Higher potassium intake is associated with a lower risk of chronic kidney disease: population-based prospective study.

BACKGROUND: High-potassium intake is associated with a lower risk of cardiovascular disease. However, the association between potassium intake and the development of chronic kidney disease (CKD) remains unclear. OBJECTIVE: The objective of this study was to investigate whether potassium intake is associated with outcomes of incident CKD. METHODS: This is a population-based prospective observational cohort study from the UK Biobank cohort between 2006 and 2010. We included 317,162 participants without CKD from the UK Biobank cohort. The main predictor was spot urine potassium-to-creatinine ratio (KCR). The primary outcome was incident CKD, which was defined by the International Classification of Disease 10 codes or Operating Procedure Codes Supplement 4 codes. RESULTS: At baseline, individuals with higher KCR had lower blood pressure, body mass index, and inflammation, and were less likely to have diabetes and hypertension. During a median follow-up of 11.9 y, primary outcome events occurred in 15,246 (4.8%) participants. In the cause-specific model, the adjusted hazard ratio (aHR) per 1-standard deviation increase in KCR for incident CKD was 0.90 [95% confidence interval (CI): 0.89, 0.92]. Compared with quartile 1 of KCR, the aHRs (95% CIs) for quartiles 2-4 were 0.98 (0.94, 1.02), 0.90 (0.86, 0.95), and 0.80 (0.76, 0.84), respectively. In sensitivity analysis with different definitions of CKD, the results were similar. In addition, further analysis with dietary potassium intake also showed a negatively graded association with the primary outcome. CONCLUSIONS: Higher urinary potassium excretion and intake were associated with a lower risk of incident CKD.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

A real-world analysis of the influence of age on maintenance hemodialysis patients: managing serum phosphorus with sucroferric oxyhydroxide as part of routine clinical care.

OBJECTIVE: Despite the growing number of elderly hemodialysis patients, the influence of age on nutritional parameters, serum phosphorus (sP), and use of phosphate-binder (PB) medications has not been well characterized. We aimed to describe age-related differences in patient characteristics in a large, real-world cohort of maintenance hemodialysis patients, and to examine the impact of age on sP management with sucroferric oxyhydroxide (SO). METHODS: We retrospectively analyzed de-identified data from 2017 adult, in-center hemodialysis patients who switched from another PB to SO monotherapy as part of routine clinical care. Changes in baseline PB pill burden, sP levels, and nutritional and dialytic clearance parameters were assessed across varying age groups through 6 months. RESULTS: At baseline, older patients had lower mean sP, serum albumin, and pre-dialysis weights compared with younger patients. Prescription of SO was associated with a 62% increase in the proportion of patients achieving sP ≤ 5.5 mg/dl and a 42% reduction in daily pill burden. The proportion of patients achieving sP ≤ 5.5 mg/dl after transitioning to SO increased by 113, 96, 68, 77, 61, 37 and 40% among those aged 19-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years, respectively. CONCLUSIONS: Older patients had worse nutritional parameters, lower pill burden, and lower sP at baseline versus younger counterparts. Prescription of SO was associated with improved sP control and reduced pill burden across all ages.

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.

The Interplay between Dietary Phosphorous, Protein Intake, and Mortality in a Prospective Hemodialysis Cohort.

(1) Background: Current dietary recommendations for dialysis patients suggest that high phosphorus diets may be associated with adverse outcomes such as hyperphosphatemia and death. However, there has been concern that excess dietary phosphorus restriction may occur at the expense of adequate dietary protein intake in this population. We hypothesized that higher dietary phosphorus intake is associated with higher mortality risk among a diverse cohort of hemodialysis patients. (2) Methods: Among 415 patients from the multi-center prospective Malnutrition, Diet, and Racial Disparities in Kidney Disease Study, we examined the associations of absolute dietary phosphorus intake (mg/day), ascertained by food frequency questionnaires, with all-cause mortality using multivariable Cox models. In the secondary analyses, we also examined the relationship between dietary phosphorus scaled to 1000 kcal of energy intake (mg/kcal) and dietary phosphorus-to-protein ratio (mg/g) with survival. (3) Results: In expanded case-mix + laboratory + nutrition adjusted analyses, the lowest tertile of dietary phosphorus intake was associated with higher mortality risk (ref: highest tertile): adjusted HR (aHR) (95% CI) 3.33 (1.75-6.33). In the analyses of dietary phosphorus scaled to 1000 kcal of energy intake, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.74 (1.08, 2.80). Similarly, in analyses examining the association between dietary phosphorus-to-protein ratio, the lowest tertile of intake was associated with higher mortality risk compared to the highest tertile: aHR (95% CI) 1.67 (1.02-2.74). (4) Conclusions: A lower intake of dietary phosphorus was associated with higher mortality risk in a prospective hemodialysis cohort. Further studies are needed to clarify the relationship between specific sources of dietary phosphorus intake and mortality in this population.

