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1.
Nat Immunol ; 20(7): 902-914, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209404

RESUMO

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.


Assuntos
Rim/imunologia , Nefrite Lúpica/imunologia , Biomarcadores , Biópsia , Análise por Conglomerados , Biologia Computacional/métodos , Células Epiteliais/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Interferons/metabolismo , Rim/metabolismo , Rim/patologia , Leucócitos/imunologia , Leucócitos/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Anotação de Sequência Molecular , Células Mieloides/imunologia , Células Mieloides/metabolismo , Análise de Célula Única , Transcriptoma
3.
J Magn Reson Imaging ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39239784

RESUMO

BACKGROUND: Kidney transplant is the treatment of choice for patients with end-stage renal disease. Early detection of allograft injury is important to delay or prevent irreversible damage. PURPOSE: To investigate the feasibility of hyperpolarized (HP) [1-13C]pyruvate MRI for assessing kidney allograft metabolism. STUDY TYPE: Prospective. SUBJECTS: Six participants (mean age, 45.2 ± 12.4 years, two females) scheduled for kidney allograft biopsy and five patients (mean age, 59.6 ± 10.4 years, two females) with renal cell carcinoma (RCC). FIELD STRENGTH/SEQUENCE: Three Tesla, T2-weighted fast spin echo, multi-echo gradient echo, single shot diffusion-weighted echo-planar imaging, and time-resolved HP 13C metabolite-selective imaging. ASSESSMENT: Five of the six kidney allograft participants underwent biopsy after MRI. Estimated glomerular filtration rate (eGFR) and urine protein-to-creatine ratio (uPCR) were collected within 4 weeks of MRI. Kidney metabolism was quantified from HP [1-13C]pyruvate MRI using the lactate-to-pyruvate ratio in allograft kidneys and non-tumor bearing kidneys from RCC patients. STATISTICAL TESTS: Descriptive statistics (mean ± SD). RESULTS: Biopsy was performed a mean of 9 days (range 5-19 days) after HP [1-13C]pyruvate MRI. Three biopsies were normal, one showed low-grade fibrosis and one showed moderate microvascular inflammation. All had stable functioning allografts with eGFR >60 mL/min/1.73 m2 and normal uPCR. One participant who did not undergo biopsy had reduced eGFR of 49 mL/min/1.73 m2 and elevated uPCR. The mean lactate-to-pyruvate ratio was 0.373 in participants with normal findings (N = 3) and 0.552 in participants with abnormal findings (N = 2). The lactate-to-pyruvate ratio was highest (0.847) in the participant with reduced eGFR and elevated uPRC. Native non-tumor bearing kidneys had a mean lactate-to-pyruvate ratio of 0.309. DATA CONCLUSION: Stable allografts with normal findings at biopsy showed lactate-to-pyruvate ratios similar to native non-tumor bearing kidneys, whereas allografts with abnormal findings showed higher lactate-to-pyruvate ratios. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

4.
Clin Transplant ; 37(2): e14881, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36504467

RESUMO

BACKGROUND: Despite improved life expectancy from a heart transplant, transplant recipients remain at high risk for renal dysfunction and failure, including end-stage kidney disease (ESKD). The onset of ESKD is a poor prognostic marker and is associated with increased mortality in this setting, as in others. There is a need to identify risk factors for ESKD among heart transplant recipients in contemporary settings. METHODS: We conducted an analysis of adult heart transplant recipients transplanted between 2008 and 2021 in the Organ Procurement and Transplantation Network database. 22 737 adult recipients of heart transplants alone were included in this analysis. We examined LVEF measured 1 year after transplant, and LVEF updated annually for association with ESKD using multivariate Cox regression models. RESULTS: LVEF at 1-year after transplant was associated with ESKD in multivariate models (Hazard Ratio 1.33 per 10-unit decrease, 95% CI 1.23-1.43, p < .001). In multivariate models using categorized LVEF, mildly reduced ejection fraction (EF 40%-50%) was associated with ESKD (HR 1.76, 95% CI 1.45-2.14, p < .001), as was reduced ejection fraction (EF < 40%, HR 2.86, 95% CI 2.01-4.07, p < .001), relative to individuals with preserved ejection fraction (EF > 50%). These associations were consistent when using annually updated ejection fraction. CONCLUSIONS: Post-transplant left ventricular ejection fraction has value in predicting end stage kidney disease among adults who receive heart transplants alone. LVEF is routinely measured as part of contemporary post heart transplant care, and a diminished LVEF should signal to clinicians that a recipient is at increased risk of renal failure.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Falência Renal Crônica , Insuficiência Renal , Adulto , Humanos , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Insuficiência Renal/etiologia
5.
BMC Nephrol ; 24(1): 119, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37127564

