Diversity of the midstream urine microbiome in adults with chronic kidney disease.

PURPOSE: To examine the characteristics of the midstream urine microbiome in adults with stage 3-5 non-dialysis-dependent chronic kidney disease (CKD). METHODS: Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2) and diuretic use were recruited from outpatient nephrology clinics. Midstream voided urine specimens were collected using the clean-catch method. The bacterial composition was determined by sequencing the hypervariable (V4) region of the bacterial 16S ribosomal RNA gene. Extraction negative controls (no urine) were included to assess the contribution of extraneous DNA from possible sources of contamination. Midstream urine microbiome diversity was assessed with the inverse Simpson, Chao and Shannon indices. The diversity measures were further examined by demographic characteristics and by comorbidities. RESULTS: The cohort of 41 women and 36 men with detectable bacterial DNA in their urine samples had a mean age of 71.5 years (standard deviation [SD] 7.9) years (range 60-91 years). The majority were white (68.0%) and a substantial minority were African-American (29.3%) The mean eGFR was 27.2 (SD 13.6) ml/min/1.73 m2. Most men (72.2%) were circumcised and 16.6% reported a remote history of prostate cancer. Many midstream voided urine specimens were dominated (> 50% reads) by the genera Corynebacterium (n = 11), Staphylococcus (n = 9), Streptococcus (n = 7), Lactobacillus (n = 7), Gardnerella (n = 7), Prevotella (n = 4), Escherichia_Shigella (n = 3), and Enterobacteriaceae (n = 2); the rest lacked a dominant genus. The samples had high levels of diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)]. Diversity measures were generally higher in participants with urgency urinary incontinence and higher estimated glomerular filtration rate (eGFR). After controlling for demographics and diabetes status, microbiome diversity was significantly associated with estimated eGFR (P < 0.05). CONCLUSIONS: The midstream voided urine microbiome of older adults with stage 3-5 non-dialysis-dependent CKD is diverse. Greater microbiome diversity is associated with higher eGFR.

Oral Anticoagulants to Prevent Stroke in Nonvalvular Atrial Fibrillation in Patients With CKD Stage 5D: An NKF-KDOQI Controversies Report.

Stroke risk may be more than 3-fold higher among patients with chronic kidney disease stage 5D (CKD-5D) compared to the general population, with the highest stroke rates noted among those 85 years and older. Atrial fibrillation (AF), a strong risk factor for stroke, is the most common arrhythmia and affects >7% of the population with CKD-5D. Warfarin use is widely acknowledged as an important intervention for stroke prevention with nonvalvular AF in the general population. However, use of oral anticoagulants for stroke prevention in patients with CKD-5D and nonvalvular AF continues to be debated by the nephrology community. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) controversies report, we discuss the existing observational studies that examine warfarin use and associated stroke and bleeding risks in adults with CKD-5D and AF. Non-vitamin K-dependent oral anticoagulants and their potential use for stroke prevention in patients with CKD-5D and nonvalvular AF are also discussed. Data from randomized clinical trials are urgently needed to determine the benefits and risks of oral anticoagulant use for stroke prevention in the setting of AF among patients with CKD-5D.

Inflammatory and Metabolic Syndrome Biomarker Analysis of Vascular Outcomes in End-stage Renal Disease.

End-stage renal disease (ESRD) presents a complex syndrome in which inflammatory and metabolic processes contribute to disease progression and development of comorbid conditions. Over $1 trillion is spent globally on ESRD care. Plasma samples collected from 83 ESRD patients prior to hemodialysis were profiled for metabolic and inflammatory biomarker concentrations. Concentrations were compared between groups with and without history of stroke, acute coronary syndrome (ACS), congestive heart failure (CHF), and coronary artery disease (CAD). The 25 patients (30.1%) with history of stroke demonstrated decreased plasma interferon-γ levels (p = 0.042) and elevated plasma resistin, interleukin (IL)-1α, and leptin levels (p = 0.008, 0.021, 0.026, respectively) when compared with ESRD patients without history of stroke. The 14 patients (16.9%) with history of ACS demonstrated elevated plasma IL-6 levels (p = 0.040) when compared with ESRD patients without history of ACS. The 30 patients (36.1%) with history of CHF demonstrated decreased plasma leptin levels (p = 0.031) and elevated plasma IL-1ß levels (p = 0.042) when compared with ESRD patients without history of CHF. Finally, the 39 patients (47.0%) with history of CAD demonstrated elevated plasma IL-1α levels (p = 0.049) when compared with ESRD patients without history of CAD. Plasma biomarker concentration disturbances were observed in ESRD patients with history of stroke, ACS, CHF, and CAD when compared with ESRD patients without such history. Proinflammatory biomarker elevations were seen in stroke, ACS, CHF and CAD, while adipocytokine aberrations were observed in both stroke and CHF. These studies demonstrate that biomarker profiling of vascular comorbidities in ESRD may provide useful diagnostic and prognostic information in the management of ESRD patients.

