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In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.

Background and Purpose-White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. Methods-The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and Ͼ90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race-ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. Results-Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (␤ 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (␤ 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (␤ 1.479; 95% CI, 1.067 to 2.050). Conclusions-The association between moderate-severe chronic kidney disease and white matter hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and/or as a marker of microangiopathy.

Cognitive impairment and chronic kidney disease (CKD) will become increasingly prevalent in the aging US population. Although evidence exists that CKD is a risk factor for cognitive decline, longitudinal studies are limited and largely have excluded ethnically diverse populations. The Northern Manhattan Study includes a population-based, prospective, stroke-free cohort. We assessed global cognitive function annually using the modified Telephone Interview for Cognitive Status (TICS-m) and estimated kidney function using CockcroftGault creatinine clearance (CCl), Modification of Diet in Renal Disease estimated GFR (eGFR), and serum creatinine (sCr). We examined the association between CKD and change in TICS-m scores over time, adjusting for sociodemographic and vascular risk factors. Of 2172 subjects (mean age 71.5 yr, mean follow-up 2.9 yr), 59% were Hispanic, 20% were black, and 63% were women. Participants with a CCl Ͻ60 ml/min and those with a CCl between 60 and 90 ml/min performed significantly worse on the TICS-m over time than those with a CCl Ͼ90 ml/min, adjusting for potential confounders. Our results were similar when we used eGFR or sCr to estimate kidney function. In conclusion, decreased kidney function associates with greater cognitive decline, even in those with mild CKD. Kidney disease may represent a novel mechanism leading to cognitive impairment and a target for early intervention.

Background and objectives Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function.Design, setting, participants, & measurements This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR,60 ml/min per 1.73 m 2 using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline ($2.5 ml/min per 1.73 m 2 per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors.Results Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m 2 . Incident eGFR,60 ml/min per 1.73 m 2 developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR,60 ml/min per 1.73 m 2 (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98).Conclusions A Mediterranean diet was associated with a reduced incidence of eGFR,60 ml/min per 1.73 m 2 and upper quartile of eGFR decline in a multiethnic cohort.

Background Acute kidney injury (AKI) is common and associates with poor clinical outcomes. Information about the incidence of AKI and effect on stroke outcomes is limited. Methods Data were analyzed from a registry of subjects with ischemic stroke and intracerebral hemorrhage (ICH) hospitalized at a single academic medical center. Admission creatinine was considered to be the baseline. AKI was defined as a creatinine increase of 0.3 mg/dL or a percentage increase of at least 50% from baseline, occurring during hospitalization. Multivariate logistic regression models were created for both stroke types, with hospital mortality as the outcome. Covariates included gender, race, age, admission creatinine, admission NIH Stroke Scale score, performance of contrast-enhanced CT scan of the head and neck, and medical co-morbidities. Results There were 528 cases of ischemic stroke with 70 deaths (13%), and 829 cases of ICH with 268 deaths (32%). The mean age was 64 years, with 56% men and 71% whites. AKI complicated 14% of ischemic stroke and 21% of ICH hospitalizations. In multivariate analysis stratified by stroke type, AKI was associated with increased hospital mortality from ischemic stroke (odds ratio (OR) 3.08, 95% confidence interval (CI) [1.49–6.35]) but not ICH (OR 0.82, 95% CI [0.50–1.35]), except for those surviving at least two days (OR 2.11, 95% CI [1.18–3.77]). Conclusions AKI occurs frequently after stroke and is associated with increased hospital mortality. Further studies are needed to establish if the association is causal and if measures to prevent AKI would result in decreased mortality.

Objective To improve global vascular risk prediction with behavioral and anthropometric factors. Background Few cardiovascular risk models are designed to predict the global vascular risk of MI, stroke, or vascular death in multi-ethnic individuals, and existing schemes do not fully include behavioral risk factors. Methods A randomly-derived, population-based, prospective cohort of 2737 community participants free of stroke and coronary artery disease were followed annually for a median of 9.0 years in the Northern Manhattan Study (mean age 69 years; 63.2% women; 52.7% Hispanic, 24.9% African-American, 19.9% white). A global vascular risk score (GVRS) predictive of stroke, myocardial infarction, or vascular death was developed by adding variables to the traditional Framingham cardiovascular variables based on the likelihood ratio criterion. Model utility was assessed through receiver operating characteristics, calibration, and effect on reclassification of subjects. Results Variables which significantly added to the traditional Framingham profile included waist circumference, alcohol consumption, and physical activity. Continuous measures for blood pressure and fasting blood sugar were used instead of hypertension and diabetes. Ten -year event-free probabilities were 0.95 for the first quartile of GVRS, 0.89 for the second quartile, 0.79 for the third quartile, and 0.56 for the fourth quartile. The addition of behavioral factors in our model improved prediction of 10 -year event rates compared to a model restricted to the traditional variables. Conclusion A global vascular risk score that combines both traditional, behavioral, and anthropometric risk factors, uses continuous variables for physiological parameters, and is applicable to non-white subjects could improve primary prevention strategies.

Introduction Reports from the United States suggest that acute kidney injury (AKI) frequently complicates COVID-19, but understanding of AKI risks and outcomes is incomplete. Additionally, whether kidney outcomes have evolved during the course of the pandemic is unknown. Methods We used electronic records to identify COVID-19 patients with and without AKI admitted to 3 New York Hospitals between March 2 and August 25, 2020. Outcomes included AKI overall and according to admission week, AKI stage, the requirement for new renal replacement therapy (RRT), mortality and recovery of kidney function. Logistic regression was utilized to assess associations of patient characteristics and outcomes. Results Out of 4732 admissions 1386 (29.3%) patients had AKI. Among those with AKI, 717 (51.7%) had Stage 1, 132 (9.5%) Stage 2, 537 (38.7%) stage 3, and 237 (17.1%) required RRT initiation. In March 536/1648 (32.5%) of patients developed AKI compared with 15/87 (17.2%) in August (P<0.001 for monthly trend) whereas RRT initiation was required in 6.9% and 0% of admission, in March and August respectively. Mortality was higher with than without AKI (51.6% vs 8.6%) and was 71.9% in individuals requiring RRT. However, most patients with AKI who survived hospitalization (77%) recovered to within 0.3 mg/dL of baseline creatinine. Among those surviving to discharge, 62% discontinued RRT. Conclusions AKI impacts a high proportion of admitted COVID-19 patients and is associated with high mortality, particularly when RRT is required. AKI incidence appears to be decreasing over time and kidney function frequently recovers in those who survive.