George Thomas

Metabolic syndrome and kidney disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVESnObservational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS AND POPULATION: We searched MEDLINE (1966 to October 2010), SCOPUS, and the Web of Science for prospective cohort confidence interval (CI) studies that reported the development of microalbuminuria or proteinuria and/or CKD in participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m(2) were extracted from individual studies and pooled using a random effects model. The results for proteinuria outcomes were not pooled because of the small number of studies.nnnRESULTSnEleven studies (n = 30,146) were included. MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m(2) (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed to increase as the number of components of MetS increased (trend P value = 0.02). In patients with MetS, the odds ratios (95% CI) for development of eGFR <60 ml/min per 1.73 m(2) for individual components of MetS were: elevated blood pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS.nnnCONCLUSIONSnMetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m(2) and microalbuminuria or overt proteinuria.

Characteristics and Outcomes of Patients Presenting With Hypertensive Urgency in the Office Setting

IMPORTANCEnThe prevalence and short-term outcomes of hypertensive urgency (systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg) are unknown. Guidelines recommend achieving blood pressure control within 24 to 48 hours. However, some patients are referred to the emergency department (ED) or directly admitted to the hospital, and whether hospital management is associated with better outcomes is unknown.nnnOBJECTIVESnTo describe the prevalence of hypertensive urgency and the characteristics and short-term outcomes of these patients, and to determine whether referral to the hospital is associated with better outcomes than outpatient management.nnnDESIGN, SETTING, AND PARTICIPANTSnThis retrospective cohort study with propensity matching included all patients presenting with hypertensive urgency to an office in the Cleveland Clinic Healthcare system from January 1, 2008, to December 31, 2013. Pregnant women and patients referred to the hospital for symptoms or treatment of other conditions were excluded. Final follow-up was completed on June 30, 2014, and data were assessed from October 31, 2014, to May 31, 2015.nnnEXPOSURESnHospital vs ambulatory blood pressure management.nnnMAIN OUTCOMES AND MEASURESnMajor adverse cardiovascular events (MACE) consisting of acute coronary syndrome and stroke or transient ischemic attack, uncontrolled hypertension (≥140/90 mm Hg), and hospital admissions.nnnRESULTSnOf 2u202f199u202f019 unique patient office visits, 59u202f836 (4.6%) met the definition of hypertensive urgency. After excluding 851 patients, 58 535 were included. Mean (SD) age was 63.1 (15.4) years; 57.7% were women; and 76.0% were white. Mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 31.1 (7.6); mean (SD) systolic blood pressure, 182.5 (16.6) mm Hg; and mean (SD) diastolic blood pressure, 96.4 (15.8) mm Hg. In the propensity-matched analysis, the 852 patients sent home were compared with the 426 patients referred to the hospital, with no significant difference in MACE at 7 days (0 vs 2 [0.5%]; Pu2009=u2009.11), 8 to 30 days (0 vs 2 [0.5%]; Pu2009=u2009.11), or 6 months (8 [0.9%] vs 4 [0.9%]; Pu2009>u2009.99). Patients sent home were more likely to have uncontrolled hypertension at 1 month (735 of 852 [86.3%] vs 349 of 426 [81.9%]; Pu2009=u2009.04) but not at 6 months (393 of 608 [64.6%] vs 213 of 320 [66.6%]; Pu2009=u2009.56). Patients sent home had lower hospital admission rates at 7 days (40 [4.7%] vs 35 [8.2%]; Pu2009=u2009.01) and at 8 to 30 days (59 [6.9%] vs 48 [11.3%]; Pu2009=u2009.009).nnnCONCLUSIONS AND RELEVANCEnHypertensive urgency is common, but the rate of MACE in asymptomatic patients is very low. Visits to the ED were associated with more hospitalizations, but not improved outcomes. Most patients still had uncontrolled hypertension 6 months later.

