The Oxford Classification predictors of chronic kidney disease in pediatric patients with IgA nephropathy☆

Fabiano, Rafaela C.G.; Araújo, Stanley A.; Bambirra, Eduardo A.; Oliveira, Eduardo A.; Silva, Ana Cristina Simões e; Pinheiro, Sérgio V.B.

doi:10.1016/j.jped.2016.09.003

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Original articles • J. Pediatr. (Rio J.) 93 (4) • Jul-Aug 2017 • https://doi.org/10.1016/j.jped.2016.09.003 copy

The Oxford Classification predictors of chronic kidney disease in pediatric patients with IgA nephropathy^☆ ☆ Please cite this article as: Fabiano RC, Araújo SA, Bambirra EA, Oliveira EA, Simões e Silva AC, Pinheiro SV. The Oxford Classification predictors of chronic kidney disease in pediatric patients with IgA nephropathy. J Pediatr (Rio J). 2017;93:389-97.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

The Oxford Classification for Immunoglobulin A nephropathy (IgAN) identifies pathological variables that may predict the decline of renal function. This study aimed to evaluate the Oxford Classification variables as predictors of renal dysfunction in a cohort of Brazilian children and adolescents with IgAN.

Methods:

A total of 54 patients with IgAN biopsied from 1982 to 2010 were assessed. Biopsies were re-evaluated and classified according to the Oxford Classification. Multivariate analysis of laboratory and pathological data was performed. The primary outcomes were decline of baseline estimated glomerular filtration rate (eGFR) greater than or equal to 50%.

Results:

Mean follow-up was 7.6 ± 5.0 years. Mean renal survival was 13.5 ± 0.8 years and probability of decline ≥50% in baseline eGFR was 8% at five years of follow-up and 15% at ten years. Ten children (18.5%) had a decline of baseline eGFR ≥ 50% and five (9.3%) evolved to end-stage renal disease. Kaplan-Meier analysis showed that baseline proteinuria, proteinuria during follow-up, endocapillary proliferation, and tubular atrophy/interstitial fibrosis were associated with the primary outcome. Multivariate Cox analysis showed that only baseline proteinuria (HR, 1.73; 95% CI, 1.20-2.50, p = 0.003) and endocapillary hypercellularity (HR, 37.18; 95% CI, 3.85-358.94, p = 0.002) were independent predictors of renal dysfunction. No other pathological variable was associated with eGFR decline in the multivariate analysis.

Conclusion:

This is the first cohort study that evaluated the predictive role of the Oxford Classification in pediatric patients with IgAN from South America. Endocapillary proliferation was the unique pathological feature that independently predicted renal outcome.

KEYWORDS
IgA nephropathy; Glomerulonephritis; Chronic kidney disease; Proteinuria; Oxford Classification

Variables	Current study	Le¹⁵15 Le W, Zeng CH, Liu Z, Liu D, Yang Q, Lin RX, et al. Validation of the Oxford Classification of IgA nephropathy for pediatric patients from China. BMC Nephrol. 2012;13:158.	Shima¹⁶16 Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Hashimura Y, et al. Validity of the Oxford Classification of IgA nephropathy in children. Pediatr Nephrol. 2012;27:783-92.	Edstrom Halling¹⁴14 Edström Halling S, Söderberg MP, Berg UB. Predictors of outcome in paediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford Classification). Nephrol Dial Transpl. 2012;27:715-22.	Oxford⁸8 Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, et al. The Oxford Classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76:534-45.
Country	Brazil	China	Japan	Sweden	Multi-national
Ethnicity
White	51.9%	-	-	NA	66%
Asian	-	100%	100%	NA	27%
African	11.1%	-	-	NA	3%
Other	37.0%	-	-	NA	4%
No. of pts (n)	54	218	161	99	265
% pts - age <18 y	100	100	100	100	22.5
Follow up (months)	91	56	54	156	62^f f Data restricted to children.
Age (y)	9.7 ± 3.3	14	11.7	9.7	13^f f Data restricted to children.
M:F	1.3:1	1.9:1	1.7:1	1.4:1	3:1^f f Data restricted to children.
Prot. at baseline	0.97 ± 1.93^c c Proteinuria expressed as g of protein/day/1.73 m2.	1.5^d d Proteinuria expressed as g of protein/day.	0.7^c c Proteinuria expressed as g of protein/day/1.73 m2.	2.0^e e Albuminuria expressed as mg of albumin/mg of creatinine.	2.0^f f Data restricted to children. ^, ^c c Proteinuria expressed as g of protein/day/1.73 m2.
Prot. F/U	0.93 ± 1.66^c c Proteinuria expressed as g of protein/day/1.73 m2.	0.6^d d Proteinuria expressed as g of protein/day.	NA	1.65^e e Albuminuria expressed as mg of albumin/mg of creatinine.	0.9^f f Data restricted to children. ^, ^c c Proteinuria expressed as g of protein/day/1.73 m2.
eGFR initial (mL/min/1.73 m ² )	143.9 ± 49.7	134	103	100	120^f f Data restricted to children.
HTN ^a a Either presence of hypertension or use of antihypertensive medications at initial evaluation. (%)	22.2	NA	NA	NA	31
RASB (%)	43.4	61.5	NA	86	56^f f Data restricted to children.
Immunosuppressive therapy ^b b Either steroids or other immunosuppressive medicine. (%)	24.5	56	16	43	48^f f Data restricted to children.
End point definition	50% decline in eGFR or ESKD	50% decline in eGFR or ESKD	CKD stages 3-5	50% decline in eGFR or ESKD	50% decline in eGFR or ESKD; slope of eGFR
No. of end point events (n)	10 (18.5%)	24 (12%)	7 (4%)	18 (18%)	58 (22%)
No. of ESKD events (n)	5 (9.3%)	NA	5 (3%)	15 (15%)	34 (13%)
Univariate HR (95%CI)
Clinical/laboratory variables	Prot. at baseline 1.44 (1.13-1.82) p = 0.003 Prot. F/U 1.72 (1.31-2.26) p < 0.001	NA	NA	NA	NA

