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1.
Kidney Int ; 105(2): 269-280, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37926421

ABSTRACT

Obesity is a leading risk factor for the development and progression of kidney disease and a major barrier to optimal management of patients with chronic kidney disease. While in the past anti-obesity drugs offered only modest weight loss efficacy in exchange for various safety and tolerability risks, a wave of safer, more tolerable, and more effective treatment options is transforming the management of obesity. This review evaluates current and future pharmacologic anti-obesity therapy in adults through a kidney-oriented lens. It also explores the goals of anti-obesity treatment, describes the underlying putative mechanisms of action, and raises important scientific questions that deserve further exploration in people with chronic kidney disease.


Subject(s)
Anti-Obesity Agents , Renal Insufficiency, Chronic , Adult , Humans , Obesity/complications , Obesity/drug therapy , Anti-Obesity Agents/adverse effects , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy
2.
Circulation ; 144(22): 1750-1759, 2021 11 30.
Article in English | MEDLINE | ID: mdl-34706555

ABSTRACT

BACKGROUND: Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function. METHODS: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL·min-1·1.73 m-2 (range, 17-123 mL·min-1·1.73 m-2). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59-0.85]; P=0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57-0.88]; P=0.001). The numeric reduction in cardiovascular death was greatest in the eGFR <60 mL·min-1·1.73 m-2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51-0.95]; P=0.02). Although patients with eGFR <60 mL·min-1·1.73 m-2 treated with icosapent ethyl had the highest numeric rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86-2.32]; P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90-2.18]; P=0.13), HRs for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter=0.92; P-interaction for serious bleeding=0.76). CONCLUSIONS: In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.


Subject(s)
Cardiovascular Diseases , Eicosapentaenoic Acid/analogs & derivatives , Glomerular Filtration Rate/drug effects , Renal Insufficiency, Chronic , Aged , Cardiovascular Diseases/complications , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/physiopathology , Double-Blind Method , Eicosapentaenoic Acid/administration & dosage , Eicosapentaenoic Acid/adverse effects , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/prevention & control
3.
Ann Surg ; 276(6): e784-e791, 2022 12 01.
Article in English | MEDLINE | ID: mdl-33914480

ABSTRACT

OBJECTIVE: A retrospective cohort study investigated the association between having surgery and risk of mortality for up to 5 years and if this association was modified by incident ESRD during the follow-up period. Summary of Background Data: Mortality risk in individuals with pre-dialysis CKD is high and few effective treatment options are available. Whether bariatric surgery can improve survival in people with CKD is unclear. METHODS: Patients with class II and III obesity and pre-dialysis CKD stages 3-5 who underwent bariatric surgery between January 1, 2006 and September 30, 2015 (n = 802) were matched to patients who did not have surgery (n = 4933). Mortality was obtained from state death records and ESRD was identified through state-based or healthcare system-based registries. Cox regression models were used to investigate the association between bariatric surgery and risk of mortality and if this was moderated by incident ESRD during the follow-up period. RESULTS: Patients were primarily women (79%), non-Hispanic White (72%), under 65 years old (64%), who had a body mass index > 40kg/m 2 (59%), diabetes (67%), and hypertension (89%). After adjusting for incident ESRD, bariatric surgery was associated with a 79% lower 5-year risk of mortality compared to matched controls (hazard ratio = 0.21; 95% confidence interval: 0.14-0.32; P < 0.001). Incident ESRD did not moderate the observed association between surgery and mortality (hazard ratio = 1.59; 95% confidence interval: 0.31-8.23; P =0.58). CONCLUSIONS: Bariatric surgery is associated with a reduction in mortality in pre-dialysis patients regardless of developing ESRD. These findings are significant because patients with CKD are at relatively high risk for death with few efficacious interventions available to improve survival.


Subject(s)
Bariatric Surgery , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Humans , Female , Aged , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Retrospective Studies , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/surgery , Bariatric Surgery/adverse effects , Proportional Hazards Models
4.
Am J Kidney Dis ; 79(3): 437-449, 2022 03.
Article in English | MEDLINE | ID: mdl-34862042

ABSTRACT

As chronic kidney disease (CKD) progresses, the requirements and utilization of different nutrients change substantially. These changes are accompanied by multiple nutritional and metabolic abnormalities that are observed in the continuum of kidney disease. To provide optimal care to patients with CKD, it is essential to have an understanding of the applicable nutritional principles: methods to assess nutritional status, establish patient-specific dietary needs, and prevent or treat potential or ongoing nutritional deficiencies and derangements. This installment of AJKD's Core Curriculum in Nephrology provides current information on these issues for the practicing clinician and allied health care workers and features basic, practical information on epidemiology, assessment, etiology, and prevention and management of nutritional considerations in patients with kidney disease. Specific emphasis is made on dietary intake and recommendations for dietary patterns, and macro- and micronutrients. In addition, special conditions such as acute kidney injury and approaches to obesity treatment are reviewed.


