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BACKGROUND: The estimated glomerular filtration rate (eGFR) and kinetic estimated glomerular filtration rate (KeGFR) have not been compared, with urinary measured creatinine clearance (mCrCl) or serum cystatin C (CysC) eGFR, soon after kidney transplantation (KTx) with prompt primary function. This study aims to compare post-KTx, urinary mCrCl, and eGFR CysC with eGFR and KeGFR. METHODS: Post-KTx, urine was collected every 12 hours from 25 of the 34 consenting subjects to calculate mCrCl and compare with Modification of Diet in Renal Disease (MDRD)-4, Jelliffe eGFR, Cockcroft-Gault creatinine clearance (CrCl), and KeGFR by Chen and Brater formulae. Serum CysC levels were also measured in the last 14 subjects to compare with creatinine, mCrCl, and eGFR CysC. RESULTS: At 12 to 96 hours post-KTx (n = 25), mCrCl was 55.8% to 13.6% higher than MDRD-4 eGFR. The mean CysC level (n = 14) was 58% to 14% lower than creatinine for up to 3.0 days post-KTx, with higher MDRD-4 eGFR CysC. Chen and Brater KeGFR were significantly lower than mCrCl and eGFR (Fig 1B, Table 1). Within 3 days post-KTx, a 50% decrease in creatinine provided ≥ 50 mL/min CrCl in 90% of cases (mean mCrCl 61.7 ± 22.8). This difference was greater when the initial creatinine was higher with the rapid decrease in creatinine. CONCLUSIONS: (1) Post-KTx eGFR/KeGFR formulae underestimated mCrCl. (2) Serum CysC levels were lower than creatinine, corresponding with higher eGFR CysC. (3) A 50% decrease from initial serum creatinine; mean mCrCl was 61.7 ± 22.8 mL/min, and 90% of them have mCrCl > 50 mL/min. Post-KTx, until creatinine is stabilized, recipients are often receiving subtherapeutic dosing of renally adjusted medications. More prospective studies are necessary, including radioisotope clearance.
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Background: The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID. Methods: A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers. Results: Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65-0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03-2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00-2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings. Conclusions: ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality.
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Key Clinical Message: Non-lupus full house nephropathy is a rare entity that is still poorly understood. It can complicate post-transplant kidneys and result in a de novo process. Treatment is difficult but can be possibly achieved with optimization of immune suppression. Abstract: Non-lupus full house nephropathy is a rare entity with an unclear incidence. It describes the kidney biopsy findings of positive deposits for IgG, IgA, IgM, C3, and C1q on immunofluorescence in the absence of the classical diagnostic features of systemic lupus nephritis. This disease entity is becoming more recognized but further studies are still needed to evaluate the incidence, etiologies, and management of this condition. Transplant glomerulopathy is a major cause for renal graft loss. It can present with a wide variety of manifestations; it can cause AKI, CKD, or glomerular inflammations through an immune complex or autoimmune-mediated damage.
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The natural direct and indirect effects in causal mediation analysis with survival data having one mediator is addressed by VanderWeele (2011) [1]. He derived an approach for (1) an accelerated failure time regression model in general cases and (2) a proportional hazards regression model when the time-to-event outcome is rare. If the outcome is not rare, then VanderWeele (2011) [1] did not derive a simple closed-form expression for the log-natural direct and log-natural indirect effects for the proportional hazards regression model because the baseline cumulative hazard function does not approach zero. We develop two approaches to extend VanderWeele's approach, in which the assumption of a rare outcome is not required. We obtain the natural direct and indirect effects for specific time points through numerical integration after we calculate the cumulative baseline hazard by (1) applying the Breslow method in the Cox proportional hazards regression model to estimate the unspecified cumulative baseline hazard; (2) assuming a piecewise constant baseline hazard model, yielding a parametric model, to estimate the baseline hazard and cumulative baseline hazard. We conduct simulation studies to compare our two approaches with other methods and illustrate our two approaches by applying them to data from the ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Consortium.
