Search

Clinical trials have demonstrated cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). However, their impact on all-cause and cause-specific hospitalization in real-world practice remains unclear. We identified patients with diabetes who initiated SGLT2i (n = 2,492), GLP-1RA (n = 1,982), or dipeptidyl peptidase-4 inhibitors (DPP4i, n = 2,492) between 2015 and 2018 in Geisinger Health System. We examined all-cause hospitalization (net benefit indicator) and cardiovascular disease (CVD) hospitalization (CV benefit indicator), as well as non-CVD hospitalization (harm indicator), using Cox proportional hazards regression. During a median follow-up of 16 months, SGLT2i and GLP-1RA were associated with lower risk of all-cause hospitalization (hazard ratio [HR] 0.85, 95% CI 0.75 to 0.95 for SGLT2i; HR 0.89, 95% CI 0.78 to 0.98 for GLP-1RA), as well as CVD hospitalization (HR 0.61, 95% CI 0.47 to 0.79) for SGLT2i; HR 0.77, 95% CI 0.60 to 0.99 for GLP-1RA) compared with DPP4i. The risks of all-cause and CVD hospitalization were similar between SGLT2i and GLP-1RA. SGLT2i was associated with substantially lower risk of myocardial infarction and heart failure hospitalization compared with DPP4i and lower risk of heart failure hospitalization compared with GLP-1RA. The risk of non-CVD hospitalization did not differ among the treatment groups. These results from real-world comparison further encourage SGLT2i and GLP-1RA use in routine diabetes care, particularly among patients at high risk of cardiovascular events.

Potentially inappropriate medication (PIM) use is an important public health problem, particularly among older adults who may need multiple pharmacologic therapies for various chronic conditions. As socioeconomic status (SES) affects the quality of healthcare that individuals receive, SES may be associated with the use of PIM in older adults. This study aimed to determine whether low SES is associated with increased use of PIM.We studied 4927 participants (aged 66-90 years) who were on at least one medication at visit five (2011-2013) of the Atherosclerosis Risk in Communities Study. We created a cumulative SES score categorized as high (7-9), middle (3-6), and low (0-2) based on education, income, and area deprivation index. We use multivariable logistic regression to examine the associations between SES and use of two or more PIM for older adults, defined by the 2019 Beers Criteria.A total of 31.0% and 6.9% of the participants used one or more PIM and two or more PIM, respectively. After adjusting for demographic characteristics and insurance type, low cumulative SES score was associated with significantly greater use of two or more PIM (odds ratio [OR] = 1.83 [95% confidence interval (CI) 1.18-2.86]), as was middle cumulative SES score (OR = 1.40 [95% CI 1.06-1.83]), compared to high cumulative SES score. The results remained significant after further adjusting for comorbidities and medication burden for low cumulative SES score (OR = 1.66 [95%CI 1.02-2.71]).We found that lower SES was associated with greater use of PIM among older adults independent of their medication burden and comorbidities, suggesting socioeconomic disparities in quality of medication management. Focused efforts targeting older adults with low SES to reduce PIM use may be needed to prevent adverse drug events.

Abstract Objectives To characterize and compare glucose-lowering medication use in type 2 diabetes in the US, Sweden, and Israel, including adoption of newer medications and prescribing patterns. Research Design and Methods We used data from the National Health and Nutrition Examination Survey (NHANES) from the US, Stockholm CREAtinine Measurements project (SCREAM) from Sweden, and Maccabi Healthcare Services from Israel. Specific pharmacotherapy for type 2 diabetes between 2007 and 2018 were examined. Results Use of glucose-lowering medications among patients with type 2 diabetes was substantially lower in the US and SCREAM than in Maccabi (66.0% in NHANES, 68.4% in SCREAM, and 88.1% in Maccabi in 2017-2018). Among patients who took at least one glucose-lowering medication in 2017-2018, metformin use was also lower in the US and SCREAM (74.1% in NHANES, 75.9% in SCREAM, and 92.6% in Maccabi) whereas sulfonylureas use was greater in the US (31.5% in NHANES, 16.0% in SCREAM, and 14.9% in Maccabi). Adoption of DPP4i and SGLT2i were slower in the US and SCREAM than Maccabi. History of atherosclerotic cardiovascular disease, heart failure, reduced kidney function, and albuminuria were not consistently associated with greater use of SGLT2i or GLP1RA across the three countries. Conclusions There were substantial differences in real-world use of glucose-lowering medications across the US, Sweden, and Israel, with more optimal pharmacologic management in Israel. Variation in access to care and medication cost across countries may have contributed to these differences. SGLT2i and GLP1RA use in high-risk patients was limited in all three countries during this time period.

