Prognostic value of the 7-year protocol biopsy of adult kidney allografts: impact of mesangiosclerosis and proteinuria

Figures & data

Figure 1. Flowchart of patients undergoing the 7-year protocol biopsy.

Table 1. Baseline clinical characteristics of patients who underwent 7-year protocol biopsies.

	All cases (n = 89)
Clinical findings
Recipient age, years	40 (31, 53)
Recipient sex, (male/female), n	49/40
Donor age, years	57 (52, 64.5)
Donor sex, (male/female), n	42/47
Cadaveric donor, n (%)	4 (4.5)
HLA mismatches, n	3 (2, 3)
Second transplantation, n (%)	6 (6.7)
ABO-incompatible, n (%)	17 (19.1)
Cold ischemic time (minute)	55 (44, 75)
Original kidney disease
IgA nephropathy, n (%)	15 (16.9)
Diabetic nephropathy, n (%)	5 (5.6)
Others, n (%)	46 (51.7)
Unknown, n (%)	23 (25.8)
TAC/CYA, n	41/48
MMF/MZ/AZ/EVR, n	74/8/2/2
Use of RASi, n (%)	70 (78.7)
Use of diuretics, n (%)	4 (4.5)
Steroid pulse therapy, n (%)	1 (1.1)
eGFR (ml/min/1.73m^2)	44.5 (33.1, 53.3)
Urine protein, n	(-): 59, (±): 17, (1+): 8, (2+): 4, (3+): 1
Diabetes, n (%)	21 (23.6)
Hypertension, n (%)	74 (83.1)
CVD, n (%)	3 (3.4)
Malignancy, n (%)	2 (2.2)
Non-adherence, n (%)	4 (4.5)
Pathological findings
Glomerular sclerosis rate (%)	26.9 (12.3, 42.4)
Acute TCMR, n (%)	0 (0)
Acute ABMR, n (%)	8 (9.0)
Chronic active ABMR, n (%)	10 (11.2)
C4d score (n = 69), n	score0: 57, score1: 7, score2: 2, score3: 3
Prior rejection, n (%)	6 (6.7)
BKVN, n (%)	0 (0)

Data are expressed as median (IQR) or n (%). The data about the CNI and other immunosuppressive agents, eGFR, proteinuria, diabetes, hypertension, and pathological findings were at the time of the 7-year protocol biopsy. TAC: tacrolimus; CYA: cyclosporine; MMF: mycophenolate mofetil; MZ: mizoribine; AZ: azathioprine; EVR: everolimus; RASi: renin-angiotensin-system inhibitor; BKVN: BK virus nephropathy; CMV: cytomegalovirus; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; TCMR: T-cell-mediated rejection; ABMR: antibody-mediated rejection.

Figure 2. Prevalence of positive Banff scores for the 7-year protocol biopsy.

Table 2. Linear univariate regression analysis results for the association between eGFR change per year and each parameter.

	Univariate
	β	Coefficient	p value
Pathological findings
glomerular sclerosis rate	0.053	0.007	0.629
t score ≥1	−0.214	−2.375	0.047
g score ≥1	−0.380	−2.382	<0.001
ptc score ≥1	−0.364	−2.281	0.001
ct score ≥2	−0.375	−2.565	<0.001
ci score ≥2	−0.375	−2.565	<0.001
cg score ≥1	−0.412	−2.692	<0.001
mm score ≥1	−0.508	−2.815	<0.001
cv score ≥1	−0.122	−1.730	0.260
ah score ≥2	−0.278	−1.436	0.009
aah score ≥2	−0.176	−0.946	0.102
ti score ≥2	−0.108	−0.784	0.319
C4d score ≥2	−0.051	−0.537	0.684
Prior rejection	−0.426	−4.345	<0.001
Clinical findings
Recipient age	0.071	0.015	0.513
Recipient sex	−0.182	−0.945	0.092
Donor age	−0.162	−0.040	0.133
Donor sex	0.101	0.523	0.352
Cadaveric donor	−0.030	−0.372	0.782
HLA mismatches	−0.173	−0.324	0.110
Second transplantation	0.085	0.868	0.434
ABO-incompatible	−0.039	−0.262	0.719
Tacrolimus/cyclosporine	−0.041	−0.216	0.703
eGFR	0.311	0.047	0.003
Proteinuria ≥1+	−0.472	−3.428	<0.001
Diabetes	0.024	0.147	0.823
Hypertension	−0.124	−0.847	0.254
Use of RASi	−0.077	−0.482	0.479
Use of diuretics	−0.042	−0.514	0.702
Steroid pulse therapy	0.090	2.185	0.407
CVD	0.069	0.984	0.523
Malignancy	−0.053	−0.922	0.623
Non-adherence	–0.053	–0.653	0.627

