RESUMO
Kidney transplant recipients (KTRs) experience more fatigue, anxiety, and depressive symptoms and lower concentration and health-related quality of life (HRQoL) compared with the general population. Anemia is a potential cause that is well-recognized and treated. Iron deficiency, however, is often unrecognized, despite its potential detrimental effects related to and unrelated to anemia. We investigated the interplay of anemia, iron deficiency, and patient-reported outcomes in 814 outpatient KTRs (62% male, age 56 ± 13 years) enrolled in the TransplantLines Biobank and Cohort Study (Groningen, The Netherlands). In total, 28% had iron deficiency (ie, transferrin saturation < 20% and ferritin < 100 µg/L), and 29% had anemia (World Health Organization criteria). In linear regression analyses, iron deficiency, but not anemia, was associated with more fatigue, worse concentration, lower wellbeing, more anxiety, more depressive symptoms, and lower HRQoL, independent of age, sex, estimated glomerular filtration rate, anemia, and other potential confounders. In the fully adjusted logistic regression models, iron deficiency was associated with an estimated 53% higher risk of severe fatigue, a 100% higher risk of major depressive symptoms, and a 51% higher chance of being at risk for sick leave/work disability. Clinical trials are needed to investigate the effect of iron deficiency correction on patient-reported outcomes and HRQoL in KTRs.
Assuntos
Transplante de Rim , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Seguimentos , Prognóstico , Falência Renal Crônica/cirurgia , Taxa de Filtração Glomerular , Transplantados/psicologia , Fatores de Risco , Anemia , Deficiências de Ferro , Anemia Ferropriva , Depressão/etiologia , Adulto , Testes de Função Renal , Fadiga/etiologia , Complicações Pós-Operatórias , Países Baixos , Idoso , Ansiedade/etiologiaRESUMO
Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.
Assuntos
Glomerulonefrite Membranosa , Transplante de Rim , Recidiva , Humanos , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/tratamento farmacológico , Transplante de Rim/efeitos adversos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Seguimentos , Prognóstico , Adulto , Taxa de Filtração Glomerular , Falência Renal Crônica/cirurgia , Complicações Pós-Operatórias , Sobrevivência de Enxerto , Testes de Função Renal , Incidência , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Taxa de SobrevidaRESUMO
INTRODUCTION: Urinary fetuin-A has been identified as a biomarker for acute kidney injury and is proposed as a biomarker for early detection of kidney function decline. We investigated whether fetuin-A could serve as a marker of graft failure in kidney transplant recipients (KTRs). METHODS: Data of KTR with a functioning graft ≥1 year that were enrolled in the TransplantLines Food and Nutrition Biobank and cohort study were used. Graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis. Urinary fetuin-A was measured using an enzyme-linked immunosorbent assay kit that detected post-translationally modified fetuin-A in the urine (uPTM-FetA). In the main analyses, 24h uPTM-FetA excretion was used. In the sensitivity analyses, we excluded the outliers in 24h uPTM-FetA excretion, and we used uPTM-FetA concentration and uPTM-FetA concentration indexed for creatinine instead of 24h uPTM-FetA excretion. RESULTS: A total of 627 KTRs (age 53 ± 13 years, 42% females) were included at 5.3 (1.9-12.2) years after transplantation. The estimated glomerular filtration rate (eGFR) was 52 ± 20 mL/min/1.73 m2 and uPTM-FetA excretion was 34 (17-74) µg/24 h. During a median follow-up of 5.3 (4.5-6.0) years after baseline measurements, 73 (12%) KTRs developed graft failure. The association of 24h uPTM-FetA excretion with increased risk of graft failure was not constant over time, with increased risk only observed after 3 years from baseline measurements, independent of potential confounders including kidney function and 24 h urinary protein excretion (hazard ratio per doubling of 24h uPTM-FetA excretion = 1.31; 95% confidence interval = 1.06-1.61). This finding was robust in the sensitivity analyses. CONCLUSIONS: Our findings suggest that uPTM-FetA can be used as a marker for early detection of graft failure in KTR. Further studies are needed to confirm our findings.