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BACKGROUND: Proton Pump Inhibitors (PPI) are among the most commonly used drugs to treat acid-related gastrointestinal disorders in the USA. Although PPI use has been linked to acute interstitial nephritis, the side effects of post-hospitalization acute kidney injury (AKI) and the progression of kidney disease still are controversial. We conducted a matched cohort study to examine the associations between PPI use and the side effects, especially in post-hospitalization AKI. METHODS: We investigated 340 participants from the multicenter, prospective, matched-cohort ASSESS-AKI study, which enrolled participants from December 2009 to February 2015. After the baseline index hospitalization, follow-up visits were conducted every six months, and included a collection of self-reported PPI use by participants. Post-hospitalization AKI was defined as the percentage increase from the nadir to peak inpatient SCr value was ≥ 50% and/or absolute increase ≥ 0.3 mg/dL in peak inpatient serum creatinine compared with baseline outpatient serum creatinine. We applied a zero-inflated negative binomial regression model to test the relationship between PPI use and post-hospitalization AKI. Stratified Cox proportional hazards regression models also were conducted to examine the association between PPI use and the risk of progression of kidney disease. RESULTS: After controlling for demographic variables, baseline co-morbidities and drug use histories, there was no statistically significant association between PPI use and risk of post-hospitalization AKI (risk ratio [RR], 0.91; 95% CI, 0.38 to 1.45). Stratified by AKI status at baseline, no significant relationships were confirmed between PPI use and the risk of recurrent AKI (RR, 0.85; 95% CI, 0.11 to 1.56) or incidence of AKI (RR, 1.01; 95% CI, 0.27 to 1.76). Similar non-significant results also were observed in the association between PPI use and the risk of progression of kidney diseases (Hazard Ratio [HR], 1.49; 95% CI, 0.51 to 4.36). CONCLUSION: PPI use after the index hospitalization was not a significant risk factor for post-hospitalization AKI and progression of kidney diseases, regardless of the AKI status of participants at baseline.
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Injúria Renal Aguda , Inibidores da Bomba de Prótons , Humanos , Estudos de Coortes , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Prospectivos , Creatinina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Fatores de Risco , Estudos RetrospectivosRESUMO
Since the pandemic began in December 2019, SARS-Cov2 has accentuated the wide gap and disparities in socioeconomic and healthcare access at individual, community, country, and regional levels. More than two years into the current pandemic, up to three-fourths of the patients are reporting continued signs and symptoms beyond the acute phase of COVID-19, and Long COVID portends to be a major challenge in the future ahead. With a comprehensive overview of the literature, we found that most studies concerning long COVID came from high and upper-middle income countries, and people of low-income and lower-and-middle income regions and vulnerable groups with comorbid conditions have been neglected. Apart from the level of income, there is a significant geographical heterogeneity in investigating the Post-Acute Sequelae of COVID-19 (PASC) or what we call now, long COVID. We believe that these recognizing health disparities is crucial from equity perspective and is the first step toward global health promotion.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/epidemiologia , RNA Viral , SARS-CoV-2 , GeografiaRESUMO
Introduction: Biomarkers of acute kidney injury (AKI) are often indexed to urine creatinine (UCr) or urine osmolarity (UOsm) to control for urine concentration. We evaluated how these approaches affect the biomarker-outcome association in patients with AKI. Methods: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Study was a cohort of hospitalized patients with and without AKI between 2009 and 2015. Using Cox proportional hazards regression, we assessed the associations and predictions (C-statistics) of urine biomarkers with a composite outcome of incident chronic kidney disease (CKD) and CKD progression. We used 4 approaches to account for urine concentration: indexing and adjusting for UCr and UOsm. Results: Among 1538 participants, 769 (50%) had AKI and 300 (19.5%) developed composite CKD outcome at median follow-up of 4.7 years. UCr and UOsm during hospitalization were inversely associated with the composite CKD outcome. The associations and predictions with CKD were significantly strengthened after indexing or adjusting for UCr or UOsm for urine kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) in patients with AKI. There was no significant improvement with indexing or adjusting UCr or UOsm for albumin, neutrophil gelatinase-associated lipocalin (NGAL), and chitinase 3-like 1 (YKL-40). Uromodulin's (UMOD) inverse association with the outcome was significantly blunted after indexing but not adjusting for UCr or UOsm. Conclusion: UCr and UOsm during hospitalization are inversely associated with development and progression of CKD. Indexing or adjusting for UCr or UOsm strengthened associations and improved predictions for CKD for only some biomarkers. Incorporating urinary concentration should be individualized for each biomarker in research and clinical applications.