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey).

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min-1·1.73 m-2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Non-dialysis dependent chronic kidney disease is associated with high total and out-of-pocket healthcare expenditures.

BACKGROUND: Previous studies have documented the high costs of non-dialysis dependent chronic kidney disease (CKD) but out-of-pocket healthcare expenditures remain poorly explored. This study described total direct and out-of-pocket expenditures for adults with non-dialysis dependent CKD and compared expenditures with those for cancer or stroke. METHODS: This study used data from the 2011-2013 Medical Expenditure Panel Survey, a national survey of healthcare expenditures in the U.S. POPULATION: Expenditures were determined for adults with the following chronic diseases: CKD defined by 585 ICD9 codes (n = 52), cancer (colon, breast or bronchus/lung) (n = 870), or stroke (n = 1104). These represent adults who were aware of their conditions or visited a healthcare provider for the condition during the study period. Generalized linear models were used to estimate the marginal effects of CKD, cancer or stroke on adjusted expenditures compared to adults without CKD, cancer or stroke (n = 72,241) while controlling for demographics and co-morbidities and incorporating the sample weights of the complex survey design. RESULTS: The mean age for group with CKD, cancer or stroke was 65.5, 66.1, and 68.2 years, respectively, while mean age for group without CKD, cancer or stroke was 47.8 years. Median values of total direct and out of pocket healthcare expenditures ranged from as high as $12,877 (Interquartile Range [IQR] $5031-$19,710) and $1439 ($688-$2732), respectively, with CKD, to as low as $1189 (IQR $196-$4388) and $226 (IQR $20-$764) in the group without CKD, cancer or stroke. After adjusting for demographics and comorbidities, the adjusted difference in total direct healthcare expenditures was $4746 (95% CI $1775-$7718) for CKD, $8608 (95% CI $6167-$11,049) for cancer and $5992 (95% CI $4208-$7775) for stroke vs. group without CKD, cancer or stroke. Adjusted difference in out-of-pocket healthcare expenditures was highest for adults with CKD ($760; 95% CI 0-$1745) and was larger than difference noted for cancer ($419; 95% CI 158-679) or stroke ($246; 95% CI 87-406) relative to group without CKD, cancer or stroke. CONCLUSIONS: Total and out of pocket health expenditures for adults with non-dialysis dependent CKD are high and may be equal to or higher than expenditures incurred by adults with cancer or stroke.

Urinary incontinence and diuretic avoidance among adults with chronic kidney disease.

PURPOSE: Diuretics remain an important medication for hypertension management among adults with chronic kidney disease (CKD), but diuretics may also worsen urinary symptoms, especially urinary incontinence (UI). This single-center pilot study examined the prevalence of UI among adults age ≥60 years with CKD using diuretics and assessed diuretic avoidance due to urinary symptoms. METHODS: Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)) and diuretic use were recruited from outpatient nephrology clinics. Urinary symptoms and diuretic avoidance were assessed using standardized questionnaires. RESULTS: The cohort of 44 women and 54 men had a mean age of 71.8 (8.4) years, and urgency-UI, stress-UI and mixed-UI (the presence of both urgency-UI and stress-UI) were reported by 44.9 % (n = 44), 36.7 % (n = 36) and 26.5 % (n = 26), respectively. Nocturia was noted in 68 % (n = 67). Overall, 15.3 % (6 men and 9 women) reported diuretic avoidance. Avoidance of diuretics was 27.3 % (n = 12), 25.5 % (n = 9) and 34.6 % (n = 9) among participants with urgency-UI, stress-UI and mixed-UI, respectively, while only 6.8 % (n = 3) of participants without any UI reported diuretic avoidance. After adjusting for age, sex and diuretic type (loop vs. others), both urgency-UI (odds ratio 5.9 95 % CI 1.5-22.8) and mixed-UI (odds ratio 5.7; 95 % CI 1.6-19.9) were significantly associated with diuretic avoidance compared to participants without urgency-UI, or mixed-UI, respectively. Stress-UI and nocturia were not significantly associated with diuretic avoidance. CONCLUSIONS: UI is common among older adults with CKD receiving diuretics. Patients with urgency-UI are more likely to avoid diuretics.

Strategies to promote adherence to nutritional advice in patients with chronic kidney disease: a narrative review and commentary.