RESUMO

BACKGROUND: Kidney transplant is the gold standard for renal replacement therapy in patients with autosomal dominant polycystic kidney disease (ADPKD), which is the fourth leading cause of kidney failure. Despite the medical and economic benefits of preemptive kidney transplant over dialysis before transplant, only 9-21% of qualifying patients receive preemptive transplants. Given the low rates of preemptive transplant, the aim of this study was to determine perceived facilitators and barriers to preemptive transplant among ADPKD patients using a qualitative approach. METHODS: Data were collected between July 2021 and January 2022 from virtual individual semi-structured interviews of 16 adult participants with ADPKD. Qualitative analysis of the recorded interviews was conducted to generate themes. RESULTS: Our findings revealed two themes specific for facilitators to preemptive transplant (social support and patient agency) and three themes specific to barriers for preemptive transplant (inadequate social support, gaps in knowledge, and institutional and systemic policies). The results also include various subthemes and the application of these themes to the social ecological model. CONCLUSIONS: These findings suggest that increasing social support and patient agency, such as through patient navigator programs and encouraging effective communication between health care providers and patients, can facilitate the transplant process. Increasing dissemination of transplant knowledge from institutions and systems to patients through paired kidney exchange education and live donor outreach can also increase timely access to preemptive kidney transplants for patients with ADPKD. Our findings are limited by our single site study in the US, which may not apply to individuals experiencing different social, cultural, and health access conditions.


Assuntos
Falência Renal Crônica , Transplante de Rim , Doenças Renais Policísticas , Rim Policístico Autossômico Dominante , Adulto , Humanos , Rim Policístico Autossômico Dominante/complicações , Diálise Renal/efeitos adversos , Doenças Renais Policísticas/complicações , Transplante de Rim/efeitos adversos , Terapia de Substituição Renal/efeitos adversos , Falência Renal Crônica/etiologia
6.
Echocardiography ; 38(11): 1879-1886, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34713484

RESUMO

BACKGROUND: Diastolic dysfunction is an early marker of cardiac pathology in end-stage kidney disease (ESKD) patients. The ratio of transmitral filling velocity (E) to early diastolic strain rate (E/e'sr) is a novel non-invasive marker of early left ventricular (LV) filling pressure obtained using two-dimensional speckle tracking echocardiography (2DSTE). METHODS: In a prospective cohort of kidney transplant (KTX) recipients with echocardiograms performed pre-transplant we obtained repeat echocardiograms at 6 months following transplant. All echocardiograms were analyzed using 2DSTE where E/e'sr and global longitudinal strain were obtained. Paired tests were used to assess changes to cardiac structure and function following KTX. RESULTS: A total of 33 patients were included in the study (mean age was 46.6 ± 13.7 years and 42% were males). The primary causes of ESKD in the cohort were glomerular disease (33%), hypertension (30%), and polycystic kidney disease (12%). The median (IQR) time spent on dialysis was 5.4 years [2.9, 7.7 years]. A reverse remodeling of the LV was observed following KTX as LV mass decreased (189.2 ± 57.5 g vs 171.1 ± 56.8 g, P = 0.014). LV filling pressure decreased as assessed by E/e'sr (103.7 ± 51.1 cm vs 72.6 ± 35.5 cm, P = 0.009). E to early diastolic mitral annular tissue velocity (E/e') did not change following KTX (9.9 ± 4.5 vs 10.3 ± 4.1, P = 0.54). Additionally, both LV internal diastolic and systolic diameter decreased significantly. CONCLUSION: Reverse cardiac remodeling following KTX was observed as improvements in LV mass and LV dimensions. LV filling pressure improved as assessed by E/e'sr decreased following KTX, whereas E/e' did not change.


