COMPLEMENT GENE MUTATIONS IN PATIENTS WITH CHRONIC KIDNEY DISEASE ON DIALYSIS (CKD-D) OF UNKNOWN ETIOLOGY: OUR EXPERIENCE FROM CENTRAL INDIA

Introduction:

Complement genes such as complement factor H (CFH), B (CFB) and I (CFI) and complement factor related (CFHR) genes underpin the occurrence of multiple kidney diseases such as C3 glomerulopathy, atypical hemolytic uremic syndrome (aHUS) and others. These diseases if not detected early can have a rapid progressive course with development of end stage kidney disease and dialysis dependence. In this study, we evaluated the complement gene mutations in patients of chronic kidney disease on dialysis (CKD-D) who had unknown etiology of CKD.

Methods:

We retrospectively analyzed the data of CKD-D patients who had mutation in complement genes and CFHR genes. Data on their demographics, profile of mutations, anti-factor H antibody (AFH-Ab) and outcomes was assessed. Complement gene mutations were assessed by multiplex ligation-dependent probe amplification (MLPA).

Results:

Among a total of 107 patients evaluated for complement gene mutations, 58 (54.2) were CKD-D at the time of the assessment. Among them, 47 (81.0) were detected with complement gene mutations. The median age of the patients was 47 years (range: 22 to 55 years) and 34 (72.3%) were males. CFH, CFB, CFHR1, CFHR3, and CFHR5 mutations were seen in 9 (19.1%), 2 (4.3%), 42 (89.4%), 41 (87.2%) and 4 (8.5%) patients, respectively. Table 1 provides the details of mutations in each of these genes. AFH-Ab was assessed in 43 (91.5%) patients and it was positive in 18 (41.8%) patients. At the time of genetic analysis, 40.4% required 3 or more antihypertensive drugs and the mean platelet count (n=30) was 1,41,178 cells /cmm. Since the diagnosis of complement gene mutations, 22 (46.8%) have undergone kidney transplant of which 7 were deceased-donor and 15 were live-donor transplants. Three (6.4%) developed aHUS after transplantation. Overall, mortality occurred in four (8.5%) patients who did not undergo transplant.

Conclusions:

In CKD-D patient with unknown etiology for CKD, assessment of complement gene mutations may provide clues to the underlying diagnosis. Screening of such patients for presence of complement gene mutations can help risk stratify the disease recurrence after transplantation. Young patients with CKD of unknown etiology who have difficult to control HTN and thrombocytopenia should be screened for complement gene mutations.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.