OBJECTIVE To characterize and compare glucose-lowering medication use in type 2 diabetes in the U.S., Sweden, and Israel, including adoption of newer medications and prescribing patterns. RESEARCH DESIGN AND METHODS We used data from the National Health and Nutrition Examination Survey (NHANES) from the U.S., the Stockholm CREAtinine Measurements (SCREAM) project from Sweden, and Maccabi Healthcare Services (Maccabi) from Israel. Specific pharmacotherapy for type 2 diabetes between 2007 and 2018 was examined. RESULTS Use of glucose-lowering medications among patients with type 2 diabetes was substantially lower in NHANES and SCREAM than in Maccabi (66.0% in NHANES, 68.4% in SCREAM, and 88.1% in Maccabi in 2017–2018). Among patients who took at least one glucose-lowering medication in 2017–2018, metformin use was also lower in NHANES and SCREAM (74.1% in NHANES, 75.9% in SCREAM, and 92.6% in Maccabi) whereas sulfonylureas use was greater in NHANES (31.5% in NHANES, 16.0% in SCREAM, and 14.9% in Maccabi). Adoption of dipeptidyl peptidase 4 inhibitors and sodium–glucose cotransporter 2 inhibitors (SGLT2i) was slower in NHANES and SCREAM than in Maccabi. History of atherosclerotic cardiovascular disease, heart failure, reduced kidney function, or albuminuria was not consistently associated with greater use of SGLT2i or glucagon-like peptide 1 receptor agonists (GLP1RA) across the three countries. CONCLUSIONS There were substantial differences in real-world use of glucose-lowering medications across the U.S., Sweden, and Israel, with more optimal pharmacologic management in Israel. Variation in access to care and medication cost across countries may have contributed to these differences. SGLT2i and GLP1RA use in patients at high risk was limited in all three countries during this time period.

Introduction: The use of potentially inappropriate medications (PIM), defined as medications for which the risk of adverse events outweighs the expected benefits, increases the risk of hospitalization, adverse drug events, and mortality in older adults. As socioeconomic status (SES) influences health care quality, the purpose of this study is to investigate whether PIM use differs by SES in older adults. Hypothesis: We hypothesized that low SES was independently associated with increased use of PIM. Methods: We studied participants (aged 66-90 years) who were on at least one medication at visit 5 (2011-2013) of the Atherosclerosis Risk in Communities (ARIC) Study. We created a cumulative SES score, based on neighborhood SES (area deprivation index [ADI]) as well as individual SES (education and income). Because PIM for older adults defined by the 2019 Beers Criteria was extremely common (31% of the population), we focused on the use of two or more PIM. We used multivariable logistic regression to examine the associations between SES and PIM use ≥2. Results: Among 4927 participants (mean age of 75.6 (SD 5.1) years, 19.6% Black, and 57.8% female), 6.9% were on two or more PIMs. Overall, compared with individuals with high cumulative SES, those with lower SES had higher odds of PIM use in a dose-dependent manner (odds ratio [OR]: 1.40 [95% confidence interval (CI), 1.06-1.83] for middle cumulative SES; 1.83 [1.18-2.86] for low cumulative SES, Table ), adjusting for demographics and insurance type. For each SES component, low neighborhood SES (i.e., high ADI) and low education was significantly associated with higher odds of PIM use, but not income. Conclusions: We found that lower SES was associated with greater use of PIM among older adults, suggesting that there exist disparities in quality of care by SES. Focused efforts targeting older adults with low SES to reduce PIM use may be needed to prevent adverse outcomes.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) impede glucose reabsorption in kidney proximal tubules, which in turn can stimulate osmotic diuresis, natriuresis, and the renin-angiotensin system. This mechanism may enhance potassium secretion via increased distal sodium and water delivery and