Assuntos
Falência Renal Crônica , Transplante de Rim , Disfunção Ventricular Esquerda , Adulto , Diástole , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular
7.
J Natl Compr Canc Netw ; 18(11): 1446-1452, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152701

RESUMO

Organ donors are systematically screened for infection, whereas screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to a lack of universal tumor testing in the posttransplant setting. Donor-transmitted malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. We describe the detection of a gastrointestinal adenocarcinoma transmitted from a young donor to 4 transplant recipients. Multidimensional histopathologic and genomic profiling showed a CDH1 mutation and MET amplification, consistent with gastric origin. At the time of writing, one patient in this series remains alive and without evidence of cancer after prompt organ explant after cancer was reported in other recipients. Because identification of a donor-derived malignancy changes management, our recommendation is to routinely perform short tandem repeat testing (or a comparable assay) immediately upon diagnosis of cancer in any organ transplant recipient. Routine testing for a donor-origin cancer and centralized reporting of outcomes are necessary to establish a robust evidence base for the future development of clinical practice guidelines.


Assuntos
Neoplasias , Transplante de Órgãos , Transplantados , Humanos , Incidência , Neoplasias/diagnóstico , Neoplasias/genética , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos
8.
Clin Transplant ; 34(8): e14000, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32502285

RESUMO

We examined a novel database linking national donor registry identifiers to records from a US pharmaceutical claims warehouse (2007-2015) to describe opioid and NSAID prescription patterns among LKDs during the first year postdonation, divided into three periods: 0-14 days, 15-182 days, and 183-365 days. Associations of opioid and NSAID prescription fills with baseline factors were examined by logistic regression (adjusted odds ratio, LCL aORUCL ). Among 23,565 donors, opioid prescriptions were highest during days 0-14 (36.6%), but 12.6% of donors filled opioids during days 183-365. NSAID prescriptions rose from 0.5% during days 0-14 to 3.3% during days 183-365. Women filled opioids more commonly than men, and black donors filled both opioids and NSAIDs more commonly than white donors. After covariate adjustment, significant correlates of opioid prescription fills during days 183-365 included obesity (aOR,1.24 1.381.53 ), less than college education (aOR,1.19 1.311.43 ), smoking (aOR,1.33 1.451.58 ), and nephrectomy complications (aOR,1.11 1.291.49 ). NSAID prescription fills in year 1 were not associated with differences in estimated glomerular filtration rate, incidence of proteinuria or new-onset hypertension at the first and second year postdonation. Prescription fills for opioids and NSAIDs for LKDs varied with demographic and clinic traits. Future work should examine longer-term outcome implications to help inform safe analgesic regimen choices after donation.


Assuntos
Transplante de Rim , Preparações Farmacêuticas , Farmácia , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Feminino , Humanos , Rim , Doadores Vivos , Masculino , Sistema de Registros
9.
Am J Kidney Dis ; 73(1): 51-61, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30037726

RESUMO

RATIONALE & OBJECTIVE: Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain. STUDY DESIGN: Post hoc longitudinal cohort analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial. SETTING & PARTICIPANTS: Stable kidney transplant recipients with elevated homocysteine levels from 30 sites in the United States, Canada, and Brazil. PREDICTOR: Urine albumin-creatinine ratio (ACR) at randomization. OUTCOMES: Allograft failure, CVD, and all-cause death. ANALYTICAL APPROACH: Multivariable Cox models adjusted for age; sex; race; randomized treatment allocation; country; systolic and diastolic blood pressure; history of CVD, diabetes, and hypertension; smoking; cholesterol; body mass index; estimated glomerular filtration rate (eGFR); donor type; transplant vintage; medications; and immunosuppression. RESULTS: Among 3,511 participants with complete data, median ACR was 24 (Q1-Q3, 9-98) mg/g, mean eGFR was 49±18 (standard deviation) mL/min/1.73m2, mean age was 52±9 years, and median graft vintage was 4.1 (Q1-Q3, 1.7-7.4) years. There were 1,017 (29%) with ACR < 10mg/g, 912 (26%) with ACR of 10 to 29mg/g, 1,134 (32%) with ACR of 30 to 299mg/g, and 448 (13%) with ACR ≥ 300mg/g. During approximately 4 years, 282 allograft failure events, 497 CVD events, and 407 deaths occurred. Event rates were higher at both lower eGFRs and higher ACR. ACR of 30 to 299 and ≥300mg/g relative to ACR < 10mg/g were independently associated with graft failure (HRs of 3.40 [95% CI, 2.19-5.30] and 9.96 [95% CI, 6.35-15.62], respectively), CVD events (HRs of 1.25 [95% CI, 0.96-1.61] and 1.55 [95% CI, 1.13-2.11], respectively), and all-cause death (HRs of 1.65 [95% CI, 1.23-2.21] and 2.07 [95% CI, 1.46-2.94], respectively). LIMITATIONS: No data for rejection; single ACR assessment. CONCLUSIONS: In a large population of stable kidney transplant recipients, elevated baseline ACR is independently associated with allograft failure, CVD, and death. Future studies are needed to evaluate whether reducing albuminuria improves these outcomes.


