of 698 biopsies with at least 7 glomeruli on a 5-year biopsy.

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Supplemental Table 1. Demographics of 835 kidney transplant recipients who were included, and 630 kidney transplant recipients who were not included in this study because of missing or inadequate 5-year biopsy.

Included in the study

(N=835) Missing (N)

Not included in the study

(N=630) Missing

(N) P value Recipients’ characteristics

Recipient’s age, years 52.7 (13.0) 0 50.7 (14.0) 0 0.006

White race, % 766 (91.7%) 0 577 (91.6%) 0 0.92

BMI at transplant, kg/m² 28.5 (6.0) 0 28.3 (6.5) 11 0.46

Pre-transplant diabetes, % 230 (27.5%) 0 179 (28.9%) 10 0.58

Pre-transplant hypertension, % 810 (97.0%) 0 547 (90.3%) 24 <0.0001

aNumber of HLA mismatches 3.1 (1.8) 1 3.1 (1.8) 6 0.48

Delayed graft function, % 38 (4.6%) 0 33 (5.2%) 0 0.54

Post-transplant characteristics

Any rejection in the first year, % 90 (10.8%) 0 60 (9.5%) 0 0.43

Borderline rejection, % 26 (3.1%) 0 25 (4.0%) 0 0.38

Acute rejection, % 58 (6.9%) 0 38 (6.0%) 0 0.48

Antibody mediated rejection, % 2 (0.2%) 0 0 (0.0%) 0 0.22

Mixed or other rejection, % 4 (0.5%) 0 --- --- ---

Post-transplant new onset diabetes, % 125 (15.0%) 0 --- --- ---

Kidney function

beGFR at 1 year, ml/min/1.73m² 55.1 (14.3) 69 62.3 (17.8) 327 <0.0001

ceGFR at 5 years, ml/min/1.73m² 52.9 (17.3) 2 62.6 (22.3) 327 <0.0001

d24hr urine protein at 1 year, mg 103 [60-193] 102 110 [65-213] 369 0.16

e24hr urine protein at 5 years, mg 108 [63-211] 62 110 [72-247] 441 0.39 Outcomes

Follow-up time, years 12.5 [10.0-15.4] 0 --- --- ---

Graft failure, % 112 (13.4%) 0 105 (16.7%) 0 0.08

Data shown as Mean (SD), N (%), or Median (IQR) for skewed data.

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Supplemental Table 2. A summary of microstructural biopsy characteristics at 3 time points.

Glomerular volume mean (SD)

At implantation biopsy, ×10⁶ m³ 2.8 (1.1) At 1-year biopsy, ×10⁶ m³ 3.3 (1.3) At 5-year biopsy, ×10⁶ m³ 3.6 (1.5)

%Globally-sclerosed glomeruli

At implantation biopsy 3.2 (6.2)

At 1-year biopsy 2.2 (5.3)

%Ischemic-appearing glomeruli

At implantation biopsy 0.8 (2.9)

Biopsy cortex area

At implantation biopsy, mm² 6.4 (2.3)

At 1-year biopsy, mm² 5.8 (2.4)

At 5-year biopsy, mm² 6.9 (3.0)

Number of sampled non-sclerosed glomeruli

At implantation biopsy, n 16.7 (8.1)

At 1-year biopsy, n 13.2 (6.8)

At 5-year biopsy, n 13.8 (7.3)

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SupplementalTable 3. Glomerular volume, %GSG and %ischemic glomeruli on a 5-year biopsy as predictors of overall graft failure and death in unadjusted analysis. There were 112 graft failures and 238 deaths with function.

Overall graft loss (350 events)

Death (238 events) HR

(95% CI) P value HR

(95% CI) P value Glomerular volume (all) 0.95

(0.82, 1.03) 0.16 0.98

(0.86, 1.12) 0.78 Glomerular volume

(non-ischemic only)

0.98

(0.88, 1.10) 0.75 0.98

(0.86, 1.12) 0.79

%GSG 1.02

(0.92, 1.14) 0.66 0.91

(0.79, 1.04) 0.17

%ischemic glomeruli 1.33

(1.21, 1.45) <0.0001 1.06

(0.93, 1.21) 0.93 HR of continuous measures are per SD.

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SupplementalTable 4. Banff scores and morphometry measures of GSG and ischemia at 5-year as predictors of allograft failure in subset of 698 biopsies with at least 7 glomeruli on a 5-year biopsy. There were 91 graft losses in this subset.

Banff scores and morphometry measures at 5-year biopsy

Unadjusted Multivariable adjusted†

Banff scores only Banff scores + Glomerular volume

Banff scores +

%GSG

Banff scores +

%Ischemic glomeruli HR

(95% CI) P value HR

(95% CI) P value ci score (1.63, 2.54) ^2.04 <0.0001 1.67

(1.29, 2.16) <0.0001 1.54

(1.16, 2.04) 0.003 1.57

(1.17, 2.10) 0.002 1.16

(0.82, 1.64) 0.39

cg score (2.20, 3.32) ^2.70 <0.0001 2.00

(1.34, 2.97) <0.0001 2.07

(1.38, 3.09) 0.0001 2.02

(1.36, 3.00) <0.0001 1.95

(1.41, 2.72) <0.0001

g score (1.59, 2.58) ^2.02 <0.0001 0.95

(0.59, 1.54) 0.84 0.95

(0.59, 1.55) 0.85 0.95

(0.59, 1.52) 0.82 0.95

(0.60, 1.50) 0.81

cv score* (1.35, 2.23) ^1.74 <0.0001 1.12

(0.82, 1.52) 0.47 1.12

(0.82, 1.51) 0.48 1.11

(0.82, 1.51) 0.49 1.11

(0.81, 1.50) 0.52

ah score (1.49, 2.28) ^1.85 <0.0001 1.45

(1.15, 1.83) 0.002 1.45

(1.15, 1.84) 0.002 1.46

(1.16, 1.86) 0.002 1.50

(1.19 1.90) <0.0001

i score (0.93, 2.14) ^1.41 0.10 --- --- --- --- --- --- --- ---

ptc score (1.55, 2.50) ^1.97 <0.0001 1.17

(0.81, 1.69) 0.40 1.18

(0.82, 1.70) 0.37 1.20

(0.83, 1.72) 0.33 1.02

(0.84, 1.69) 0.32

Glomerular volume

0.74

(0.57, 0.96) 0.022 --- --- 0.82

(0.637, 1.08) 0.16 --- --- --- ---

%GSG (1.14, 1.67) ^1.38 0.0008 --- --- --- --- 1.10

(0.90, 1.34) 0.36 --- ---

%ischemic glomeruli

1.76

(1.52, 2.03) <0.0001 --- --- --- --- --- --- 1.42

(1.15, 1.75) <0.0001

c-statistic‡ ^--- 0.760/0.744 0.776/0.754 0.757/0.737 0.781/0.770

*cv score could not be graded in four 5-year biopsies.

†adding recipient’s age to each of the 4 models did not substantively change any of the results.

‡second value is a mean c-statistic after 10-fold cross-validation.