Introduction: Clinical trials have shown cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, adoption of SGLT2i in clinical practice has been slow, perhaps in part due to safety concerns. We aimed to assess the association between SGLT2i and risk of all-cause hospitalization as the totality of severe adverse events and benefits, comparing to risks associated with DPP4 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1RA). Methods: We identified patients with type 2 diabetes who initiated SGLT2i (n=2492), DPP4i (n=4762) or GLP1RA (n=1982) between 2015 and 2018 in Geisinger and performed 1:1 propensity score matching on SGLT2i (n=2171) vs. DPP4i (n=2171) and SGLT2i (n=1605) vs. GLP1RA (n=1605). We examined all-cause hospitalization as the main outcome. We also considered two positive controls (major adverse cardiovascular event [MACE] defined as cardiovascular death, myocardial infarction, and stroke; and heart failure [HF] hospitalization), and a negative control (hospitalization due to major bleeding). Results: Mean (SD) age was 58 (13) and 56 (13) years and 46% and 53% were women in the SGLT2i-DPP4i and SGLT2i-GLP1RA matched sample, respectively. During a median follow-up of 14 months, SGLT2i had similar risk of all-cause hospitalization compared with DPP4i (HR [95% CI] 0.85 [0.72-1.01]) or GLP1RA (HR 0.93 [0.77-1.13]). SGLT2i was associated with significantly lower risk of MACE and HF hospitalization compared with DPP4i (MACE: HR 0.70 [0.37, 0.98]; HF: HR 0.61 [0.38, 0.97]) but not with GLP1RA (MACE: HR 1.02 [0.50, 2.08]; HF: HR 0.72 [0.42, 1.23]). Risk of hospitalization due to bleeding was similar between SGLT2i vs. DPP4i or SGLT2i vs. GLP1RA. Conclusions: In this real-world comparison of antidiabetes medications, SGLT2i may be as safe as DPP4i with significant cardiac benefits and have comparable risk-benefit profiles compared with GLP1RA. These results further encourage SGLT2i use in routine diabetes care, particularly among patients at high risk of MACE. Disclosure B. Lyu: None. M. Grams: None. A. R. Chang: Advisory Panel; Self; Reata Pharmaceuticals, Inc., Relypsa Inc., Research Support; Self; Novo Nordisk Inc. L. A. Inker: None. J. Coresh: Consultant; Self; Healthy. io, Research Support; Self; National Institutes of Health, National Kidney Foundation. J. Shin: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K01DK121825)

Background Hypomagnesemia is common in kidney transplant recipients (KTRs). We sought to explore the relationship between Mg and outcomes in KTRs, which may be associated with mortality and thus, may be a potential intervention target to improve outcomes. Methods We followed KTRs performed between 01/2000 and 6/2016 at a large US transplant center from 6 months post-transplant to graft failure, death, or loss to follow-up. Using Mg as a time-dependent variable, associations between Mg and outcomes any time after 6-months post-transplant were evaluated. Results 3,680 KTRs with 50,413 Mg measurements met inclusion criteria. 657 deaths occurred over a median follow-up of 5.1 years. Compared to Mg of 1.5-1.8 mg/dL, both lower (HR 1.17, 95% Confidence interval (CI): 1.07-1.28) and higher (HR 1.16, 95% CI: 1.09-1.23) Mg levels were associated with greater risk of mortality. Similar U-shaped associations were observed for Mg and cardiovascular disease-related mortality (HR for Mg ≤1.5 mg/dL: 1.31; CI: 1.03-1.68) and infection-related mortality (HR for Mg ≤1.5 mg/dL: 1.28; CI: 1.09-1.51), although relationships for Mg >1.8 mg/dL were not statistically significant. Conclusions Mg exhibits a U-shaped association with mortality in KTRs, with levels between 1.5-1.8 mg/dL associated with the lowest risk.