Assuntos
Albuminúria/epidemiologia , Albuminúria/urina , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/urina , Creatinina/urina , Transplante de Rim , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/urina , Causas de Morte , Estudos de Coortes , Método Duplo-Cego , Feminino , Sobrevivência de Enxerto , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição de Risco , Resultado do Tratamento
10.
Hepatology ; 68(5): 1953-1960, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29698588

RESUMO

Acute kidney injury (AKI) is a critical determinant of outcomes in hospitalized patients with cirrhosis, but little is known of the impact of AKI in the outpatient setting. We analyzed 385 adult outpatients with cirrhosis listed for liver transplant at a single center; excluded were those with severe hepatic encephalopathy, with hepatocellular carcinoma, or on hemodialysis. Baseline serum creatinine (bCr) was defined as the lowest value recorded, peak Cr as the highest value, ΔCr as peak Cr minus bCr, AKI as a rise in serum Cr (sCr) by ≥0.3 mg/dL from bCr, persistent kidney injury as elevation of sCR by ≥0.3 mg/dL from bCr on each subsequent clinical assessment. Among 385 outpatients with cirrhosis, bCr was ≤0.70, 0.70-0.97, and ≥0.97 mg/dL in 28%, 38%, and 34%, respectively. At a median follow-up of 16 (range 8-28) months, 143 (37%) had one or more AKI episode, which increased significantly by bCr group (24% versus 37% versus 48%, P = 0.001). Of these 143 with AKI, 13% developed persistent kidney injury. A multivariable Cox regression analysis highlighted that bCr (hazard ratio [HR], 2.96) and ΔCr (HR, 2.05) were the only factors independently associated with the development of persistent kidney injury (P < 0.001). The likelihood of death/delisting increased by bCr group (14% versus 19% versus 28%, P = 0.03). A competing risk analysis demonstrated that each 1 mg/dL increase in bCr was independently associated with a 62% higher risk of death/delisting when accounting for transplantation and adjusting for confounders. Conclusion: AKI is not only common in outpatients with cirrhosis but even "clinically normal" bCr levels significantly impact the risk of persistent kidney injury and waitlist mortality, supporting the need for a lower clinical threshold to initiate monitoring of renal function and implementation of kidney-protective strategies.


Assuntos
Injúria Renal Aguda/etiologia , Creatinina/sangue , Cirrose Hepática/complicações , Listas de Espera/mortalidade , Injúria Renal Aguda/sangue , Injúria Renal Aguda/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Rim , Cirrose Hepática/sangue , Cirrose Hepática/mortalidade , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
11.
BMC Nephrol ; 20(1): 324, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31419965

