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The prescription of dialysate potassium concentration during short daily and long nocturnal (high dose) hemodialysis (HD) is challenging due to limited clinical experience with such modalities. The aim here is to propose a quantitative approach for prescribing dialysate potassium concentrations during high-dose HD. Potassium kinetic parameters based on a pseudo one-compartment model from 547 patients participating in the HEMO Study were used for prediction purposes in this study. Patients were categorized based on the prescribed dialysate potassium concentration during thrice weekly HD as 1K (mean of 1.02 mEq/L, N = 60), 2K (2.01 mEq/L, N = 437), or 3K (3.01 mEq/L, N = 50). Dialysate potassium concentrations were then predicted for each patient during short daily and long nocturnal HD based on a pseudo one-compartment model to maintain the identical weekly dialytic potassium removal and predialysis serum potassium concentration as during thrice weekly HD. Predicted prescribed dialysate potassium concentrations for short daily HD were 0.18-0.45 mEq/L higher than during thrice weekly HD but were approximately 4 (3.72-4.26) mEq/L for all patients during long nocturnal HD. The intradialytic decrease in serum potassium concentration was predicted to be reduced by more than one-half during short daily HD and by approximately three-quarters during long nocturnal HD of that during thrice weekly HD. Prescribed dialysate potassium concentration during high-dose HD modalities can be quantitatively predicted using a pseudo one-compartment kinetic model. High-dose HD modalities may improve clinical outcomes by reducing intradialytic decreases in serum potassium.

Hyperkalemia in hemodialysis patients is associated with high mortality, but prescription of low dialysate potassium concentrations to decrease serum potassium levels is associated with a high incidence of sudden cardiac arrest or sudden death. Improved clinical outcomes for these patients may be possible if rapid and substantial intradialysis decreases in serum potassium concentration can be avoided while maintaining adequate potassium removal. Data from kinetic modeling sessions during the HEMO Study of the dependence of serum potassium concentration on time during hemodialysis treatments and 30 minutes postdialysis were evaluated using a pseudo one-compartment model. Kinetic estimates of potassium mobilization clearance (KM) and predialysis central distribution volume (Vpre) were determined in 551 hemodialysis patients. The studied patients were 58.8 ± 14.4 years of age with predialysis body weight of 72.1 ± 15.1 kg; 306 (55.4%) of the patients were female and 337 (61.2%) were black. KM and Vpre for all patients were non-normally distributed with values of 158 (111, 235) (median [interquartile range]) mL/min and 15.6 (11.4, 22.8) L, respectively. KM was independent of dialysate potassium concentration (P > 0.2), but Vpre was lower at higher dialysate potassium concentration (R = −0.188, P

Provider and patient enthusiasm for frequent home nocturnal hemodialysis (FHNHD) has been renewed; however, the cost-effectiveness of this technique is unknown. We performed a cost-utility analysis of FHNHD compared with conventional hemodialysis (CvHD; 4 hours three times per week) from a health payer perspective over a lifetime horizon using patient information from the Alberta NHD randomized controlled trial. Costs, including training costs, were obtained using microcosting and administrative data (CAN$2012). We determined the incremental cost per quality-adjusted life year (QALY) gained. Robustness was assessed using scenario, sensitivity, and probabilistic sensitivity analyses. Compared with CvHD (61% in-center, 14% satellite, and 25% home dialysis), FHNHD led to incremental cost savings (−$6700) and an additional 0.38 QALYs. In sensitivity analyses, when the annual probability of technique failure with FHNHD increased from 7.6% (reference case) to ≥19%, FHNHD became unattractive (>$75,000/QALY). The cost/QALY gained became $13,000 if average training time for FHNHD increased from 3.7 to 6 weeks. In scenarios with alternate comparator modalities, FHNHD remained dominant compared with in-center CvHD; cost/QALYs gained were $18,500, $198,000, and $423,000 compared with satellite CvHD, home CvHD, and peritoneal dialysis, respectively. In summary, FHNHD is attractive compared with in-center CvHD in this cohort. However, the attractiveness of FHNHD varies by technique failure rate, training time, and dialysis modalities from which patients are drawn, and these variables should be considered when establishing FHNHD programs.

