肾小球皮质密度对随访5年的IgA肾病不良预后的预测△

doi:10.24920/J1001-9294.2017.021

Abstract

Objective

To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m², or for patients with time-average proteinuria < 0.5 g/d.

Methods

A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis.

Results

A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm² (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm²) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m²(six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m² vs. -8.1±21.4 ml/min per 1.73 m², P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did.

Conclusion

GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m²of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Key words: glomerular density, IgA nephropathy, renal progression

Chen Zhen-jie, Li Hang, Cai Jian-fang, Zhang Xin, Li Chao, Zou Pei-mei, Li Ming-xi, Chen Li-meng, Li Xue-mei, Li Xue-wang, Wen Yu-bing. The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy^△[J].Chinese Medical Sciences Journal, 2017, 32(3): 145-151.

Figures/Tables 5

Table 1

Table 2

Figure 1.

Table 3

Figure 2.

References 22.

1.	Wyatt RJ, Julian BA.IgA nephropathy. N Engl J Med 2013; 368(25):2402-14. doi: 10.1056/NEJMra1206793.
2.	Elsherbiny HE, Alexander MP, Kremers WK, Park WD, Poggio ED, Prieto M, et al.Nephron hypertrophy and glomerulosclerosis and their association with kidney function and risk factors among living kidney donors. Clin J Am Soc Nephrol 2014; 9(11):1892-902. doi: 10.2215/ CJN.02560314.
3.	Tsuboi N, Kawamura T, Koike K, Okonogi H, Hirano K, Hamaguchi A, et al.Glomerular density in renal biopsy specimens predicts the long-term prognosis of IgA nephropathy. Clin J Am Soc Nephrol 2010; 5(1):39-44. doi: 10.2215/CJN.04680709.
4.	Hewitson TD, Darby IA, Bisucci T, Jones CL, Becker GJ.Evolution of tubulointerstitial fibrosis in experimental renal infection and scarring. J Am Soc Nephrol 1998; 9(4):632-42.
5.	Le W, Liang S, Hu Y, Deng K, Bao H, Zeng C, et al.Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant 2012; 27(4):1479-85. doi: 10.1093/ndt/gfr527.
6.	Coppo R, Troyanov S, Bellur S, Cattran D, Cook HT, Feehally J, et al.Validation of the Oxford classification of IgA nephropathy cohorts with different presentations and treatments. Kidney Int 2014; 86(4):828-36. doi: 10. 1038/ki.2014.63.
7.	Sarcina C, Tinelli C, Ferrario F, Visciano B, Pani A, De Silvestri A, et al.Corticosteroid treatment influences TA-proteinuria and renal survival in IgA nephropathy. PLoS One 2016; 11(7):e0158584. doi: 10.1371/journal.pone. 0158584.
8.	Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150(9): 604-12. doi: 10.7326/0003-4819-150-9-200905050-00006.
9.	Coresh J, Turin TC, Matsushita K, Sang Y, Ballew SH, Appel LJ, et al.Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. JAMA 2014; 311(24):2518-31. doi: 10.1001/ jama.2014.6634.
10.	Levey AS, Inker LA, Matsushita K, Greene T, Willis K, Lewis E, et al.GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis 2014; 64(6):821-35. doi: 10.1053/j.ajkd.2014.07.030.
11.	Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, 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(5):534-45. doi: 10.1038/ki.2009.243.
12.	Trimarchi H, Barratt J, Cattran DC, Cook HT4, Coppo R, Haas M, et al. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int 2017; 91(5):1014-21. doi: 10.1016/j.kint.2017.02.003.
13.	Hoy WE, Bertram JF, Hughson MD.Nephron hypertrophy and glomerulosclerosis in normal donor kidneys. Clin J Am Soc Nephrol 2014; 9(11):1832-4. doi: 10.2215/CJN. 08680814.
14.	Luyckx VA, Brenner BM.Birth weight, malnutrition and kidney-associated outcomes—a global concern. Nat Rev Nephrol 2015; 11(3):135-49. doi: 10.1038/nrneph.2014.251.
15.	Koike K, Ikezumi Y, Tsuboi N, Kanzaki G, Haruhara K, Okabayashi Y, et al.Glomerular density and volume in renal biopsy specimens of children with proteinuria relative to preterm birth and gestational age. Clin J Am Soc Nephrol 2017; 12(4):585-90. doi: 10.2215/CJN.05650516.
16.	Haruhara K, Tsuboi N, Kanzaki G, Koike K, Suyama M, Shimizu A, et al.Glomerular density in biopsy-proven hypertensive nephrosclerosis. Am J Hypertens 2015; 28(9): 1164-71. doi: 10.1093/ajh/hpu267.
17.	Nyengaard J, Bendtsen T.Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 1992; 232(2):194-201. doi: 10.1002/ar.1092320205.
18.	Tsuboi N, Utsunomiya Y, Kanzaki G, Koike K, Ikegami M, Kawamura T, et al.Low glomerular density with glomerulomegaly in obesity-related glomerulopathy. Clin J Am Soc Nephrol 2012; 7(5):735-41. doi: 10.2215/CJN.07270711.
19.	Koike K, Tsuboi N, Utsunomiya Y, Kawamura T, Hosoya T.Glomerular density-associated changes in clinicopathological features of minimal change nephrotic syndrome in adults. Am J Nephrol 2011; 34(6):542-8. doi: 10.1159/ 000334360.
20.	Radhakrishnan J, Cattran DC.The KDIGO practice guideline on glomerulonephritis: reading between the (guide) lines—application to the individual patient. Kidney Int 2012; 82(8):840-56. doi: 10.1038/ki.2012.280.
21.	Tesar V1, Troyanov S, Bellur S, Verhave JC, Cook HT, Feehally J, et al. Corticosteroids in IgA nephropathy: a retrospective analysis from the VALIGA study. J Am Soc Nephrol 2015; 26(9):2248-58. doi: 10.1681/ASN.20140 70697.
22.	Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, et al.Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med 2015; 373(23): 2225-36. doi: 10.1056/NEJMoa1415463.