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Zinc is the second most abundant essential trace element in the human body with important regulatory functions in cellular and subcellular levels in several tissues. Zinc deficiency is associated with the development and progression of chronic kidney disease (CKD) and its complications. With the progression of CKD to end-stage kidney disease (ESKD) and initiation of dialysis, zinc is further removed from the body, potentiating the zinc deficiency. Dietary intake plays a major role in zinc-deficiency-related risks and progression of CKD. By taking into account the evidence from clinical studies depicting the mutual correlations between zinc and CKD, and the plausibility based on animal studies, it can be deduced that zinc deficiency has a causative role in CKD and its progression. This review highlights the role of zinc deficiency in kidney disease and the possible indication for supplementation of zinc at various stages of CKD. DOI: 10.52547/ijkd.6702.
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Falência Renal Crônica , Insuficiência Renal Crônica , Animais , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , ZincoRESUMO
Clustered or longitudinal data are commonly encountered in clinical trials and observational studies. This type of data could be collected through a real-time monitoring scheme associated with some specific event, such as disease recurrence, hospitalization, or emergency room visit. In these contexts, the cluster size could be informative because of its potential correlation with disease status, since more frequency of observations may indicate a worsening health condition. However, for some clusters/subjects, there are no measures or relevant medical records. Under such circumstances, these clusters/subjects may have a considerably lower risk of an event occurrence or may not be susceptible to such events at all, indicating a nonignorable zero cluster size. There is a substantial body of literature using observations from those clusters with a nonzero informative cluster size only, but few works discuss informative nonignorable zero-sized clusters. To utilize the information from both event-free and event-occurring participants, we propose a weighted within-cluster-resampling (WWCR) method and its asymptotically equivalent method, dual-weighted generalized estimating equations (WWGEE) by adopting the inverse probability weighting technique. The asymptotic properties are rigorously presented theoretically. Extensive simulations and an illustrative example of the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study are performed to analyze the finite-sample behavior of our methods and to show their advantageous performance compared to the existing approaches.
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Modelos Estatísticos , Projetos de Pesquisa , Análise por Conglomerados , Simulação por Computador , HumanosRESUMO
Chronic kidney disease (CKD) is associated with substantial morbidity, mortality, cost, and increased caregiver burden. Peer mentoring (PM) improves multiple outcomes in various chronic diseases. The effect of PM on caregiver burden among caregivers of patients with CKD has not been studied. We conducted a randomized clinical trial to test the effectiveness of a structured PM program on burden of care among caregivers of patients with CKD. We randomized 86 caregivers to receive 6 months of intervention in 1 of 3 groups: (1) face-to-face PM (n = 29); (2) online PM (n = 29); and (3) usual care: textbook-only (n = 28). Peer mentors were caregivers of patients with CKD, who received 16â h of instruction. All participants received a copy of a textbook, which contains detailed information about kidney disease. Participants in the PM groups received FTF or online PM for 6 months. The outcome was time-related change in the Zarit Burden Interview (ZBI) score. There was a statistically significant decrease in the ZBI score (SE: -3.44; CI: -6.31, -0.57 [p = 0.002]) compared with baseline, among the online PM group. Online PM led to decreased caregiver burden among caregivers of patients with CKD. The study was limited to English-speaking subjects with computer literacy.
