Dietary potassium intake, kidney function, and survival in a nationally representative cohort.

BACKGROUND: In healthy adults, higher dietary potassium intake is recommended given that potassium-rich foods are major sources of micronutrients, antioxidants, and fiber. Yet among patients with advanced kidney dysfunction, guidelines recommend dietary potassium restriction given concerns about hyperkalemia leading to malignant arrhythmias and mortality. OBJECTIVES: Given sparse data informing these recommendations, we examined associations of dietary potassium intake with mortality in a nationally representative cohort of adults from the NHANES. METHODS: We examined associations between daily dietary potassium intake scaled to energy intake (mg/1000 kcal), ascertained by 24-h dietary recall, and all-cause mortality among 37,893 continuous NHANES (1999-2014) participants stratified according to impaired and normal kidney function (estimated glomerular filtration rates <60 and ≥60 mL · min-1 · 1.73 m-2, respectively) using multivariable Cox models. We also examined the impact of the interplay between dietary potassium, source of potassium intake (animal- compared with plant-based sources), and coexisting macronutrient and mineral consumption upon mortality. RESULTS: Among participants with impaired and normal kidney function, the lowest tertile of dietary potassium scaled to energy intake was associated with higher mortality (ref: highest tertile) [adjusted HR (aHR): 1.18; 95% CI: 1.02, 1.38 and aHR: 1.17; 95% CI: 1.06, 1.28, respectively]. Compared with high potassium intake from plant-dominant sources, participants with low potassium intake from animal-dominant sources had higher mortality irrespective of kidney function. Among participants with impaired kidney function, pairings of low potassium intake with high protein, low fiber, or high phosphorus consumption were each associated with higher death risk. CONCLUSIONS: Lower dietary potassium scaled to energy intake was associated with higher mortality, irrespective of kidney function. There was also a synergistic relation of higher potassium intake, plant-based sources, and macronutrient/mineral consumption with survival. Further studies are needed to elucidate pathways linking potassium intake and coexisting dietary factors with survival in populations with and without chronic kidney disease.

Assessing Global Kidney Nutrition Care.

BACKGROUND AND OBJECTIVES: Nutrition intervention is an essential component of kidney disease management. This study aimed to understand current global availability and capacity of kidney nutrition care services, interdisciplinary communication, and availability of oral nutrition supplements. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The International Society of Renal Nutrition and Metabolism (ISRNM), working in partnership with the International Society of Nephrology (ISN) Global Kidney Health Atlas Committee, developed this Global Kidney Nutrition Care Atlas. An electronic survey was administered among key kidney care stakeholders through 182 ISN-affiliated countries between July and September 2018. RESULTS: Overall, 160 of 182 countries (88%) responded, of which 155 countries (97%) answered the survey items related to kidney nutrition care. Only 48% of the 155 countries have dietitians/renal dietitians to provide this specialized service. Dietary counseling, provided by a person trained in nutrition, was generally not available in 65% of low-/lower middle-income countries and "never" available in 23% of low-income countries. Forty-one percent of the countries did not provide formal assessment of nutrition status for kidney nutrition care. The availability of oral nutrition supplements varied globally and, mostly, were not freely available in low-/lower middle-income countries for both inpatient and outpatient settings. Dietitians and nephrologists only communicated "sometimes" on kidney nutrition care in ≥60% of countries globally. CONCLUSIONS: This survey reveals significant gaps in global kidney nutrition care service capacity, availability, cost coverage, and deficiencies in interdisciplinary communication on kidney nutrition care delivery, especially in lower-income countries.

The Impact of RDNs on Non-Communicable Diseases: Proceedings from The State of Food and Nutrition Series Forum.