RESUMO

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of cardiovascular morbidity and mortality. Impaired left ventricular (LV) global longitudinal strain (GLS) can be a sign of subclinical cardiac dysfunction even in patients with otherwise preserved ejection fraction (EF). Transmitral early filling velocity to early diastolic strain rate (E/SRe) is a novel measure of LV filling pressure, which is often affected early in cardiac disease. METHODS: A total of 110 ADPKD patients not on dialysis were included in this prospective study. All patients underwent an extensive echocardiographic examination including two-dimensional speckle tracking. GLS and strain rates were measured. The distribution of GLS and E/SRe was determined and patient characteristics were compared by median levels of GLS (- 17.8%) and E/SRe (91.4 cm). Twenty healthy participants were included as control group. RESULTS: There was a significantly worse GLS in the ADPKD patients (mean: - 17.8 ± 2.5%) compared to the healthy controls (mean: - 21.9 ± 1.9%), p < 0.001. The same was true for E/SRe (mean: 10.0 ± 0.3 cm) compared to the control group (mean: 6.5 ± 0.3 cm), p < 0.001. In simple logistic regression, male gender (OR: 4.74 [2.10-10.71], p < 0.001), fasting glucose (odds ratio (OR) 1.05 [1.01-1.10], p = 0.024), htTKV (OR: 1.07 [1.01-1.13], p = 0.013), HDL cholesterol (OR: 0.97 [0.94, 0.996], p = 0.025), triglycerides (OR: 1.01 [1.00-1.02], p = 0.039), hemoglobin (OR: 1.50 [1.11-2.04], p = 0.009), and ß-blocker use (OR: 1.07 [1.01, 1.13], p = 0.013) were all associated with higher GLS. After multivariate logistic regression with backward model selection, only male gender (OR: 5.78 [2.27-14.71], p < 0.001) and ß-blocker use (OR: 14.00 [1.60, 122.51], p = 0.017) remained significant. In simple logistic regression models, BMI (OR: 1.11 [1.02-1.20], p = 0.015), systolic blood pressure (OR: 1.03 [1.00-1.06], p = 0.027) and ß-blocker use (OR: 17.12 [2.15-136.20], p = 0.007) were associated with higher E/SRe - a novel measure of left ventricular filling pressure. After backward elimination, only ß-blocker use (OR: 17.22 [2.16, 137.14], p = 0.007) remained significant. CONCLUSION: Higher GLS and E/SRe are common in ADPKD patients, even in patients with preserved eGFR and normal left ventricular EF. GLS and E/SRe may aid in cardiovascular risk stratification in patients with ADPKD as they represent early markers of cardiac dysfunction.


Assuntos
Contração Miocárdica/fisiologia , Rim Policístico Autossômico Dominante/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/sangue , Rim Policístico Autossômico Dominante/complicações , Estudos Prospectivos , Análise de Regressão , Fatores Sexuais , Volume Sistólico , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem
13.
Clin Nephrol ; 90(4): 237-245, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106364

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disease. It carries high lifetime morbidity not only due to chronic kidney disease, but also due to a higher risk of cardiovascular death. Multiple metabolic abnormalities associated with ADPKD including insulin resistance and hyperlipidemia as well as subclinical cardiovascular abnormalities, such as left ventricular hypertrophy (LVH), contribute to this cardiovascular risk. These conditions may manifest before evidence of worsening estimated glomerular filtration rate (eGFR). Renal oxidative stress also occurs early in the disease and is a driver of ADPKD progression. Animal models have shown that calorie restriction may mitigate these inflammatory processes. Further research is required to show whether attenuation of metabolic abnormalities associated with ADPKD may improve renal and cardiovascular morbidity.
.


Assuntos
Hipertrofia Ventricular Esquerda/fisiopatologia , Resistência à Insulina , Metabolismo dos Lipídeos , Rim Policístico Autossômico Dominante/fisiopatologia , Animais , Doenças Assintomáticas , Anormalidades Cardiovasculares , Taxa de Filtração Glomerular , Humanos , Hiperlipidemias/etiologia , Hipertrofia Ventricular Esquerda/etiologia , Estresse Oxidativo , Rim Policístico Autossômico Dominante/complicações
14.
BMC Nephrol ; 18(1): 214, 2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28679364

RESUMO

BACKGROUND: Autosomal dominant polycystic kidney disease (PKD) is the most common genetic renal disease and the fourth leading cause of end-stage renal disease in the United States. Although there is no cure for PKD, several treatments are considered to be beneficial, including blood pressure control, exercise, low-salt diet, and high volume water intake. However, levels of understanding of the importance of these treatments and adherence to these recommendations vary among patients. This study explores illness perception models of patients with PKD to reveal barriers in adherence to prescribed therapies; satisfaction with medical care; and sources of medical information. METHODS: We designed a phenomenological interview study to evaluate illness perception models of individuals with PKD. Patients were identified from the national PKD Foundation e-mail distribution list (N = 190) and responded voluntarily to an introductory survey (N = 50). Seventeen PKD patients in the Bay Area were scheduled for one-on-one in-depth interviews with one trained interviewer (W-CT). Open-ended questions administered with an interview guide were used to evaluate patients' beliefs. RESULTS: Mean age was 56.6 +/- 12 years (range 29-78); 65% were female. Many of the PKD patients in this study were highly motivated and willing to incorporate blood pressure, exercise, low-salt diet, and high volume water intake into their daily routines. Barriers to adherence to these therapies include personal beliefs and confusion due to unclear recommendations. CONCLUSIONS: These findings suggest there is variability between what patients understand about their disease and treatments and what they believe their doctors have told them. Not all physicians focus on lifestyle-based treatments, but the majority of PKD patients in our study are motivated and willing to incorporate blood pressure control, exercise, low-salt diet, and high volume water intake into their daily routines and would like specific recommendations on how to implement these. These findings support a role for further exploring patient beliefs about the disease and its necessary treatments in order to design strategies to improve communication and meet the needs of these patients.