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The new era of digitalized knowledge and information technology (IT) has improved efficiency in all medical fields, and digital health solutions are becoming the norm. There has also been an upsurge in utilizing digital solutions during the COVID-19 pandemic to address the unmet mental healthcare needs, especially for those unable to afford in-person office-based therapy sessions or those living in remote rural areas with limited access to mental healthcare providers. Despite these benefits, there are significant concerns regarding the widespread use of such technologies in the healthcare system. A few of those concerns are a potential breach in the patients' privacy, confidentiality, and the agency of patients being at risk of getting used for marketing or data harnessing purposes. Digital phenotyping aims to detect and categorize an individual's behavior, activities, interests, and psychological features to properly customize future communications or mental care for that individual. Neuromarketing seeks to investigate an individual's neuronal response(s) (cortical and subcortical autonomic) characteristics and uses this data to direct the person into purchasing merchandise of interest, or shaping individual's opinion in consumer, social or political decision making, etc. This commentary's primary concern is the intersection of these two concepts that would be an inevitable threat, more so, in the post-COVID era when disparities would be exaggerated globally. We also addressed the potential "dark web" applications in this intersection, worsening the crisis. We intend to raise attention toward this new threat, as the impacts might be more damming in low-income settings or/with vulnerable populations. Legal, health ethics, and government regulatory processes looking at broader impacts of digital marketing need to be in place.
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A 60-year-old Caucasian female with sero-positive rheumatoid arthritis (RA) was evaluated as a potential kidney donor for her brother-in-law with end-stage kidney disease (ESKD) secondary to c-antineutrophil cytoplasmic antibody (c-ANCA) associated vasculitis (AAV) and membranous nephropathy (MN). With little to no data supporting or contradicting this unique scenario, in addition to the varying viewpoints expressed by the different specialists, our multidisciplinary transplant committee encountered a difficult decision of whether to approve a candidate with RA for a living kidney donation or not. As a result, we carried out a careful literature review addressing aspects of recipients' outcomes following kidney transplants from a living donor with RA, especially when the recipient has AAV, living donor's short- and long-term outcomes post kidney donation, renal disease in AAV and RA, and maintenance of disease remission.
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Abatacepte/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Plasmaferese/métodos , Adulto , Protocolos Clínicos , Cálculos da Dosagem de Medicamento , Sobrevivência de Enxerto , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Knowledge about benefits of kidney transplantation (KT) is an important determinant of the patients' decision to pursue KT. We investigated factors associated with End Stage Renal Disease (ESRD) patients' knowledge about KT benefits. METHODS: We randomly invited 1,400 dialysis patients to complete a survey about benefits of KT. Using multivariate analysis, we calculated odds ratios for the probability of choosing the correct responses. RESULTS: Of 673 participants, 17.6% agreed with benefit of KT for older patients, 36.5% agreed with benefit of KT for diabetic patients, and 31.5% agreed with benefit of pre-emptive KT. Non-white (OR: 0.68) and older (OR: 0.65) participants were less likely to agree with the survival benefit of KT. Older participants were less likely to agree with benefit of KT for older (OR: 0.64), and diabetic patients (OR: 0.54). Participants with less than high school education were less likely to agree with benefit of pre-emptive KT (OR: 0.58). Participants with a previous KT were more likely to agree with benefit of KT for older (OR: 2.32), and diabetic patients (OR: 2.50), and with the benefit of pre-emptive KT (OR: 2.34). Participants who had received 3 or more modes of education about KT were more likely to agree with benefit of KT for diabetic patients (OR: 2.04), and with benefit of pre-emptive KT (OR:1.67). CONCLUSIONS: Dialysis patients have limited knowledge about benefits of KT. Previous KT, exposure to 3 or more modes of KT education, and education attainment are significant contributors to knowledge about KT benefits.