Oxford variables
M	1.32 (0.37-4.71) p = 0.674	2.1 (0.84-5.1) p = 0.1	11.1 (1.9-210.4) p = 0.006	7.07 (2.25-22.22) p < 0.001	0.06 (0.01-0.45) p = 0.006
E	15.34 (2.97-79.17) p < 0.001	0.6 (0.2-2.3) p = 0.5	4.2 (0.7-79.6) p = 0.1	7.15 (2.21-23.13) p < 0.001	NA
S	1.74 (0.46-6.55) p = 0.414	9.2 (1.2-68.6) p = 0.03	3.4 (0.5-16.0) p = 0.2	2.38 (0.85-6.70) p = 0.101	3.1 (1.4-7.3) p = 0.009
T	NA	4.3 (1.8-1.5) p = 0.001	135.2 (5.3-3419.7) p = 0.008	5.92 (2.14-16.37) p < 0.001	3.5 (1.9-6.5) p < 0.001

Multivariate HR (95% CI)
Clinical/laboratory variables	Prot. at baseline 1.73 (1.20-2.50) p = 0.003	NA	NA	NA	NA

Oxford variables
M	NA	NA	10.8 (1.3-312.0) p = 0.03	4.98 (1.43-17.34) p = 0.012	0.11 (0.01-0.80) p = 0.03
E	37.18 (3.85-358.94) p = 0.002	NA	NA	6.62 (1.98-22.42) p = 0.002	NA
S	NA	NA	NA	NA	NA
T	NA	2.9 (1.0-7.9) p = 0.04	91.7 (3.3-2676.4) p = 0.01	4.22 (1.48-12.03) p = 0.007	5.0 (2.3-11.1) p < 0.001

Variables	n	eGFR (mL/min/1.73 m²)	%HTN	% Proteinuria (>1 g/day/1.73 m²)	% RASB	% ISS
Mesangial hypercellularity
≤0.5	36	155 ± 79	17.1	11.4	48.6	25.7
>0.5	18	124 ± 40	27.7	27.8	33.3	22.2
p-value		0.576	0.366	0.133	0.289	0.780

Endocapillary proliferation (E)
Absent (E0)	49	144 ± 44	20.8	12.5	58.3	22.9
Present (E1)	5	152 ± 91	25.0	60.0	40.0	40.0
p-value		0.077	0.965	0.007^a a p < 0.05.	0.431	0.398

Segmental glomerulosclerosis (S)
Absent (S0)	41	146 ± 45	20.0	15.0	57.5	25.0
Present (S1)	13	141 ± 63	23.1	23.1	53.8	23.1
p-value		0.413	0.812	0.500	0.817	0.889

Tubular atrophy/interstitial fibrosis (T)
0-25% (T0)	52	147 ± 49	19.6	13.7	56.8	23.5
≥25% (T1 and T2)	2	99 ± 55	50.0	100	50.0	50.0
p-value		0.874	0.299	0.001^a a p < 0.05.	0.848	0.393

Crescent (C)
Absent (C0)	50	146 ± 51	22.4	16.3	40.8	24.5
Present (C1)	4	133 ± 16	0	25.0	75.0	25.0
p-value		0.156	0.287	0.657	0.185	0.982

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[1] * Corresponding author. E-mail:acssilva@hotmail.com (A.C. Simões e Silva).