Characteristics	All patients	Glomerular density		t value	P value
Characteristics	All patients	≤2.18/mm²	>2.18/mm²	t value	P value
n Age^§ (yrs)	173	58	115
n Age^§ (yrs)	36.2 ± 9.9	36.6 ± 9.3	36.0±10.3	–0.25	0.001
Male [n (%)]	74 (42.8)	25 (43.1)	49 (42.6)		0.54
Diabetes [n (%)]	15 (8.7)	3 (5.2)	12 (10.4)		0.19
Hypertension [n (%)]	71 (41.0)	31 (53.4)	40 (34.8)		0.014
Body mass index^§ (kg/m²)	24.5 ± 3.9	24.3 ± 3.6	24.5 ± 4.1	–0.12	0.75
Mean arterial pressure^§ (mm Hg)	96.0 ± 13.3	98.4 ± 14.2	94.8 ± 12.6	2.17	0.09
Proteinuria [g/d, median (Q1, Q3)]	2.0 (0.9, 4.0)	2.2 (1.0, 3.8)	2.0 (0.9, 4.0)		0.94
eGFR^§ (ml/min per 1.73 m²)	80.0 ± 25.4	67.9 ± 22.0	86.0 ± 24.9	–4.73	<0.001
Serum creatinine^§ (μmol/L)	100.3 ± 39.8	113.0 ± 39.0	89.8 ± 27.8	3.99	<0.001
Uric acid^§ (μmol/L)	361.0 ± 109.2	405.8 ± 114.2	338.3 ± 99.6	5.08	<0.001
Total cholesterol [mmol/L, median (Q1, Q3)]	5.6 (4.7, 6.7)	5.6 (4.7, 6.6)	5.5 (4.7, 6.8)		0.94
Triglycerides^§ (mmol/L)	2.2 ± 1.2	2.1 ± 1.2	2.2 ± 1.2	–0.33	0.48
Pathological variables
Glomerular density^§ (per mm²)	2.7 ± 1.1	1.5 ± 0.4	3.3 ± 0.9	–8.21	<0.001
Global glomerulosclerosis^§ (%)	26.1 ± 18.4	40.8 ± 18.8	18.6 ± 13.0	8.19	<0.001
Maximal glomerular diameter^§ (μm)	216.3 ± 25.8	224.1 ± 22.6	212.4 ± 26.4	2.57	0.004
M1 [n (%)]	102 (59.0)	35 (60.3)	67 (58.3)		0.46
E1 [n (%)]	52 (30.1)	15 (25.9)	37 (32.2)		0.25
S1 [n (%)]	163 (94.2)	56 (96.6)	107 (93.0)		0.29
T1 [n (%)]	58 (33.5)	21 (36.2)	37 (32.2)		0.36
T2 [n (%)]	17 (9.8)	14 (24.1)	3 (2.6)		<0.001