In the United States, nutrition-related morbidities are rising steadily at rates corresponding to increasing overweight and obesity in the population. Such morbidities take huge tolls on personal health and impose high costs on health care systems. In 2019, the Academy of Nutrition and Dietetics (Academy) and the Academy of Nutrition and Dietetics Foundation (Academy Foundation) embarked on a new project titled "The State of Food and Nutrition Series" to demonstrate the value of nutrition interventions led by registered dietitian nutritionists for individuals with the following 3 high-priority non-communicable diseases that affect many in the United States and globally: type 2 diabetes mellitus, chronic kidney disease, and hypertension. Poor nutritional status contributes to disease onset and progression in these non-communicable diseases, and appropriate medical nutrition therapy can prevent or delay worsening and ameliorate poor health outcomes. However, many people who have these conditions do not have access to an registered dietitian nutritionist, and consequently do not receive the nutrition care they need. On February 19-20, 2020 in Arlington, VA, as the first stage in The State of Food and Nutrition Series, the Academy and the Academy Foundation gathered health care policymakers, clinicians, and researchers from across the country for the State of Food and Nutrition Series Forum, where Academy leaders sought input to build a comprehensive research strategy that will quantify the impact of patient access to registered dietitian nutritionist-led nutrition interventions for type 2 diabetes mellitus, chronic kidney disease, and hypertension. This article summarizes the findings of that forum.

Novel intestinal dialysis interventions and microbiome modulation to control uremia.

PURPOSE OF REVIEW: In patients with chronic kidney disease (CKD), the gut plays a key role in the homeostasis of fluid and electrolyte balance and the production and disposal of uremic toxins. This review summarizes the current evidence on the gut-targeted interventions to control uremia, fluid overload, hyperkalemia and hyperphosphatemia in CKD. RECENT FINDINGS: Studies have emerged that support the concept of intestinal dialysis, such as colonic perfusion with a Malone antegrade continence enema stoma or colonic irrigation with a rectal catheter, as a promising adjuvant approach to control uremia in CKD, although most findings are preliminary. The use of AST-120, an oral adsorbent, has been shown to reduce circulating levels of indoxyl sulfate and p-cresol sulfate and have potential renoprotective benefits in patients with advanced CKD. Diarrhea or inducing watery stools may modulate fluid retention and potassium and phosphorus load. Accumulating evidence indicates that plant-based diets, low-protein diets, and pre-, pro-, and synbiotic supplementation may lead to favorable alterations of the gut microbiota, contributing to reduce uremic toxin generation. The effects of these gut-targeted interventions on kidney and cardiovascular outcomes are still limited and need to be tested in future studies including clinical trials. SUMMARY: Interventions aimed at enhancing bowel elimination of uremic toxins, fluid and electrolytes and at modulating gut microbiota may represent novel therapeutic strategies for the management of uremia in patients with CKD.

Nutrition and Obesity Impacts on Kidney Health.

