Chronic kidney disease (CKD) affects >10% of the adult population. Each year, approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which is costly and associated ...with functional impairments, worse health-related quality of life, and high early-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The scientific premise of the PLADO stems from the observations that high protein diets with high meat intake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of constipation with resulting hyperkalemia from the typical low fiber intake. A plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.
Background Kidney biopsy provides important information for nephrologists, but the risk of complications has not been systematically described. Study Design Meta-analysis of randomized controlled ...trials and prospective or retrospective observational studies. Setting & Population Adults undergoing native kidney biopsy in an inpatient or outpatient setting. Selection Criteria for Studies MEDLINE indexed studies from January 1980 through June 2011; sample size of 50 or more. Intervention Native kidney biopsy with automated biopsy device and real-time ultrasonographic guidance. Outcomes Macroscopic hematuria and erythrocyte transfusion rates and factors associated with these outcomes. Results 34 studies of 9,474 biopsies met inclusion criteria. The rate of macroscopic hematuria was 3.5% (95% CI, 2.2%-5.1%), and erythrocyte transfusion was 0.9% (95% CI, 0.4%-1.5%). Significantly higher rates of transfusion were seen with the following: 14-gauge compared with smaller needles (2.1% vs 0.5%; P = 0.009), studies with mean serum creatinine level ≥2.0 mg/dL (2.1% vs 0.4%; P = 0.02), ≥50% women (1.9% vs 0.6%; P = 0.03), and ≥10% of biopsies for acute kidney injury (1.1% vs 0.04%; P < 0.001). Higher transfusion rates also were observed in studies with a mean age of 40 years or older (1.0% vs 0.2%; P = 0.2) and mean systolic blood pressure ≥130 mm Hg (1.4% vs 0.1%; P = 0.09). Similar relationships were noted for the macroscopic hematuria rate with the same predictors, but none was statistically significant. Limitations Publication bias, few randomized controlled trials, and missing data. Conclusions Native kidney biopsy using automated biopsy devices and real-time ultrasonography is associated with a relatively small risk of macroscopic hematuria and erythrocyte transfusion requirement. Using smaller gauge needles may lower complication rates. Patient selection may affect outcome because studies with higher serum creatinine levels, more women, and higher rates of acute kidney injury had higher complication rates. Future studies should further evaluate risk factors for complications.
Background. Kidney failure is associated with muscle wasting and physical impairment. Moderate- to high-intensity strength training improves physical performance, nutritional status and quality of ...life in people with chronic kidney disease and in dialysis patients. However, the effect of low-intensity strength training has not been well documented, thus representing the objective of this pilot study. Methods. Fifty participants (mean ± SD, age 69 ± 13 years) receiving long-term haemodialysis (3.7 ± 4.2 years) were randomized to intra-dialytic low-intensity strength training or stretching (attention-control) exercises twice weekly for a total of 48 exercise sessions. The primary study outcome was physical performance assessed by the Short Physical Performance Battery score (SPPB) after 36 sessions, if available, or carried forward from 24 sessions. Secondary outcomes included lower body strength, body composition and quality of life. Measurements were obtained at baseline and at completion of 24 (mid), 36 (post) and 48 (final) exercise sessions. Results. Baseline median (IQR) SPPB score was 6.0 (5.0), with 57% of the participants having SPPB scores below 7. Exercise adherence was 89 ± 15%. The primary outcome could be computed in 44 participants. SPPB improved in the strength training group compared to the attention-control group 21.1% (43.1%) vs. 0.2% (38.4%), respectively, P = 0.03. Similarly, strength training participants exhibited significant improvements from baseline compared to the control group in knee extensor strength, leisure-time physical activity and self-reported physical function and activities of daily living (ADL) disability; all P < 0.02. Adverse events were common but not related to study participation. Conclusions. Intra-dialytic, low-intensity progressive strength training was safe and effective among maintenance dialysis patients. Further studies are needed to establish the generalizability of this strength training program in dialysis patients.
Background Heart failure (HF) is one of the leading causes of morbidity and mortality among Americans. Despite increased interest in end-of-life care, the implications of do-not-resuscitate (DNR) ...orders in acutely ill patients with HF remain unclear. The goals of this observational study were to describe the use of DNR orders and their impact on treatment approaches in residents of a large New England metropolitan area hospitalized with acute heart failure. Methods Use of HF performance measures, including assessment of left ventricular function, use of angiotensin receptor blocking agents, anticoagulation, smoking cessation counseling, and use of nonpharmacologic strategies, was examined through review of the medical records of 4,537 metropolitan Worcester (MA) residents admitted to 11 central Massachusetts hospitals with acute HF in 1995 and 2000 according to the presence of DNR orders. Results Patients with DNR orders were less likely to have had their left ventricular function assessed (31% vs 43%) as well as receive renin-angiotensin system blockade (49% vs 57%), anticoagulation (65% vs 78%), or nonpharmacologic interventions (87% vs 92%) as compared to patients without DNR orders. Patients with DNR orders were significantly less likely to have received any quality assurance measure for acute HF (adjusted hazard ratio 0.63, 95% confidence interval 0.40-0.99) than patients without DNR orders. Conclusions The use of quality assurance measures in acute HF is markedly lower in patients with DNR orders. The implications of DNR orders need to be further clarified in the treatment of patients with acute HF.