Characteristics	Unadjusted	Model 1	Model 2	Model 3	Model 4
Glomerular density (per mm²)
>2.18/mm²	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)	1.0 (Ref)
≤2.18/mm²	12.41 (4.26, 36.18)	14.05 (4.79, 41.21)	13.14 (4.08, 42.39)	10.80 (3.03, 8.45)	7.21 (1.82, 28.52)
Age		0.94 (0.90, 0.99)	0.92 (0.87, 0.98)	0.93 (0.88, 1.00)	0.94 (0.89, 1.00)
Gender		1.49 (0.66, 3.34)	2.18 (0.85, 5.57)	2.11 (0.80, 5.58)	2.14 (0.81, 5.66)
Hypertension			0.80 (0.33, 1.80)	0.85 (0.32, 2.31)	0.90 (0.34, 2.38)
Proteinuria			1.12 (0.95 ,1.32)	1.09 (0.89, 1.34)	1.13 (0.91, 1.40)
eGFR			0.98 (0.96, 1.00)	0.99 (0.97, 1.01)	0.99 (0.97, 1.02)
Corticosteroids			4.38 (1.23, 15.53)	4.33 (1.07, 17.46)	6.16 (0.40, 27.11)
RAS blockers			0.65 (0.08, 5.53)	0.64 (0.07, 6.21)	0.84 (0.08, 8.76)
Immunosuppressive agents			2.27 (0.79, 6.55)	2.18 (0.70, 6.74)	2.08 (0.66, 6.57)
M1				1.07 (0.42, 2.73)	1.13 (0.44, 2.94)
E1				1.03 (0.40, 2.69)	1.19 (0.45, 3.20)
S1				0.87 (0.08, 9.98)	0.80 (0.07, 9.75)
T1-2				1.02 (0.98, 1.06)	1.01 (0.97, 1.05)
Maximal glomerular diameter				1.00 (0.98, 1.03)	1.01 (0.99, 1.03)
Global glomerulosclerosis percent					1.02 (1.00, 1.06)

Characteristics	Glomerular density		t value	P value
Characteristics	≤1.99/mm²	>1.99/mm²	t value	P value
Age^§ (yrs)	33.8±9.2	41.7±10.4	-2.66	0.01
Male [n (%)]	10 (45.5)	10 (45.5)		1.00
Body mass index^§ (kg/m²)	23.3±3.6	25.4±4.4	-1.74	0.09
Mean arterial pressure^§ (mm Hg)	99.6±14.4	98.2±10.9	0.36	0.72
Proteinuria^§ (g/d)	3.9±2.9	2.7±2.5	1.51	0.14
eGFR^§ (ml/min per 1.73 m²)	46.8±7.8	51.2±9.0	-1.72	0.09
Uric acid^§ (μmol/L)	460.5±84.4	408.2±91.2	1.98	0.06
Total cholesterol^§ (mmol/L)	6.3±1.6	5.7±1.5	1.37	0.18
Triglycerides^§ (mmol/L)	2.3±1.3	2.6±1.2	-0.72	0.47
Pathological variables
Maximal glomerular diameter^§ (μm)	224.8±26.9	211.8±19.8	1.61	0.08
M1 [n (%)]	14 (63.6)	9 (40.9)		0.13
E1 [n (%)]	8 (36.4)	7 (31.8)		0.75
S1 [n (%)]	22 (100.0)	21 (95.5)		0.31
T1 [n (%)]	11 (50.0)	10 (45.5)		0.76
T2 [n (%)]	6 (27.3)	5 (22.7)		0.73

[1]	Li-xian Sun, Wen-ling Ye, Yu-bing Wen, Xue-mei Li. Postpartum Atypical Hemolytic Uremic Syndrome: an Unusual and Severe Complication Associated with IgA Nephropathy [J]. Chinese Medical Sciences Journal, 2015, 30(3): 189-192.
[2]	Rong-rong Li, Hang Li, Yu-bin Wen, Qing-yuan Huang, Lin Duan, Yan Li. Clinicopathological Analysis of 155 Patients with Persistent Isolated Hematuria [J]. Chinese Medical Sciences Journal, 2014, 29(3): 148-155.

Early edition

Current issue

Archive

Specialties & Topics

Author center

Reviewer center

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy^△

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 5

References 22.

Related Articles 2

Metrics

Recommended 10