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INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Assuntos

Aloenxertos , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Hiperparatireoidismo , Transplante de Rim , Complicações Pós-Operatórias , Humanos , Transplante de Rim/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Seguimentos , Hiperparatireoidismo/etiologia , Hiperparatireoidismo/patologia , Prognóstico , Fatores de Risco , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Aloenxertos/patologia , Complicações Pós-Operatórias/etiologia , Testes de Função Renal , Falência Renal Crônica/cirurgia , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue

RESUMO

BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

RESUMO

PURPOSE: We evaluated the renal arterial resistive index (RRI), urine monocyte chemotactic protein 1 (uMCP-1), and urine neutrophil gelatinase-associated lipocalin (uNGAL) to predict acute kidney injury (AKI) in critically ill cancer patients. METHODS: In this prospective study, we included patients without AKI. We compared the area under the curve (AUC) of RRI, uMCP-1, and uNGAL to predict any stage of AKI and stage-3 AKI with the DeLong method, and we established cutoff points with the Youden index. RESULTS: We included 64 patients, and 43 (67.2%) developed AKI. The AUC to predict AKI were: 0.714 (95% CI 0.587-0.820) for the RRI, 0.656 (95% CI 0.526-0.770) for uMCP-1, and 0.677 (95% CI 0.549-0.789) for uNGAL. The AUC to predict stage-3 AKI were: 0.740 (95% CI 0.615-0.842) for the RRI, 0.757 (95% CI 0.633-0.855) for uMCP-1, and 0.817 (95% CI 0.701-0.903) for uNGAL, without statistical differences among them. For stage 3 AKI prediction, the sensitivity and specificity were: 56.3% and 87.5% for a RRI > 0.705; 70% and 79.2% for an uMCP-1 > 2169 ng/mL; and 87.5% and 70.8% for a uNGAL > 200 ng/mL. The RRI was significantly correlated to age (r = 0.280), estimated glomerular filtration rate (r = - 0.259), mean arterial pressure (r = - 0.357), and serum lactate (r = 0.276). CONCLUSION: The RRI, uMCP-1, and uNGAL have a similar ability to predict AKI. The RRI is more specific, while urine biomarkers are more sensitive to predict stage 3 AKI. The RRI correlates with hemodynamic variables. The novel uMCP-1 could be a useful biomarker that needs to be extensively studied.

Assuntos

Injúria Renal Aguda , Neoplasias , Humanos , Injúria Renal Aguda/diagnóstico , Biomarcadores , Quimiocina CCL2 , Estado Terminal , Lipocalina-2 , Estudos Prospectivos

RESUMO

PURPOSE: We evaluated disease knowledge/self-management skills among low-income Mexican young adults maintained on dialysis and to test the effectiveness of the A.L.L. Y.O.U. N.E.E.D. I.S. L.O.V.E (AYNIL) Manual - Spanish Version on patient-reported outcomes. This is a low literacy teaching tool designed with patients and educators' input. DESIGN AND METHODS: A quasi-experimental study was conducted in 17 chronic dialysis patients at Mexico City's Hospital General de México, Dr. Eduardo Liceaga. Ages 18-30-year-old completed disease knowledge/self-management and quality of life measures before the intervention and 6 weeks later. RESULTS: Significant increases were observed on disease knowledge/self-management scores in the STARx questionnaire from 47 (IQ: 40,51) to 50 (IQ: 48,54) p = 0.04. The UNC-TRxANSITION Index increased significantly from 4.8 (IQ: 3.9,5.7) to 7.7 (IQ: 7.5,8.2) p ≤0.001. Significant increases in scores were detected in the "Burden of kidney disease" (p = 0.008), "Effects of kidney disease" " (p = 0.03) and " Dialysis staff encouragement" (p = 0.027) based on the KDQoL survey. CONCLUSIONS: In this vulnerable population, the Spanish version of the A.L.L. Y.O.U. N.E.E.D. I.S. L.O.V.E. - AYNIL Manual improved CKD/ESRD disease knowledge/self-management skills and HRQoL. This study highlighted the need for low-literacy educational tools to improve patient-reported outcomes. PRACTICE IMPLICATIONS: Young adults with CKD/ESRD can benefit from patient-centered educational interventions to enhance their autonomy and the development of self-management behaviors that improve patient-reported outcomes and potential complications of the disease. Special attention is needed in low-income patients with low rates of adherence to treatments and poor self-management skills.