Subject(s)
Nutritional Status , Renal Insufficiency, Chronic , Curriculum , Dietary Supplements , Humans , Renal Dialysis , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy
5.
Am J Kidney Dis ; 80(6): 783-793, 2022 12.
Article in English | MEDLINE | ID: mdl-36280397

ABSTRACT

The National Kidney Foundation (NKF) and The Obesity Society (TOS) cosponsored a multispecialty international workshop in April 2021 to advance the understanding and management of obesity in adults with chronic kidney disease (CKD). The underlying rationale for the workshop was the accumulating evidence that obesity is a major contributor to CKD and adverse outcomes in individuals with CKD, and that effective treatment of obesity, including lifestyle intervention, weight loss medications, and metabolic surgery, can have beneficial effects. The attendees included a range of experts in the areas of kidney disease, obesity medicine, endocrinology, diabetes, bariatric/metabolic surgery, endoscopy, transplant surgery, and nutrition, as well as patients with obesity and CKD. The group identified strategies to increase patient and provider engagement in obesity management, outlined a collaborative action plan to engage nephrologists and obesity medicine experts in obesity management, and identified research opportunities to address gaps in knowledge about the interaction between obesity and kidney disease. The workshop's conclusions help lay the groundwork for development of an effective, scientifically based, and multidisciplinary approach to the management of obesity in people with CKD.


Subject(s)
Bariatric Surgery , Diabetes Mellitus , Renal Insufficiency, Chronic , Adult , Humans , Obesity/complications , Obesity/therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Kidney
6.
J Ren Nutr ; 32(4): 382-388, 2022 07.
Article in English | MEDLINE | ID: mdl-34334288

ABSTRACT

OBJECTIVE: The goal of this study was to systematically evaluate the quality of electronic applications (apps) available for chronic kidney disease (CKD) dietary management. METHODS: The review consisted of (1) a systematic search for all mobile CKD diet apps available on the App Store and Google Play Store, (2) an evaluation to determine how well existing apps met criteria for an ideal app, and (3) a systematic literature review of publications found through Google Scholar, Mendeley, and PubMed that reviewed specific CKD diet apps and the broader field. RESULTS: After applying systematic search criteria, 10 unique apps were identified. Ten of 14 criteria considered necessary in an ideal CKD diet app were applied to the 13 apps. Important criteria such as tailoring recommendations to CKD stage or individual dietary needs, tracking nutrient intake, allowing data to be accessible to clinicians, availability on different app platforms, and including CKD-friendly recipes were not consistently available in the apps. None of the apps used the most contemporary nutrition guidelines on which to base their recommendations. While the literature suggests there is demand for CKD diet apps, common shortcomings of available apps including barriers to usability, inclusion of erroneous information, the requirement of a high e-literacy level, user costs, lack of privacy, security, and interactive features, and the inability of caregivers or family members to use apps to assist in patient care. CONCLUSIONS: The few CKD dietary apps currently on the market for people with CKD have notable limitations in terms of content and software design. Opportunities therefore exist for improving on available CKD diet apps and thereby fulfilling an important unmet need for patients with CKD.


Subject(s)
Mobile Applications , Renal Insufficiency, Chronic , Diet , Energy Intake , Humans , Nutrition Policy
7.
J Ren Nutr ; 32(6): 768-771, 2022 11.
Article in English | MEDLINE | ID: mdl-35367357