Our recent work proposed a pseudo one-compartment model for describing intradialysis and postdialysis rebound kinetics of phosphorus. In this model, phosphorus is removed directly from a central distribution volume with the rate of phosphorus mobilization from a second, very large compartment proportional to the phosphorus mobilization clearance. Here, we evaluated factors of phosphorus mobilization clearance and postdialysis central distribution volume from 774 patients in the HEMO Study. Phosphorus mobilization clearance and postdialysis central distribution volume were 87 (65, 116) ml/min, median (interquartile range), and 9.4 (7.2, 12.0) liter, respectively. The phosphorus mobilization clearance was significantly higher for male patients than for female patients. Both the phosphorus mobilization clearance and the postdialysis central distribution volume were significantly associated with postdialysis body weight but negatively with the predialysis serum phosphorus concentration. The postdialysis central distribution volume was also significantly associated with age. Overall, the postdialysis central distribution volume was 13.6% of the postdialysis body weight. Thus, the phosphorus mobilization clearance during hemodialysis is higher when predialysis serum phosphorus concentration is low and higher in male patients than in female patients. The central distribution volume of phosphorus is a space approximating the extracellular fluid volume.

The kinetics of plasma phosphorus concentrations during hemodialysis (HD) are complex and cannot be described by conventional one- or two-compartment kinetic models. It has recently been shown by others that the physiologic (or apparent distribution) volume for phosphorus (Vr-P) increases with increasing treatment time and shows a large variation among patients treated by thrice weekly and daily HD. Here, we describe the dependence of Vr-P on treatment time and predialysis plasma phosphorus concentration as predicted by a novel pseudo one-compartment model. The kinetics of plasma phosphorus during conventional and six times per week daily HD were simulated as a function of treatment time per session for various dialyzer phosphate clearances and patient-specific phosphorus mobilization clearances (K(M)). Vr-P normalized to extracellular volume from these simulations were reported and compared with previously published empirical findings. Simulated results were relatively independent of dialyzer phosphate clearance and treatment frequency. In contrast, Vr-P was strongly dependent on treatment time per session; the increase in Vr-P with treatment time was larger for higher values of K(M). Vr-P was inversely dependent on predialysis plasma phosphorus concentration. There was significant variation among predicted Vr-P values, depending largely on the value of K(M). We conclude that a pseudo one-compartment model can describe the empirical dependence of the physiologic volume of phosphorus on treatment time and predialysis plasma phosphorus concentration. Further, the variation in physiologic volume of phosphorus among HD patients is largely due to differences in patient-specific phosphorus mobilization clearance.

Summary Background and objectives Despite reporting estimated GFR (eGFR), use of evidence-based interventions in CKD remains suboptimal. This study sought to determine the effect of an enhanced eGFR laboratory prompt containing specific management recommendations, compared with standard eGFR reporting in CKD. Design, setting, participants, & measurements A cluster randomized trial of a standard or enhanced eGFR laboratory prompt was performed in 93 primary care practices in Alberta, Canada. Although all adult patients with CKD (eGFR 2 ) were included, medication data were only available for elderly patients (aged ≥66 years). The primary outcome, the proportion of patients with diabetes or proteinuria receiving an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), was assessed in elderly CKD patients. Results There were 5444 elderly CKD patients with diabetes or proteinuria who were eligible for primary outcome assessment, irrespective of baseline ACEi/ARB use. ACEi/ARB use in the subsequent year was 77.1% and 76.9% in the standard and enhanced prompt groups, respectively. In the subgroup of elderly patients with an eGFR 2 , ACEi/ARB use was higher in the enhanced prompt group. Among 22,092 CKD patients, there was no difference in the likelihood of a composite clinical outcome (death, ESRD, doubling of serum creatinine, or hospitalization for myocardial infarction, heart failure, or stroke) over a median of 2.1 years. Conclusions In elderly patients with CKD and an indication for ACEi/ARB, an enhanced laboratory prompt did not increase use of these medications.