Rationale & Objective Evidence is mixed regarding the optimal choice of the first permanent vascular access for elderly patients receiving hemodialysis (HD). Lacking data from randomized controlled trials, we used a target trial emulation approach to compare arteriovenous fistula (AVF) versus arteriovenous graft (AVG) creation among elderly patients receiving HD. Study Design Retrospective cohort study. Setting & Participants Elderly patients included in the US Renal Data System who initiated HD with a catheter and had an AVF or AVG created within 6 months of starting HD. Exposure Creation of an AVF versus an AVG as the incident arteriovenous access. Outcomes All-cause mortality, all-cause and cause-specific hospitalization, and sepsis. Analytical Approach Target trial emulation approach, high-dimensional propensity score and inverse probability of treatment weighting, and instrumental variable analysis using the proclivity of the operating physician to create a fistula as the instrumental variable. Results A total of 19,867 patients were included, with 80.1% receiving an AVF and 19.9% an AVG. In unweighted analysis, AVF creation was associated with significantly lower risks of mortality and hospitalization, especially within 6 months after vascular access creation. In inverse probability of treatment weighting analysis, AVF creation was associated with lower incidences of mortality and hospitalization within 6 months after creation (hazard ratios of 0.82 [95% CI, 0.75-0.91] and 0.82 [95% CI, 0.78-0.87] for mortality and all-cause hospitalization, respectively), but not between 6 months and 3 years after access creation. No association between AVF creation and mortality, sepsis, or all-cause, cardiovascular disease–related, or infection-related hospitalization was found in instrumental variable analyses. However, AVF creation was associated with a lower risk of access-related hospitalization not due to infection. Limitations Potential for unmeasured confounding, analyses limited to elderly patients, and absence of data on actual access use during follow-up. Conclusions Using observational data to emulate a target randomized controlled trial, the type of initial arteriovenous access created was not associated with the risks of mortality, sepsis, or all-cause, cardiovascular disease–related, or infection-related hospitalization among elderly patients who initiated HD with a catheter.

AIMS. Nondipping blood pressure (BP) is associated with higher risk for hypertension and advanced target organ damage. Insomnia is the most common sleep complaint in the general population. We sought to investigate the association between sleep quality and insomnia and BP nondipping cross-sectionally and longitudinally in a large, community-based sample. METHODS: A subset of the Wisconsin Sleep Cohort (n=502 for cross-sectional analysis and n=260 for longitudinal analysis) were enrolled in the analysis. Polysomnography measures were used to evaluate sleep quality. Insomnia symptoms were obtained by questionnaire. Blood pressure was measured by 24-hour ambulatory BP monitoring.Logistic regression models estimated cross-sectional associations of sleep quality and insomnia with BP nondipping. Poisson regression models estimated longitudinal associations between sleep quality and incident nondipping over a mean 7.4 years of follow-up. Systolic and diastolic nondipping were examined separately. RESULTS. In cross-sectional analyses, difficulty falling asleep, longer waking after sleep onset, shorter and longer total sleep time, lower sleep efficiency and lower rapid eye movement stage sleep were associated with higher risk of systolic and diastolic BP nondipping. In longitudinal analyses, the adjusted relative risks (95% confidence interval) of incident systolic nondipping were 2.1 (1.3–3.5) for 1 hour longer waking after sleep onset, 2.1 (1.1–5.1) for 7–8h total sleep time, and 3.7 (1.3–10.7) for ≥ 8h total sleep time (compared to total sleep time 6–7 hours), and 1.9 (1.1–3.4) for sleep efficiency

Despite advancements in symptom management for heart failure (HF), this devastating clinical syndrome remains the leading cause of death in the developed world. Studies using animal models have greatly advanced our understanding of the molecular mechanisms underlying HF; however, differences in cardiac physiology and the manifestation of HF between animals, particularly rodents, and humans necessitates the direct interrogation of human heart tissue samples. Nevertheless, an ever-present concern when examining human heart tissue samples is the potential for artefactual changes related to temperature changes during tissue shipment or sample processing. Herein, we examined the effects of temperature on the post-translational modifications (PTMs) of sarcomeric proteins, the proteins responsible for muscle contraction, under conditions mimicking those that might occur during tissue shipment or sample processing. Using a powerful top-down proteomics method, we found that sarcomeric protein PTMs were differentially affected by temperature. Specifically, cardiac troponin I and enigma homolog isoform 2 showed robust increases in phosphorylation when tissue was incubated at either 4 °C or 22 °C. The observed increase is likely due to increased cyclic AMP levels and activation of protein kinase A in the tissue. On the contrary, cardiac troponin T and myosin regulatory light chain phosphorylation decreased when tissue was incubated at 4 °C or 22 °C. Furthermore, significant protein degradation was also observed after incubation at 4 °C or 22 °C. Overall, these results indicate that temperature exerts various effects on sarcomeric protein PTMs and careful tissue handling is critical for studies involving human heart samples. Moreover, these findings highlight the power of top-down proteomics for examining the integrity of cardiac tissue samples.