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INTRODUCTION: CKD is associated with decreased quality of life (QOL). Peer mentoring (PM) leads to improved QOL in various chronic diseases. The effectiveness of PM on QOL of patients with CKD has not been previously studied. We conducted a randomized clinical trial to test the effectiveness of face-to-face (FTF) and online mentoring by trained peers, compared with usual care, on CKD patients' QOL. METHODS: We randomized 155 patients in one of 3 groups: (1) FTF PM (n = 52), (2) online PM (n = 52), and (3) textbook only (n = 51). Peer mentors were patients with CKD, who received formal training through 16 h of instruction. Participants in all 3 groups received a copy of an informational textbook about CKD. Participants assigned to PM received either 6 months of FTF or online PM. The outcomes included time-related changes in domain scores of the Kidney Disease Quality of Life (KDQOL)-36 for each of the groups over the 18-month study period. RESULTS: Compared with baseline, online PM led to improved scores in domains of the KDQOL-36 at 18 months: Effects of Kidney Disease (p = 0.01), Burden of Kidney Disease (p = 0.01), Symptoms and Problems of Kidney Disease (p = 0.006), SF-12 Physical Composite Summary (p = 0.001), and SF-12 Mental Composite Summary (p < 0.001). There were no statistically significant changes from baseline in domain scores of KDQOL-36 within the FTF PM and textbook-only groups. CONCLUSIONS: Among patients with CKD, online PM led to increased scores in domains of the KDQOL-36 at 18 months. The study was limited to English-speaking subjects with computer literacy and internet access.
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PURPOSE: To find out what is known from literature about Long COVID until January 30, 2021. METHODS: We undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist. RESULTS: Of 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management). CONCLUSIONS: The controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness.
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COVID-19 , COVID-19/complicações , Fadiga , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
Coronavirus disease 2019 (COVID19) was identified in December 2019 and is still expanding in most parts of the world. The wide variety of affected organs is likely based upon the shared expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) important entry-receptor angiotensin-converting enzyme 2 (ACE2). For this reason, the broad distribution of ACE2 receptors in different tissues plays a crucial role in the multi-organ dysfunction and fatality due to COVID-19. Because of the high prevalence of acute kidney injury (AKI) in patients with COVID-19, we review the molecular understanding into viral infection mechanisms and implications for AKI. Furthermore, mechanisms of the AKI to chronic kidney disease (CKD) progression, such as the relative contribution of immune cell reaction, fibroblasts activation, endothelial dysfunction, and subsequent hypoxia may contribute to the association of AKI with worse outcomes during this virus pandemic. We highlight the state of the knowledge on SARS-CoV-2-dependent mechanisms for AKI and list the potential management choices for the prevention of AKI aggravation and the impending possibility of CKD. Finally, we intend to provide a much better understanding of why Coronavirus induces AKI and its subsequent progression to CKD in the coming years and further discuss the acute and long-term renal consequences.