PURPOSE Mathematical models of phosphorus kinetics and mass balance during hemodialysis are in early development. We describe a theoretical phosphorus steady state mass balance model during hemodialysis based on a novel pseudo one-compartment kinetic model. METHODS The steady state mass balance model accounted for net intestinal absorption of phosphorus and phosphorus removal by both dialysis and residual kidney function. Analytical mathematical solutions were derived to describe time-dependent intradialytic and interdialytic serum phosphorus concentrations assuming hemodialysis treatments were performed symmetrically throughout a week. RESULTS Results from the steady state phosphorus mass balance model are described for thrice weekly hemodialysis treatment prescriptions only. The analysis predicts 1) a minimal impact of dialyzer phosphorus clearance on predialysis serum phosphorus concentration using modern, conventional hemodialysis technology, 2) variability in the postdialysis-to-predialysis phosphorus concentration ratio due to differences in patient-specific phosphorus mobilization, and 3) the importance of treatment time in determining the predialysis serum phosphorus concentration. CONCLUSIONS We conclude that a steady state phosphorus mass balance model can be developed based on a pseudo one-compartment kinetic model and that predictions from this model are consistent with previous clinical observations. The predictions from this mass balance model are theoretical and hypothesis-generating only; additional prospective clinical studies will be required for model confirmation.

Twenty-four-hour urine and dialysate collections provide accepted means to assess adequacy in peritoneal dialysis (PD). Recent publications suggest that creatinine clearance (CrCl) estimated from the Modification of Diet in Renal Disease (MDRD) equations (eCrCl) accurately approximates measured CrCl (mCrCl) derived from 24-hour collections of urine and dialysate and might serve as an alternative means to assess small-solute clearance and adequacy in PD.Post hoc analysis of data from patients enrolled in ADEMEX was used to assess agreement between mCrCl and eCrCl derived by four- and six-variable MDRD equations (4V-MDRDE and 6V-MDRDE, respectively). Additionally, associations among mCrCl, eCrCl, and survival were determined.Acceptable precision was observed between mCrCl and 4V-MDRDE-eCrCl and 6V-MDRDE-eCrCl for the entire cohort. Precision was markedly diminished when analysis was limited to functionally anuric patients with mCrCl12 ml/min per 1.73 m². Although there was no association between survival and mCrCl, for every 1-ml/min per 1.73 m² increase in 4V- and 6V-MDRDE-eCrCl, there was a 6% and 4% increase in risk of death, respectively. There was a negative association between MDRDE-eCrCl and creatinine appearance rates, suggesting MDRDE-eCrCl is significantly confounded by individual differences in muscle mass.MDRDE-eCrCl provides demographically comparable values to 24-hour urine and dialysate collections across the ADEMEX cohort. However, MDRDEs should not be used to assess small-solute removal or adequacy in individual PD patients or to predict outcome in any cohort of patients over narrow ranges of limited clearance.

End-stage renal disease (ESRD) is a significant global health problem that places a considerable burden on health care resources. The leading cause of death in ESRD patients is cardiovascular disease, which is often preceded by changes in cardiac geometry, including left ventricular hypertrophy (LVH). Treatments that result in regression of LVH have been shown to lead to better clinical outcomes. Globally, most ESRD patients receive conventional hemodialysis (CHD) 3 times per week, but mortality rates remain high and quality of life (QoL) is poor. Increasing the frequency of HD to 5 or 6 times per week, either as short daily HD (SDHD) or nocturnal HD (NHD), can improve QoL, reduce cardiovascular risk and prolong survival, compared with CHD. Improvements in these end points are likely driven by enhancements in fluid management, blood pressure control, mineral metabolism and left ventricular mass regression. From a practical standpoint, SDHD and NHD are best delivered at home. Barriers to adoption of home HD are chiefly modifiable, and may include lack of a care partner or family support, fear of cannulation and access disconnection, and uncertainty in one's ability to learn the procedures required to perform self-HD. On a positive note, substantial progress has been made to overcome these and other perceived barriers.

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized-controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24-0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty-one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium-phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long-term cardiovascular and bone-related outcomes requires further investigation.

Background Effluent fluid is analyzed to determine Kt/V urea and creatinine clearance as measures of adequacy of peritoneal dialysis. To avoid the physical mixing of fluids and to minimize handling of full effluent bags, a multiple-aliquot method of sampling was developed and compared to the traditional batch method. Methods The batch method and the multiple-aliquot method were performed for 31 consecutive patients. Pooled fluid urea and creatinine measurements were determined for each method. PD Adequest 2.0 (Baxter Healthcare, Deerfield, IL, USA) was used to derive calculated peritoneal dialysis parameters. Results Urea dialysate levels, calculated weekly urea clearances, protein catabolic rate, and Kt/V were not statistically different ( p > 0.05) between the 2 methods. Dialysate creatinine and creatinine clearance with the 2 methods were statistically distinct but the differences were not clinically important. The processing time per set of patient effluent bags was reduced from 45 to 18 minutes, handling of the bags was minimized, and error associated with inadequate mixing of pooled fluids was avoided. Conclusion The multiple-aliquot method generates accurate and timely results to assess peritoneal dialysis prescription adequacy while reducing staff effort.