Background: Arteriovenous (AV) access dysfunction is a common complication in hemodialysis patients. Markers of vascular calcification are associated with cardiovascular outcomes and mortality in this population, but their association with vascular access outcomes is unknown. In this study, we aimed to evaluate the association between selected vascular calcification makers and vascular access complications in a cohort of hemodialysis patients. Method: Fetuin-A, osteopontin (OPN), osteoprotegerin (OPG), and bone morphogenetic protein-7 (BMP-7) were measured in blood samples from 219 dialysis patients in the Choice for Healthy Outcomes in Caring for end-stage renal disease study; these patients were using a permanent vascular access. Participants were followed for up to 1 year or until the occurrence of a vascular access intervention or replacement. Associations with AV fistula (AVF) and AV graft (AVG) intervention-free survival were assessed in models adjusted for demographic characteristics, comorbidities, and inflammation. Results: A total of 24 out 103 participants with an AVF and 43 out of 116 participants with an AVG had an intervention during follow-up. Lower fetuin-A, higher OPN, and higher BMP-7 were associated with a higher risk of AVF intervention (adjusted hazard ratios [aHR] for highest versus lowest tertile = 0.30 [95% CI 0.10–0.94]) for fetuin-A, 3.84 (95% CI 1.16–12.74) for OPN, and 3.49 (95% CI 1.16–10.52) for BMP-7. OPG was not significantly associated with the risk of AVF intervention. The associations of OPN and BMP-7 with AVF intervention appeared stronger among participants without diabetes (aHR 8.06; 95% CI 1.11–58.57 for OPN and aHR 2.55; 95% CI 1.08–6.08 for BMP-7, respectively) than among their counterparts with diabetes (p interaction = 0.06). None of the markers studied were significantly associated with AVG interventions. Conclusion: Lower fetuin-A and higher OPN and BMP-7 are associated with complications in AVF but not in AVG, suggesting a role for calcification in the pathogenesis AVF failure.

Rationale & objective Creation of an arteriovenous fistula (AVF), compared to an AV graft (AVG), is associated with longer initial catheter dependence after starting hemodialysis but longer access survival and lower long-term catheter dependence. The extent of these potential long-term benefits in elderly patients is unknown. We assessed catheter dependence after AVF or AVG placement among elderly patients who initiated HD without a permanent access in place. Study design Retrospective cohort study. Setting& participants Patients ≥67 years of age identified in the United States Renal Data System (USRDS) who had a first AVF (n=14,532) or AVG (n=3391) placed within 1 year after HD initiation between May 2012 and May 2017. Exposure AVF versus AVG placement in first year of hemodialysis. Outcome Catheter dependence after AVF or AVG placement assessed using CROWNWeb data. ANALYTICAL APPROACH: - Generalized estimating equations and negative binomial regression for catheter use over time and Cox proportional hazards models for mortality. Results Creation of an AVF versus AVG was associated with greater catheter dependence at one month (95.6% vs. 92.5%) and at three months (82.8% vs. 41.2%), but lower catheter dependence at 12 months (14.2% vs. 15.8%) and at 36 months (8.2% vs. 15.0%). Creation of an AVF, however, remained significantly associated with greater cumulative catheter-dependent days (80.1 vs 54.6 days per person-year) and a lower proportion of catheter-free survival time (78.1% vs 85.1%) after three years of follow-up. Limitations Potential for unmeasured confounding and analyses limited to elderly patients. Conclusions Creation of an AVF was associated with significantly greater cumulative catheter dependence than placement of an AVG in an elderly population initiating HD without a permanent access. As the long-term benefits in terms of catheter dependency of an AVF are not realized in many elderly patients, specific patient characteristics should be considered when making decisions regarding vascular access.