Clinical Background and Epidemiology: Nutrition and obesity are both important and common clinical issues in chronic kidney disease (CKD). Protein-energy wasting predicts adverse clinical outcomes in CKD. Obesity is associated with poor health outcomes. Nutrition management, specifically a protein-restricted diet, has been shown to ameliorate glomerular injury and progressive CKD by reducing glomerular hyperfiltration and hypertension. A protein-restricted diet has favorable metabolic and hemodynamic effects and effects on CKD-mineral bone disease that may favorably impact patients' outcomes. On the other hand, obesity may adversely affect kidney function both directly by placing an increased metabolic demand on the kidneys and indirectly through various humoral mechanisms mediated via adiponectin, leptin, and resistin that lead to hyperinsulinemia, insulin resistance, abnormal lipid metabolism, activation of renin-angiotensin aldosterone system, chronic inflammation, and oxidative stress, and could result in the development of obesity-related glomerulopathy. It is therefore important to raise more awareness of the two clinical issues and promote a healthy lifestyle with proper nutrition and exercise in CKD management. Challenges and Solutions: There are global shortage of dietitians and challenges in accessibility and availability of renal dietitians in many emerging countries as well as lack of reimbursement of dietitians' consultations. Many patients may not have the opportunity to be monitored and reviewed by dieticians on a regular basis. In addition, there are practical challenges in enforcing patients' adherence to a protein-restricted diet. Patients and nephrologists from developed countries may\not appreciate the need to adopt a protein restricted diets as dialysis is readily available. Furthermore, keto-analogues or nutrition supplements are not reimbursed in many parts of the world. Increased government advocacy, prioritization of renal nutrition care, and more trained renal dietitians are required in many parts of the world. More government resource allocation is required to increase renal dietitians' manpower in nephrology centers so to enable multidisciplinary nutrition management in CKD and end-stage kidney disease. On the other hand, prevention and treatment of obesity require lifestyle modifications including calorie restriction and adequate exercise, and they need to be maintained lifelong. Such changes may be difficult in modern societies with the "fast food culture" and increasing prevalence of sedentary lifestyles. Changes in lifestyle may become even more difficult as long-term complications such as diabetes and cardiovascular disease set in, which may further limit patients' mobility. To tackle the obesity epidemic, we need a global action plan to prevent and control non-communicable diseases. We need a concerted population-wide intervention by national governments, health policy planners, and professional organizations to target obesity and CKD by promoting healthy lifestyle factors and healthy diets. Pharmacologic and surgical interventions such as bariatric surgery for obesity require further evaluation in CKD.

Laxative use in patients with advanced chronic kidney disease transitioning to dialysis.

BACKGROUND: Constipation is highly prevalent in patients with chronic kidney disease (CKD), particularly among those with end-stage renal disease (ESRD), partly due to their dietary restrictions, comorbidities and medications. Laxatives are typically used for constipation management; however, little is known about laxative use and its associated factors in patients with advanced CKD transitioning to ESRD. METHODS: In a retrospective cohort of 102 477 US veterans transitioning to dialysis between October 2007 and March 2015, we examined the proportion of patients who filled a prescription for any type of laxative within each 6-month period over 36 months pre- and post-transition to ESRD. Factors associated with laxative use during the last 1-year pre-ESRD period were identified by multivariable logistic regression. RESULTS: The proportion of patients prescribed laxatives increased as patients progressed to ESRD, peaking at 37.1% in the 6 months immediately following ESRD transition, then remaining fairly stable throughout the post-ESRD transition period. Among laxative users, stool softeners were the most commonly prescribed (∼30%), followed by hyperosmotics (∼20%), stimulants (∼10%), bulk formers (∼3%), chloride channel activator (<1%) and several combinations of these. The use of anticoagulants, oral iron supplements, non-opioid analgesics, antihistamines and opioid analgesics were among the factors independently associated with pre-ESRD laxative use. CONCLUSION: The use of laxatives increased considerably as patients neared transition to ESRD, likely mirroring the increasing burden of drug-induced constipation during the ESRD transition period. Findings may provide novel insight into better management strategies to alleviate constipation symptoms and reduce medication requirements in patients with advanced CKD.

ß-Blocker Use and Risk of Mortality in Heart Failure Patients Initiating Maintenance Dialysis.

RATIONAL & OBJECTIVE: Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether ß-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included. EXPOSURES: Patients were considered treated with ß-blockers if they had a quantity of drug dispensed covering the dialysis transition date. OUTCOMES: All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis. ANALYTICAL APPROACH: Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between ß-blocker use and study outcomes. RESULTS: 3,503 patients were included in the study. There were 2,115 (60.4%) patients using ß-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any ß-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization. LIMITATIONS: The observational nature of our study could not fully account for residual confounding. CONCLUSIONS: Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment.

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Association of thyroid status prior to transition to end-stage renal disease with early dialysis mortality.