Assuntos
Anti-Hipertensivos/uso terapêutico , Dieta Hipossódica/métodos , Ingestão de Líquidos/fisiologia , Exercício Físico/fisiologia , Doenças Renais Policísticas/terapia , Comportamento de Redução do Risco , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Dieta Hipossódica/psicologia , Exercício Físico/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/psicologia , Resultado do Tratamento
15.
J Am Soc Nephrol ; 27(7): 2109-21, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26538631

RESUMO

Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/urina , Ácido Fólico/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/urina , Biomarcadores/urina , Estudos de Coortes , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
Arterioscler Thromb Vasc Biol ; 34(1): 231-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24177327

RESUMO

OBJECTIVE: Endothelial dysfunction is a possible mechanism to explain the association between atherosclerosis and kidney disease. This study evaluated circulating soluble endothelial cell-selective adhesion molecule (sESAM), a marker of endothelial dysfunction, as a risk factor for kidney function decline and albuminuria. APPROACH AND RESULTS: In the Heart and Soul Study, we measured sESAM from baseline serum samples and defined elevated levels of sESAM by the highest quartile (quartile 4 [Q4]: >65.4 ng/mL). We evaluated the associations of high sESAM with baseline estimated glomerular filtration rate (eGFR) and ratio of urine albumin to creatinine (ACR), and with longitudinal changes in eGFR and ACR. Among 990 participants with sESAM measurements, median sESAM was 54.5 ng/mL (interquartile range, 45.3-65.8). After multivariable adjustment, elevated levels of sESAM were strongly and independently associated with baseline reduced eGFR <60 mL/min per 1.73 m(2) (odds ratio [OR], 11.44; P<0.0001) and ACR ≥30 mg/g (OR, 5.23; P<0.0001). Associations of sESAM (Q4 versus quartile 1 [Q1]) with change in ACR (ß=54.47; P<0.0001) were also significant after full adjustment. The association with change in eGFR (1.56%; P=0.0049) was not statistically significant after application of the Bonferroni correction for multiple markers. In unadjusted models, sESAM was associated with rapid kidney function loss, defined as 3% annual eGFR decline (OR, 2.28; P=0.0003), although this was attenuated by adjustment (OR, 2.11; P=0.0095). CONCLUSIONS: sESAM is associated with albuminuria and reduced kidney function in both cross-sectional and longitudinal analyses. These findings implicate endothelial dysfunction as a potential contributor to the elevated kidney disease risk in persons with cardiovascular disease.


Assuntos
Albuminúria/sangue , Moléculas de Adesão Celular/sangue , Doença da Artéria Coronariana/sangue , Endotélio Vascular/fisiopatologia , Rim/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Albuminúria/urina , Biomarcadores/sangue , Biomarcadores/urina , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Modelos Lineares , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Prospectivos , Fatores de Risco , São Francisco , Fatores de Tempo , Regulação para Cima
18.
Transpl Int ; 28(10): 1172-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26011061

RESUMO

We assessed the prevalence of abdominal aortic calcification (AAC) in older living kidney donors and its effect on recipient eGFR and graft histology. A total of 292 consecutive living pairs with donor age ≥50 from 2003 to 2013 were identified (mean age 56; range 50-78; F/M: 1.8). Donor AAC was determined by prenephrectomy unenhanced CT. Recipient eGFR and spot urine protein: creatinine ratios (UPCRs) were recorded. A total of 180 recipients had 6-month protocol biopsies. AAC was present in 40.7% of donors, and they were older (58.6 versus 54.7 years old, P < 0.0001) and more likely to be male (77.6% vs. 37.3%, P = 0.004). There was no significant difference in eGFR or spot UPCR up to 36 months in recipients of allografts from donors with versus without AAC. At 6-month biopsy, there was a higher percentage of allografts with vascular fibrous intimal thickening and arteriolar hyaline thickening from donors with versus without AAC (vascular fibrous intimal thickening: 38.8% vs. 7.1% and arteriolar hyaline thickening: 35.8% vs. 7.1%; P < 0.001 for both). The presence of donor AAC predicts the presence of vascular disease [vascular fibrous intimal thickening (OR: 7.2; CI:2.9-17.9) and arteriolar hyaline thickening (OR:5.7; CI:2.3-14.1)] in allografts at 6 months. Donor AAC is predictive of renal vascular disease and may help to improve the screening of potential donors and inform post-transplant management.