We conducted a randomized controlled trial to compare the quality of life of 52 patients undergoing nocturnal hemodialysis and conventional hemodialysis. Quality of life was measured using a number of established methods including the Kidney Disease Quality of Life Short Form and the preference-based Euroqol EQ-5D questionnaire (whose scores varied from 0 to 1). The primary outcome was a change in the Euroqol EQ-5D index scores between baseline and 6 months. We performed additional analyses comparing change in quality of life from pre-randomization (when patients were unaware of treatment allocation) to 6 months. Other analyses considered the impact of nocturnal hemodialysis on four pre-selected Kidney Disease Quality of Life Short Form domains, and the longer term impact of nocturnal hemodialysis on quality of life. Compared with conventional hemodialysis, nocturnal hemodialysis increased Euroqol-EQ-5D index scores by 0.05, which was not significantly different from baseline. When six-month values were compared with pre-randomization values rather than baseline values, the between group difference was larger (0.12) though it was still not statistically significant (P=.06). Nocturnal hemodialysis was associated with clinically and statistically significant improvements in selected kidney-specific quality of life domains (P=.01 for effects of kidney disease; P=.02 for burden of kidney disease). Our primary quality of life analysis did not demonstrate a statistically significant change between nocturnal hemodialysis and conventional hemodialysis, though statistically significant and clinically important changes in some secondary kidney-disease- specific measures were observed.

New guidelines for the management of chronic kidney disease have been developed by the Canadian Society of Nephrology (Appendix 1 contains the full-text guidelines; available at [www.cmaj.ca/cgi/content/full/179/11/1154/DC1][1]). These guidelines describe key aspects of the management of chronic

BACKGROUND In patients with chronic kidney disease (CKD), anemia is associated with left ventricular hypertrophy and adverse cardiovascular and clinical outcomes. Moreover, anemia is associated with a reduction in quality of life, particularly when the hemoglobin level drops below 100 g/l. 1 Thus, the goal of treating anemia in iron-replete patients with erythropoietic-stimulating agents (ESAs) is to reduce the likelihood of cardiovascular events, improve patients’ survival, and improve patients’ quality of life while minimizing any deleterious effects of the drug. Given that ESAs increase blood pressure and have other potential side effects, it is also important to assess whether the quantity of the ESA used might contribute to adverse events such as more rapid deterioration of kidney function, earlier requirement for dialysis, and vascular access failure. It is acknowledged that, if left untreated, patients with severe anemia may require blood transfusions, which have associated risks and costs, and possible implications for patients awaiting a kidney transplant. In light of this, in most developed countries, the question for CKD patients with significant anemia has often not been whether to use ESAs, but when to use them and what target hemoglobin level to aim for. 2 The earliest anemia correction studies in nondialysischronic kidney disease (ND-CKD) and hemodialysis-chronic kidney disease (HD-CKD) patients compared the use of erythropoietin a with placebo. 3–5 Most early studies were not designed and powered to examine clinical outcomes other than quality of life, and no differences were apparent in such other outcomes. Several of the studies showed improvements in quality of life compared with placebo. 3–5 Subsequent randomized control trials (RCTs) have tended to examine the impact of using ESAs to achieve different target hemoglobin level ranges on surrogate endpoints, such as left ventricular (LV) mass, where patients with the lower hemoglobin target would be less likely to require the use of an ESA or would require lower doses to maintain the prespecified lower target hemoglobin. Two RCTs 6,7 in HDCKD patients compared with the use of ESAs to achieve intermediate hemoglobin and high hemoglobin targets. Although both studies showed no difference in progression of LV mass, the higher target hemoglobin led to improved quality of life in some of the domains, but the size of this

Supplemental therapies are treatment strategies to enhancethe responsiveness of erythropoietic-stimulating.agents(ESAs) in the management of anemia in chronic kidneydisease (CKD) patients, including those who exhibitresistance to ESAs. The desired outcome is an improvementin hemoglobin levels, reduction in ESA dose, or both.Although the outcomes of these studies (hemoglobin level,ESA dose) are arguably the relevant outcomes of interest, asthe outcome is not a ‘clinical outcome,’ each of the studies isassigned either a Grade C or D level of evidence.