In patients with advanced (estimated glomerular filtration rate <25 mL/min/1.73 m2) non-dialysis-dependent chronic kidney disease (CKD) the optimal transition of care to renal replacement therapy ...(RRT), i.e. dialysis or transplantation, is not known. Mortality and hospitalization risk are extremely high upon transition and in the first months following the transition to dialysis. Major knowledge gaps persist pertaining to differential or individualized transitions across different demographics and clinical measures during the 'prelude' period prior to the transition, particularly in several key areas: (i) the best timing for RRT transition; (ii) the optimal RRT type (dialysis versus transplant), and in the case of dialysis, the best modality (hemodialysis versus peritoneal dialysis), format (in-center versus home), frequency (infrequent versus thrice-weekly versus more frequent) and vascular access preparation; (iii) the post-RRT impact of pre-RRT prelude conditions and events such as blood pressure and glycemic control, acute kidney injury episodes, and management of CKD-specific conditions such as anemia and mineral disorders; and (iv) the impact of the above prelude conditions on end-of-life care and RRT decision-making versus conservative management of CKD. Given the enormous changes occurring in the global CKD healthcare landscape, as well as the high costs of transitioning to dialysis therapy with persistently poor outcomes, there is an urgent need to answer these important questions. This review describes the key concepts and questions related to the emerging field of 'Transition of Care in CKD', systematically defines six main categories of CKD transition, and reviews approaches to data linkage and novel prelude analyses along with clinical applications of these studies.
Most patients with end-stage renal disease in the United States are initiated on thrice-weekly hemodialysis (HD) regimens. However, an incremental approach to HD may provide several patient benefits. ...We tested whether initiation of incremental HD does or does not compromise survival compared with a conventional HD regimen. The survival of 434 incremental, 50,162 conventional, and 160 frequent HD patients were compared using Cox regression analysis after matching for demographic and comorbid factors in a longitudinal national cohort of adult incident HD patients enrolled between January 2007 and December 2011. Sensitivity analysis included adjustment for residual kidney function. After adjustment for residual kidney function, all-cause mortality was not significantly different in the incremental compared with conventional HD group (hazard ratio 0.88, 95% confidence interval 0.72–1.08), but was higher in the frequent compared with the conventional HD group (hazard ratio, 1.56, 95% confidence interval 1.21–2.03). The comorbidity burden modified the association of treatment frequency and mortality, with higher comorbidity associated with higher mortality in the incremental HD group (hazard ratio, 1.77, 95% confidence interval 1.20–2.62) for a Charlson Comorbidity Index of ≥5. Thus, among incident HD patients with low or moderate comorbid disease, survival was similar for patients initiated on an incremental or conventional HD regimen. Clinical trials are needed to examine the safety and effectiveness of incremental HD and the selected patient populations who may benefit from an incremental approach to HDs initiation.
Patients receiving twice-weekly or less-frequent hemodialysis (HD) may need to undergo higher ultrafiltration rates (UFRs) to maintain acceptable fluid balance. We hypothesized that higher UFRs are ...associated with faster decline in residual kidney function (RKF) and a higher rate of mortality.
Retrospective cohort study.
1,524 patients with kidney failure who initiated maintenance HD at a frequency of twice or less per week for at least 6 consecutive weeks at some time between 2007 and 2011 and for whom baseline data for UFR and renal urea clearance were available.
Average UFR during the first patient-quarter during less-frequent HD (<6, 6-<10, 10-<13, and≥13mL/h/kg).
Time to all-cause and cardiovascular death, slope of decline in RKF during the first year after initiation of less-frequent HD (with slopes above the median categorized as rapid decline).
Cox proportional hazards regression for time to death and logistic regression for the analysis of rapid decline in RKF.
Among 1,524 patients, higher UFR was associated with higher all-cause mortality; HRs were 1.43 (95% CI, 1.09-1.88), 1.51 (95% CI, 1.08-2.10), and 1.76 (95% CI, 1.23-2.53) for UFR of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg). Higher UFR was also associated with higher cardiovascular mortality. Baseline RKF modified the association between UFR and mortality; the association was attenuated among patients with renal urea clearance≥5mL/min/1.73m2. Higher UFR had a graded association with rapid decline in RKF; ORs were 1.73 (95% CI, 1.18-2.55), 1.89 (95% CI, 1.12-3.17), and 2.75 (95% CI, 1.46-5.18) at UFRs of 6 to<10, 10 to<13, and≥13mL/h/kg, respectively (reference: UFR < 6mL/h/kg).