Assuntos
Transplante de Rim , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Transplante de Rim/efeitos adversos , Estudos de Coortes , alfa-2-Glicoproteína-HS , Biomarcadores/urina , Diálise Renal , TransplantadosRESUMO
BACKGROUND AND HYPOTHESIS: Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most eGFR equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (CysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR. METHODS: We assessed the performance of CKD-EPI equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cystatin C (eGFRCysC-2012), or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation measured GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex-stratified and height-indexed). RESULTS: Pre-donation eGFRcombined 2012 and eGFRcombined 2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined 2021 was most accurate for estimating both pre-donation (bias 0.01±11.9 mL/min/1.73m2) and post-donation mGFR (bias 1.3±8.5 mL/min/1.73 m2). In donors with high/low muscle mass, CysC-based equations (with or without creatinine) performed better compared to equations based on only creatinine. CONCLUSIONS: In conclusion, combined eGFR equations yielded a better estimate of pre- and post-donation mGFR, compared to estimates based on creatinine or CysC only. The added value of CysC seems particularly pronounced in donors with high or low muscle mass.
RESUMO
Kidney transplantation is the best treatment for kidney failure in older patients. However, little is known regarding changes in health-related quality of life (HRQoL) from before to after transplantation and determinants of HRQoL in older kidney transplant recipients (KTR). We studied both, using data of older (≥65 years) patients waitlisted for kidney transplantation and older KTR 1 year after transplantation from the TransplantLines Biobank and Cohort Study. HRQoL was assessed using the SF-36 questionnaire. We included 145 older waitlisted patients (68% male, age 70 ± 4 years) and 115 older KTR at 1 year after transplantation (73% male, age 70 ± 4 years). Both mental (48.5 ± 8.4 versus 51.2 ± 7.7, p = 0.009) and physical (47.4 ± 8.5 versus 52.1 ± 7.2, p < 0.001) HRQoL were higher among included KTR, compared to the waitlisted patients. In paired analyses among 46 patients with HRQoL-data both before and after transplantation, there was a trend towards increased mental HRQoL (49.1 ± 8.4 to 51.6 ± 7.5, p = 0.054), and significantly increased physical HRQoL (48.1 ± 8.0 to 52.4 ± 6.7, p = 0.001) after transplantation. Among all assessed factors, the number of patient-reported immunosuppressive drug-related side effects was most strongly negatively associated with both mental and physical HRQoL. In conclusion, HRQoL is significantly higher among older KTR after kidney transplantation compared to older waitlisted patients.
Assuntos
Transplante de Rim , Qualidade de Vida , Listas de Espera , Humanos , Masculino , Feminino , Idoso , Inquéritos e Questionários , Estudos de Coortes , Transplantados/psicologia , Falência Renal Crônica/cirurgiaRESUMO
BACKGROUND: Ex vivo normothermic machine perfusion (NMP) is a promising tool for assessing an isolated kidney prior to transplantation. However, there is no consensus on the perfusate's optimal oxygen-carrying capacity to support renal function. To investigate the association of hemoglobin levels with renal function parameters, a retrospective analysis of isolated, normothermically, perfused porcine kidneys was performed. METHODS: Between 2015 and 2021, a total of 228 kidneys underwent 4 h of NMP with perfusates that varied in hemoglobin levels. A generalized linear model was used to determine the association of hemoglobin levels with time-weighted means of renal function markers, such as fractional sodium excretion (FENa) and creatinine clearance (CrCl). Stratified by baseline hemoglobin level (<4.5, 4.5-6, or >6 mmol/L), these markers were modeled over time using a generalized linear mixed-effects model. All models were adjusted for potential confounders. RESULTS: Until a hemoglobin level of around 5 mmol/L was reached, increasing hemoglobin levels were associated with superior FENa and CrCl. Thereafter, this association plateaued. When hemoglobin levels were categorized, hemoglobin <4.5 mmol/L was associated with worse renal function. Hemoglobin levels were neither significantly associated with proteinuria during NMP nor with ATP levels at the end of NMP. Hemoglobin levels >6 mmol/L showed no additional benefits in renal function. CONCLUSION: In conclusion, we found an association between baseline hemoglobin levels and superior renal function parameters, but not injury, during NMP of porcine kidneys. Furthermore, we show that performing a retrospective cohort study of preclinical data is feasible and able to answer additional questions, reducing the potential use of laboratory animals.
