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Introduction:
Information on long term renal-outcome and response to immunosuppression in children with dense deposit disease (DDD), C3 glomerulonephritis (C3GN) or immune complex MPGN (IC-MPGN) is limited.
Material and methods:
Patients, aged below 18 years, with DDD, C3GN or IC-MPGN diagnosed by histopathology, immunofluorescence and electron microscopy were included. Remission was serum albumin >2.5 g/dL with 24-hours urine protein <100 mg/1.73m2 (complete) or 100-1000 mg/1.73m2 (partial) and improved or stable eGFR (±15ml/1.73m2/min); adverse outcome was eGFR<30 mL/min/1.73 m2 or death.
Results:
Clinical presentation of 65 included patients was comparable between groups (Table 1). Serum C3 <70 mg/dl was more frequent in C3 glomerulopathy (DDD and C3GN) compared to IC-MPGN (72% vs. 40%; P=0.02). Therapy comprised ACE-inhibition and steroids with mycophenolate mofetil (MMF; 52), tacrolimus (22), cyclophosphamide (19), azathioprine (4), IV rituximab (5) and plasma exchanges (4). Remission-rate was 27% and 35% with MMF (1000 mg/m2/day; n=48) and tacrolimus (n=20), respectively (P=0.6); decline in proteinuria was insignificant with either therapy [median 2.7 to 1.9 g/day; P=0.23]. Sustained complete remission occurred in 8%, 11% and 7% of patients with DDD, C3GN and IC-MPGN, respectively; 33% had recurrence of nephrotic range proteinuria following partial/complete remission for 29±17 months. Progression to ESRD was similar between C3 glomerulopathy (34%) and IC-MPGN (27%; log-rank=0.216). Renal survival was 70.5%, 72.7% and 83.6% at 5-years and 27.4%, 72.7% and 83.6% at last follow-up in DDD, C3GN and IC-MPGN, respectively (47 months, range 6-125; log-rank >0.1). In multivariate analysis, complete or partial remission (HR 393.8; P=0.015), IFTA>15% (HR 20.4; P=0.02) and rapidly progressive renal failure (HR 27.9; P=0.02) predicted adverse outcome at last follow-up; the diagnosis of DDD did not influence renal survival (P=0.15).
Table 1
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DDD (N=38)
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C3GN (N=12)
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IC-MPGN (N=15)
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P
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Age, yr
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9.6 (8-11)
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11.5 (9.4-13.6)
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9 (7.6-10.2)
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0.41
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Boys
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19 (50)
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10 (83)
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11 (73)
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0.07
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First clinical manifestation
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Nephrotic syndrome
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21 (55)
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6 (50)
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12 (80)
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0.18
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Rapidly progressive GN
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8 (21)
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1 (8)
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-
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0.10
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Acute GN
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6 (16)
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5 (42)
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3 (20)
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0.17
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Chronic GN
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3 (7.9)
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-
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-
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0.50
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Stage 2 hypertension
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16 (42.1)
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4 (33)
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5 (33)
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0.82
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eGFR, ml/min/1.73 m2
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66 (23-88)
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67 (51-101)
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85 (77-119)
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0.18
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Serum C3 (mg/dl)
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37 (15-62)
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36 (19-79)
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84 (30-106)
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0.12
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Complete or partial remission
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At 3-month
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10 (26)
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2 (17)
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1 (6.7)
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0.29
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At 12-months
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13 (34)
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4 (33)
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1 (6.7)
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0.07
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At last follow-up
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11 (29)
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5 (42)
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3 (20)
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0.48
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eGFR 30-60 ml/1.73m2/min
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17 (45)
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2 (17)
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4 (27)
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0.16
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End stage renal disease/ death
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16 (37)
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1 (8)
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4 (27)
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0.08
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Values are median (interquartile range) or N (%)
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Conclusions:
Clinal presentation and response to immunosuppression is similar in C3 glomerulopathy or IC-MPGN. Tacrolimus or MMF fail to significantly lower proteinuria.
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