Infectious disease is recognized as an important complication among patients with end-stage renal disease, contributing to excess morbidity and health care costs. However, recent epidemiological studies have revealed that even mild to moderate stages of chronic kidney disease (CKD) substantially increase risk of infection. Regarding underlying mechanisms, evidence suggests various aspects of altered immune response in patients with CKD including impaired function of T cells, B cells and neutrophil. Multiple conditions surrounding CKD, such as older age, diabetes, and cardiovascular disease are important contributors in the increased susceptibility to infection in this population. In addition, several mechanisms impairing immune function have been hypothesized including accumulated uremic toxins, increased oxidative stress, endothelial dysfunction, low-grade inflammation, and mineral and bone disorders. In terms of prevention strategies, influenza and pneumococcal vaccines are most feasible and important. Nevertheless, the extent of vaccine utilization in CKD has not been well documented. In addition, antibody response to vaccination may be reduced in CKD patients, and thus a vaccine delivery strategy (e.g., dose and frequency) may need to be optimized among patients with CKD. Through this review, we demonstrate that infection is a major but underrecognized complication of CKD. As CKD is recognized as a serious public health issue, dedicated research is needed to better characterize the burden of infectious disease associated with CKD, understand the pathophysiology of infection in patients with CKD, and develop effective strategies to prevent infection and its sequela in this high risk population.

Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60–65 versus <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR = 1.73, [95% CI 1.50–2.01]), hypertension (8 studies; 2.87 [2.09–3.93]), diabetes (9 studies; 3.20 [2.26–4.53]), and CVD (10 studies; 4.97 [3.76–6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19. Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be informative for predicting the risk of severe COVID-19.

A rest period of 3 to 5 minutes before blood pressure (BP) measurement is recommended in hypertension guidelines but can be challenging to implement. We conducted a randomized trial to determine the effects of resting for <5 minutes on BP. In a cross-over design, 113 participants (mean age 55 years, 36% male, 75% Black) had 4 sets of triplicate BP measurements with the order of rest for the first 3 sets (0 minutes, 2 minutes, 5 minutes ₁ ) randomized. The fourth set was always a second 5-minute rest period (5 minutes ₂ ), from which we calculated the difference between 5 minutes ₁ and 5 minutes ₂ (5 minutes ₁ −5 minutes ₂ ), a measure of intrinsic BP variability. To determine if there was no difference between BPs obtained after resting 0 minutes or 2 minutes versus 5 minutes ₁ , we tested whether 5 minutes ₁ −0 minutes or 5 minutes ₁ −2 minutes was within a prespecified noninferiority margin of ±2 mm Hg compared with 5 minutes ₁ −5 minutes ₂ . Overall, mean BP was similar across 5 minutes ₁ (128/75), 5 minutes ₂ (127/76), 2 minutes (127/74), and 0 minutes (127/74). Compared with the average absolute 5 minutes ₁ −5 minutes ₂ difference (5.3/3.0 mm Hg), the absolute systolic BP difference of differences did not cross our noninferiority margin for 0 minutes rest (0.2 [95% CI, 0.8–1.2]) but did for 2 minutes rest (−1.7 [−2.8 to −0.6]). Among those with systolic BP <140, the absolute difference of differences for both 0 and 2 minutes did not cross the ±2 mm Hg margin; however, those with systolic BP ≥140 had differences that did exceed this threshold. Our findings suggest that shorter rest periods may be a reasonable alternative to 5 minutes for most individuals. Implementation could substantially improve the efficiency of hypertension screening programs. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04031768.