Assuntos
Hemoglobinas , Rim , Preservação de Órgãos , Perfusão , Animais , Estudos Retrospectivos , Hemoglobinas/análise , Hemoglobinas/metabolismo , Perfusão/métodos , Rim/fisiopatologia , Suínos , Preservação de Órgãos/métodos , Transplante de Rim , Testes de Função Renal/métodos , Creatinina/sangueRESUMO
The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.53-0.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation.
Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Idoso , Transplante de Rim/efeitos adversos , Estudos de Coortes , Antígenos HLA-DR , Rim , Doadores de Tecidos , Teste de Histocompatibilidade , Sobrevivência de EnxertoRESUMO
RATIONALE & OBJECTIVE: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. EXPOSURE: PPI use, PPI type, PPI dosage, and duration of PPI use. OUTCOME: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. ANALYTICAL APPROACH: Logistic and linear regression. RESULTS: We included 937 kidney transplant recipients (mean age 56±13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P<0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P<0.001), lower physical HRQoL (regression coefficient-8.54, 95% CI, -11.54 to-5.54, P<0.001), and lower mental HRQoL (regression coefficient-4.66, 95% CI, -7.15 to-2.17, P<0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. LIMITATIONS: Residual confounding and inability to assess causal relationships. CONCLUSIONS: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. PLAIN-LANGUAGE SUMMARY: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.
Assuntos
Transplante de Rim , Qualidade de Vida , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Estudos de Coortes , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Transversais , Bancos de Espécimes Biológicos , TransplantadosRESUMO
BACKGROUND: Neurocognitive impairment is common in kidney transplant recipients (KTRs). Adequate brain functioning requires energy and neurotransmitter activity, for which iron is essential. We aimed to investigate iron deficiency (ID) as a potentially modifiable risk factor for cognitive impairment in KTRs. METHODS: We analyzed stable KTRs participating in the TransplantLines Biobank and Cohort study. Participants underwent neuropsychological tests for memory, mental speed, and attention and executive functioning. ID was defined as ferritin <100 µg/mL or 100-299 µg/mL with transferrin saturation (TSAT) ≤20%. Associations between iron status and norm scores of neurocognitive outcomes, corrected for age, sex and education, were assessed using multivariable linear regression analyses adjusted for potential confounders including hemoglobin. RESULTS: We included 166 KTRs [median (IQR) age 57 (45-65) years, 59% male, estimated glomerular filtration rate 51±18 mL/min/1.73 m2]. Time since transplantation was 5.8 (1.0-12.0) years. Prevalence of ID was 65%. ID was independently associated with lower scores for mental speed (std.ß = -0.19, P = .02) and attention and executive functioning (std.ß = -0.19, P = .02), and tended to be associated with worse memory (std.ß = -0.16, P = .07). Lower plasma ferritin levels were associated with worse memory (std.ß = 0.23, P = .007), mental speed (std.ß = 0.34, P < .001), and attention and executive functioning (std.ß = 0.30, P = .001). Lower TSAT was associated with worse memory (std.ß = 0.19, P = .04) and mental speed (std.ß = 0.27, P = .003), and tended to be associated with worse attention and executive functioning (std.ß = 0.16, P = .08). CONCLUSIONS: Iron-deficient KTRs performed worse on neurocognitive tasks measuring memory, mental speed, and attention and executive functioning. These findings set the stage for prospective studies addressing whether ID correction restores cognitive function after kidney transplantation.
Assuntos
Deficiências de Ferro , Transplante de Rim , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bancos de Espécimes Biológicos , Cognição , Estudos de Coortes , Ferritinas , Ferro , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Transplantados , IdosoRESUMO
BACKGROUND: Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs. METHODS: In cohort A (57% male, age 53 ± 13 years), we measured plasma endotrophin in 690 prevalent KTRs ≥1 year after transplantation. The non-overlapping cohort B included 500 incident KTRs with serial endotrophin measurements before and after kidney transplantation to assess trajectories and intra-individual variation of endotrophin. RESULTS: In cohort A, endotrophin was higher in KTRs compared with healthy controls. Concentrations were positively associated with female sex, diabetes, cardiovascular disease, markers of inflammation and kidney injury. Importantly, endotrophin was associated with graft failure {hazard ratio [HR] per doubling 1.87 [95% confidence interval (CI) 1.07-3.28]} and mortality [HR per doubling 2.59 (95% CI 1.73-3.87)] independent of potential confounders. Data from cohort B showed that endotrophin concentrations strongly decrease after transplantation and remain stable during post-transplantation follow-up [intra-individual coefficient of variation 5.0% (95% CI 3.7-7.6)]. CONCLUSIONS: Plasma endotrophin is strongly associated with graft failure and mortality among KTRs. These findings suggest a key role of abnormal extracellular matrix turnover and fibrosis in graft and patient prognosis among KTRs and highlight the need for (interventional) studies targeting the profibrotic state of KTRs. The intra-individual stability after transplantation indicates potential use of endotrophin as a biomarker and outcome measure of fibrosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02811835.