ABSTRACT

OBJECTIVE: Type 2 diabetic kidney disease (DKD) is the most common global cause of kidney disease and failure. Obesity is a major risk factor for DKD due to its causal relationship with diabetes, hypertension, and other factors promoting kidney disease. We therefore investigated whether metabolic surgery such as Roux-en-Y gastric bypass is more effective than state-of-the-art medical therapy (i.e., renin-angiotensin-aldosterone system, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists) in treating DKD. DESIGN AND METHODS: In a post hoc analysis of the Microvascular Outcomes after Metabolic Surgery trial, we compared the likelihood of regression of microalbuminuria as the primary endpoint and other renal and metabolic secondary endpoints in a population of patients with obesity, type 2 diabetes, microalbuminuria, and early chronic kidney disease followed for 24 months. Nine patients underwent Roux-en-Y gastric bypass, and 24 patients were on state-of-the-art medical therapy. RESULTS: The gastric bypass arm had a significantly higher rate of regression of microalbuminuria (P < .001), borderline significant reduction in mean urine albumin-to-creatinine ratio (P = .055), and much greater weight loss (P = .001). There were no statistically significant differences between arms in estimated glomerular filtration rate, risk of developing estimated glomerular filtration rate <60 mL/min/1.73 m2 over 5 years, mean hemoglobin A1c, systolic blood pressure, low-density lipoprotein cholesterol, or the American Diabetes Association triple endpoint. CONCLUSION: We found that metabolic surgery offers more kidney protection than state-of-the-art triple therapy for DKD at 24 months. Prospective studies in this area are necessary to better define the benefits and risks of medical versus surgical treatment of DKD.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Gastric Bypass , Obesity, Morbid , Humans , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/surgery , Diabetic Nephropathies/complications , Prospective Studies , Treatment Outcome , Obesity/complications , Obesity/surgery , Obesity/epidemiology , Albuminuria/complications , Obesity, Morbid/complications , Obesity, Morbid/surgery
8.
J Am Soc Nephrol ; 32(4): 777-790, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33602674

ABSTRACT

Obesity is a leading public health problem that currently affects over 650 million individuals worldwide. Although interest in the adverse effects of obesity has grown exponentially in recent years, less attention has been given to studying its management in individuals with CKD. This relatively unexplored area should be considered a high priority because of the rapid growth and high prevalence of obesity in the CKD population, its broad impact on health and outcomes, and its modifiable nature. This article begins to lay the groundwork in this field by providing a comprehensive overview that critically evaluates the available evidence related to obesity and kidney disease, identifies important gaps in our knowledge base, and integrates recent insights in the pathophysiology of obesity to help provide a way forward in establishing guidelines as a basis for managing obesity in CKD. Finally, the article includes a kidney-centric algorithm for management of obesity that can be used in clinical practice.

9.
J Am Soc Nephrol ; 32(1): 161-176, 2021 01.
Article in English | MEDLINE | ID: mdl-33067383

ABSTRACT

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.


Subject(s)
Acute Kidney Injury/therapy , Acute Kidney Injury/virology , COVID-19/complications , Critical Care , Renal Replacement Therapy , Acute Kidney Injury/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Cohort Studies , Female , Hospital Mortality , Hospitalization , Humans , Incidence , Logistic Models , Male , Middle Aged , Risk Factors , Survival Rate , United States , Young Adult
10.
Int J Mol Sci ; 23(17)2022 Aug 29.
Article in English | MEDLINE | ID: mdl-36077177

ABSTRACT

Hemodialysis patients (HDPs) have higher blood pressure, higher levels of inflammation, a higher risk of cardiovascular disease, and unusually low plasma n-3 polyunsaturated fatty acid (PUFA) levels compared to healthy subjects. The objective of our investigation was to examine the levels of endocannabinoids (eCBs) and oxylipins (OxLs) in female HDPs compared to healthy matched female controls, with the underlying hypothesis that differences in specific PUFA levels in hemodialysis patients would result in changes in eCBs and OxLs. Plasma phospholipid fatty acids were analyzed by gas chromatography. Plasma was extracted and analyzed using ultra-performance liquid chromatography followed by electrospray ionization and tandem MS for eCBs and OxLs. The global untargeted metabolite profiling of plasma was performed by GCTOF MS. Compared to the controls, HDPs showed lower levels of plasma EPA and the associated OxL metabolites 5- and 12-HEPE, 14,15-DiHETE, as well as DHA derived 19(20)-EpDPE. Meanwhile, no changes in arachidonylethanolamide or 2-arachidonylglycerol in the open circulation were detected. Higher levels of multiple N-acylethanolamides, monoacylglycerols, biomarkers of progressive kidney disease, the nitric oxide metabolism-linked citrulline, and the uremic toxins kynurenine and creatine were observed in HDP. These metabolic differences in cCBs and OxLs help explain the severe inflammatory and cardiovascular disease manifested by HDPs, and they should be explored in future studies.