Cardiac Resynchronization Therapy in CKD: A Systematic Review

BACKGROUNDnCardiac resynchronization therapy (CRT) confers morbidity and mortality benefits to selected patients with heart failure. This systematic review examined effects of CRT in CKD patients (estimated GFR [eGFR] <60 ml/min per 1.73 m(2)).nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnMEDLINE and Scopus (from 1990 to December 2012) and conference proceedings abstracts were searched for relevant observational studies and randomized controlled trials (RCTs). Studies comparing the following outcomes were included: (1) CKD patients with and without CRT and (2) CKD patients with CRT to non-CKD patients with CRT. Mortality, eGFR, and left ventricular ejection fraction data were extracted and pooled when appropriate using a random-effects model.nnnRESULTSnEighteen studies (14 observational studies and 4 RCTs) were included. There was a modest improvement in eGFR with CRT among CKD patients (mean difference 2.30 ml/min per 1.73m(2); 95% confidence interval, 0.33 to 4.27). Similarly, there was a significant improvement in left ventricular ejection with CRT in CKD patients (mean difference 6.24%; 95% confidence interval, 3.46 to 9.07). Subgroup analysis of three RCTs reported lower rates of death or hospitalization for heart failure with CRT (versus other therapy) in the CKD population. Survival outcomes of CKD patients (compared with the non-CKD population) with CRT differed among observational studies and RCTs.nnnCONCLUSIONSnCRT improves left ventricular and renal function in the CKD population with heart failure. Given the increasing use of cardiac devices, further studies examining the effects of CRT on mortality in CKD patients, particularly those with advanced kidney disease, are warranted.

Convective therapies for removal of middle molecular weight uremic toxins in end-stage renal disease: a review of the evidence.

The increasing number of patients requiring renal replacement therapy poses a challenge to maintain quality of care in the setting of limited resources. The commonly used modalities include hemodialysis and peritoneal dialysis, and using a “urea‐centric” model to increase the clearance of small molecular weight uremic toxins beyond current guidelines does not appear to confer additional clinical benefits in terms of morbidity and mortality. Convective therapies including hemofiltration and hemodiafiltration, which also have higher middle molecule clearances, might offer significant benefits compared to diffusive therapy. We review the available evidence on convective therapies and their effects on middle molecular weight uremic toxins, particularly β2 microglobulin because of its known associated morbidity. It is the authors’ opinion that more emphasis should be placed on true uremic toxins such as β2 microglobulin rather than surrogate uremic toxins like urea. Larger studies are also needed to study the merits of convective therapies, with a focus on cardiovascular morbidity and mortality.

Association of Metabolic Syndrome With Kidney Function and Histology in Living Kidney Donors

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMIu2009>u200925u2009kg/m2 instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, pu2009<u20090.001). This finding was associated with impaired kidney function recovery following donation. At last follow‐up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (pu2009<u20090.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

Renal denervation to treat resistant hypertension: Guarded optimism.

Renal sympathetic denervation has shown promise in treating hypertension resistant to drug therapy. This procedure lowers blood pressure via targeted attenuation of renal sympathetic tone, and it has a favorable safety profile. But although there is reason for cautious optimism, we should keep in mind that the mechanisms of hypertension are complex and multifactorial, and further study of this novel therapy and its long-term effects is needed. Can a percutaneous catheter-based procedure cure resistant hypertension? The limited data available so far look good.

Prevalence and Prognostic Significance of Apparent Treatment Resistant Hypertension in Chronic Kidney Disease: Report from the Chronic Renal Insufficiency Cohort Study

The association between apparent treatment resistant hypertension (ATRH) and clinical outcomes is not well studied in chronic kidney disease. We analyzed data on 3367 hypertensive participants in the Chronic Renal Insufficiency Cohort (CRIC) to determine prevalence, associations, and clinical outcomes of ATRH in nondialysis chronic kidney disease patients. ATRH was defined as blood pressure ≥140/90 mm Hg on ≥3 antihypertensives, or use of ≥4 antihypertensives with blood pressure at goal at baseline visit. Prevalence of ATRH was 40.4%. Older age, male sex, black race, diabetes mellitus, and higher body mass index were independently associated with higher odds of having ATRH. Participants with ATRH had a higher risk of clinical events than participants without ATRH—composite of myocardial infarction, stroke, peripheral arterial disease, congestive heart failure (CHF), and all-cause mortality (hazard ratio [95% confidence interval], 1.38 [1.22–1.56]); renal events (1.28 [1.11–1.46]); CHF (1.66 [1.38–2.00]); and all-cause mortality (1.24 [1.06–1.45]). The subset of participants with ATRH and blood pressure at goal on ≥4 medications also had higher risk for composite of myocardial infarction, stroke, peripheral arterial disease, CHF, and all-cause mortality (hazard ratio [95% confidence interval], (1.30 [1.12–1.51]) and CHF (1.59 [1.28–1.99]) than those without ATRH. ATRH was associated with significantly higher risk for CHF and renal events only among those with estimated glomerular filtration rate ≥30 mL/min per 1.73 m2. Our findings show that ATRH is common and associated with high risk of adverse outcomes in a cohort of patients with chronic kidney disease. This underscores the need for early identification and management of patients with ATRH and chronic kidney disease.

