External Validation of the International IgA Nephropathy Prediction Tool in Older Adult Patients

Figures & data

Figure 1 Flowchart of patients screened, recruited, and included in the final analysis.

Table 1 Characteristics of Participants in the Older Adults Validation Cohort, the Original Derivation Cohort, and the Original Validation Cohort

Characteristic	Older Adults Validation Cohort	Original Derivation Cohort	Original Validation Cohort
Patients, no.	165	2781	1146
Follow-up, median (IQR), yr	5.1 (2.3–8.8)	4.8(3.0–7.6)	5.8(3.4–8.5)
Age, median (IQR), yr	64 (62–67)	36(28–45)	35(27–45)
Males	99 (60%)	1608(58%)	565(49%)
eGFR at biopsy, median (IQR), mL/min per 1.73 m^2	50.8 (36–73)	83(57–108)	90(65–113)
Mean arterial pressure at biopsy, median (IQR), mmHg	100 (93–109)	97(89–106)	93(85–103)
Proteinuria at biopsy, median (IQR), g/d	2.13 (0.9–3.4)	1.2(0.7–2.2)	1.3(0.6–2.4)
<0.5	18(11%)	383(14%)	221(19%)
0.5–1.0	29(18%)	772(28%)	209(18%)
1.0–2.0	31(19%)	817(30%)	352(31%)
2.0–3.0	33(20%)	360(13%)	145(13%)
>3.0	54(32%)	415(15%)	215(19%)
MEST histologic score
M1	82(50%)	1054(38%)	481(42%)
E1	30(18%)	478(17%)	476(42%)
S1	91(55%)	2137(77%)	912(80%)
T1	66(40%)	686(25%)	207(18%)
T2	32(19%)	128(5%)	122(11%)
Crescents	52(32%)	953(34%)	642(56%)
C1	44(27%)	N/A	N/A
C2	8(5%)	N/A	N/A
RASB use
At biopsy	73(44%)	862(32%)	320(30%)
After biopsy	97(59%)	2400(87%)	708(66%)
Immunosuppression use
At biopsy	4(2%)	252(9%)	81(7%)
After biopsy	23(14%)	1209(44%)	359(31%)
Primary outcome
50% decline in eGFR	24(14.5%)	420(15%)	210(18%)
Kidney failure	22(13.3%)	372(13%)	155(14%)
Total primary outcome	35(21%)	492(18%)	213(19%)

Notes: The primary outcome was a combined event that included either a permanent >50% reduction in eGFR or kidney failure (eGFR <15 mL/min/1.73 m² or kidney replacement therapy), whichever occurred first.

Abbreviations: IQR, interquartile range; MEST, mesangial and endocapillary hypercellularity, segmental glomerulosclerosis, and tubular atrophy/interstitial fibrosis; M, mesangial hypercellularity; E, endocapillary hypercellularity; S, segmental glomerulosclerosis; T, tubular atrophy/interstitial fibrosis; N/A, not applicable; RAAS, renin-angiotensin-aldosterone system.

Table 2 Concordance Statistics, Calibration Slopes, Net Reclassification Improvements, and Integrated Discrimination Improvements of Full Models in the Older Adults External Validation Cohort

Variable	Full Model without Race	Full Model with Race
Harrell c index	0.790(0.717–0.863)	0.788(0.712–0.865)
AUC at 3 yr	0.89	0.88
AUC at 5 yr	0.82	0.72
Calibration slope	0.92(0.88 to 0.95)	0.88(0.85 to 0.91)
5-yr performance compared with the full model with race
NRI	0.09 (−0.27 to 0.34)
NRI (events)	0.06 (−0.25 to 0.31)
NRI (no events)	0.04 (−0.06 to 0.08)
IDI	0.003 (−0.009 to 0.019)

Notes: Values in parentheses represent 95% confidence intervals. For NRI and IDI, statistically significant improvement is indicated by a 95%confidence interval that does include zero.

Abbreviations: AUC, the area under the receiver operating characteristic curve; NRI, net reclassification improvement; IDI, integrated discrimination improvement.

Table 3 Associations of the Risk Groups with the Composite Outcome of 50% Decline in Estimated Glomerular Filtration Rate or Kidney Failure in Patients with Over 5-Year Follow-Up (n=165)

Risk Group	Events, n (%)	HR (95% CI)	P–value
Full model with race
Low risk	2(7.41%)	1	–
Intermediate risk	10(18.18%)	2.43(1.03 to 5.75)	0.19
Higher risk	11(19.64%)	4.78(1.82 to 12.56)	0.01
Highest risk	12(44.44%)	17.49(4.32 to 70.82)	<0.0001
P value for trend	–	–	<0.0001
Full model without race
Low risk	1(3.70%)	1	–
Intermediate risk	11(20.00%)	3.12(0.88 to 11.05)	0.07
Higher risk	11(19.64%)	5.31(1.58 to 17.87)	0.007
Highest risk	12(44.44%)	15.79(4.79 to 52.11)	<0.0001
P value for trend	–	–	<0.0001

Notes: ^aRisk groups were based on percentiles of the linear predictor (low risk: <16th, intermediate risk: 16th-50th, higher risk: 50th-84th, highest risk: >84th). ^bLow risk group is the reference group. ^cP values are for the HRs in the subgroups.

Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 2 The Time-dependent receiver operating characteristic (ROC) curves and the Kaplan-Meier curves confirmed the excellent distinguishing ability of both full models.

Notes: (a and b) show the receiver operating curve analysis at 3 years and 5 years for both full models, respectively. (c and d) respectively show the Kaplan-Meier curves of the primary outcome in 4 risk groups distinguished by the Full model with race and the full model without race: the well-separated curves indicate good discriminant ability of both the models. The 4 risk groups were defined as <16th (low risk), 16th −50th (intermediate risk), 50th −84th (higher risk), and >84th (the highest risk) percentiles of the linear predictor from the full model without and with race, respectively.

Abbreviations: AUC, the area under the receiver operating characteristic (ROC) curve.

Figure 3 The full model without race more accurately prognoses the risk associated with primary outcomes in the older adult cohort.

Notes: (a) Comparison of observed and predicted risks of the primary outcome during the follow-up period. Predicted risks are mean predicted risk curves (blue and pink solid lines), observed risks were estimated by the Kaplan–Meier method (black solid line), and the grey dashed lines represent 95% confidence intervals of the observed risks. (b and c) Comparison of observed and predicted risks of the primary outcome throughout follow-up. The full prediction models with and without race were analyzed by subgroups based on the percentile of the linear predictor (<16th in yellow, 16th-50th in blue, 50th-84th in green, and >84th in pink) in the older adult cohorts. Predicted risks are mean predicted survival curves (dotted lines), and observed risks are Kaplan-Meier curves (solid lines).

Figure 4 Calibration plots at 3 years for (a and b) the full model with race and (c and d) the full model without race, and at 5 years for (e and f) the full model with race and (g and h) the full model without race.

Notes: Plots by risk groups are (a, c, e, and g, and by fifths of predicted risk are b, d, f, and h). The dashed lines indicate perfect calibration, in which predicted risks are the same as the observed risks. Vertical lines in observed groups represent 95% confidence intervals. Risk groups were based on percentiles of the linear predictor (group 1(low risk);<16th, group 2 (intermediate risk); 16th-50th, group 3 (higher risk); 50th-84th, group 4(highest risk: >84th)).

Data Sharing Statement

The raw data supporting the conclusions of this article will be made available by the authors without undue reservation. Correspondence and requests for materials should be addressed to Guang-yan Cai.