The data of pathological findings, CNI, eGFR, proteinuria, diabetes, and hypertension, use of RASi, use of diuretics, and steroid pulse therapy were collected at the time of the 7-year protocol biopsy. eGFR: estimated glomerular filtration rate; RAS renin-angiotensin system inhibitors.

Table 3. Linear multivariate regression analysis results for the association between eGFR change per year and each parameter.

	Multivariate
	β	Coefficient	p value	VIF
model 1
t score ≥1	−0.145	−1.606	0.135	1.269
g score ≥1	0.003	0.021	0.979	2.099
ptc score ≥1	−0.208	−1.305	0.057	1.608
ci score ≥2	−0.151	−1.032	0.150	1.487
cg score ≥1	−0.107	−0.698	0.339	1.718
mm score ≥1	−0.292	−1.620	0.007	1.528
ah score ≥2	−0.077	−0.396	0.411	1.190
Prior rejection	−0.145	−1.481	0.149	1.374
model 2
t score ≥1	−0.143	−1.592	0.118	1.279
g score ≥1	−0.038	−0.240	0.747	2.177
ptc score ≥1	−0.166	−1.037	0.112	1.647
ci score ≥2	−0.013	−0.088	0.905	1.798
cg score ≥1	−0.071	−0.463	0.504	1.736
mm score ≥1	−0.273	−1.510	0.008	1.543
ah score ≥2	−0.081	−0.418	0.359	1.192
Prior rejection	−0.109	−1.115	0.252	1.391
eGFR	0.116	0.018	0.202	1.273
Proteinuria ≥1	−0.271	−1.970	0.004	1.296
model 3
t score ≥1	−0.160	−1.774	0.077	1.289
g score ≥1	−0.047	−0.296	0.684	2.180
ptc score ≥1	−0.159	−0.994	0.119	1.649
ci score ≥2	0.018	0.121	0.868	1.831
cg score ≥1	−0.040	−0.261	0.702	1.770
mm score ≥1	−0.213	−1.182	0.038	1.669
ah score ≥2	−0.086	−0.446	0.317	1.193
Prior rejection	−0.078	−0.792	0.410	1.427
eGFR	0.104	0.016	0.246	1.279
Proteinuria ≥1+	−0.116	−0.840	0.319	2.166
mm ≥1 with proteinuria ≥1+	−0.275	−2.617	0.036	2.717

The data of eGFR and proteinuria were at the time of the 7-year protocol biopsy. VIF, valiance inflation factor; eGFR, estimated glomerular filtration rate.

Figure 3. Main diagnoses of mm-positive lesions.

Figure 4. Graft survival between (a) mm < 1 and mm ≥ 1; (b) proteinuria < 1+, proteinuria 1+, and proteinuria ≥ 2+.

Figure 5. Graft survival between (a) mm ≥ 1 with ABMR and mm ≥ 1 without ABMR; (b) mm ≥ 1 with proteinuria and mm ≥ 1 without proteinuria; (c) proteinuria with mm ≥ 1 and without mm ≥ 1.

Figure 6. Overlap among graft loss cases with mm ≥ 1, cg ≥ 1, and proteinuria ≥ 1+.