**Background:** Frailty is a state of increased vulnerability to stressors due to decline in multiple physiological systems. In kidney transplant (KT) candidates and recipients, frailty is common and associated with adverse outcomes. This review summarizes the pathogenesis and intervention strategies for frailty in this population.
**Methods:** The authors reviewed published literature on frailty in KT candidates and recipients, covering definition, epidemiology, assessment tools, relationship with transplantation outcomes, pathogenesis, and interventions.
**Key Results:** The prevalence of frailty before KT is approximately 20%, with pre-frailty in approximately 30%. After KT, frailty worsens in the short term (33.3% at 1 month postoperatively) but improves by 3 months (17.2%). Long-term frailty may not correlate with time after transplantation; at 6 months, frailty and pre-frailty prevalence were 11.2% and 26.8%, respectively. A national US survey (2000–2018) reported frailty prevalence of 16.4% in KT candidates and 14.3% in recipients.
Frailty is associated with multiple adverse outcomes: frail recipients had 1.6 times higher risk of hospital stay >2 weeks, 60% increased risk of readmission within 1 month, 94% increased risk of delayed graft function (DGF), and 6.20-fold increased DGF incidence when accompanied by depression. Frail KT recipients were 1.29 times more likely to experience mycophenolate reduction (MDR) due to immunosuppressive intolerance, and MDR was associated with a 5.24-fold increased risk of graft loss. Five-year survival rates for non-frail, pre-frail, and frail candidates were 91.5%, 86.0%, and 77.5%, respectively, with frailty increasing the risk of death by 117%.
The pathogenesis involves general mechanisms (chronic low-grade inflammation with elevated IL-6, IL-1, CRP, TNF-α; immunosenescence; sarcopenia via muscle mass loss and dysfunction) and disease-specific pathways. In KT candidates (ESRD patients), unique factors include uremic toxin accumulation, renal endocrine dysfunction, persistent inflammation, intestinal flora imbalance, and insulin resistance. In KT recipients, postoperative frailty depends on preoperative status, with surgical injury, postoperative complications, immunosuppressive therapy (glucocorticoids causing metabolic disorders, calcineurin inhibitors accelerating telomere shortening), and potential graft loss contributing to frailty.
Interventions include traditional approaches (physical exercise, nutrition improvement, drug therapy, compound prehabilitation, psychological interventions) and emerging therapies (mesenchymal stem cells to inhibit chronic inflammation, fecal microbiota transplantation, dietary interventions to increase microbial diversity).
**Clinical Implications:** Frailty is a modifiable risk factor in KT candidates and recipients. Early identification using tools like the physical frailty phenotype (PFP) or short physical performance battery (SPPB) allows for preoperative intervention. Successful KT can improve frailty, but perioperative factors may worsen it temporarily. Combined traditional and pathogenesis-targeted interventions may offer the best outcomes. More research is needed on animal models, cell signaling pathways, and multicenter prospective studies to validate intervention strategies.