ESPN 51th Annual Meeting

ESPN 2018


 
Therapy and outcome of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis
PRIYANKA KHANDELWAL 1 HIMANSHI SAINI 1 GEETIKA SINGH 1 ADITI SINHA 1 ARVIND BAGGA 1 PANKAJ HARI 1

1- ALL INDIA INSTITUTE OF MEDICAL SCIENCES
 
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

DDD (N=38)
C3GN (N=12)
IC-MPGN (N=15)
P
Age, yr
9.6 (8-11)
11.5 (9.4-13.6)
9 (7.6-10.2)
0.41
Boys
19 (50)
10 (83)
11 (73)
0.07
First clinical manifestation     




       Nephrotic syndrome                  
21 (55)
6 (50)
12 (80)
0.18
       Rapidly progressive GN
8 (21)
1 (8)
-
0.10
       Acute GN
6 (16)
5 (42)
3 (20)
0.17
       Chronic GN
3 (7.9)
-
-
0.50
Stage 2 hypertension
16 (42.1)
4 (33)
5 (33)
0.82
eGFR, ml/min/1.73 m2
66 (23-88)
67 (51-101)
85 (77-119)
0.18
Serum C3 (mg/dl)
37 (15-62)
36 (19-79)
84 (30-106)
0.12
Complete or partial remission




       At 3-month
10 (26)
2 (17)
1 (6.7)
0.29
       At 12-months
13 (34)
4 (33)
1 (6.7)
0.07
       At last follow-up
11 (29)
5 (42)
3 (20)
0.48
eGFR 30-60 ml/1.73m2/min
17 (45)
2 (17)
4 (27)
0.16
End stage renal disease/ death
16 (37)
1 (8)
4 (27)
0.08

Values are median (interquartile range) or N (%) 




 

 

Conclusions:

Clinal presentation and response to immunosuppression is similar in C3 glomerulopathy or IC-MPGN. Tacrolimus or MMF fail to significantly lower proteinuria.