Introduction:
There are 3 pathways of complement activation-Classical, Lectin and Alternative pathway The alternative pathway is persistently active at a low level . Complement regulators are present to prevent its uncontrolled activation . The major complement factor regulators are Factor H(CFH) , Factor I (CFI), MCP (CD 46).Dysregulation of alternative pathway can lead on to Atypical HUS (TMA) and C3 glomerulopathy.They have varied clinical and pathological presentations .Genetic study is essential for diagnosis and in further management especially with regard to renal transplantation .Aim of this case series is to analyse the varied clinical presentations of disorders of complement dysregulation and to highlight the importance of genetic testing in diagnosis and treatment.
Methods:
Case series – 7 cases of complement dysregulation disorders from the year 2011-2024 in a tertiary health care centre in central Kerala,India
Results:
Recurrent AKI
Case 1– 35 year old male with recurrent transient episodes of worsening renal function precipitated by short febrile illness in last 2 years , now persistent renal dysfunction & proteinuria.Biopsy done with electron microscopy s/o C3 glomerulonephritis .Genetic study – CFHR5 mutation
Post partum AKI
Case 2 -26 year old lady , G3P2L2A0 post LSCS day 1 developed dialysis dependent renal failure ,severe anemia secondary to MAHA and thrombocytopenia, improved with plasma exchange & hemodialysis in 3 weeks , biopsy-TMA .Genetic study not done.
Childhood AKI
Case 3- 8 year old boy with history of transient episodes of renal failure precipitated by upper respiratory tract infection, now presented with oliguric dialysis requiring renal failure,severe anemia and thrombocytopenia .Renal biopsy- moderate global glomerulosclerosis,ATI .Genetic study -heterozygous deletion in CFHR1 and CFHR3.
CKD with refractory anemia
Case 4–34 yrs, lady with refractory anemia , renal failure , low C3 and retinal drusen . She progressed to ESRD requiring MHD .Genetic study- duplication in CFHR1 and CFHR3
Malignant hypertension
Case 5 - 35 yrs ,malignant HT,renal faiilre ( Cr -5). Renal biopsy – moderate glomerulosclerosis(41%).Genetic study- heterozygous deletion CFHR1,CFHR3
Case 6 – 42/M , malignant HT . Renal biopsy - TMA .Genetic study – CD46 mutation.
ESRD of unknown etiology-
Case 7- 36/M on Maintenance hemodialysis , came for renal transplant work up. Genetic study–homozygous deletion CFHR1, CFHR3
In our case series , minimum age was 8 years and maximum age was 42 years. Among the patients in our case series , mutations in CFHR1 and CFHR3 were identified in four patients, while a CFHR5 mutation was observed in one patient, and a CD46 mutation was detected in another. Out of the 7 patients , only one patient had a low C3.
Conclusions:
Case series highlights the bizzare presentations of disorders of complement dysregulation,which without genetic testing would have got labelled as a chronic glomerular disease of unknown etiology .Low C3 levels may be seen but do not rule out a complement dysregulation disorder.Genetic tests done appropriately helps in reaching a definitive diagnosis and thereby to institute appropriate measures to prevent its progression and to plan renal transplantation. This includes the need for genetic testing in a potential living related donor and addressing the elevated risk of post-transplant disease recurrence.
The content presented in this abstract was submitted for ISN SC conference held at Hyderabad in February 2024.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.