Chronic kidney disease (CKD) requires extensive changes to food and lifestyle. Poor adherence to diet, medications, and treatments has been estimated to vary between 20% and 70%, which in turn can contribute to increased mortality and morbidity. Delivering effective nutritional advice in patients with CKD coordinates multiple diet components including calories, protein, sodium, potassium, calcium, phosphorus, and fluid. Dietary intake studies have shown difficulty in adhering to the scope and complexity of the CKD diet parameters. No single educational or clinical strategy has been shown to be consistently effective across CKD populations. Highest adherence has been observed when both diet and education efforts are individualized to each patient and adapted over time to changing lifestyle and CKD variables. This narrative review and commentary summarizes nutrition education literature and published strategies for providing nutritional advice in CKD. A cohort of practical and effective strategies for increasing dietary adherence to nutritional advice are provided that include communicating with "talking control" principles, integrating patient-owned technology, acknowledging the typical food pattern may be snacking rather than formal meals, focusing on a single goal rather than multiple goals, creating active learning and coping strategies (frozen sandwiches, visual hands-on activities, planting herb gardens), and involving the total patient food environment.

Neurologic Complications of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an increasing problem worldwide and is now being recognized as a global health burden particularly for cardiovascular and cerebrovascular events. The incidence of stroke increases in the presence of CKD with a 3-fold increased rate reported in ESRD. Atrial fibrillation (AF) increases the risk of stroke in CKD. There is conflicting observational evidence regarding benefit of anticoagulation in CKD for prevention of stroke in AF as risk of bleeding is high. Overall, anticoagulant in CKD may be beneficial in appropriate patients with meticulous monitoring of international normalized ratio (INR). Neurological manifestations related to electrolyte disorders, drug toxicity, and uremia are common in CKD. Appropriate drug dosing, awareness of potential side effects of medications, prompt diagnosis, and treatment are essential in preventing long-term morbidity and mortality.

Medical nutrition therapy in adults with chronic kidney disease: integrating evidence and consensus into practice for the generalist registered dietitian nutritionist.

Chronic kidney disease is classified in stages 1 to 5 by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative depending on the level of renal function by glomerular filtration rate and, more recently, using further categorization depending on the level of glomerular filtration rate and albuminuria by the Kidney Disease Improving Global Outcomes initiative. Registered dietitian nutritionists can be reimbursed for medical nutrition therapy in chronic kidney disease stages 3 to 4 for specific clients under Center for Medicare and Medicaid Services coverage. This predialysis medical nutrition therapy counseling has been shown to both potentially delay progression to stage 5 (renal replacement therapy) and decrease first-year mortality after initiation of hemodialysis. The Joint Standards Task Force of the American Dietetic Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition Dietetic Practice Group, and the National Kidney Foundation Council on Renal Nutrition collaboratively published 2009 Standards of Practice and Standards of Professional Performance for generalist, specialty, and advanced practice registered dietitian nutritionists in nephrology care. The purpose of this article is to provide an update on current recommendations for screening, diagnosis, and treatment of adults with chronic kidney disease for application in clinical practice for the generalist registered dietitian nutritionist using the evidence-based library of the Academy of Nutrition and Dietetics, published clinical practice guidelines (ie, National Kidney Foundation Council on Renal Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition Care Process model, and peer-reviewed literature.

Nervous system disorders in dialysis patients.

Neurologic complications are frequently encountered in dialysis patients. These may be due to the uremic state or to dialysis therapy, and require careful assessment. With longer survival of dialysis patients, these neurologic complications may significantly affect morbidity, mortality, and patients' well-being. Central nervous system involvement includes uremic encephalopathy as well as dialysis disequilibrium disorder. Both are rarely seen because of current improved understanding of their pathogenesis and treatment. Manifestations of atherosclerosis, stroke, and other neuropathies are present in this population and are not significantly altered by dialysis therapy. In recent years, increasing numbers of sleep disorders are being recognized. Peripheral nervous system involvement is also noted, including myopathy and related categories. In this chapter, we address clinical and pathophysiologic aspects of nervous system disorders in dialysis patients while discussing available therapeutic options to address the neurologic involvement.

Nutrition interventions to address cardiovascular outcomes in chronic kidney disease.

The high mortality in chronic kidney disease has been linked to cardiovascular risk and these patients are considered at high risk. Dietary intervention can directly address nutritional risk factors in lipid management, calcium-phorphorus balance, and body composition to reduce risk of cardiovascular disease. Nutrient intake can also indirectly address less overt risks of dental health, nutritional supplements, and compliance issues.

Medical nutrition therapy in chronic kidney failure: integrating clinical practice guidelines.

This review updates earlier published recommendations and integrates current clinical practice guidelines for nutritional care in chronic kidney disease as recommended by the National Kidney Foundation Kidney Dialysis Outcome Quality Initiative (K/DOQI). The scope covers chronic kidney disease in adults prior to kidney failure (Stages 1-4), chronic kidney failure with hemodialysis or peritoneal dialysis replacement therapy (Stage 5), and management after kidney transplantation. Multiple diet parameters are necessary to provide optimal nutritional health, including monitoring of calories, protein, sodium, fluid, potassium, calcium, and phosphorus, as well as other individualized nutrients. Emphasis is placed on continuity of care within changing kidney function and treatment modality status. The rising incidence of chronic kidney disease will increase the probability of the non-renal specialist dietetics professional delivering care to this patient population.