Article Figures & Data
Figures
- Figure 1.
Flowchart of the inclusion of patients.
- Figure 2.
Patient outcomes. The solid line represents renal survival without progression. The dot and dashed line represents partial remission defined as proteinuria <3.5 g/d and <50% since baseline, the long dashed line partial remission (proteinuria <2.0 g/d), and the short dashed line complete remission (proteinuria <0.2 g/d).
- Figure 3.
Left: ROC curves for prognostic accuracy of urinary excretion rate of α1- (dashed line) and β2-microglobulin (solid line) and IgG (dot and dashed line). Both α1- and β2-microglobulin excretions rates are expressed in μg/min and IgG in mg/24 h. Areas under the curve were as follows: uα1m: 0.81 (95% confidence interval: 0.73 to 0.88), uβ2m: 0.81 (0.73 to 0.89), and IgG: 0.75 (0.66 to 0.84). Right: ROC curves for the prognostic accuracy of α1- (dashed line) and β2-microglobulin (solid line) and IgG (dot and dashed line). When expressed as mg/10 mmol creatinine. Areas under the ROC curve were as follows: uα1m/creat: 0.80 (0.72 to 0.87), uβ2m/creat: 0.80 (0.72 to 0.88), and uIgG/creat: 0.74 (0.66 to 0.83).
Tables
Number of subjects (% male) 129 (68%) Age at time of biopsy (years)a 51 (43 to 61) Time between biopsy and urine analysis (months)a 2 (1 to 4) Survival time (months)a 25 (13 to 51) MAP (mmHg)a 97 (86 to 106) Laboratorya serum creatinine (μmol/L) 88 (76 to 103) serum albumin (g/L) 23 (19 to 28) serum cholesterol (mmol/L) 7.3 (5.7 to 9.2) eGFRMDRD4 (ml/min per 1.73 m2) 75 (60 to 87) Urine samples proteinuria (g/10 mmol creatinine)a 8.0 (5.6 to 10.7) proteinuria <4.0 g/10 mmol (%) 9 proteinuria ≥4.0 and <8.0 g/10 mmol (%) 41 proteinuria ≥8.0 and <12 g/10 mmol (%) 35 proteinuria ≥12 g/10 mmol (%) 15 β2-microglobulin (μg/min)a 0.6 (0.2 to 4.8) α1-microglobulin (μg/min)a 41 (23 to 72) IgG (mg/24 h)a 257 (116 to 490) β2-microglobulin (mg/10 mmol creatinine)a 0.9 (0.3 to 7.0) α1-microglobulin (mg/10 mmol creatinine)a 36 (57 to 113) IgG (mg/10 mmol creatinine)a 262 (110 to 485) Selectivity indexb 0.19 ± 0.09 Medication (%) ACEi/ARB use at time of biopsy 22 ACEi/ARB use during follow-up 99 statin use at time of biopsy 13 statin use during follow-up 90 Outcomes progression (%) 47 50% rise in serum creatinine (n) 30 25% rise and serum creatinine ≥135 μmol/L (n) 24 clinical progression (n) 6 spontaneous remission (%) 47 partial remission [<2 g/10 mmol] (n) 61 partial remission [<3.5 g/10 mmol and 50% reduction] (n) 63 complete remission (%) (n) 26 - Table 2.
Test characteristics for urinary low-molecular-weight protein excretion to predict progression in 129 iMN patients
Threshold Value Sensitivity (%) Specificity (%) PPV (%) NPV (%) False Positives (n) False Negatives (n) Test Positives (n) uβ2m ≥0.5 μg/min 80 67 68 79 23 12 71 ≥1.0 μg/min 73 75 72 76 17 16 61 ≥1.5 μg/min 65 83 76 73 12 21 51 ≥2.0 μg/min 58 83 76 70 12 24 47 ≥2.5 μg/min 55 84 75 68 11 27 44 uα1m ≥40 μg/min 77 71 70 78 20 14 66 ≥50 μg/min 65 83 76 73 12 21 51 ≥60 μg/min 57 86 77 69 10 26 44 ≥70 μg/min 45 88 77 65 8 33 35 ≥80 μg/min 42 90 78 64 11 27 44 iMN, idiopathic membranous nephropathy; PPV, positive predictive value; NPV, negative predictive value; uβ2m, urinary β2-microglobulin; uα1m, urinary α1-microglobulin. Test positives are the number of patients with a urinary α1- and β2-microglobulin excretion greater than the threshold value.
- Table 3.