The risk of subsequent cytomegalovirus infection (CMV) in kidney transplant recipients (KTR) after diagnosis of BK polyomavirus viremia (BKV) is unclear, and current evidence is conflicting. We reviewed all KTR transplanted at our institution between 1/1/2005 and 12/31/2015. Follow-up began 3 months after transplantation to avoid confounding effects of prophylaxis. Clinically significant BKV, defined as detectable BK viremia >1000 copies/mL via molecular diagnostic testing (PCR), was treated as a time-varying exposure with 1-year follow-up. This viral load cutoff was chosen to ensure a more homogenous population that would be considered to have clinically significant BK viremia that necessitated management via immunosuppressive modification. Patients were then screened for subsequent CMV infection. 2435 RTX recipients met inclusion criteria; of these, 314 developed BKV during follow-up (BK+). Lymphocyte depletion, tacrolimus maintenance, and biopsy-proven rejection were significantly higher in the BK+ group. BK+ was associated with lower risk of subsequent CMV infection (BK+ HR 0.45, 95% CI 0.22-0.94, P = .03, relative risk reduction 55%). When adjusted for significant confounding factors, CMV incidence remained reduced in the BK+ population (HR 0.47, 95% CI 0.22-0.98, P = .04). This large series of KTR demonstrates that BKV is associated with lower risk of subsequent CMV infection.

The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P < 0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P < 0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P < 0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28-2.96, P < 0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31-3.58, P < 0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65-5.09, P < 0.01) and mortality (HR 1.82, 95% CI: 1.12-4.24, P = 0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1 year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies.

Obstructive sleep apnea (OSA) is common but underdiagnosed among patients with kidney disease. This study examines whether the diagnosis of OSA in kidney transplant recipients (KTR) affected death, death-censored graft failure (DCGF), and acute rejection (AR). We analyzed the records of KTR who underwent transplant between 2000 and 2015. A total of 4014 kidney transplants were performed during the study period. Of these, 415 (10.3%) had a diagnosis of pretransplant OSA. Pretransplant OSA was associated with a higher risk of death in unadjusted analyses. After adjustment for potential confounders, pretransplant OSA was not associated with risk of death (HR = 1.04, 95% CI: 0.80-1.36). Similarly, pretransplant OSA was associated with a slightly higher incidence of DCGF or AR but neither associations were significant (HR: 1.23, 95% CI: 0.85-1.47 for DCGF; HR 1.10, 95% CI: 0.90-1.36 for AR). A total of 117 (3.3%) were diagnosed with de novo OSA after transplant. Similar to the pretransplant OSA, unadjusted HR for death was significantly higher in the de novo OSA group (HR: 1.48, 95% CI: 1.19-1.84); however, after adjustment, de novo OSA was not significantly associated with risk of death (HR: 1.15, 95% CI: 0.92-1.45). Similarly, DCGF and AR rates were not significantly associated with de novo OSA (HR: 1.10, 95% CI: 0.84-1.44 for DCGF; HR 1.10, 95% CI: 0.90-1.33 for AR). Our work did not detect significant associations between OSA and risk of death, graft failure, and rejection but the estimates might be underestimated due to underdiagnosis of OSA.

BACKGROUND Cytomegalovirus (CMV) infection in kidney transplant recipients has been anecdotally observed with concomitant or subsequent opportunistic infections (OI), but this association has yet to be defined or quantified. METHODS Patients who received a renal transplant between 1/1/2005 and 6/30/2014 and developed CMV infection were matched to controls in a ratio of 1:2 and the rates of opportunistic co-infection were calculated within pre-specified time frames (-30 days to +90 days and -30 days to +180 days). The primary outcome was composite OI rate, and secondary outcomes included time to OI and patient and graft outcomes. CMV-OI association rates were estimated via conditional logistic regression. RESULTS There were 2405 patients who received a renal transplant during the study period; 394 cases of CMV infection were identified. These cases were matched to 783 controls for a total of 805 participants. OI occurred in 14 patients in the CMV case group (CMV+) and in 5 patients in the control group (CMV-) in the -30 to +90 day time period (3.55% vs 0.64%, OR = 5.60, 95% CI: 2.02-12.55). When considering 180-day follow-up, OI occurred in 17 CMV+ patients and 8 CMV- patients (4.3% vs 1%, OR = 4.25, 95% CI: 1.83-9.85). Mean time from CMV diagnosis to OI was 33 ± 64 days (median 7 days). Mortality was 3 times more likely in the group with concomitant OI (CMV+/OI+) as compared to a matched cohort of patients with CMV infection without OI (CMV+/OI-) (unadjusted HR 3.02, 1.64-5.55, Tables 6 and 7). Cumulative survival for CMV+/OI+ patients was significantly worse than CMV+/OI- patients (P