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Injúria Renal Aguda , COVID-19 , Insuficiência Renal Crônica , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/virologia , Enzima de Conversão de Angiotensina 2 , COVID-19/complicações , Humanos , Pandemias , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/virologia , SARS-CoV-2RESUMO
Renal dysfunction is associated with poor long-term outcomes after liver transplantation. We examined the renal sparing effect of everolimus (EVR) compared to standard calcineurin inhibitor (CNI) immunosuppression with direct measurements of renal function over 24 months. METHODS: This was a prospective, randomized, open-label trial comparing EVR and mycophenolic acid (MPA) with CNI and MPA immunosuppression. An Investigational New Drug Application (IND # 113882) was obtained with the Food and Drug Administration as EVR is only approved for use with low-dose tacrolimus. Serum creatinine, 24-hour urine creatinine clearance, iothalamate clearance, Cockcroft-Gault creatinine clearance (CrCl), and Modification of Diet in Renal Disease estimated glomerular filtration rate were prospectively measured at 4 study visits. Nonparametric statistical tests were used for analyses, including the Mann-Whitney U test for continuous outcomes and Pearson's chi-square test for binary outcomes. Effect size was measured using Cohen's d. Patients also completed quality of life surveys using the FACT-Hep instrument at each study visit. Comparison between the 2 groups was performed using the Student t test. RESULTS: Each arm had 12 subjects; 4 patients dropped out in the EVR arm and 1 in the CNI arm by 24 months. Serum creatinine (P = 0.015), Modification of Diet in Renal Disease estimated glomerular filtration rate (P = 0.013), and 24-hour urine CrCL (P = 0.032) were significantly better at 24 months with EVR. Iothalamate clearance showed significant improvement at 12 months (P = 0.049) and a trend toward better renal function (P = 0.099) at 24 months. There was no statistical significance with Cockcroft-Gault CrCl. Adverse events were not significantly different between the 2 arms. The EVR group also showed significantly better physical, functional, and overall self-reported quality of life (P = 0.01) at 24 months. CONCLUSIONS: EVR with MPA resulted in significant long-term improvement in renal function and quality of life at 24 months after liver transplantation compared with standard CNI with MPA immunosuppression.
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Repeated measures are often collected in longitudinal follow-up from clinical trials and observational studies. In many situations, these measures are adherent to some specific event and are only available when it occurs; an example is serum creatinine from laboratory tests for hospitalized acute kidney injuries. The frequency of event recurrences is potentially correlated with overall health condition and hence may influence the distribution of the outcome measure of interest, leading to informative cluster size. In particular, there may be a large portion of subjects without any events, thus no longitudinal measures are available, which may be due to insusceptibility to such events or censoring before any events, and this zero-inflation nature of the data needs to be taken into account. On the other hand, there often exists a terminal event that may be correlated with the recurrent events. Previous work in this area suffered from the limitation that not all these issues were handled simultaneously. To address this deficiency, we propose a novel joint modeling approach for longitudinal data adjusting for zero-inflated and informative cluster size as well as a terminal event. A three-stage semiparametric likelihood-based approach is applied for parameter estimation and inference. Extensive simulations are conducted to evaluate the performance of our proposal. Finally, we utilize the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study for illustration.
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Modelos Estatísticos , Projetos de Pesquisa , Humanos , Funções Verossimilhança , Estudos Longitudinais , RecidivaRESUMO
BACKGROUND: Acute kidney injury (AKI) and obesity are independent risk factors for chronic kidney disease (CKD). This study aimed to determine if obesity modifies risk for CKD outcomes after AKI. METHODS: This prospective multisite cohort study followed adult survivors after hospitalization, with or without AKI. The primary outcome was a combined CKD event of incident CKD, progression of CKD and kidney failure, examined using time-to-event Cox proportional hazards models, adjusted for diabetes status, age, pre-existing CKD, cardiovascular disease status and intensive care unit admission, and stratified by study center. Body mass index (BMI) was added as an interaction term to examine effect modification by body size. RESULTS: The cohort included 769 participants with AKI and 769 matched controls. After median follow-up of 4.3 years, among AKI survivors, the rate of the combined CKD outcome was 84.7 per1000-person-years with BMI ≥30 kg/m2, 56.4 per 1000-person-years with BMI 25-29.9 kg/m2, and 72.6 per 1000-person-years with BMI 20-24.9 kg/m2. AKI was associated with a higher risk of combined CKD outcomes; adjusted-HR 2.43 (95%CI 1.87-3.16), with no evidence that this was modified by BMI (p for interaction = 0.3). After adjustment for competing risk of death, AKI remained associated with a higher risk of the combined CKD outcome (subdistribution-HR 2.27, 95%CI 1.76-2.92) and similarly, there was no detectable effect of BMI modifying this risk. CONCLUSIONS: In this post-hospitalization cohort, we found no evidence for obesity modifying the association between AKI and development or progression of CKD.