BACKGROUND: Advanced chronic kidney disease (CKD) patients, including those receiving dialysis, have a high prevalence of thyroid dysfunction. Although hypothyroidism is associated with higher death risk in end-stage renal disease (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD period impacts mortality after dialysis initiation. METHODS: Among US veterans with CKD identified from the national Veterans Affairs database that transitioned to dialysis over the period from October 2007 to September 2011, we examined the association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year pre-dialysis ('prelude') period with all-cause mortality in the first year following dialysis initiation. RESULTS: Among 15 335 patients in the 1-year prelude cohort, TSH levels >5.0 mIU/L were associated with higher mortality in expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were observed for TSH >5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95% CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer gradations of TSH in the 1-year prelude cohort demonstrated that incrementally higher levels >5.0 mIU/L were associated with increasingly higher mortality in expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04-1.33) and 1.28 (1.03-1.59) for TSH levels >5.0-10.0 mIU/L and >10.0 mIU/L, respectively. In the 2- and 5-year cohorts, mortality associations persisted most strongly for those with TSH >10.0 mIU/L, particularly after laboratory covariate adjustment. CONCLUSIONS: Among new ESRD patients, there is a dose-dependent relationship between higher pre-ESRD TSH levels >5.0 mIU/L and post-ESRD mortality. Further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population.

Precision Medicine for Nutritional Management in End-Stage Kidney Disease and Transition to Dialysis.

Chronic kidney disease (CKD) is a global public health burden. Dialysis is not only costly but may not be readily available in developing countries. Even in highly developed nations, many patients may prefer to defer or avoid dialysis. Thus, alternative options to dialysis therapy or to complement dialysis are needed urgently and are important objectives in CKD management that could have huge clinical and economic implications globally. The role of nutritional therapy as a strategy to slow CKD progression and uremia was discussed as early as the late 19th and early 20th century, but was only seriously explored in the 1970s. There is a revival of interest recently owing to encouraging data as well as the increase of precision medicine with an emphasis on a personalized approach to CKD management. Although part of the explanation for the inconclusive data may relate to variations in study design and dietary prescription, diversity in genetic make-up, variations in the non-nutritional management of CKD, intra-individual variations in responses to dietary and nondietary treatment, psychosocial factors, and dietary compliance issues, these all may contribute to the heterogeneous data and responses. This brings in the evolving concept of precision medicine, in which disease management should be tailored and individualized according not only to clinical manifestations but also to the genetic make-up and biologic responses to therapy, which may vary depending on genetic composition. Precision nutrition management also should take into account patient demographics, social, psychological, education, and compliance factors, which all may influence the therapeutic needs and responses to the nutritional therapy prescribed. In this review, we provide a novel concept of precision medicine in nutritional management in end-stage kidney disease with a transition to dialysis and propose how this may be the way forward for nutritional therapy in the CKD population.

Eating During Hemodialysis Treatment: A Consensus Statement From the International Society of Renal Nutrition and Metabolism.

Poor nutritional status and protein-energy wasting are common among maintenance dialysis patients and associated with unfavorable outcomes. Providing foods, meal trays, snack boxes, and/or oral nutritional supplements during hemodialysis can improve nutritional status and might also reduce inflammation, enhance health-related quality of life, boost patient satisfaction, and improve survival. Potential challenges include postprandial hypotension and other hemodynamic instabilities, aspiration risk, gastrointestinal symptoms, hygiene issues, staff burden, reduced solute removal, and increased costs. Differing in-center nutrition policies exist within organizations and countries around the world. Recent studies have demonstrated clinical benefits and highlight the need to work toward clear guidelines. Meals or supplements during hemodialysis may be an effective strategy to improve nutritional status with limited reports of complications in real-world scenarios. Whereas larger multicenter randomized trials are needed, meals and supplements during hemodialysis should be considered as a part of the standard-of-care practice for patients without contraindications.

Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function.

BACKGROUND AND OBJECTIVES: The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m2) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. RESULTS: A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance (Pinteraction=0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance (i.e., <1.5 ml/min per 1.73 m2), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance (i.e., ≥1.5 ml/min per 1.73 m2; Pinteraction<0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk (Ptrend<0.001 for both) irrespective of residual renal urea clearance strata (Pinteraction=0.34 and Pinteraction=0.53, respectively). CONCLUSIONS: Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population.

Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and Mortality Outcomes.

BACKGROUND: Whether the benefits of phosphorus binders extend to those without end stage renal disease is uncertain. Among a large diverse non-dialysis chronic kidney disease (CKD) population with hyperphosphatemia, we sought to evaluate phosphorus binder use and compare mortality risk between patients prescribed and not prescribed binders. METHODS: A retrospective cohort study within an integrated health system (January 1, 1998 - December 31, 2012) among CKD patients (age ≥18) was performed. Non-dialysis CKD patients with 2 separate estimated glomerular filtrate rate (eGFR) <30 mL/min/1.73 m2 and serum phosphorus ≥5.0 mg/dL within 180 days of eGFR were included. Multivariable cox proportional hazards and inverse probability of treatment-weighted models were used to estimate mortality hazard ratios (HRs) for patients who received phosphorus binders compared to no binders. RESULTS: Among 10,165 study patients, 2,733 subjects (27%) received phosphorus binders. Compared to the no-phosphorus-binder group, the binder group had mortality HRs (95% CI) of 0.86 (0.79-0.94) and 0.86 (0.80-0.93) using traditional multivariable and inverse probability of treatment-weighted models respectively. Sensitivity analyses removing patients who were prescribed binders >180 days after index date revealed no difference in mortality between those with binders and with no binders. CONCLUSION: Our findings from a real-world clinical environment revealed that 27% of hyperphosphatemic non-dialysis CKD patients were prescribed binders. They also had lower risk of mortality compared to those not prescribed phosphorus binders. However, the lower mortality risk was not observed when we accounted for immortal time bias. Whether phosphorus binder use in CKD improves survival remains to be determined.

Updates in hyperkalemia: Outcomes and therapeutic strategies.

Hyperkalemia is a frequent clinical abnormality in patients with chronic kidney disease, and it is associated with higher risk of mortality and malignant arrhythmias. Severe hyperkalemia is a medical emergency, which requires immediate therapies, followed by interventions aimed at preventing its recurrence. Current treatment paradigms for chronic hyperkalemia management are focused on eliminating predisposing factors, such as high potassium intake in diets or supplements, and the use of medications known to raise potassium level. Among the latter, inhibitors of the renin-angiotensin aldosterone system are some of the most commonly involved medications, and their discontinuation is often the first step taken by clinicians to prevent the recurrence of hyperkalemia. While this strategy is usually successful, it also deprives patients of the recognized benefits of this class, such as their renoprotective effects. The development of novel potassium binders has ushered in a new era of hyperkalemia management, with a focus on chronic therapy while maintaining the use of beneficial, but hyperkalemia-inducing medications such as renin-angiotensin aldosterone system inhibitors. This review article examines the incidence and clinical consequences of hyperkalemia, and its various treatment options, with special emphasis on novel therapeutic agents and the potential benefits of their application.

Effect of high-protein meals during hemodialysis combined with lanthanum carbonate in hypoalbuminemic dialysis patients: findings from the FrEDI randomized controlled trial.

