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World J Transplant. Sep 18, 2026; 16(3): 120969
Published online Sep 18, 2026. doi: 10.5500/wjt.120969
Kidney transplant outcomes in patients with complement dysregulation
Manish Balwani, Amit Pasari, Pranjal Kashiv, Vishal Ramteke, Priyanka Tolani, Nishtha Manuja, Mohit Kurundwadkar, Shubham Dubey, Twinkle Pawar, Sunny Malde, Sushrut Gupta, Kapil Sejpal, Vijay Jeyachandran, Vivek B Kute
Manish Balwani, Amit Pasari, Department of Nephrology, Saraswati Kidney Care Center, Nagpur 440015, Mahārāshtra, India
Manish Balwani, Amit Pasari, Nishtha Manuja, Mohit Kurundwadkar, Shubham Dubey, Twinkle Pawar, Sunny Malde, Sushrut Gupta, Kapil Sejpal, Vijay Jeyachandran, Department of Nephrology, Jawaharlal Nehru Medical College, Wardha 442001, Mahārāshtra, India
Pranjal Kashiv, Department of Nephrology, All India Institute of Medical Sciences, Nagpur 441108, Mahārāshtra, India
Vishal Ramteke, Department of Nephrology, Max Super Speciality Hospital, Nagpur 440030, Mahārāshtra, India
Priyanka Tolani, Department of Internal Medicine, Jawaharlal Nehru Medical College, Wardha 442001, Mahārāshtra, India
Vivek B Kute, Department of Nephrology, Institute of Kidney Diseases and Research Center, Dr HL Trivedi Institute of Transplantation Sciences, Ahmedabad 380016, Gujarat, India
Author contributions: Balwani M and Pasari A contributed to the conception, supervised patient management, provided senior oversight of data interpretation, and critically revised the manuscript for important intellectual content; Balwani M, Pasari A, and Kashiv P contributed to the design of the study; Kashiv P was responsible for data analysis, interpretation of results, drafting of the manuscript, and coordination of all stages of manuscript preparation and revision; Ramteke V and Tolani P contributed to patient evaluation, clinical data collection; Manuja N, Kurundwadkar M, Pawar T, Dubey S, Malde S, Gupta S, Sejpal K, Jeyachandran V, and Kute VB contributed to data acquisition and verification; Ramteke V, Tolani P, Kurundwadkar M, Pawar T, Dubey S, Malde S, Gupta S, Sejpal K, Jeyachandran V, and Kute VB contributed to the critical review of the manuscript; Kurundwadkar M, Pawar T, Dubey S, Malde S, Gupta S, Sejpal K, Jeyachandran V, and Kute VB contributed to patient management; All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work.
AI contribution statement: AI tools including ChatGPT and Grammarly were used in a limited capacity for language refinement, grammatical correction, and improvement of readability of the manuscript text. All scientific concepts, clinical observations, data interpretations, and conclusions are the original work of the authors. The authors take full responsibility for the entire content of the manuscript.
Institutional review board statement: The study protocol was reviewed by the SKCC Institutional Ethics Committee, SS Multispecialty Hospital, Nagpur, Maharashtra, India (approval No. ECR/1725/Inst/MH/2022), and was granted exemption from full review due to its retrospective design involving anonymized clinical data.
Informed consent statement: The requirement for individual informed consent was waived by the Institutional Ethics Committee owing to the retrospective nature of the study and use of anonymized data.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: No additional data are available.
Corresponding author: Manish Balwani, MD, DM, Professor, Department of Nephrology, Saraswati Kidney Care Center, Near Jai Prakash Metro Station, Nagpur 440015, Mahārāshtra, India.
balwani.manish@yahoo.com
Received: March 12, 2026
Revised: May 3, 2026
Accepted: June 12, 2026
Published online: September 18, 2026
Processing time: 171 Days and 17.2 Hours
BACKGROUND
Complement dysregulation is a key mechanism underlying atypical hemolytic uremic syndrome and complement-mediated thrombotic microangiopathy in kidney transplantation, and is associated with post-transplant recurrence, graft dysfunction, and graft loss. Although Western cohort data are well established, integrated transplant outcome data combining genetic analysis, anti-factor H (AFH) antibody profiling, and individualized therapy from Indian and other South Asian populations remain limited, despite a distinct biologic profile in this region.