Assuntos
Aorta Abdominal/patologia , Doenças da Aorta/epidemiologia , Aterosclerose/epidemiologia , Transplante de Rim , Doadores Vivos , Calcificação Vascular/epidemiologia , Fatores Etários , Aorta Abdominal/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/fisiopatologia , Aortografia , Arteríolas/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Biópsia , Creatinina/urina , Seleção do Doador , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Rim/fisiologia , Rim/ultraestrutura , Masculino , Pessoa de Meia-Idade , Prevalência , Proteinúria/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Túnica Íntima/patologia , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/fisiopatologia
19.
Am Heart J ; 168(6): 931-9.e2, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25458658

RESUMO

BACKGROUND: Subclinical volume overload in the absence of diagnosed heart failure (HF) may be an underrecognized contributor to kidney function decline in coronary artery disease (CAD) patients. We evaluated associations of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of ventricular stretch, with change in estimated glomerular filtration rate (eGFR). METHODS: We evaluated 535 patients with stable CAD and no history of HF, who were enrolled in the Heart and Soul Study and followed for 5 years. N-terminal pro-B-type natriuretic peptide was measured at baseline. We evaluated the associations of NT-proBNP with change in kidney function over 5 years: (a) annual percent change in eGFR, (b) rapid kidney function loss (> 3% per year for 5 years), and (c) incident eGFR < 60 mL/min per 1.73 m2. In multivariable models, we adjusted for demographics, comorbid conditions, echocardiographic parameters, medications, and baseline kidney function. RESULTS: Among 535 participants, median NT-proBNP was 130.6 (interquartile range 61.8-280.9) pg/mL, and median B-type natriuretic peptide (BNP) was 32.5 (14.4-75.9) pg/mL. Individuals with NT-proBNP levels in the highest quartile (> 280.9 pg/mL) had a greater odds of rapid kidney function loss after full adjustment (odds ratio 2.95; 95% CI 1-8.65; P = .0492). Associations with incident eGFR < 60 mL/min per 1.73 m2 were also significant (adjusted odds ratio 4.23; 95% CI 1.05-16.98; P = .0422). Results were similar when analyzed using BNP as the predictor. CONCLUSIONS: N-terminal pro-B-type natriuretic peptide and BNP are strongly and independently associated with accelerated kidney function loss, even in the absence of clinical HF. These findings suggest that subclinical cardiovascular dysfunction may contribute to elevated kidney disease risk in persons with CAD.


Assuntos
Doença da Artéria Coronariana , Insuficiência Cardíaca , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Insuficiência Renal , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fluxo Sanguíneo Renal Efetivo , Insuficiência Renal/sangue , Insuficiência Renal/diagnóstico , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Fatores de Risco , Estados Unidos/epidemiologia , Função Ventricular/fisiologia
20.
Am J Kidney Dis ; 63(4): 567-72, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24200462

RESUMO

BACKGROUND: The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers. STUDY DESIGN: Cross-sectional prospective. SETTING & PARTICIPANTS: Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36). PREDICTORS: We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C. OUTCOMES: Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C. MEASUREMENTS: We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs). RESULTS: Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96). LIMITATIONS: No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors. CONCLUSIONS: All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation prior to freezing. For optimal fidelity, urine for IL-18 measurement should not be stored at 25°C before long-term storage or analysis.


Assuntos
Injúria Renal Aguda/urina , Biomarcadores/urina , Idoso , Idoso de 80 Anos ou mais , Centrifugação , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Congelamento , Humanos , Masculino , Estudos Prospectivos , Coleta de Urina/métodos , Coleta de Urina/normas
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