Baseline characteristics for progressors and nonprogressors classified according to initial excretion of β2-microglobulin ≥1.0 μg/min
Progressors Nonprogressorsa Pb β2m ≥ 1.0 β2m < 1.0 β2m < 1.0 β2m ≥ 1.0 Number of subjects (% male subjects) 44 (75) 16 (62) 52 (65) 17 (65) 0.69 Age at time of biopsy (years)c 57 (47 to 64) 49 (44 to 58) 49 (38 to 60) 56 (51 to 64) 0.02 Time between biopsy and urine analysis (months) 2 (1 to 4) 2 (0 to 2) 1 (1 to 4) 2 (1 to 4) 0.88 Survival time (months) 11 (6 to 25) 16 (7 to 25) 53 (28 to 84) 41 (24 to 54) MAP (mmHg) 100 (89 to 112) 94 (81 to 105) 93 (86 to 104) 99 (92 to 104) 0.16 Laboratory serum creatinine (μmol/L) 110 (97 to 119) 90 (68 to 95) 80 (70 to 87) 86 (82 to 91) <0.001 serum albumin (g/L) 20 (17 to 24) 23 (18 to 26) 27 (23 to 31) 22 (17 to 25) <0.001 serum cholesterol (mmol/L) 8.4 (7.0 to 9.8) 8.5 (5.7 to 9.3) 6.5 (5.5 to 7.7) 6.1 (5.3 to 7.3) 0.004 eGFRMDRD4 (ml/min per 1.73 m2) 58 (53 to 67) 75 (65 to 97) 85 (78 to 93) 75 (67 to 80) <0.001 Urine samples proteinuria (g/10 mmol creatinine) 10.7 (9.3 to 12.7) 5.5 (4.8 to 8.7) 6.2 (4.7 to 8.5) 9.1 (5.9 to 11.0) <0.001 β2-microglobulin (μg/min) 7.8 (2.3 to 13.8) 0.3 (0.1 to 0.5) 0.1 (0.2 to 0.4) 2.6 (1.3 to 7.7) α1-microglobulin (μg/min) 106 (61 to 131) 31 (20 to 44) 22 (12 to 37) 50 (39 to 83) IgG (mg/24 h) 511 (356 to 776) 157 (74 to 217) 119 (62 to 219) 351 (158 to 607) Selectivity index>d 0.27 ± 0.08 0.11 ± 0.05 0.15 ± 0.07 0.21 ± 0.08 <0.001 Medication (%) ACEi/ARB use at time of biopsy 36 20 16 6 0.03 ACEi/ARB use during follow-up 100 100 98 100 0.68 statin use at time of biopsy 20 7 10 6 0.26 statin use during follow-up 93 93 84 94 0.43 Outcomes progression (%) 100 100 0 0 50% rise in serum creatinine (n) 18 12 25% rise and serum creatinine >135 μmol/L (n) 24 0 clinical progression (n) 2 4 Spontaneous remission (%) partial remission: < 2.0 g/10 mmol 0 0 90 82 partial remission: <3.5 g/10 mmol and ≥50% reduction 0 0 94 82 complete remission 0 0 40 29 β2-microglobulin, β2m; MAP, mean arterial pressure; eGFRMDRD4, estimated GFR calculated with the Modification of Diet in Renal Disease formula; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.
↵a Misclassified progressors are those patients who did show progression but had uβ2m < 1.0 μg/min.
↵b ANOVA was used to compare continuous data between the four groups and chi-squared tests to compare medication use and gender.
↵c Values are medians with interquartile range in parentheses.
↵d Values are mean ± SD.
- Table 4.
Classification according to uβ2m excretion at baseline and repeated measurement versus patient outcome in 44 patients with repeated measurements
Measurement Outcome (n) Baseline Repeated Progression No Progression uβ2m ≥ 1.0 μg/min uβ2m ≥ 1.0 μg/min 11 0 uβ2m ≥ 1.0 μg/min uβ2m < 1.0 μg/min 3 1 uβ2m < 1.0 μg/min uβ2m ≥ 1.0 μg/min 10 2 uβ2m < 1.0 μg/min uβ2m < 1.0 μg/min 0 17 The positive predictive value for patients with a least one measurement ≥1.0 μg/min was 89%. The negative predictive value for patients with both measurements <1.0 μg/min was 100%. Of the 11 patients who were classified as progressors and had uβ2m > 1.0 μg/min, three had a 50% rise in serum creatinine, seven had a 25% rise and serum creatinine >135 μmol/L, and one patient had severe nephrotic syndrome. uβ2m, urinary β2-microglobulin.
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Epidemiology and Outcomes
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