Globally, it is known that the incidence of end-stage renal disease is higher among Aboriginals, but it is unknown whether this is due to an increased prevalence of chronic kidney disease or other unidentified factors. We studied 658,664 people of non–First Nations and 14,989 people of First Nations and found that the age- and sex-adjusted prevalence of chronic kidney disease was significantly higher among those of non–First Nations compared to those of First Nations (67.5 versus 59.5 per 1000 population; P 0.0001). However, severe chronic kidney disease (estimated glomerular filtration rate 30 ml/min per 1.73 m 2 ) was almost two-fold higher among people of First Nations (P 0.0001). Cox proportional hazards models suggested that compared to people of non–First Nations, those of First Nations with chronic kidney disease had a 77% increased risk of death after adjusting for age, gender, diabetes and baseline eGFR. In conclusion, whether the higher incidence of end-stage renal disease among people of First Nations is due to suboptimal management of chronic kidney disease and its associated comorbidities, more rapid loss of kidney function, or other unidentified factors remains to be determined.

Objective To provide updated, evidence-based recommendations for the prevention and management of hypertension in adults. Options and Outcomes For lifestyle and pharmacological interventions, evidence was reviewed from randomized controlled trials and systematic reviews of trials. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. For treatment of patients with kidney disease, the progression of kidney dysfunction was also accepted as a clinically relevant primary outcome. Evidence A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to update the 2006 Canadian Hypertension Education Program recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. Recommendations Dietary lifestyle modifications for prevention of hypertension, in addition to a well-balanced diet, include a dietary sodium intake of less than 100mmol/day. In hypertensive patients, the dietary sodium intake should be limited to 65mmol/day to 100mmol/day. Other lifestyle modifications for both normotensive and hypertensive patients include: performing 30min to 60 min of aerobic exercise four to seven days per week; maintaining a healthy body weight (body mass index of 18.5kg/m2 to 24.9kg/m2) and waist circumference (less than 102cm in men and less than 88 cm in women); limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women; following a diet reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and considering stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and any comorbid conditions: blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients require more than one agent to achieve these blood pressure targets. In adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor plus diuretic combination is preferred; in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered. Validation All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

Background The VIVIA Hemodialysis System (Baxter Healthcare Corporation, Deerfield, IL, USA) was designed for patient use at home to reduce the burden of treatment and improve patient safety. It has unique features including extended use of the dialyzer and blood set through in situ hot-water disinfection between treatments; generation of on-line infusible-quality dialysate for automated priming, rinseback and hemodynamic support during hypotension and a fully integrated access disconnect sensor. Methods The safety and performance of VIVIA were assessed in two clinical studies. A first-in-man study was a prospective, single-arm study that involved 22 prevalent hemodialysis (HD) patients who were treated for ∼4 h, four times a week, for 10 weeks. A second clinical study was a prospective, single-arm study (6-8 h of dialysis treatment at night three times a week) that involved 17 prevalent patients treated for 6 weeks. Results There were 1114 treatments from the two studies (first-in-man study, 816; extended duration study, 298). Adverse events (AEs) were similar in the two studies to those expected for prevalent HD patients. No deaths and no device-related serious AEs occurred. Adequacy of dialysis ( Kt / V ) urea in both clinical trials was well above the clinical guidelines. VIVIA performed ultrafiltration accurately as prescribed in the two studies. The majority of patients achieved 10 or more uses of the dialyzer. Endotoxin levels and bacterial dialysate sampling met infusible-quality dialysate standards. Conclusion These results confirm the safety and expected performance of VIVIA.

Background andobjectivesThecalcimimeticcinacalcet reduced therisk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients. Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. ResultsOlderpatients hadhigher baselineprevalenceof diabetesmellitusandCV comorbidity. Annualizedrates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. Conclusions In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone. Clin J Am Soc Nephrol 10: ccc–ccc, 2015. doi: 10.2215/CJN.07730814

Clinical practice guidelines are systematically developed statements to assist practitioners and patients reach appropriate health care decisions. If developed properly, clinical practice guidelines assimilate and translate an abundance of evidence published on a daily basis into practice recommendations and, in doing so, reduce the use of unnecessary or harmful interventions, and facilitate the treatment of patients to achieve maximum benefit and minimum risk at an acceptable cost. Traditionally, clinical practice guidelines were consensus-based statements, often riddled with expert opinion. It is now recognized that clinical practice guidelines should be developed according to a transparent process involving principles of bias minimization and systematic evidence retrieval and review, with a focus on patient-relevant outcomes. The process for the development, implementation, and evaluation of clinical practice guidelines is reviewed in this chapter.

