Increased mortality after kidney transplantation in mildly frail recipients.

Background: Physical Frailty Phenotype (PFP) is the most used frailty instrument among kidney transplant recipients, classifying patients as pre-frail if they have 1-2 criteria and as frail if they have ≥3. However, different definitions of robustness have been used among renal patients, including only those who have 0 criteria, or those with 0-1 criteria. Our aim was to determine the impact of one PFP criterion on transplant outcomes. Methods: We undertook a retrospective study of 296 kidney transplant recipients who had been evaluated for frailty by PFP at the time of evaluating for transplantation. Results: Only 30.4% of patients had 0 criteria, and an additional 42.9% showed one PFP criterion. As PFP score increased, a higher percentage of women and cerebrovascular disease were found. Recipients with 0-1 criteria had lower 1-year mortality after transplant than those with ≥2 (1.8% vs 10.1%), but this difference was already present when we only considered those who scored 0 (mortality 1.1%) and 1 (mortality 2.4%) separately. The multivariable analysis confirmed that one PFP criterion was associated to a higher risk of patient death after kidney transplantation [hazard ratio 3.52 (95% confidence interval 1.03-15.9)]. Conclusions: Listed kidney transplant candidates frequently show only one PFP frailty criterion. This has an independent impact on patient survival after transplantation.

Outcomes of Frail Patients While Waiting for Kidney Transplantation: Differences between Physical Frailty Phenotype and FRAIL Scale.

Frailty is associated with poorer outcomes among patients waiting for kidney transplantation (KT). Several different tools to measure frailty have been used; however, their predictive value is unknown. This is a prospective longitudinal study of 449 KT candidates evaluated for frailty by the Physical Frailty Phenotype (PFP) and the FRAIL scale. During the study period, 296 patients received a KT, while 153 remained listed. Patients who did not get receive a transplant were more frequently frail according to PFP (16.3 vs. 7.4%, p = 0.013). Robust patients had fewer hospital admissions during the 1st year after listing (20.8% if PFP = 0 vs. 43.4% if ≥1, and 27.1% if FRAIL = 0 vs. 48.9% if ≥1) and fewer cardiovascular events (than FRAIL ≥ 1) or major infectious events (than PFP ≥ 1). According to PFP, scoring 1 point had an impact on patient survival and chance of transplantation in the univariate analysis. The multivariable analysis corroborated the result, as candidates with PFP ≥ 3 had less likelihood of transplantation (HR 0.45 [0.26-0.77]). The FRAIL scale did not associate with any of these outcomes. In KT candidates, pre-frailty and frailty according to both the PFP and the FRAIL scale were associated with poorer results while listed. The PFP detected that frail patients were less likely to receive a KT, while the FRAIL scale did not.

Frailty in kidney transplant candidates: a comparison between physical frailty phenotype and FRAIL scales.

BACKGROUND: Frailty is common among advanced chronic kidney disease (CKD) patients who are kidney transplant (KT) candidates, and predisposes to poor outcomes after transplantation. However, frailty is not routinely measured during pretransplant work-up and it is unknown which metric should be used in this specific population. Our aim was to establish frailty prevalence in KT candidates according to different frailty scales. METHODS: Prospective longitudinal study of 451 KT candidates evaluated for frailty by both Physical Frailty Phenotype (PFP) and FRAIL scale at the time of inclusion on the KT waiting list. Clinical and functional characteristics including sociodemographics, comorbidities, disability and nutritional status were recorded. Agreement between PFP and FRAIL scales as well as dissonant patients were analyzed. RESULTS: Mean age was 60.9 years and 31.7% were female. Comorbidity burden among patients was high, with 36.9% and 16.2% presenting with diabetes and ischemic coronary disease, respectively. Disabilities were also frequent. More than 70% of patients presented with ≥ 1 PFP criteria while this percentage for ≥ 1 FRAIL criteria was 45.4%. Agreement between PFP and FRAIL was not good (kappa index 0.317). There were 132 patients who were pre-frail or frail according to PFP but non-frail according to the FRAIL scale and they presented with fewer comorbidities and less disability. CONCLUSIONS: Frailty is frequent in advanced CKD patients, although its prevalence may vary according to different scales. Agreement between PFP and FRAIL scale is not good, and FRAIL scale might misclassify as robust patients those frail/prefrail patients who are in better health conditions.

Frailty among chronic kidney disease patients on the kidney transplant waiting list: the sex-frailty paradox.

BACKGROUND: Frailty is defined as decreased physiologic reserve and resistance to stressors that predisposes patients towards poor health results. Its prevalence in chronic kidney disease (CKD) patients who are kidney transplant (KT) candidates is high. Frailty is associated with a higher rate of complications and mortality after transplant. It is unknown whether frailty phenotype differs depending on sex in this population. METHODS: This was a prospective longitudinal study of 455 KT candidates evaluated for frailty by physical frailty phenotype at the time of inclusion on the KT waiting list. Pre-frailty was defined as the presence of two criteria and frailty as three or more criteria. Univariate and multivariate analyses searched for associations of frailty status, frailty components and gender differences. RESULTS: Thirty percent of the total cohort resulted to be pre-frail (20%) or frail (10.3%), but disparities were observed between sexes, with 22.5% of men and 47.2% of women falling into one of these categories. Among frailty criteria, women presented with a higher percentage of exhaustion (39.6% versus 17%) and slowness (22.2% versus 9.6%) compared with men. Comorbidity burden was higher among frail men, whereas social factors were poorer between frail women. Disability was common among those patients who were frail, both men and women. CONCLUSIONS: Frailty is twice as frequent in advanced CKD women as men. Frailty criteria distribution and phenotype seem to differ among sexes, which might have implications in terms of specific and individualized interventions to improve their status before transplantation.

Activation of final complement components after kidney transplantation as a marker of delayed graft function severity.

BACKGROUND: Ischaemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients. METHODS: We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies (n = 12) and a control group of 1-year protocol biopsies without tissue damage (n = 4) were stained for C5b-9, C3b and FH. RESULTS: SC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142 mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0-7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients. CONCLUSIONS: Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.

Relevance of KDPI value and acute rejection on kidney transplant outcomes in recipients with delayed graft function - a retrospective study.

Delayed graft function (DGF) is associated with poorer graft survival and higher rate of acute rejection (AR). It is unknown whether this negative influence relies on the increased risk of AR or the DGF itself. The different Kidney Donor Profile Index (KDPI) values may also play a role in this interaction. Retrospective study aimed to evaluate the impact of DGF on graft function and graft survival in a subset of KT recipients (2004-2017). We also analyzed the relationship between KDPI and DGF. The study includes 601 KT, 226 of them (37%) developed DGF. Graft survival was lower in patients with DGF compared with non-DGF patients. Multivariable analysis revealed DGF as risk factor for graft loss, independently of the presence or not of acute rejection. Between DGF patients, we observed poorer graft survival in patients with higher KDPI value (>85%). We observed a trend of a greater impact of KDPI in patients with DGF, although this interaction was not statistically significant. Additionally, we observed poorer 12-month graft function in DGF patients. DGF is related to poorer graft survival independently of the developed acute rejection. This negative impact might be influenced by high KDPI values.