Lupus nephritis and kidney transplantation: A narrative review of patient and graft outcomes

Table 3 Determinants and key indicators for transplant matching in lupus nephritis and its clinical implications

Indicator	Type	Significance	Implications in LN
HLA matching	Genetic/immunological	Cornerstone of transplant success; closer matching reduces rejection and improves graft survival	Mismatches, especially at HLA-DR and HLA-C loci, increase rejection risk; careful prioritization of typing is critical
PRA and DSA	Immunological	Elevated PRA and DSAs indicate heightened sensitization from transfusions, pregnancies, or disease activity	High titers are strongly associated with graft rejection, including hyperacute rejection; pre-transplant interventions (plasma exchange, IVIG, rituximab, proteasome inhibitors) can reduce risk
Disease quiescence and serological activity	Clinical/serological	Active disease increases recurrence and systemic complications	Anti-dsDNA, complement (C3, C4), and anti-C1q must be monitored to confirm remission before transplantation
CDC-XM	Laboratory test	Detects HLA and non-HLA antibodies but is prone to false positives in autoimmune patients	May misinterpret sensitization due to non-specific binding, prozone effect, incomplete typing, or non-HLA antibodies
FCXM	Laboratory test	More sensitive than CDC; detects pre-formed antibodies against donor lymphocytes	Preferred method; pronase digestion enhances the accuracy of B-cell cross-matching
High-Resolution HLA typing (sequencing-based)	Genetic/Laboratory	Provides precise identification of donor-specific HLA antibodies	Improves matching accuracy; limited feasibility in deceased donor transplantation due to time constraints
Non-HLA Antibodies (MICA, AT1R, poikilodulin, myocardin, microtubulin, collagen)	Immunological	Account for approximately 38% of graft losses vs 18% from HLA mismatches	Contribute to fibrosis, immune modulation, and graft failure; must be considered in risk stratification
Crossmatch testing (general)	Laboratory test	Negative crossmatch essential to prevent hyperacute rejection	Provides safeguard against unforeseen immunological incompatibilities in autoimmune background
Comorbid conditions and systemic involvement	Clinical	LN often coexists with cardiovascular disease, neuropsychiatric lupus, or vasculitis	Extra-renal involvement must be controlled before transplantation to avoid poor outcomes
Donor characteristics	Clinical	Donor age, health, and source (living vs deceased) influence graft survival	Living donor transplantation is preferred; it allows better timing, reduces dialysis exposure, and improves prognosis
Immunological risk stratification	Clinical/immunological	Helps tailor immunosuppressive regimens post-transplant	LN recipients require vigilant balancing to prevent rejection and recurrence while minimizing infection/malignancy risks

LN: Lupus nephritis; HLA: Human Leukocyte Antigen; PRA: Panel reactive antibody; DSAs: Donor-specific antibodies; IVIG: Intravenous immunoglobulin; Anti-dsDNA: Anti-double-stranded deoxyribonucleic acid; anti-C1q: Anti-complement component 1q; C3: Complement component 3; C4: Complement component 4; CDC-XM: Complement-dependent cytotoxicity crossmatch; FCXM: Flow cytometry crossmatch; CDC: Complement-dependent cytotoxicity; MICA: Major histocompatibility complex class I chain-related molecule A; AT1R: Angiotensin II type 1 receptor.