Residual confounding from unobserved differences across exposure categories.
Higher UFR was associated with worse outcomes, including shorter survival and more rapid loss of RKF, among patients receiving regular HD treatments at a frequency of twice or less per week.
A significant number of dietary restrictions are imposed traditionally and uniformly on maintenance dialysis patients, whereas there is very little data to support their benefits. Recent studies ...indicate that dietary restrictions of phosphorus may lead to worse survival and poorer nutritional status. Restricting dietary potassium may deprive dialysis patients of heart‐healthy diets and lead to intake of more atherogenic diets. There is little data about the survival benefits of dietary sodium restriction, and limiting fluid intake may inherently lead to lower protein and calorie consumption, when in fact dialysis patients often need higher protein intake to prevent and correct protein‐energy wasting. Restricting dietary carbohydrates in diabetic dialysis patients may not be beneficial in those with burnt‐out diabetes. Dietary fat including omega‐3 fatty acids may be important caloric sources and should not be restricted. Data to justify other dietary restrictions related to calcium, vitamins, and trace elements are scarce and often contradictory. The restriction of eating during hemodialysis treatment is likely another incorrect practice that may worsen hemodialysis induced hypoglycemia and nutritional derangements. We suggest careful relaxation of most dietary restrictions and adoption of a more balanced and individualized approach, thereby easing some of these overzealous restrictions that have not been proven to offer major advantages to patients and their outcomes and which may in fact worsen patients' quality of life and satisfaction. This manuscript critically reviews the current paradigms and practices of recommended dietary regimens in dialysis patients including those related to dietary protein, carbohydrate, fat, phosphorus, potassium, sodium, and calcium, and discusses the feasibility and implications of adherence to ardent dietary restrictions and future research.
The inverse association between body mass index (BMI) and mortality observed in patients treated with maintenance hemodialysis (MHD), also known as the obesity paradox, may be a result of residual ...confounding. Marginal structural model (MSM) analysis, a technique that accounts for time-varying confounders, may be more appropriate to investigate this association. We hypothesize that after applying MSM, the inverse association between BMI and mortality in MHD patients is attenuated.
We examined the associations between BMI and all-cause mortality among 123 624 adult MHD patients treated during 2001-6. We examined baseline and time-varying BMI using Cox proportional hazards models and MSM while considering baseline and time-varying covariates, including demographics, comorbidities and markers of malnutrition and inflammation.
The patients included 45% women and 32% African Americans with a mean age of 61(SD 15) years. In all models, BMI showed a linear incremental inverse association with mortality. Compared with the reference (BMI 25 to <27.5 kg/m(2)), a BMI of <18 kg/m(2) was associated with a 3.2-fold higher death risk hazard ratio (HR) 3.17 (95% CI 3.05-3.29), and mortality risks declined with increasing BMI with the greatest survival advantage of 31% lower risk HR 0.69 (95% CI 0.64-0.75) observed with a BMI of 40 to <45 kg/m(2).
The linear inverse relationship between BMI and mortality is robust across models including MSM analyses that more completely account for time-varying confounders and biases.
Background Chronic pain is a common condition in the general population. However, large epidemiologic studies examining the role of pain in the deterioration of kidney function, development of ...chronic kidney disease, and risk for death are lacking. Study Design Retrospective cohort study. Setting & Participants A nationally representative cohort of 2,360,056 US veterans with baseline estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m2 , followed up from October 2004 to September 2006. Predictor 4 pain categories were compared: none (score, 0), mild (1-4), moderate (5-6), or severe (≥7). Outcomes eGFR decline (determined by eGFR slope) and combined incident eGFR < 60 mL/min/1.73 m2 or all-cause death. Measurements We examined the pain management pattern and association of reported pain with (1) rapid eGFR decline and (2) a composite outcome of incident eGFR < 60 mL/min/1.73 m2 or all-cause death using logistic regression and Cox models adjusted for baseline eGFR, demographics, comorbid conditions, cardiovascular risk factors, and depression. Results ∼60% of veterans reported pain of any severity during the baseline period. The most commonly prescribed analgesics were opioids. In a dose-response relationship, veterans reporting moderate or severe pain had a higher risk for faster eGFR decline compared with those reporting none (ORs of 1.11 95% CI, 1.09-1.14 and 1.17 95% CI, 1.13-1.21 for moderate and severe pain, respectively). In combined analyses, veterans reporting moderate or severe pain both had 30% higher risk of the combined outcome (incident eGFR, 60 mL/min/1.73 m2 or death) compared with those reporting none (HRs of 1.30 95% CI, 1.28-1.31 and 1.30 95% CI, 1.28-1.32 for moderate and severe pain, respectively). Limitations Lack of granular data regarding type and location of pain. Conclusions We observed a high prevalence of pain and analgesic prescription in the US veteran population with normal eGFRs. Pain was associated with a higher incidence of eGFRs < 60 mL/min/1.73 m2 , faster kidney function decline, and higher mortality.