Causes of Death in End-Stage Kidney Disease: Comparison between the United States Renal Data System and a Large Integrated Health Care System.

INTRODUCTION: Using a large diverse population of incident end-stage kidney disease (ESKD) patients from an integrated health system, we sought to evaluate the concordance of causes of death (CODs) between the underlying COD from the United States Renal Data System (USRDS) registry and CODs obtained from Kaiser Permanente Southern California (KPSC). METHODS: A retrospective cohort study was performed among incident ESKD patients who had mortality records and CODs reported in both KPSC and USRDS databases between January 1, 2007, and December 31, 2016. Underlying CODs reported by the KPSC were compared to the CODs reported by USRDS. Overall and subcategory-specific COD agreements were assessed using Cohen's weighted kappa statistic (95% CI). Proportions of positive and negative agreement were also determined. RESULTS: Among 4,188 ESKD patient deaths, 4,118 patients had CODs recorded in both KPSC and USRDS. The most common KPSC CODs were circulatory system diseases (35.7%), endocrine/nutritional/metabolic diseases (24.2%), genitourinary diseases (12.9%), and neoplasms (9.6%). Most common USRDS CODs were cardiac disease (46.9%), withdrawal from dialysis (12.6%), and infection (10.1%). Of 2,593 records with causes listed NOT as "Other," 453 (17.4%) had no agreement in CODs between the USRDS and the underlying, secondary, tertiary, or quaternary causes recorded by KPSC. In comparing CODs recorded within KPSC to the USRDS, Cohen's weighted kappa (95% CI) was 0.20 (0.18-0.22) with overall agreement of 36.4%. CONCLUSION: Among an incident ESKD population with mortality records, we found that there was only fair or slight agreement between CODs reported between the USRDS registry and KPSC, a large integrated health care system.

Medical nutrition therapy using plant-focused low-protein meal plans for management of chronic kidney disease in diabetes.

PURPOSE OF REVIEW: Nearly half of all Americans with chronic kidney disease (CKD) also have type-2-diabetes (T2D). Whereas traditional and emerging pharmacotherapies are increasingly frequently used for the management of CKD in diabetes (CKD/DM), the role of integrated or multimodal interventions including the potentially synergistic and additive effect of diet and lifestyle modifications in addition to pharmacotherapy has not been well examined, in sharp contrast to the well-known integrated approaches to heart disease. RECENT FINDINGS: Low-carbohydrate low-fat diets are often recommended in T2D, whereas low-protein diets (LPD) are recommended by guidelines for nondiabetic CKD with increasing emphasis on plant-based protein sources. High-protein diets with greater animal protein lead to glomerular hyperfiltration, especially in patients with T2D, and faster decline in renal function. Guidelines provide differing recommendations regarding the amount (low vs high) and source (plant vs animal) of dietary protein intake (DPI) in CKD/DM. Some such as KDIGO recommend 0.8 g/kg/day based on insufficient evidence for DPI restriction in CKD/DM, whereas KDOQI and ISRNM recommend a DPI of 0.6 to <0.8 g/kg/day. A patient-centered plant-focused LPD for the nutritional management of CKD/DM (PLAFOND), a type of PLADO diet comprising DPI of 0.6 to <0.8 g/kg/day with >50% plant-based sources, high dietary fiber, low glycemic index, and 25-35 Cal/kg/day energy, can be implemented by renal dietitians under Medical Nutrition Therapy. SUMMARY: Potential risks vs benefits of high vs low protein intake in CKD/DM is unknown, for which expert recommendations remain opinion based. Randomized controlled studies are needed to examine safety, acceptability and efficacy of PLAFOND.