Assuntos
Colágeno Tipo VI , Rim , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Rim/patologia , Fibrose , Fatores de RiscoRESUMO
BACKGROUND: Cognitive impairment is often present shortly after transplantation in kidney transplant recipients (KTR). To date, it is unknown whether these impairments persist in thelong term, to what extent they are associated with disease-related variables and whether they affect societal participation and quality of life (QoL) of KTR. METHOD: This study was part of the TransplantLines Biobank & Cohort Study in the University Medical Center Groningen. A total of 131 KTR, with a mean age of 53.6 years (SD = 13.5) transplanted ≥1 year ago (M = 11.2 years, range 1-41.7 years), were included and compared with 306 healthy controls (HC). KTR and HC were well matched; there were no significant differences regarding age, sex and education. All participants were assessed with neuropsychological tests measuring memory, mental speed, attention and executive functioning, and with questionnaires examining societal participation and QoL. RESULTS: Compared with HC, KTR performed significantly worse on memory, mental speed and measures of executive functioning (all P-values <0.05). Moreover, 16% of KTR met the criteria for mild cognitive impairment (MCI), compared with 2.6% of the HC. MCI in KTR was not significantly correlated with age- and disease-related variables. Poorer cognitive functioning was significantly related to lower levels of societal participation and to lower QoL (all P-values <0.01). CONCLUSIONS: This study shows long-term cognitive impairments in KTR, which are not related to disease-related variables. Neuropsychological assessment is important to timely signal these impairments, given their serious negative impact on societal participation and QoL.
Assuntos
Disfunção Cognitiva , Transplante de Rim , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Qualidade de Vida/psicologia , Transplante de Rim/efeitos adversos , Transplante de Rim/psicologia , Estudos de Coortes , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Cognição , Transplantados/psicologia , Testes NeuropsicológicosRESUMO
BACKGROUND: Fatigue and impaired health-related quality of life (HRQoL) are common among kidney transplant recipients (KTR). We hypothesized that both may partially be attributable to poor sleep. METHODS: Cross-sectional and longitudinal data of KTR enrolled in the TransplantLines Biobank and Cohort Study were used. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire. Individual strength (i.e. a composite of fatigue, concentration, motivation and physical activity), societal participation and HRQoL were assessed using validated questionnaires. RESULTS: We included 872 KTR (39% female, age 56 ± 13 years) and 335 healthy controls. In total, 33% of male KTR and 49% of female KTR reported poor sleep quality, which was higher compared with male and female healthy controls (19% and 28%, respectively, P < .001 for both). In logistic regression analyses, female sex, anxiety, active smoking, low protein intake, physically inactive lifestyle, low plasma magnesium concentration, using calcineurin inhibitors, not using mTOR inhibitors and using benzodiazepine agonists were associated with poor sleep quality. In adjusted linear regression analyses, poor sleep was strongly and independently associated with lower individual strength [standardized ß (st.ß) = 0.59, 95% confidence interval (CI) 0.45 to 0.74, P < .001], poorer societal participation (frequency: st.ß = -0.17, 95% CI -0.32 to -0.01, P = .04; restrictions: st.ß = -0.36, 95% CI -0.51 to -0.21, P < .001; satisfaction: st.ß = -0.44, 95% CI -0.59 to -0.28, P < .001) and lower HRQoL (physical: st.ß = -0.53, 95% CI -0.68 to -0.38, P < .001; mental: st.ß = -0.64, 95% CI -0.78 to -0.50, P < .001). The associations with poorer societal participation and lower HRQoL were strongly mediated by individual strength (P < .001 for all), yet the suggested direct effects of poor sleep quality on HRQoL remained significant (Pphysical = .03, Pmental = .002). Longitudinal data of 292 KTR showed that sleep quality improves after kidney transplantation in males (P < .001), but not in females (P = .9). CONCLUSIONS: Poor sleep quality is common among KTR, and may be a potential target to improve fatigue, societal participation and HRQoL among KTR.