Subject(s)
Cardiovascular Diseases , Fatty Acids, Omega-3 , Cardiovascular Diseases/etiology , Endocannabinoids , Fatty Acids , Fatty Acids, Unsaturated , Female , Humans , Oxylipins , Renal Dialysis
11.
Am J Kidney Dis ; 76(3 Suppl 1): S1-S107, 2020 09.
Article in English | MEDLINE | ID: mdl-32829751

ABSTRACT

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for nutrition in kidney diseases since 1999. Since the publication of the first KDOQI nutrition guideline, there has been a great accumulation of new evidence regarding the management of nutritional aspects of kidney disease and sophistication in the guidelines process. The 2020 update to the KDOQI Clinical Practice Guideline for Nutrition in CKD was developed as a joint effort with the Academy of Nutrition and Dietetics (Academy). It provides comprehensive up-to-date information on the understanding and care of patients with chronic kidney disease (CKD), especially in terms of their metabolic and nutritional milieu for the practicing clinician and allied health care workers. The guideline was expanded to include not only patients with end-stage kidney disease or advanced CKD, but also patients with stages 1-5 CKD who are not receiving dialysis and patients with a functional kidney transplant. The updated guideline statements focus on 6 primary areas: nutritional assessment, medical nutrition therapy (MNT), dietary protein and energy intake, nutritional supplementation, micronutrients, and electrolytes. The guidelines primarily cover dietary management rather than all possible nutritional interventions. The evidence data and guideline statements were evaluated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.


Subject(s)
Nutrition Therapy/standards , Renal Insufficiency, Chronic/therapy , Diet, Protein-Restricted , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Dietary Supplements , Electrolytes/administration & dosage , Energy Intake , Evidence-Based Medicine , Fatty Acids, Omega-3/administration & dosage , Humans , Micronutrients/administration & dosage , Nutrition Assessment , Nutritional Support/methods , Renal Insufficiency, Chronic/diet therapy , Vitamins/administration & dosage
12.
Ren Fail ; 42(1): 624-628, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32654577

ABSTRACT

Bariatric surgery is known to attenuate glomerular hyperfiltration over the long term and thereby protect the kidney from mechanical damage. Whether this effect is directly related to weight loss or is independent of weight as are some of its other beneficial metabolic effects is not known. We explored this question in a preliminary study that directly measured glomerular filtration rate (GFR) before, immediately after, and again many months after Roux-en-Y gastric bypass after large weight loss had occurred. We simultaneously measured stimulated circulating glucagon-like peptide-1, which is upregulated after Roux-en-Y gastric bypass and is a putative mediator of GFR after bariatric surgery. We found no weight-independent effect of Roux-en-Y gastric bypass on GFR nor an association between circulating GLP-1 levels and GFR. These findings, if confirmed in larger studies, will help steer future enquiries in this area.


Subject(s)
Gastric Bypass , Glomerular Filtration Rate , Glucagon-Like Peptide 1/blood , Kidney/physiology , Obesity, Morbid/surgery , Biomarkers/blood , Body Mass Index , Female , Humans , Kidney/blood supply , Middle Aged , Weight Loss
13.
Curr Opin Nephrol Hypertens ; 28(6): 537-544, 2019 11.
Article in English | MEDLINE | ID: mdl-31436552

ABSTRACT

PURPOSE OF REVIEW: Through its direct adverse effects on the kidney and via associated intermediate disease states like type 2 diabetes and hypertension, obese has arguably become the master risk factor for chronic kidney disease (CKD). The purpose of this review is to critically evaluate bariatric surgery, which is the most effective weight reduction strategy available, as a renoprotective strategy. RECENT FINDINGS: Recent randomized studies confirm that bariatric surgery is effective at improving or even remitting major CKD risk factors such as type 2 diabetes and hypertension. In addition, observational studies performed primarily in patients without preexisting CKD report improvements in estimated glomerular filtration rate and albuminuria after bariatric surgery. Yet this literature is limited by study design, participant selection, statistical power, and measurement issues that must be overcome to better define kidney-related benefits, especially with regard to harder kidney-related and other clinical endpoints. SUMMARY: Encouraging data exist on the renoprotective effects of bariatric surgery. However, important knowledge gaps still remain. Future research should focus on studying, ideally in randomized fashion, the renoprotective effects of bariatric surgery in patients with preexisting CKD to better define the benefit-risk ratio for each patient.


