Jordana B. Cohen

Cardiovascular and Renal Effects of Weight Reduction in Obesity and the Metabolic Syndrome

Obesity is a critical public health issue worldwide. Patients with obesity have markedly increased morbidity and mortality compared to the general population. The increased health risks of obesity in part are due to its close association with each of the other components of the metabolic syndrome, including hypertension, dyslipidemia, and insulin resistance. Accordingly, obese individuals are at particularly increased risk of cardiovascular disease and chronic kidney disease. Modest weight loss results in improvements in serum cholesterol levels, blood pressure, and glycemic profiles. Lifestyle interventions for weight loss have long been the mainstay of treatment in obesity. However, the existing literature demonstrates limited weight loss sustainability and inconsistent cardiovascular and renal benefits using these modalities. In addition to improvements in intermediate risk factors, surgical interventions provide a more lasting impact on long-term cardiovascular and renal outcomes, though carry higher short-term risks due to perioperative complications.

National outcomes of kidney transplantation from deceased diabetic donors

Use of deceased diabetic donor kidneys has increased over recent decades. However, scarce patient and allograft survival data are available taking into account recipient diabetes status. Here we performed a retrospective cohort study using data from the United Network of Organ Sharing in patients transplanted from 1994 to 2014. Multivariable Cox regression assessed recipient outcomes of 9, 074 diabetic versus 152, 555 non-diabetic donor kidneys. Recipients of diabetic donor kidneys had elevated rates of all-cause allograft failure (hazard ratio 1.21, 95% confidence interval 1.16-1.26) and death (1.19, 1.13-1.24) compared to recipients of kidneys from non-diabetic donors. Younger recipients of diabetic donor kidneys had worse allograft survival than older recipients of non-diabetic donor kidneys. There was significant interaction between donor and recipient diabetes status. To minimize the effect of unmeasured confounders, we used paired analyses of recipients of mate-kidneys from the same donor, with one diabetic recipient and the other non-diabetic. Among discordant recipient pairs of diabetic donor kidneys, diabetic recipients had significantly higher risk of allograft failure (1.27, 1.05-1.53) and death (1.53, 1.22-1.93) than non-diabetic recipients. After stratifying by Kidney Donor Profile Index risk category, diabetic recipients of diabetic donor kidneys continued to have worse allograft survival compared to all other patients. Thus, risks are associated with the use of diabetic donor kidneys. Understanding these risks will enable clinicians to better educate potential recipients.

Kidney allograft offers: Predictors of turndown and the impact of late organ acceptance on allograft survival

There is growing interest in understanding patterns of organ acceptance and reducing discard. Little is known about how donor factors, timing of procurement, and geographic location affect organ offer decisions. We performed a retrospective cohort study of 47 563 deceased donor kidney match‐runs from 2007 to 2013. Several characteristics unrelated to allograft quality were independently associated with later acceptance in the match‐run: Public Health Service increased‐risk donor status (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 2.29‐2.69), holiday or weekend procurement (aOR 1.11, 95% CI 1.07‐1.16), shorter donor stature (aOR 1.53 for <150 cm vs reference >180 cm, 95% CI 1.28‐1.94), and procurement in an area with higher intensity of market competition (aOR 1.71, 95% CI 1.62‐1.78) and with the longest waiting times (aOR 1.41, 95% CI 1.34‐1.49). Later acceptance in the match‐run was associated with delayed graft function but not all‐cause allograft failure (adjusted hazard ratio 1.01, 95% CI 0.96‐1.07). Study limitations include a lack of match‐run data for discarded organs and the possibility of sequence inaccuracies for some nonlocal matches. Interventions are needed to reduce turndowns of viable organs, especially when decisions are driven by infectious risk, weekend or holiday procurement, geography, or other donor characteristics unrelated to allograft quality.