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Transplante de Rim , Qualidade de Vida , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , Estudos de Coortes , Estudos Transversais , Qualidade do Sono , Fadiga/epidemiologia , Fadiga/etiologia , TransplantadosRESUMO
BACKGROUND: One of the challenges in living kidney donor screening is to estimate remaining kidney function after donation. Here we developed a new model to predict post-donation measured glomerular filtration rate (mGFR) from pre-donation serum creatinine, age and sex. METHODS: In the prospective development cohort (TransplantLines, n = 511), several prediction models were constructed and tested for accuracy, precision and predictive capacity for short- and long-term post-donation 125I-iothalamate mGFR. The model with optimal performance was further tested in specific high-risk subgroups (pre-donation eGFR <90 mL/min/1.73 m2, a declining 5-year post-donation mGFR slope or age >65 years) and validated in internal (n = 509) and external (Mayo Clinic, n = 1087) cohorts. RESULTS: In the development cohort, pre-donation estimated GFR (eGFR) was 86 ± 14 mL/min/1.73 m2 and post-donation mGFR was 64 ± 11 mL/min/1.73 m2. Donors with a pre-donation eGFR ≥90 mL/min/1.73 m2 (present in 43%) had a mean post-donation mGFR of 69 ± 10 mL/min/1.73 m2 and 5% of these donors reached an mGFR <55 mL/min/1.73 m2. A model using pre-donation serum creatinine, age and sex performed optimally, predicting mGFR with good accuracy (mean bias 2.56 mL/min/1.73 m2, R2 = 0.29, root mean square error = 11.61) and precision [bias interquartile range (IQR) 14 mL/min/1.73 m2] in the external validation cohort. This model also performed well in donors with pre-donation eGFR <90 mL/min/1.73 m2 [bias 0.35 mL/min/1.73 m2 (IQR 10)], in donors with a negative post-donation mGFR slope [bias 4.75 mL/min/1.73 m2 (IQR 13)] and in donors >65 years of age [bias 0.003 mL/min/1.73 m2 (IQR 9)]. CONCLUSIONS: We developed a novel post-donation mGFR prediction model based on pre-donation serum creatinine, age and sex.
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Radioisótopos do Iodo , Transplante de Rim , Humanos , Idoso , Taxa de Filtração Glomerular , Estudos Prospectivos , Creatinina , Rim , Doadores VivosRESUMO
Solid organ transplant recipients (SOTR) frequently report tremor. Data concerning tremor-related impairment and its potential impact on health-related quality of life (HRQoL) are lacking. This cross-sectional study assesses impact of tremor on activities of daily living and HRQoL using validated questionnaires among SOTR enrolled in the TransplantLines Biobank and Cohort Study. We included 689 SOTR (38.5% female, mean [±SD] age 58 [±14] years) at median [interquartile range] 3 [1-9] years after transplantation, of which 287 (41.7%) reported mild or severe tremor. In multinomial logistic regression analyses, whole blood tacrolimus trough concentration was an independent determinant of mild tremor (OR per µg/L increase: 1.11, 95% CI: 1.02 to 1.21, p = 0.019). Furthermore, in linear regression analyses, severe tremor was strongly and independently associated with lower physical and mental HRQoL (ß = -16.10, 95% CI: -22.23 to -9.98, p < 0.001 and ß = -12.68, 95% CI: -18.23 to -7.14, p < 0.001 resp.). SOTR frequently report tremor-related impairment of activities of daily living. Tacrolimus trough concentrations appeared as a main determinant of tremor among SOTR. The strong and independent association of tremor-related impairment with lower HRQoL warrants further studies into the effects of tacrolimus on tremor. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT03272841.