BACKGROUND: Inadequate protein intake and hypoalbuminemia, indicators of protein-energy wasting, are among the strongest mortality predictors in hemodialysis patients. Hemodialysis patients are frequently counseled on dietary phosphorus restriction, which may inadvertently lead to decreased protein intake. We hypothesized that, in hypoalbuminemic hemodialysis patients, provision of high-protein meals during hemodialysis combined with a potent phosphorus binder increases serum albumin without raising phosphorus levels. METHODS: We conducted a randomized controlled trial in 110 adults undergoing thrice-weekly hemodialysis with serum albumin <4.0 g/dL recruited between July 2010 and October 2011 from eight Southern California dialysis units. Patients were randomly assigned to receive high-protein (50-55 g) meals during dialysis, providing 400-500 mg phosphorus, combined with lanthanum carbonate versus low-protein (<1 g) meals during dialysis, providing <20 mg phosphorus. Prescribed nonlanthanum phosphorus binders were continued over an 8-week period. The primary composite outcome was a rise in serum albumin of ≥0.2 g/dL while maintaining phosphorus between 3.5-<5.5 mg/dL. Secondary outcomes included achievement of the primary outcome's individual endpoints and changes in mineral and bone disease and inflammatory markers. RESULTS: Among 106 participants who satisfied the trial entrance criteria, 27% ( n = 15) and 12% ( n = 6) of patients in the high-protein versus low-protein hemodialysis meal groups, respectively, achieved the primary outcome (intention-to-treat P-value = 0.045). A lower proportion of patients in the high-protein versus low-protein intake groups experienced a meaningful rise in interleukin-6 levels: 9% versus 31%, respectively (P = 0.009). No serious adverse events were observed. CONCLUSION: In hypoalbuminemic hemodialysis patients, high-protein meals during dialysis combined with lanthanum carbonate are safe and increase serum albumin while controlling phosphorus.

North American experience with Low protein diet for Non-dialysis-dependent chronic kidney disease.

Whereas in many parts of the world a low protein diet (LPD, 0.6-0.8 g/kg/day) is routinely prescribed for the management of patients with non-dialysis-dependent chronic kidney disease (CKD), this practice is infrequent in North America. The historical underpinnings related to LPD in the USA including the non-conclusive results of the Modification of Diet in Renal Disease Study may have played a role. Overall trends to initiate dialysis earlier in the course of CKD in the US allowed less time for LPD prescription. The usual dietary intake in the US includes high dietary protein content, which is in sharp contradistinction to that of a LPD. The fear of engendering or worsening protein-energy wasting may be an important handicap as suggested by a pilot survey of US nephrologists; nevertheless, there is also potential interest and enthusiasm in gaining further insight regarding LPD's utility in both research and in practice. Racial/ethnic disparities in the US and patients' adherence are additional challenges. Adherence should be monitored by well-trained dietitians by means of both dietary assessment techniques and 24-h urine collections to estimate dietary protein intake using urinary urea nitrogen (UUN). While keto-analogues are not currently available in the USA, there are other oral nutritional supplements for the provision of high-biologic-value proteins along with dietary energy intake of 30-35 Cal/kg/day available. Different treatment strategies related to dietary intake may help circumvent the protein- energy wasting apprehension and offer novel conservative approaches for CKD management in North America.

Comparisons of sleep apnoea rate and outcomes among patients with resistant and non-resistant hypertension.

BACKGROUND AND OBJECTIVE: We directly compared sleep apnoea (SA) rates and risk of cardiovascular and mortality outcomes among SA patients with resistant hypertension (RH) and non-RH within a large diverse hypertension population. METHODS: A retrospective cohort study between 1 January 2006 and 31 December 2010 among hypertensive adults (age ≥ 18 years) was performed within an integrated health system. Rates of SA in RH and non-RH were determined. Multivariable logistic regression analyses were used to calculate OR for SA. Cox proportional hazard modelling was used to estimate hazard ratios (HRs) for cardiovascular and mortality outcomes between SA in RH versus SA in non-RH adjusting for age, gender, race, BMI, chronic kidney disease and other comorbidities. RESULTS: SA was identified in 33 682 (7.2%) from 470 386 hypertensive individuals. SA in RH accounted for 5806 (9.6%) compared to SA in non-RH 27 876 individuals (6.8%). Multivariable OR (95% CI) for SA was 1.16 (1.12, 1.19), 3.57 (3.47, 3.66) and 2.20 (2.15, 2.25) for RH versus non-RH, BMI ≥ 30, and males, respectively. Compared to SA in non-RH individuals, SA in RH had a multivariable adjusted HR (95% CI) of 1.24 (1.13, 1.36), 1.43 (1.28, 1.61), 0.98 (0.85, 1.12) and 1.04 (0.95, 1.14) for ischaemic heart event (IHE), congestive heart failure (CHF), stroke and mortality, respectively. CONCLUSION: We observed a modest increase in likelihood for SA among RH compared to non-RH patients. Risks for IHE and CHF were higher for SA in RH compared to SA in non-RH patients; however, there were no differences in risk for stroke and mortality.