Effect of kidney donor hepatitis C virus serostatus on renal transplant recipient and allograft outcomes

Abstract Background Hepatitis C virus (HCV) infection is common in dialysis patients and renal transplant recipients and has been associated with diminished patient and allograft survival. HCV-positive (HCV+) kidneys have been used in HCV-positive (HCV+) recipients as a means of facilitating transplantation and expanding the organ donor pool; however, the effect of donor HCV serostatus in the modern era is unknown. Methods Using national transplant registry data, we created a propensity score–matched cohort of HCV+ recipients who received HCV-positive donor kidneys compared to those transplanted with HCV-negative kidneys. Results Transplantation with an HCV+ kidney was associated with an increased risk of death {hazard ratio [HR] 1.43 [95% confidence interval (CI) 1.18–1.76]; P < 0.001} and allograft loss [HR 1.39 (95% CI 1.16–1.67); P < 0.001] compared with their propensity score–matched counterparts. However, HCV+ kidneys were not associated with an increased risk of acute rejection [odds ratio 1.16 (95% CI 0.84–1.61); P = 0.35]. Conclusions While use of HCV+ donor kidneys can shorten the wait for renal transplantation and maximize organ utility for all candidates on the waiting list, potential recipients should be counseled about the increased risks associated with HCV+ kidney.

Obesity, Renin-Angiotensin System Blockade and Risk of Adverse Renal Outcomes: A Population-Based Cohort Study.

Background: Obesity substantially increases the risk of the development of chronic kidney disease. Adipose tissue expresses all of the components of the renin-angiotensin system (RAS), contributing to the high prevalence of hypertension in obese patients and driving renal hyperfiltration and subsequent glomerular injury. Methods: We performed a retrospective cohort study using a United Kingdom primary care database, evaluating the effect of time-updated exposure to RAS blockade versus all other antihypertensive medications in obese, hypertensive, non-diabetic patients. We used Cox proportional hazards modeling with and without marginal structural modeling to assess the hazards of developing a primary outcome of 50% reduction in estimated glomerular filtration rate (eGFR) (across 2 consecutive values), end stage renal disease or death. Results: A total of 219,701 patients met inclusion criteria, with a median 7.2 years of follow-up. Median baseline eGFR was 72.6 ml/min/1.73 m2. Compared to other antihypertensive medications, patients treated with RAS blockade had a modestly elevated hazard of adverse renal outcomes using traditional Cox regression (hazard ratio (HR) 1.04, 95% CI 1.01-1.07) and no significantly increased hazard by marginal structural modeling (HR 1.02, 95% CI 0.97-1.08). Patients treated with RAS blockade had a significantly reduced hazard of incident diabetes, but no significant difference in mortality. Conclusion: This study, conducted in a large real-world cohort, provides evidence that RAS blockade may not provide benefit with regard to longitudinal renal outcomes in obese, hypertensive patients. Further research is needed to elucidate the hemodynamic and renoprotective role of antihypertensive medications in obese patients.

Belatacept Compared to Tacrolimus for Kidney Transplantation: A Propensity Score Matched Cohort Study.

Background Although tacrolimus is the basis of most maintenance immunosuppression regimens for kidney transplantation, concerns about toxicity have made alternative agents, such as belatacept, attractive to clinicians. However, limited data exist to directly compare outcomes with belatacept-based regimens to tacrolimus. Methods We performed a propensity score matched cohort study of adult kidney transplant recipients transplanted between May 1, 2001, and December 31, 2015, using national transplant registry data to compare patient and allograft survival in patients discharged from their index hospitalization on belatacept-based versus tacrolimus-based regimens. Results In the primary analysis, we found that belatacept was not associated with a statistically significant difference in risk of patient death (hazard ratio, 0.84; 95% confidence interval [CI], 0.61-1.15, P = 0.28) or allograft loss (hazard ratio, 0.83; 95% CI, 0.62-1.11; P = 0.20) despite an increased risk of acute rejection in the first year posttransplant (odds ratio, 3.12; 95% CI, 2.13-4.57; P < 0.001). These findings were confirmed in additional sensitivity analyses that accounted for use of belatacept in combination with tacrolimus, transplant center effects, and differing approaches to matching. Conclusions Belatacept appears to have similar longitudinal risk of mortality and allograft failure compared with tacrolimus-based regimens. These data are encouraging but require confirmation in prospective randomized controlled trials.

Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the Waitlist

BACKGROUND AND OBJECTIVES Use of diabetic donor kidneys has been a necessary response to the donor organ shortage. Recipients of diabetic donor kidneys have higher mortality risk compared with recipients of nondiabetic donor kidneys. However, the survival benefit of transplantation with diabetic donor kidneys over remaining on the waitlist has not been previously evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed an observational cohort study of 437,619 kidney transplant candidates from the Organ Procurement and Transplantation Network database, including 8101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. We used time-varying Cox proportional hazards modeling to assess the mortality risk of accepting a diabetic donor kidney compared with remaining on the waitlist or receiving a nondiabetic donor kidney. RESULTS Among transplant recipients, median follow-up was 8.9 years and mortality rate was 35 deaths per 1000 person-years. Recipients of diabetic donor kidneys had 9% lower mortality compared with remaining on the waitlist or transplantation with a nondiabetic donor kidney (adjusted hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.98). Although recipients of nondiabetic donor kidneys with a Kidney Donor Profile Index score >85% had lower mortality risk (adjusted hazard ratio, 0.86; 95% confidence interval, 0.81 to 0.91), recipients of diabetic donor kidneys with an index score >85% did not show any difference (adjusted hazard ratio, 1.09; 95% confidence interval, 0.97 to 1.22). Patients aged <40 years attained no survival benefit from transplantation with diabetic donor kidneys; diabetic patients at centers with long waitlist times attained the greatest survival benefit. CONCLUSIONS Diabetic donor kidneys appear associated with higher mortality risk compared with nondiabetic donor kidneys, but offer greater survival benefit compared with remaining on the waitlist for many candidates. Patients with high risk of mortality on the waitlist at centers with long wait times appear to benefit most from transplantation with diabetic donor kidneys.

Assessing the accuracy of the OMRON HEM-907XL oscillometric blood pressure measurement device in patients with nondialytic chronic kidney disease

The OMRON HEM−907XL is a commercial oscillometric blood pressure (BP) monitor that was used in the Systolic Blood Pressure Intervention Trial (SPRINT), in which 28% of participants had chronic kidney disease (CKD). This study examined the accuracy of the monitor in nondialytic patients with CKD. Eighty‐seven patients met inclusion criteria. The authors used a modified Association for the Advancement of Medical Instrumentation (AAMI) protocol, with one observer recording measurements from the monitor and two blinded physicians obtaining simultaneous aneroid values by auscultation. Using AAMI method 1, there was a 2.5±9.5 mm Hg difference in OMRON and aneroid systolic BP, and a −1.6±6.5 mm Hg difference in diastolic BP. Using AAMI method 2, there was a 5.1±7.4 mm Hg difference in systolic BP and a −0.2±5.4 mm Hg difference in diastolic BP. In patients with CKD, the OMRON HEM‐907XL appears to be accurate for measuring diastolic BP, but did not perform as well for systolic BP.

Hypertension in Obesity and the Impact of Weight Loss

Purpose of ReviewSeveral interrelated mechanisms promote the development of hypertension in obesity, often contributing to end organ damage including cardiovascular disease and chronic kidney disease.Recent FindingsThe treatment of hypertension in obesity is complicated by a high prevalence of resistant hypertension, as well as unpredictable hemodynamic effects of many medications. Weight loss stabilizes neurohormonal activity and causes clinically significant reductions in blood pressure. While lifestyle interventions can improve blood pressure, they fail to consistently yield sustained weight loss and have not demonstrated long-term benefits. Bariatric surgery provides more permanent weight reduction, corresponding with dramatic declines in blood pressure and attenuation of long-term cardiovascular risk.SummaryHypertension is closely linked to the prevalence, pathophysiology, and morbidity of obesity. There are multiple barriers to managing hypertension in obesity. Surgical weight loss offers the most promise in reducing blood pressure and decreasing end organ damage in this patient population.

Integrating Out-of-Office Blood Pressure in the Diagnosis and Management of Hypertension

Guidelines for the diagnosis and monitoring of hypertension were historically based on in-office blood pressure measurements. However, the US Preventive Services Task Force recently expanded their recommendations on screening for hypertension to include out-of-office blood pressure measurements to confirm the diagnosis of hypertension. Out-of-office blood pressure monitoring modalities, including ambulatory blood pressure monitoring and home blood pressure monitoring, are important tools in distinguishing between normotension, masked hypertension, white-coat hypertension, and sustained (including uncontrolled or drug-resistant) hypertension. Compared to in-office readings, out-of-office blood pressures are a greater predictor of renal and cardiac morbidity and mortality. There are multiple barriers to the implementation of out-of-office blood pressure monitoring which need to be overcome in order to promote more widespread use of these modalities.