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Transplante de Órgãos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividades Cotidianas , Estudos de Coortes , Estudos Transversais , Qualidade de Vida , Tacrolimo , Transplantados , TremorRESUMO
Early non-invasive detection and prediction of graft function after kidney transplantation is essential since interventions might prevent further deterioration. The aim of this study was to analyze the dynamics and predictive value of four urinary biomarkers: kidney injury molecule-1 (KIM-1), heart-type fatty acid binding protein (H-FABP), N-acetyl-ß-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in a living donor kidney transplantation (LDKT) cohort. Biomarkers were measured up to 9 days after the transplantation of 57 recipients participating in the VAPOR-1 trial. Dynamics of KIM-1, NAG, NGAL, and H-FABP significantly changed over the course of 9 days after transplantation. KIM-1 at day 1 and NAG at day 2 after transplantation were significant predictors for the estimated glomerular filtration rate (eGFR) at various timepoints after transplantation with a positive estimate (p < 0.05), whereas NGAL and NAG at day 1 after transplantation were negative significant predictors (p < 0.05). Multivariable analysis models for eGFR outcome improved after the addition of these biomarker levels. Several donor, recipient and transplantation factors significantly affected the baseline of urinary biomarkers. In conclusion, urinary biomarkers are of added value for the prediction of graft outcome, but influencing factors such as the timing of measurement and transplantation factors need to be considered.
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Injúria Renal Aguda , Transplante de Rim , Humanos , Lipocalina-2 , Transplante de Rim/efeitos adversos , Proteína 3 Ligante de Ácido Graxo , Doadores Vivos , Rim , Injúria Renal Aguda/diagnóstico , BiomarcadoresRESUMO
Single-kidney glomerular filtration rate (GFR) increases after living kidney donation due to compensatory hyperfiltration and structural changes. The implications of inter-individual variability in this increase in single-kidney GFR are unknown. Here, we aimed to identify determinants of the increase in single-kidney GFR at three-month postdonation, and to investigate its relationship with long-term kidney function. In a cohort study in 1024 donors, we found considerable inter-individual variability of the early increase in remaining single-kidney estimated GFR (eGFR) (median [25th-75th percentile]) 12 [8-18] mL/min/1.73m2. Predonation eGFR, age, and cortical kidney volume measured by CT were the main determinants of the early postdonation increase in single-kidney eGFR. Individuals with a stronger early increase in single-kidney eGFR had a significantly higher five-year postdonation eGFR, independent of predonation eGFR and age. Addition of the postdonation increase in single-kidney eGFR to a model including predonation eGFR and age significantly improved prediction of a five-year postdonation eGFR under 50 mL/min/1.73m2. Results at ten-year follow-up were comparable, while accounting for left-right differences in kidney volume did not materially change the results. Internal validation using 125I-iothalamate-based measured GFR in 529 donors and external validation using eGFR data in 647 donors yielded highly similar results. Thus, individuals with a more pronounced increase in single-kidney GFR had better long-term kidney function, independent of predonation GFR and age. Hence, the early postdonation increase in single-kidney GFR, considered indicative for kidney reserve capacity, may have additional value to eGFR and age to personalize follow-up intensity after living kidney donation.
Assuntos
Transplante de Rim , Doadores Vivos , Estudos de Coortes , Taxa de Filtração Glomerular , Humanos , Rim , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Nefrectomia/efeitos adversosRESUMO
Of all kidney transplants, half are still lost in the first decade after transplantation. Here, using genetics, we probed whether interleukin 6 (IL-6) could be a target in kidney transplantation to improve graft survival. Additionally, we investigated if a genetic risk score (GRS) based on IL6 and IL10 variants could improve prognostication of graft loss. In a prospective cohort study, DNA of 1271 donor-recipient kidney transplant pairs was analyzed for the presence of IL6, IL6R, IL10, IL10RA, and IL10RB variants. These polymorphisms and their GRS were then associated with 15-year death-censored allograft survival. The C|C-genotype of the IL6 polymorphism in donor kidneys and the combined C|C-genotype in donor-recipient pairs were both associated with a reduced risk of graft loss (p = .043 and p = .042, respectively). Additionally, the GRS based on IL6, IL6R, IL10, IL10RA, and IL10RB variants was independently associated with the risk of graft loss (HR 1.53, 95%-CI [1.32-1.84]; p < .001). Notably, the GRS improved risk stratification and prediction of graft loss beyond the level of contemporary clinical markers. Our findings reveal the merits of a polygenic IL-6-based risk score strengthened with IL-10- polymorphisms for the prognostication and risk stratification of late graft failure in kidney transplantation.