Novel conservative management of chronic kidney disease via dialysis-free interventions.

PURPOSE OF REVIEW: In advanced chronic kidney disease (CKD) patients with progressive uremia, dialysis has traditionally been the dominant treatment paradigm. However, there is increasing interest in conservative and preservative management of kidney function as alternative patient-centered treatment approaches in this population. RECENT FINDINGS: The primary objectives of conservative nondialytic management include optimization of quality of life and treating symptoms of end-stage renal disease (ESRD). Dietetic-nutritional therapy can be a cornerstone in the conservative management of CKD by reducing glomerular hyperfiltration, uremic toxin generation, metabolic acidosis, and phosphorus burden. Given the high symptom burden of advanced CKD patients, routine symptom assessment using validated tools should be an integral component of their treatment. As dialysis has variable effects in ameliorating symptoms, palliative care may be needed to manage symptoms such as pain, fatigue/lethargy, anorexia, and anxiety/depression. There are also emerging treatments that utilize intestinal (e.g., diarrhea induction, colonic dialysis, oral sorbents, gut microbiota modulation) and dermatologic pathways (e.g., perspiration reduction) to reduce uremic toxin burden. SUMMARY: As dialysis may not confer better survival nor improved patient-centered outcomes in certain patients, conservative management is a viable treatment option in the advanced CKD population.

Association between hypothyroidism and chronic kidney disease observed among an adult population 55 years and older.

Hypothyroidism and chronic kidney disease (CKD) are highly prevalent conditions with a potential mechanistic link. We sought to determine whether hypothyroidism is associated with CKD among a large diverse community-based cohort.A cross-sectional study was performed (January 1, 1990-December 31, 2017) within a large integrated health system. Individuals age ≥55 years of age with outpatient measurements of thyroid stimulating hormone (TSH) and ≥2 serum creatinine values were included. Hypothyroidism was defined as TSH >4 mIU/L and/or receipt of thyroid hormone replacement and further categorized as hypothyroid status: TSH >4 mcIU/mL and attenuated-hypothyroid status: TSH <4 mcIU/mL with receipt of thyroid hormone replacement. Euthyroidism was defined as TSH <4 mIU/L and no thyroid hormone replacement. Our primary measure was CKD defined as an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m. Multivariable logistic regression adjusting for age, sex, race, and comorbidities was used to estimate odds ratios (OR) for CKD by thyroid status.Among 378,101 individuals, 114,872 (30.4%) had hypothyroidism among whom 31,242 and 83,630 had hypothyroid and attenuated-hypothyroid statuses, respectively. Individuals with hypothyroidism had a CKD OR (95%CI) of 1.25 (1.21-1.29) compared with those with euthyroidism. Granular examination of thyroid statuses showed that hypothyroid and attenuated-hypothyroid statuses had CKD ORs (95% CI) of 1.59 (1.52-1.66) and 1.12 (1.08-1.16), respectively. A similar relationship was observed in analyses that defined CKD as an eGFR <60 L/min/1.73 m.Among individuals 55 years and older, we observed that those with hypothyroidism were more likely to have CKD. A stronger association was found among patients of hypothyroid status compared with attenuated-hypothyroid status suggesting a dose dependent relationship.

Sub-acute hyponatraemia more than chronic hyponatraemia is associated with serious falls and hip fractures.