Subject(s)
Bariatric Surgery/methods , Obesity/complications , Renal Insufficiency, Chronic/prevention & control , Glomerular Filtration Rate , Humans , Risk Factors , Weight Loss
14.
Am J Kidney Dis ; 74(6): 761-770, 2019 12.
Article in English | MEDLINE | ID: mdl-31331758

ABSTRACT

RATIONALE & OBJECTIVE: The association between bariatric surgery, type 2 diabetes, and chronic kidney disease (CKD) is poorly understood. We studied whether remission of type 2 diabetes induced by bariatric surgery influences markers of kidney disease, if CKD is associated with remission of diabetes after bariatric surgery, and if baseline levels of gut hormones and peptides modify these associations. STUDY DESIGN: Prospective observational study. STUDY PARTICIPANTS: 737 bariatric surgery patients with type 2 diabetes who participated in a multicenter cohort study for up to 5 years. PREDICTORS: Demographics, blood pressure, medications, type of bariatric surgery, anthropometrics, markers of kidney disease, and circulating levels of gut hormones and peptides. OUTCOMES: Estimated glomerular filtration rate (eGFR), urinary albumin excretion, prognostic risk for CKD, and remission of diabetes. ANALYTICAL APPROACH: Linear mixed models for eGFR; generalized linear mixed models with logit link for albuminuria, prognostic risk for CKD, and diabetes remission. RESULTS: Remission of diabetes at 5 years post-bariatric surgery was not independently associated with eGFR but was associated with lower risk for moderate/severe increase in albuminuria (risk ratio, 0.66; 95% CI, 0.48-0.90) and stabilization in prognostic risk for CKD. These findings were modified by baseline ghrelin level. Lower preoperative eGFR and greater prognostic risk for CKD were independently associated with reduced likelihood of diabetes remission. The association with preoperative GFR was modified by C-peptide level. Higher baseline circulating ghrelin level was independently associated with a lower prognostic risk for CKD. LIMITATIONS: A minority of participants had baseline CKD; lack of comparison group; no information on duration of diabetes, other clinical end points, or kidney biopsy results. CONCLUSIONS: Remission of type 2 diabetes 5 years after bariatric surgery was associated with improvements in albuminuria and stabilized prognostic risk for CKD, but not with eGFR. Lower kidney function and greater prognostic risk at the time of bariatric surgery was linked to a lower likelihood of diabetes remission. These results highlight the need to identify the mechanisms through which bariatric surgery may delay the long-term progression of CKD in type 2 diabetes.


Subject(s)
Bariatric Surgery/methods , Body Mass Index , Diabetes Mellitus, Type 2/epidemiology , Obesity/epidemiology , Renal Insufficiency, Chronic/epidemiology , Weight Loss/physiology , Blood Glucose/analysis , Cohort Studies , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Longitudinal Studies , Male , Middle Aged , Obesity/diagnosis , Patient Safety , Prospective Studies , Recovery of Function , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/therapy , Risk Assessment , Time Factors , Treatment Outcome
15.
J Am Soc Nephrol ; 29(4): 1289-1300, 2018 04.
Article in English | MEDLINE | ID: mdl-29335242

ABSTRACT

Obesity is linked to the development and progression of CKD, but whether bariatric surgery protects against CKD is poorly understood. We, therefore, examined whether bariatric surgery influences CKD risk. The study included 2144 adults who underwent bariatric surgery from March of 2006 to April of 2009 and participated in the Longitudinal Assessment of Bariatric Surgery-2 Study cohort. The primary outcome was CKD risk categories as assessed by the Kidney Disease Improving Global Outcomes (KDIGO) consortium criteria using a combination of eGFR and albuminuria. Patients were 79% women and 87% white, with a median age of 46 years old. Improvements were observed in CKD risk at 1 and 7 years after surgery in patients with moderate baseline CKD risk (63% and 53%, respectively), high baseline risk (78% and 56%, respectively), and very high baseline risk (59% and 23%, respectively). The proportion of patients whose CKD risk worsened was ≤10%; five patients developed ESRD. Sensitivity analyses using year 1 as baseline to minimize the effect of weight loss on serum creatinine and differing eGFR equations offered qualitatively similar results. Treatment with bariatric surgery associated with an improvement in CKD risk categories in a large proportion of patients for up to 7 years, especially in those with moderate and high baseline risk. These findings support consideration of CKD risk in evaluation for bariatric surgery and further study of bariatric surgery as a treatment for high-risk obese patients with CKD.


