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Complement mediated TMA (cTMA) and complement component 3 glomerulonephritis (C3GN) are two distinct complement mediated kidney diseases. cTMA is characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. C3GN results from uncontrolled activation of the alternative complement pathway leading to the deposition of C3 in the glomerulus. We sought to describe characteristic differences between these two conditions in a large cohort of patients from Bengaluru, India.
All cases of cTMA and kidney biopsy-proven C3GN from 2019-2022 at a tertiary care center from South India were included. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. All patients received protocolized medical therapy; patients with C3GN were treated with steroids and cyclophosphamide, while those with complement mediated TMA received plasmapheresis in addition to cyclophosphamide and steroids. Protocolised medical management (renin-angiotensin-aldosterone inhibition and diuretics) was provided in both the cases. Demographic, clinical and lab parameters were reported and compared.
A total of 25 cTMA cases and 19 C3GN cases were included in the study. Both C3GN (52.7%) and cTMA (48%) were more common in males. Patients with C3GN typically presented in the fourth decade of life while cTMA cases presented in the third decade. Secondary hypertension was common in the cTMA group (92% vs 78.9%, compared to C3GN). 60% of patients with cTMA had either recent or current infection compared to 21.1% of C3GN patients (P=0.04). The majority of cTMA cases had IFTA of <25% (84%) compared to C3GN (57.9%) although this was not statistically significant. Both C3GN and cTMA most commonly presented as rapidly progressive kidney failure and acute kidney injury. A total of 76% of patients in the cTMA group required kidney replacement therapy as compared to 47.4% in the C3GN group (P=0.009). 44% of cTMA cases had anti-factor H antibody positivity compared to 15.8% of C3GN patients (P=0.02). Finally, 44% of cases in cTMA group had complete recovery compared to 47.4% in C3GN group at the end of 2.8 years of follow-up
VARIABLES
Diagnosis
P value
cTMA
C3GN
Age in years
26.72±19.26
31.37±18.84
0.200
Serum Creatinine (mg/dl)
7.04±4.28
6.18±5.80
0.104
Proteinuria (g/day)
1.87±1.91
2.84±2.90
0.001**
Haemoglobin (g/dl)
8.49±2.21
8.53±1.54
0.143
Total White Cell Count
10952.00±6062.94
8760.53±3696.55
0.343
Platelet Count
160996.08±120986.46
255336.84±179247.81
0.034*
Sodium (mEq/l)
135.04±4.76
136.42±3.66
0.168
Potassium (mEq/l)
4.26±0.80
4.44±0.62
0.845
Urea
107.24±43.90
99.96±70.35
Serum Albumin
3.43±0.67
3.02±0.77
0.124
Total Follow up
2.88±0.88
2.79±0.92
0.149
Recovery
P Value
TMA
VS TMA
COMPLETE RECOVERY
11(44%)
9(47.4%)
0.677
PARTIAL RECOVERY
7(28%)
3(15.8%)
NO RECOVERY
7(36.8%)
Total
25(100%)
19(100%)
Secondary HTN, association with infection, anti-factor H positivity and requirement of KRT were predominant in the cTMA group compared to C3GN group. Though both the diseases are due to alternate pathway dysregulation, the clinical features and prognosis are variable, with cTMA
having a poorer prognosis compared to C3GN.