Assuntos
Interleucina-10 , Interleucina-6 , Humanos , Interleucina-10/genética , Interleucina-6/genética , Estudos Prospectivos , Rim , Fatores de Risco , AloenxertosRESUMO
BACKGROUND: Work can have a major positive impact on health and wellbeing. Employment of kidney transplant recipients (KTR) of working age is much lower than in the general population. The first aim of this study was to examine the impact of a preemptive kidney transplantation (PKT) on employment, in addition to other possible influencing factors. The second aim was to explore differences in work ability, absenteeism and work performance among employed KTR with different types of transplantations. METHODS: A cross-sectional survey study was conducted between 2018 and 2019 in nine Dutch hospitals. PKT as potential predictor of employment was examined. Furthermore, work ability, absenteeism and loss of work performance were compared between employed preemptive recipients with a living donor (L-PKT) and non-preemptive recipients with a living donor (L-nPKT) and with a deceased donor (D-nPKT). RESULTS: Two hundred and twenty four KTR participated; 71% reported having paid work. Paid work was more common among PKT recipients (82% vs. 65% in L-nPKT and 55% in D-nPKT) and recipients who were younger (OR .950, 95%CI .913-.989), had no comorbidities (1 comorbidity: OR .397, 95%CI .167-.942; 2 comorbidities: OR .347, 95%CI .142-.844), had less fatigue (OR .974, 95%CI .962-.987) and had mentally demanding work tasks (only in comparison with physically demanding tasks, OR .342, 95%CI .145-.806). If recipients were employed, D-nPKT recipients worked fewer hours (mean 24.6±11.3 vs. PKT 31.1±9.6, L-nPKT 30.1±9.5) and D-nPKT and L-nPKT recipients received more often supplemental disability benefits (32 and 33.3%, respectively) compared to PKT recipients (9.9%). No differences were found for self-reported ability to work, sick leave (absenteeism) and loss of work performance with the exception of limitations in functioning at work. CONCLUSIONS: Preemptive kidney transplantation recipients with a kidney from a living donor are employed more often, work more hours per week (only in comparison with D-nPKT) and have a partial disability benefit less often than nPKT recipients. More knowledge regarding treatments supporting sustainable participation in the labor force is needed as work has a positive impact on recipients' health and wellbeing and is also beneficial for society as a whole.
Assuntos
Falência Renal Crônica , Transplante de Rim , Estudos Transversais , Emprego , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos , Países BaixosRESUMO
Pregnancy after solid organ transplantation (SOT) has potential risks for the offspring. Most existing research focused on short-term pregnancy outcomes. The aim of this systematic review was to evaluate available data concerning longer term outcomes (>1 year) of these children. A systematic literature search, following PRISMA guidelines, of PubMed and Embase was performed from the earliest date of inception through to 6th April 2022. Publications on all types of (combined) SOT were eligible for inclusion. In total, 53 articles were included. The majority assessed offspring after kidney (78% of offspring) or liver transplantation (17% of offspring). 33 studies included offspring aged >4 years and five offspring aged >18 years. One study was included on fathers with SOT. The majority of the 1,664 included children after maternal SOT had normal intellectual, psychomotor, and behavioral development. Although prematurity and low birth weight were commonly present, regular growth after 1 year of age was described. No studies reported opportunistic or chronic infections or abnormal response to vaccinations. In general, pregnancy after SOT appears to have reassuring longer term outcomes for the offspring. However, existing information is predominantly limited to studies with young children. Longer prospective studies with follow-up into adulthood of these children are warranted.
Assuntos
Transplante de Órgãos , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Transplante de Órgãos/efeitos adversos , Pais , Gravidez , Resultado da Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Calcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients. METHODS: Stable adult kidney transplant recipients 6-60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months. RESULTS: Overall, 446 renal transplant recipients were randomized to belatacept conversion ( n =223) or CNI continuation ( n =223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, -2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m 2 with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder. CONCLUSIONS: Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA.Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based, NCT01820572.