Subject(s)
Gastric Bypass , Gastroplasty , Obesity/complications , Renal Insufficiency, Chronic/prevention & control , Adult , Albuminuria/epidemiology , Albuminuria/etiology , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Laparoscopy , Male , Middle Aged , Obesity/surgery , Postoperative Complications/blood , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Period , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/etiology , Risk , Risk Reduction Behavior
16.
J Ren Nutr ; 27(5): 340-345, 2017 09.
Article in English | MEDLINE | ID: mdl-28533101

ABSTRACT

OBJECTIVE: Overweight and obesity have become increasingly common among end-stage renal disease patients on hemodialysis. Yet, little attention has been given to what hemodialysis patients themselves think of their weight, how they perceive it affects their health, and their attitudes about or desire for weight reduction. We explored these issues using a survey that we designed specifically for the dialysis population. DESIGN AND METHODS: Sixty-six chronic hemodialysis patients from a US urban center with a body mass index ≥25 kg/m2 and stable weight were recruited to participate in a cross-sectional study. The 12-question weight-related survey was validated by retesting a random portion of the study population. RESULTS: Based on test-retest results, the survey had good to excellent validity. Seventy-nine percent of patients were black, 49% were male, 29% were overweight, and 71% were obese. In general, the patients underestimated their weight excess though 73% were interested in weight loss, of whom nearly half reported attempting to do so mostly through diet and exercise. The majority of participants interested in losing weight felt that doing so would improve their physical and emotional health. The most common barrier to weight reduction was a belief that it was too difficult (55%), followed by a lack of motivation, money, time, resources, and knowledge. Diet was the most common weight loss strategy (85%) considered, whereas bariatric surgery was the least common (6.1%). CONCLUSIONS: A majority of overweight and obese hemodialysis patients believe their excess weight is adversely impacting their health and quality of life and therefore wish to lose weight.


Subject(s)
Attitude to Health , Kidney Failure, Chronic/therapy , Obesity/psychology , Overweight/psychology , Renal Dialysis , Adult , Aged , Body Mass Index , Body Weight , Cross-Sectional Studies , Diet , Exercise , Female , Health Knowledge, Attitudes, Practice , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/psychology , Male , Middle Aged , Motivation , Obesity/complications , Overweight/complications , Quality of Life , Urban Population , Weight Loss
17.
Am J Physiol Renal Physiol ; 310(8): F717-F725, 2016 04 15.
Article in English | MEDLINE | ID: mdl-26764206

ABSTRACT

The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical 18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.


Subject(s)
Glucose/metabolism , Kidney/diagnostic imaging , Microscopy, Fluorescence, Multiphoton/methods , Positron-Emission Tomography/methods , Animals , Deoxyglucose , Fluorine Radioisotopes , Kidney/metabolism , Male , Mice , Rats , Rats, Sprague-Dawley
18.
J Ren Nutr ; 25(3): 257-64, 2015 May.
Article in English | MEDLINE | ID: mdl-25446839

ABSTRACT

Because of concern that United States (US) chronic hemodialysis patients are at high risk for the development of vitamin deficiencies, the great majority of such patients are routinely supplemented with a multivitamin. This policy is supported by major US dialysis providers and nonprofit organizations. Yet routine multivitamin supplementation expands hemodialysis patients' already large pill burden, probably accounts for many millions of dollars in annual costs, and in light of previous reports may even carry with it the possibility of increased risk of adverse outcomes. An analysis of the benefits of routine multivitamin supplementation in US patients is therefore in order. We performed a systematic review of the medical literature between 1970 and 2014 using the Ovid MEDLINE database to address this question. We conclude that there is insufficient evidence to support routine multivitamin use and recommend that the decision to supplement be made on an individual basis.