Changes in Markers of Mineral and Bone Disorders and Mortality in Incident Hemodialysis Patients.

BACKGROUND: Abnormalities in mineral and bone disorder (MBD) markers are common in patients with chronic kidney disease. However, previous studies have not accounted for their changes over time, and it is unclear whether these changes are associated with survival. METHODS: We examined the association of change in MBD markers (serum phosphorus (Phos), albumin-corrected calcium (Ca(Alb)), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP)) during the first 6 months of hemodialysis (HD) with all-cause mortality across baseline MBD strata using survival models adjusted for clinical characteristics and laboratory measurements in 102,754 incident HD patients treated in a large dialysis organization between 2007 and 2011. RESULTS: Across all MBD markers (Phos, Ca(Alb), iPTH and ALP), among patients whose baseline MBD levels were higher than the reference range, increase in MBD levels was associated with higher mortality (reference group: MBD level within reference range at baseline and no change at 6 months follow-up). Conversely, decrease in Phos and iPTH, among baseline Phos and iPTH levels lower than the reference range, respectively, were associated with higher mortality. An increase in ALP was associated with higher mortality across baseline strata of ALP ≥80 U/l. However, patients with baseline ALP <80 U/l trended towards a lower risk of mortality irrespective of the direction of change at 6 months follow-up. CONCLUSIONS: There is a differential association between changes in MBD markers with mortality across varying baseline levels in HD patients. Further study is needed to determine if consideration of both baseline and longitudinal changes in the management of MBD derangements improves outcomes in this population.

Dietary restrictions in dialysis patients: is there anything left to eat?

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 relationship between thyroid function and estimated glomerular filtration rate in patients with chronic kidney disease.

BACKGROUND: Recent studies have shown an increasing risk of hypothyroidism with incrementally lower estimated glomerular filtration rate (eGFR) in cohorts comprised of patients with normal to mildly impaired kidney function. We sought to confirm these findings in a nationally representative cohort of Veterans Affairs patients with moderate-to-severe chronic kidney disease (CKD). METHODS: This study examined the association between kidney function and hypothyroidism among 461 607 veterans with Stage 3 to 5 CKD who underwent repeated measurements of serum creatinine and thyrotropin (TSH) at identical time points between October 2004 and September 2006. Kidney function was defined by eGFR using the Chronic Kidney Disease Epidemiology Collaboration formula. In primary analyses, the association between eGFR and hypothyroidism (defined as serum TSH > 5 mIU/L and/or receipt of thyroid hormone supplementation) was estimated using multivariable random effects logistic regression. In secondary analyses, the association between eGFR and serum TSH level was estimated using multivariable random effects linear regression. RESULTS: At baseline, 68.9, 25.5, 5.3 and 0.3% of patients had Stage 3A, 3B, 4 and 5 CKD, respectively. For every 10 mL/min/1.73 m(2) lower eGFR, there was an 18% higher risk of hypothyroidism: adjusted odds ratio 1.18 [95% confidence interval (CI) 1.17-1.20, P < 0.001]. In secondary analyses, we observed that a 10 mL/min/1.73 m(2) lower eGFR was associated with a 0.11 mIU/L higher serum TSH (95% CI 0.10-0.11 mIU/L higher serum TSH, P < 0.001). CONCLUSIONS: In a nationally representative cohort of patients with moderate-to-severe CKD, there is an inverse association between eGFR and risk of hypothyroidism.