Renal Resistive Index and Mortality in Chronic Kidney Disease

Renal resistive index (RRI) measured by Doppler ultrasonography is associated with cardiovascular events and mortality in hypertensive, diabetic, and elderly patients. We studied the factors associated with high RRI (≥0.70) and its associations with mortality in chronic kidney disease patients without renal artery stenosis. We included 1962 patients with an estimated glomerular filtration rate of 15 to 59 mL/min per 1.73 m2 who also had RRI measured (January 1, 2005, to October 2011) from an existing chronic kidney disease registry. Participants with renal artery stenosis (60%–99% or renal artery occlusion) were excluded. Multivariable logistic regression model was used to study factors associated with high RRI (≥0.70), and its association with mortality was studied using Kaplan–Meier plots and Cox proportional hazards model. Hypertension was prevalent in >90% of the patients. In the multivariable logistic regression, older age, female sex, diabetes mellitus, coronary artery disease, peripheral vascular disease, higher systolic blood pressure, and the use of &bgr; blockers were associated with higher odds of having RRI≥0.70. During a median follow-up of 2.2 years, 428 patients died. After adjusting for covariates, RRI≥0.70 was associated with increased mortality (adjusted hazard ratio, 1.29; 95% confidence interval, 1.02–1.65; P<0.05). This association was more pronounced among younger patients and those with stage 3 chronic kidney disease. Noncardiovascular/non–malignancy-related deaths were higher in those with RRI≥0.70. RRI≥0.70 is associated with higher mortality in hypertensive chronic kidney disease patients without clinically significant renal artery stenosis after accounting for other significant risk factors. Its evaluation may allow early identification of those who are at risk thereby potentially preventing or delaying adverse outcomes.

Particle emissions from microalgae biodiesel combustion and their relative oxidative potential

Microalgae are considered to be one of the most viable biodiesel feedstocks for the future due to their potential for providing economical, sustainable and cleaner alternatives to petroleum diesel. This study investigated the particle emissions from a commercially cultured microalgae and higher plant biodiesels at different blending ratios. With a high amount of long carbon chain lengths fatty acid methyl esters (C20 to C22), the microalgal biodiesel used had a vastly different average carbon chain length and level of unsaturation to conventional biodiesel, which significantly influenced particle emissions. Smaller blend percentages showed a larger reduction in particle emission than blend percentages of over 20%. This was due to the formation of a significant nucleation mode for the higher blends. In addition measurements of reactive oxygen species (ROS), showed that the oxidative potential of particles emitted from the microalgal biodiesel combustion were lower than that of regular diesel. Biodiesel oxygen content was less effective in suppressing particle emissions for biodiesels containing a high amount of polyunsaturated C20-C22 fatty acid methyl esters and generated significantly increased nucleation mode particle emissions. The observed increase in nucleation mode particle emission is postulated to be caused by very low volatility, high boiling point and high density, viscosity and surface tension of the microalgal biodiesel tested here. Therefore, in order to achieve similar PM (particulate matter) emission benefits for microalgal biodiesel likewise to conventional biodiesel, fatty acid methyl esters (FAMEs) with high amounts of polyunsaturated long-chain fatty acids (≥C20) may not be desirable in microalgal biodiesel composition.

Effect of Intensive Insulin Therapy and Pentastarch Resuscitation on Acute Kidney Injury in Severe Sepsis

Critically ill patients frequently develop acute kidney injury (AKI), particularly in the setting of advanced age and comorbidities superimposed on sepsis and acute circulatory or respiratory failure. 1 Hyperglycemia is also common during critical illness, 2 and tight glycemic control has been reported to decrease mortality in some critically ill patients, with secondary outcomes showing a lower incidence of AKI. 3-6 Patients with sepsis require fluid resuscitation to avoid decreased perfusion and organ dysfunction, including AKI. There is continued debate about the use of crystalloids versus colloids for volume replacement in patients with sepsis. 7,8 Colloid solutions may be useful in situations of major volume depletion and increased capillary permeability for improving tissue perfusion. Colloid solutions include hydroxyethyl starches (HESs), gelatin, dextran, and the natural colloid albumin. The selection of colloids depends on safety profiles, cost, and availability, with HES preparations widely used in Europe. Several HES preparations are available, with different combinations of molecular weight (MW) and molar substitution. 9 Reported adverse effects of HESs include coagulopathy, anaphylactoid reactions, and renal impairment, which was recently summarized in the American Journal of Kidney Diseases. 10