Assuntos

Autogestão , Adolescente , Adulto , Estudos de Viabilidade , Humanos , México , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Diálise Renal , Adulto Jovem

RESUMO

BACKGROUND: Female renal transplant recipients (RTR) are at high risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer. The aim of this study was to estimate the incidence of cervical intraepithelial lesions (IL) and HPV infection, and their associated factors, in Mexican RTR. METHODS: This is a prospective cohort study conducted between January 2011 and December 2017. Demographic, clinical, and gynecological data were collected using a previously designed questionnaire. Gynecological examination, cervical cytology, and detection of high- and low-risk HPV DNA were undertaken prior to and after the renal transplant (RT). Colposcopically guided biopsies were obtained from patients who presented high grade squamous intraepithelial lesions (HSIL) during the follow-up period. Diagnoses were established according to the Bethesda system. RESULTS: Among 130 RTR, 62 were eligible for our study. The overall incidence of IL was 17.7% (95% CI, 8% to 27%), (11/62 patients), at 25.6 ± 10.7 months post-RT. Nine out of the eleven affected patients had low-grade squamous intraepithelial lesions (81.8%) and only two had HSIL (18.2%). The incidence of HPV infection, determined in a subgroup of 30 RTR, was 53.3% (95% CI, 35% to 71%), (16 out of 30 patients), at 18.3 ± 8.9 months post-RT. High-risk HPV genotypes were present in 62.5% of HPV positive cases (10/16). In 11 patients (36.6%), HPV infection was not associated to IL. CONCLUSIONS: HPV infection and cervical IL are common in the early posttransplant period. Our findings support the need of screening for cervical cancer to detect precancerous changes in RTR and the need of strengthening the knowledge of medical personnel on this issue.

Assuntos

Transplante de Rim , Infecções por Papillomavirus , Displasia do Colo do Útero , Feminino , Humanos , Incidência , Transplante de Rim/efeitos adversos , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Estudos Prospectivos , Esfregaço Vaginal , Displasia do Colo do Útero/epidemiologia

RESUMO

BACKGROUND: Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). OBJECTIVE: To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. METHODS: This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and < -4 for PHES. All participants were also screened for cognitive function and depression. RESULTS: Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy. CONCLUSIONS: It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents.

Assuntos

Fusão Flicker , Encefalopatia Hepática/diagnóstico , Testes Neuropsicológicos , Psicometria , Insuficiência Renal Crônica/complicações , Adolescente , Adulto , Estudos Transversais , Feminino , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/fisiopatologia , Encefalopatia Hepática/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Índice de Gravidade de Doença , Adulto Jovem

RESUMO

Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here.

Assuntos

Canais de Cátion TRPV/fisiologia , Animais , Cálcio/metabolismo , Bovinos , Endotélio Vascular/metabolismo , Humanos , Rim/metabolismo , Camundongos , Microcirculação , Dor/metabolismo , Permeabilidade , Prognóstico , Domínios Proteicos , Ratos , Vasos Retinianos , Pele/metabolismo

RESUMO

Resumen Tres enfermedades con alta prevalencia en la población adulta, especialmente en México, son la diabetes mellitus tipo 2, la hipertensión arterial y la hiperuricemia-gota; entre ellas comparten características fisiopatológicas que favorecen su aparición como Aceptado: 11 de junio 2019 un conjunto en los pacientes y cuyos tratamientos van frecuentemente de la mano, lo que ha permitido que en las siguientes líneas puedan describirse tales enfermedades Correspondencia como los tres desafortunados enemigos de la salud de la población. Manuel González Ortiz.

