Table 6.

Clinical features, complement assessment, genetic screening, and histologic features in patients classified according to the clusters obtained through the three-step algorithm for cluster definition

VariableCluster 1Cluster 2Cluster 3Cluster 4Overall P Value
N56402849
Sex, % men574857610.62
Data at onset
 Age, yr15.3 (±12.4)18 (±12.7)15 (±10.8)26.3 (±19.8)a,b,c<0.001
 Microhematuria, %898793730.08
 Gross hematuria, %363043310.65
 Proteinuria, %939886860.17
 Nephrotic syndrome, %3268a,c,d2118<0.001
 Renal impairment, %1323c431a,c0.01
 Trigger event, %322632290.92
 Familiarity for nephropathy, %161311170.89
Serum C3, mg/dl31.6 (±21.2)21 (±18.8)a,c35.6 (±35.6)96.2 (±28.8)a,b,c<0.001
Serum C4, mg/dl21.6 (±9.7)20.6 (±12.6)24.2 (±9.2)21.8 (±7.5)0.53
Plasma SC5b-9, ng/ml1297 (±1281)c,d2003 (±1389)a,c,d523 (±508)d308 (±154)<0.001
Low serum C3 and normal C4, %95788642a,b,c<0.001
LPV carriers, %3425142a,b<0.001
C3NeF positive, %5260797a,b,c<0.001
LPV carriers and/or C3NeF, %7575839a,b,c<0.001
Data during follow-up, %
 Nephrotic syndrome4890a,c,d5047<0.001
 High BP27452557a,c0.004
 CKD274525470.06
 ESRD584160.20
 Thrombotic microangiopathy20012a,b0.01
Histologic features
Time onset to biopsy, yr, median (IQR)0.4 (0.1–2.1)0.3 (0.0–1.9)0.4 (0.4–3.8)0.4 (0.0–3.0)0.23
Light microscopy
 Sclerotic glomeruli, %4 (±8)6 (±12)2 (±6)16 (±21)a,b,c<0.001
 Crescents, %6 (±17)3 (±8)6 (±19)6 (±17)0.73
 Degree of mesangial proliferatione2 (±0.9)1.7 (±1.1)1.9 (±0.8)1.6 (±1)0.22
 Degree of endocapillary proliferatione1.3 (±1.2)d1.6 (±1)c,d1 (±1.1)0.6 (±0.8)<0.001
 Degree of interstitial inflammatione0.4 (±0.6)b,d0.8 (±0.7)0.7 (±0.9)1 (±0.9)0.001
 Degree of interstitial fibrosise0.3 (±0.6)0.5 (±0.8)0.2 (±0.4)0.8 (±0.9)a,c0.003
 Degree of arteriolar sclerosise0.1 (±0.5)0.2 (±0.5)0.1 (±0.2)0.6 (±1)a,b,c<0.001
IFe
 C32.7 (±0.5)2.7 (±0.5)2.8 (±0.3)2.5 (±0.7)a,c0.04
 IgA0.1 (±0.4)b,d0.4 (±0.7)c0.1 (±0.3)0.4 (±0.8)<0.01
 IgG0.3 (±0.8)1.5 (±1)a,c0.4 (±0.7)1.2 (±1.2)a,c<0.001
 IgM0.6 (±0.8)1.3 (±0.9)a,c,d0.7 (±0.6)0.8 (±1)0.001
 C1q0 (±0.1)c,d1.7 (±0.7)a,c,d0.2 (±0.5)d0.7 (±0.9)<0.001
 Fibrinogen0.4 (±0.8)0.5 (±0.9)0.3 (±0.7)0.1 (±0.3)a,b0.05
Electron microscopy, %
 Mesangial deposits72725050a,b0.04
 Subepithelial deposits484911a,b,d43<0.01
 Subepithelial hump-like deposits221411200.55
 Subendothelial deposits778711a,b,d70<0.001
 Intramembranous granular deposits60540a,b,d40<0.001
 Intramembranous highly electron-dense ribbon-like deposits00100a,b,d0<0.001
  • Quantitative variables are expressed as mean (±SD) unless otherwise specified. Serum C3: reference 90–180 mg/dl; serum C4: reference 10–40 mg/dl; plasma SC5b-9: reference ≤400 ng/ml. IQR, interquartile range.

  • a Significantly different versus cluster 1.

  • b Significantly different versus cluster 2.

  • c Significantly different versus cluster 3.

  • d Significantly different versus cluster 4.

  • e Degrees of mesangial proliferation, endocapillary proliferation, interstitial inflammation, interstitial fibrosis, and arteriolar sclerosis as well as IF findings were graded using a scale of 0–3, including 0, trace (0.5+), 1+, 2+, and 3+.