Subject(s)
Renal Dialysis , Vitamins/administration & dosage , Adult , Avitaminosis/prevention & control , Dietary Supplements/adverse effects , Drug Costs , Humans , Nutritional Requirements , Renal Insufficiency, Chronic/therapy , United States , Vitamins/adverse effects , Vitamins/economics
19.
Am J Kidney Dis ; 63(4): 598-603, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24387796

ABSTRACT

BACKGROUND: Obesity-associated elevations in glomerular filtration rate (GFR) are common and may play a role in the development of kidney disease, so identifying the underlying mechanism is important. We therefore studied whether reductions in dietary protein intake, which is known to modulate GFR, explain why GFR decreases after bariatric surgery-induced weight loss. STUDY DESIGN: Cohort study with participants as their own controls. SETTING & PARTICIPANTS: 8 severely obese patients with normal kidney function were recruited from bariatric surgery centers in Indianapolis, IN. All participants were placed on a fixed-protein (50-g/d) diet for 1 week before and after a minimum of a 20-kg weight loss by bariatric surgery and were followed up closely by dieticians for adherence. PREDICTOR: Ad lib versus low-protein diet before versus after bariatric surgery. OUTCOME: Measured GFR, using repeated-measures analysis, was used to estimate the independent effects of diet and surgery. MEASUREMENT: GFR was measured using plasma iohexol clearance. RESULTS: A median of 32.9 (range, 19.5-54.4)kg was lost between the first presurgery visit and first postsurgery visit. Dietetic evaluations and urinary urea excretion confirmed that patients generally adhered to the study diet. GFRs on an ad lib diet were significantly higher before compared to after surgery (GFR medians were 144 (range, 114-178) and 107 (range, 85-147) mL/min, respectively; P=0.01). Although bariatric surgery (-26mL/min; P=0.005) and dietary sodium intake (+7.5mL/min per 100mg of dietary sodium; P=0.001) both influenced GFR, consuming a low-protein diet did not (P=0.7). LIMITATIONS: Small sample size; mostly white women; possible lack of generalizability. CONCLUSIONS: The decrease in GFR observed after bariatric surgery is explained at least in part by the effects of surgery and/or dietary sodium intake, but not by low dietary protein consumption.


Subject(s)
Bariatric Surgery , Dietary Proteins/administration & dosage , Glomerular Filtration Rate/physiology , Weight Loss/physiology , Adult , Cohort Studies , Diet, Protein-Restricted , Female , Humans , Male , Middle Aged , Postoperative Period , Preoperative Period , Sodium, Dietary/administration & dosage
20.
Am J Nephrol ; 39(1): 8-15, 2014.
Article in English | MEDLINE | ID: mdl-24356416

ABSTRACT

BACKGROUND/AIMS: Identifying the best method to estimate the glomerular filtration rate (GFR) in bariatric surgery patients has important implications for the clinical care of obese patients and research into the impact of obesity and weight reduction on kidney health. We therefore performed such an analysis in patients before and after surgical weight loss. METHODS: Fasting measured GFR (mGFR) by plasma iohexol clearance before and after bariatric surgery was obtained in 36 severely obese individuals. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using serum creatinine only, the CKD-EPI equation using serum cystatin C only and a recently derived equation that uses both serum creatinine and cystatin C (CKD-EPIcreat-cystC) and then compared to mGFR. RESULTS: Participants were primarily middle-aged white females with a mean baseline body mass index of 46 ± 9, serum creatinine of 0.81 ± 0.24 mg/dl and mGFR of 117 ± 40 ml/min. mGFR had a stronger linear relationship with inverse cystatin C before (r = 0.28, p = 0.09) and after (r = 0.38, p = 0.02) surgery compared to the inverse of creatinine (before: r = 0.26, p = 0.13; after: r = 0.11, p = 0.51). mGFR fell by 17 ± 35 ml/min (p = 0.007) following surgery. The CKD-EPIcreat-cystC was unquestionably the best overall performing estimating equation before and after surgery, revealing very little bias and a capacity to estimate mGFR within 30% of its true value over 80% of the time. This was true whether or not mGFR was indexed for body surface area. CONCLUSIONS: In severely obese bariatric surgery patients with normal kidney function, cystatin C is more strongly associated with mGFR than is serum creatinine. The CKD-EPIcreat-cystC equation best predicted mGFR both before and after surgery.


Subject(s)
Bariatric Surgery/methods , Glomerular Filtration Rate , Obesity/surgery , Adult , Body Surface Area , Body Weight , Creatinine/blood , Cystatin C/blood , Female , Humans , Iohexol/analysis , Kidney/physiology , Kidney Function Tests , Male , Middle Aged , Renal Insufficiency, Chronic/complications
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