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Abstract Three diseases with a high prevalence in the adult population, especially in Mexico, are type 2 diabetes mellitus, arterial hypertension and hyperuricemia-gout; they share among them pathophysiological characteristics that favor their appearance as a group in the patients and whose treatments are frequently in the same way, the above-mentioned has allowed that in the following lines can be described such diseases as the three to;35(4):596-608. unfortunate enemies of the health of the population.

RESUMO

Mineralocorticoid receptor antagonism prevents acute kidney injury induced by ischemia-reperfusion in rodent and pig preclinical models. In a pilot study, we showed that spironolactone (25 mg) reduced oxidative stress after 5 days of kidney transplant (KT). In the present study, we investigated the effects of higher doses (50 and 100 mg) of spironolactone on kidney function, tubular injury markers, and oxidative stress in living donor KT recipients. We included KT recipients aged 18 yr or older who received immunosuppression therapy with IL-2 receptor antagonist, mycophenolate mofetil, corticosteroids, and tacrolimus with negative cross-match, and compatible blood group. Patients were randomized to receive placebo (n = 27), spironolactone (50 mg, n = 25), or spironolactone (100 mg, n = 25). Treatment was given from 3 days before and up to 5 days after KT. Serum creatinine, K+, urine neutrophil gelatinase-associated lipocalin-2, heat shock protein 72, and 8-hydroxy-2-deoxyguanosine levels were assessed. As expected, kidney function was improved after KT. Serum K+ remained in the normal range along the study. There was no significant effect of spironolactone on urinary neutrophil gelatinase-associated lipocalin-2 levels, whereas the increase in urinary heat shock protein 72 levels tended to be less intense in the 100 mg spironolactone-treated group (P = 0.054). In the placebo-treated group, urinary 8-hydroxylated-guanosine levels increased on days 3 and 5 after transplantation. This effect was prevented in patients that received spironolactone. In conclusion, spironolactone reduces the acute increase in urinary oxidative stress in living donor KT recipients.

Assuntos

Antioxidantes/uso terapêutico , Transplante de Rim/métodos , Rim/efeitos dos fármacos , Rim/cirurgia , Doadores Vivos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Espironolactona/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina/urina , Adulto , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Biomarcadores/urina , Método Duplo-Cego , Feminino , Proteínas de Choque Térmico HSP72/urina , Humanos , Imunossupressores/uso terapêutico , Rim/metabolismo , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Lipocalina-2/urina , Masculino , México , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Projetos Piloto , Espironolactona/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem

RESUMO

INTRODUCTION: Ureteral stricture (US) in the kidney transplant recipient is a rare complication that can lead to morbidity and graft loss. Risk factor recognition is crucial in the prevention and management of this entity. Delayed graft function (DGF), as defined by the need for dialysis in the first week after transplantation, has been proposed as a risk factor in previous studies. Our objective is to determine the impact of DGF in US development in kidney transplant patients. METHODS: We designed a matched case-control study. US cases in kidney transplant recipients were identified in the 2008-2017 period. We defined US as the rise in serum creatinine associated with findings suggesting obstruction in ultrasound, scintigraphy, or retrograde pyelogram; any other cause of graft dysfunction was excluded. Controls were defined as kidney transplant recipients from the same population and period without US, matched in a 1:2 fashion by age, sex, and donor type. RESULTS: From 532 kidney transplant patients, 31 cases and 62 controls were included. Cumulative US incidence was 58 per 1000 cases. When calculating for odds ratio (OR), post-operative urinoma (OR 3.2; 95% confidence interval [CI] 2.36-4.37) and ureteral duplication (OR 3.29; 95% CI 2.40-4.51) were associated with an increased risk for US, while DGF was not found to be statistically significant as a risk factor (OR 3.3; 95% CI 0.96-11.52). No statistically significant differences were found between groups in other pre- and post-transplant-related factors CONCLUSIONS:: DGF was not associated with US in our cohort; however, ureteral duplication and postoperative urinoma were associated with an increased risk of graft ureteral stenosis development.