Significance Statement: Whether incident cardiovascular disease increases the long-term risk of ESKD is not well studied. The authors assessed the association of incident major cardiovascular diseases (heart failure, atrial fibrillation, coronary heart disease, and stroke) with risk of ESKD in 9047 participants of a prospective cohort study. They found that each of these major cardiovascular diseases was significantly and independently associated with the risk of ESKD, with a particularly strong association for heart failure. The association was stronger for heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction. These findings highlight the importance of managing kidney disease after cardiovascular disease. The potentially distinct contribution to ESKD of heart failure with preserved ejection fraction versus heart failure with reduced ejection fraction deserves future investigation. Background: Cardiorenal syndrome is a well known concept, bolstered by extensive investigations of CKD as a risk factor of cardiovascular disease. However, data on whether cardiovascular disease increases long-term risk of ESKD are sparse. Methods: We assessed the association of incident hospitalization with major cardiovascular diseases (heart failure, atrial fibrillation, coronary heart disease, and stroke) with subsequent risk of ESKD among individuals enrolled in the Atherosclerosis Risk in Communities study; the analysis included 9047 individuals without prevalent cardiovascular disease at their fourth study visit. Each relevant incident cardiovascular disease event was entered into multivariable Cox proportional hazard models as a time-varying exposure to estimate hazard ratios. Results: During a median follow-up of 17.5 years, there were 2598 cases of hospitalization with cardiovascular disease (heart failure, n=1269; atrial fibrillation, n=1337; coronary heart disease, n=696; and stroke, n=559) and 210 cases of incident ESKD. The incidence of major cardiovascular disease was associated with increased risk of ESKD, with the highest risk for heart failure (hazard ratio, 11.40; 95% confidence interval, 8.38 to 15.50), followed by coronary heart disease, atrial fibrillation, and stroke. When we analyzed heart failure with preserved ejection fraction and heart failure with reduced ejection fraction separately, the risk was nominally higher for heart failure with preserved ejection fraction. Conclusions: Major incident cardiovascular disease events were associated with ESKD, independent of kidney risk factors. In particular, heart failure showed a very strong association with ESKD. Our findings highlight the importance of monitoring and managing kidney disease in patients with cardiovascular disease. The potentially distinct contribution to ESKD of heart failure with preserved versus reduced ejection fraction deserves future investigation.

The commonly accepted threshold of glomerular filtration rate (GFR) to define chronic kidney disease (CKD) is less than 60 mL/min/1.73 m². This threshold is based partly on associations between estimated GFR (eGFR) and the frequency of adverse outcomes. The association is weaker in older adults, which has created disagreement about the appropriateness of the threshold for these persons. In addition, the studies measuring these associations included relatively few outcomes and estimated GFR on the basis of creatinine level (eGFR_cr), which may be less accurate in older adults. To evaluate associations in older adults between eGFR_cr versus eGFR based on creatinine and cystatin C levels (eGFR_cr-cys) and 8 outcomes. Population-based cohort study. Stockholm, Sweden, 2010 to 2019. 82 154 participants aged 65 years or older with outpatient creatinine and cystatin C testing. Hazard ratios for all-cause mortality, cardiovascular mortality, and kidney failure with replacement therapy (KFRT); incidence rate ratios for recurrent hospitalizations, infection, myocardial infarction or stroke, heart failure, and acute kidney injury. The associations between eGFR_cr-cys and outcomes were monotonic, but most associations for eGFR_cr were U-shaped. In addition, eGFR_cr-cys was more strongly associated with outcomes than eGFR_cr. For example, the adjusted hazard ratios for 60 versus 80 mL/min/1.73 m² for all-cause mortality were 1.2 (95% CI, 1.1 to 1.3) for eGFR_cr-cys and 1.0 (CI, 0.9 to 1.0) for eGFR_cr, and for KFRT they were 2.6 (CI, 1.2 to 5.8) and 1.4 (CI, 0.7 to 2.8), respectively. Similar findings were observed in subgroups, including those with a urinary albumin-creatinine ratio below 30 mg/g. No GFR measurements. Compared with low eGFR_cr in older patients, low eGFR_cr-cys was more strongly associated with adverse outcomes and the associations were more uniform. Swedish Research Council, National Institutes of Health, and Dutch Kidney Foundation.