BACKGROUND: Falls and hip fractures among older people are associated with high morbidity and mortality. Hyponatraemia may be a risk for falls/hip fractures, but the effect of hyponatraemia duration is not well understood. AIMS: To evaluate individuals with periods of sub-acute and chronic hyponatraemia on subsequent risk for serious falls and/or hip fractures. METHODS: Retrospective cohort study in the period 1 January 1998 to 14 June 2016 within an integrated health system of individuals aged ≥55 years with ≥2 outpatient serum sodium measurements. Hyponatraemia was defined as sodium <135 mEq/L with sub-acute (<30 days) and chronic (≥30 days) analysed as a time-dependent exposure. Multivariable Cox proportional-hazards modelling was used to estimate hazard ratios (HR) for serious falls/hip fractures based on sodium category. RESULTS: Among 1 062 647 individuals totalling 9 762 305 sodium measurements, 96 096 serious falls/hip fracture events occurred. Incidence (per-1000-person-years) of serious falls/hip fractures were 11.5, 27.9 and 19.8 for normonatraemia, sub-acute and chronic hyponatraemia. Any hyponatraemia duration compared to normonatraemia had a serious falls/hip fractures HR (95%CI) of 1.18 (1.15, 1.22), with sub-acute and chronic hyponatraemia having HR of 1.38 (1.33, 1.42) and 0.91 (0.87, 0.95), respectively. Examined separately, the serious falls HR was 1.37 (1.32, 1.42) and 0.92 (0.88, 0.96) in sub-acute and chronic hyponatraemia, respectively. Hip fracture HR were 1.52 (1.42, 1.62) and 1.00 (0.92, 1.08) for sub-acute and chronic hyponatraemia, respectively, compared to normonatraemia. CONCLUSIONS: Our findings suggest that early/sub-acute hyponatraemia appears more vulnerable and associated with serious falls/hip fractures. Whether hyponatraemia is a marker of frailty or a modifiable risk factor for falls remains to be determined.

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.

Dialysis Provider and Outcomes among United States Veterans Who Transition to Dialysis.

BACKGROUND AND OBJECTIVES: Veterans with ESKD initiate dialysis under the Veterans Health Administration (VHA), an integrated health system, or are outsourced to non-VHA providers. It is unknown whether outcomes differ according to their dialysis provider at initiation. We sought to evaluate the association between dialysis provider and mortality and hospitalization among United States veterans initiating dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 68,727 United States veterans who initiated dialysis in 2007-2014, we examined the association of dialysis provider (VHA versus non-VHA) at initiation with mortality and hospitalization rates in the first 12 months post-initiation. Associations were examined across adjusted models, accounting for demographics and comorbidities. RESULTS: Patients were 72±11 years, 5% were women, 24% were black, and 10% (n=7584) initiated at VHA dialysis centers. VHA dialysis center patients were younger, more likely to be black, had fewer cardiovascular comorbidities, and lower eGFR at dialysis initiation. VHA provider patients were more likely to be hospitalized in the first 12 months (adjusted incidence rate ratio, 1.10; 95% confidence interval, 1.07 to 1.14), but had lower all-cause mortality risk (adjusted hazard ratio, 0.87; 95% confidence interval, 0.83 to 0.93) in fully adjusted models. CONCLUSIONS: Veteran patients initiating dialysis with a VHA dialysis provider appear to have a lower mortality risk but higher hospitalization rates than veterans initiating dialysis at non-VHA dialysis units.

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.

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.

The role of low protein diet in ameliorating proteinuria and deferring dialysis initiation: what is old and what is new.

In the management of patients with chronic kidney diseases (CKD), a low-protein diet usually refers to a diet with protein intake of 0.6 to 0.8 grams per kilogram of body weight per day (g/kg/day) and should include at least 50% high-biologic-value protein. It may be supplemented with essential acids or nitrogen-free ketoanalogues if <0.6 g/kg/d. Low-protein diet can reduce proteinuria especially in non-diabetic CKD patients. In hypoalbuminemic patients it may lead to an increase in serum albumin level. By lowering proteinuria, decreasing nitrogen waste products, ameliorating metabolic burden, mitigating oxidative stress and acidosis, and lowering phosphorus burden, a low-protein diet can help delay dialysis start in advanced CKD. Low-protein diet is safe, since most CKD patients can maintain nitrogen balance by mechanisms of decreasing amino acid oxidation and protein degradation in addition to increased utilization of amino acids for protein synthesis. We suggest a dietary protein intake below 1.0 g/kg/day when estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2 or when there is solitary kidney or proteinuria at any level of GFR. Protein intake should be reduced progressively based on severity and progression of CKD and patient's nutritional status with a target of 0.6-0.8 g/kg/d in most patients with eGFR <45 mL/min/1.73 m2. The risk of protein-energy wasting can be overcome by careful attention to quantity and quality of the ingested proteins, sufficient energy intake of 30-35 Kcal/kg/d, and use of dietary supplements. Long-term observations and individualized approaches are needed to further demonstrate the benefits and safety of low-protein diet.

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.

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.