AIM
To evaluate clinical characteristics, complement biologic profile, post-transplant recurrence, and graft outcomes in kidney transplant recipients with complement dysregulation managed at a tertiary transplant center in Central India, with particular emphasis on genotype-phenotype correlation and outcomes in a resource-constrained setting.
METHODS
This single-center retrospective cohort study included kidney transplant recipients with evidence of complement dysregulation identified from January 2018 to March 2025 at a tertiary transplant center in Central India. Complement dysregulation was defined as the presence of a pathogenic or likely pathogenic complement gene variant, AFH antibody positivity, or both. Genetic testing was performed using multiplex ligation-dependent probe amplification and/or clinical exome sequencing covering the alternative complement pathway gene panel, and AFH antibodies were measured using enzyme-linked immunosorbent assay. All patients underwent comprehensive evaluation including hematological, biochemical, and complement (C3, C4) profiling, with kidney biopsy when clinically feasible. The primary outcome was post-transplant recurrence of thrombotic microangiopathy; secondary outcomes included graft loss, patient survival, renal function, and treatment response. Median post-transplant follow-up was approximately 12 months.
RESULTS
Of the 335 patients evaluated for complement abnormalities, 136 had complement dysregulation, of whom 38 underwent kidney transplantation and constituted the study cohort. Mean age was 36.3 ± 9.3 years, 84.2% were male, and 97.4% had hypertension; 73.7% were on maintenance hemodialysis at diagnosis. Complement genetic abnormalities were identified in 34/38 recipients (89.5%), with CFHR1-CFHR3 structural variants predominating (78.9%) and complement factor H abnormalities in 18.4%; no pathogenic variants were detected in CFI, C3, CD46, THBD, or DGKE. AFH antibodies were detected in 15 patients (39.5%), with 11 having concomitant genetic abnormalities. Pre-transplant immunomodulation with plasma exchange and rituximab reduced mean AFH antibody levels from 179.9 AU/mL to 59.7 AU/mL (approximately 67% reduction). Post-transplant recurrence occurred in 7/38 recipients (18.4%), all biopsy-confirmed, donor-specific antibody and C4d-negative, and clustered within 1-3 weeks of transplantation; recurrence occurred exclusively in patients with complement genetic abnormalities, and not in those with isolated AFH antibody positivity. All 7 recipients with recurrence maintained functioning grafts after disease-directed therapy. Overall patient survival was 94.7%; two deaths (5.3%) were attributable to severe infections, and one graft loss followed invasive mucormycosis unrelated to recurrent disease.
CONCLUSION
In this Indian transplant cohort with complement dysregulation, CFHR1-CFHR3 structural variants and AFH antibody positivity defined the predominant biologic substrate, post-transplant recurrence clustered within the early weeks after transplantation, and disease-directed therapy with plasma exchange, rituximab, and selective eculizumab achieved durable graft preservation despite limited access to long-term complement inhibition. Comprehensive pre-transplant complement evaluation and biologic risk stratification are essential for safe transplantation in complement-mediated kidney disease, particularly in resource-limited settings.
Core Tip: Complement dysregulation is an important but underrecognized determinant of post-transplant thrombotic microangiopathy. In this retrospective cohort of 38 kidney transplant recipients with complement dysregulation, CFHR1-CFHR3 structural variants predominated, anti-factor H antibodies were frequent, and recurrence occurred in 18.4%. All recurrences developed within the first 1-3 weeks post-transplant and were confined to recipients with complement genetic abnormalities. All episodes were successfully controlled with individualized therapy. Overall patient survival was 94.7%. These findings support systematic complement evaluation, biologic risk stratification, and early targeted intervention to optimize transplant selection, reduce recurrence risk, and improve post-transplant graft outcomes in complement-mediated kidney disease.