Background: Chronic kidney disease is common among the elderly, and these patients are at risk of progressive kidney dysfunction. Aim: To develop an index to predict rapid progression of kidney dysfunction. Design: Community-based cohort divided into derivation ( n = 6789) and validation ( n = 3395) subsets. Methods: We identified 10 184 subjects aged ⩾66 years from computerized laboratory data. Prescription drug data was used to define disease categories and medication exposure, and an index for predicting rapid progression of kidney dysfunction (⩾25% decline in glomerular filtration rate over a 2-year period) was obtained from a logistic regression model in the derivation cohort. The risk score for each subject was calculated by summing the component variables together, which were subsequently categorized into five risk classes. Results: Five predictors of rapid progression were identified: age >75 years, cardiac disease, diabetes mellitus, gout, and use of anti-emetic medications. Rates of rapid progression for risk classes I through V were 8.6%, 10.9%, 13.9%, 15.6%, and 24.1%, respectively, for the derivation cohort, and 8.4%, 11.6%, 15.5%, 17.3%, 21.9%, respectively, for the validation cohort. The risk index distinguished between low and high risk of rapid progression, with a 2.5-fold greater risk for the highest, compared to the lowest, risk decile. Discussion: Readily available clinical data can be used to identify most elderly at risk of rapid progression of kidney dysfunction. This simple index could help clinicians to identify patients at risk, and implement strategies to slow the progression of kidney dysfunction.

Background: Racial differences in health outcomes in general are well documented; however, few studies examined the impact of East Asian and Indo Asian race on choice of dialytic modality and survival among patients with end-stage renal disease (ESRD). Methods: We compared the use of peritoneal dialysis (PD) and survival among East Asian, Indo Asian, and white patients with ESRD initiating dialysis therapy in Canada between January 1, 1990, and December 31, 2000. Results: Of 10,338 patients, 5.7% were East Asian, 3.2% were Indo Asian, and 91% were white. After controlling for sociodemographics and comorbidities, East Asian and Indo Asian patients were significantly more likely to initiate dialysis therapy on PD compared with white patients (odds ratio, 1.63; 95% confidence interval [CI], 1.36 to 1.96; odds ratio, 1.52; 95% CI, 1.21 to 1.93, respectively), with no difference in likelihood of technique failure. East Asian and Indo Asian patients had a lower risk for death after the initiation of dialysis therapy (irrespective of modality) compared with white patients, with adjusted hazard ratios of 0.66 (95% CI, 0.58 to 0.76) for East Asian patients and 0.63 (95% CI, 0.53 to 0.75) for Indo Asian patients. The survival benefit for East Asian and Indo Asian patients was similar in the subgroup that initiated dialysis therapy with PD. Conclusion: We found that Asian patients with ESRD were more likely to initiate dialysis therapy using PD, with improved survival after the initiation of dialysis therapy, compared with white patients. Elucidation of factors in East Asian and Indo Asian ESRD populations that result in improved outcomes may have implications for ESRD treatment for other racial groups.

Background: In a universal, public health care system, access to kidney transplantation should not be influenced by residence location. We determined the likelihood of kidney transplantation from deceased donors among Canadian dialysis patients living in 7 geographic regions. Within each region we also determined whether distance from the closest transplant centre was associated with the likelihood of transplantation. Methods: A random sample of 7034 subjects initiating dialysis in Canada between 1996 and 2000 was studied. We used Cox proportional hazards models to examine the relation between residence location and the likelihood of kidney transplantation from deceased donors over a median period of 2.4 years. Results: There were significant differences in the likelihood of kidney transplantation from deceased donors and predicted waiting times between the different geographic regions. For example, the adjusted relative likelihood of transplantation in Alberta was 3.74 (95% confidence interval [CI] 2.95–4.76) compared with the likelihood in Ontario ( p Interpretation: The adjusted likelihood of undergoing a kidney transplant from a deceased donor varied substantially between geographic regions in Canada. In contrast, the likelihood of transplantation within regions was not affected by distance from the closest transplant centre.

Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.

Although anemia is common in older adults, its prognostic significance is uncertain. A total of 17 030 community-dwelling subjects 66 years and older were identified between July 1 and December 31, 2001, and followed until December 31, 2004. Cox proportional hazards analyses were performed to determine the associations between anemia (defined as hemoglobin < 110 g/L) and hemoglobin and all-cause mortality, all-cause hospitalization, and cardiovascular-specific hospitalization. Overall, there were 1983 deaths and 7278 first hospitalizations. In patients with normal kidney function, adjusting for age, sex, diabetes mellitus, and comorbidity, anemia was associated with an increased risk for death (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.55-5.12), first all-cause hospitalization (HR, 2.16; 95% CI, 1.88-2.48), and first cardiovascular-specific hospitalization (HR, 2.49; 95% CI, 1.99-3.12). An inverse J-shaped relationship between hemoglobin and all-cause mortality was observed; the lowest risk for mortality occurred at hemoglobin values between 130 to 150 g/L for women and 140 to 170 g/L for men. Anemia is associated with an increased risk for hospitalization and death in community-dwelling older adults. Consideration should be given to redefine “normal” hemoglobin values in the elderly. Clinical trials are also necessary to determine whether anemia correction improves quality or quantity of life in this population.

A systematic review of the effect of nocturnal hemodialysis on blood pressure, left ventricular hypertrophy, anemia, mineral metabolism, and health-related quality of life.BackgroundNocturnal hemodialysis is a novel form of dialysis where patients perform dialysis 6 nights per week while they sleep. Multiple publications report significant improvements in selected clinical outcomes, although the strength of these results is limited by shortcomings in study design. A systematic review of the current available literature was undertaken to examine the effect of nocturnal hemodialysis on key health outcomes.MethodsAn inclusive search of medical databases was undertaken to identify all nocturnal hemodialysis studies. These results were manually reviewed for relevance to nocturnal hemodialysis and its impact on the following predefined health outcomes: blood pressure control, left ventricular hypertrophy, anemia, mineral metabolism, and health related quality of life. Case reports, short-term studies (

Chronic kidney disease1 (CKD) is a worldwide public health problem. In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. The number of individuals with kidney failure treated by dialysis and transplantation exceeded 320 000 in 1998 and is expected to surpass 650 000 by 2010.1,2 There is an even higher prevalence of earlier stages of CKD (Table 1).1,3 Kidney failure requiring treatment with dialysis or transplantation is the most visible outcome of CKD. However, cardiovascular disease (CVD) is also frequently associated with CKD, which is important because individuals with CKD are more likely to die of CVD than to develop kidney failure,4 CVD in CKD is treatable and potentially preventable, and CKD appears to be a risk factor for CVD. In 1998, the National Kidney Foundation (NKF) Task Force on Cardiovascular Disease in Chronic Renal Disease issued a report emphasizing the high risk of CVD in CKD.5 This report showed that there was a high prevalence of CVD in CKD and that mortality due to CVD was 10 to 30 times higher in dialysis patients than in the general population (Figure 1 and Table 2).6–18 The task force recommended that patients with CKD be considered in the “highest risk group” for subsequent CVD events and that treatment recommendations based on CVD risk stratification should take into account the highest-risk status of patients with CKD. View this table: TABLE 1. Stages of CKD Figure 1. Cardiovascular mortality defined by death due to arrhythmias, cardiomyopathy, cardiac arrest, myocardial infarction, atherosclerotic heart disease, and pulmonary edema in general population (GP; National Center for Health Statistics [NCHS] multiple cause of mortality data files International Classification of Diseases, 9th Revision [ICD 9] codes 402, 404, 410 to 414, and …

BACKGROUND Vertical displacement of the arm relative to the heart causes inverse changes in blood pressure of approximately 0.8 mmHg for every centimetre change in arm position. Therefore a potential confounding issue in assessing diurnal variation in blood pressure during ambulatory blood pressure monitoring (ABPM) is arm position during sleep. An increase in the number of patients with 'excessive' nocturnal dipping (> 20% decrease in night/day blood pressure) was observed following the creation of an instructional videotape in which patients were advised to muffle the noise of the monitor with a pillow at night. This raised the possibility that patients were placing their arm on top of the pillow reducing nocturnal blood pressure readings. DESIGN Ambulatory blood pressure monitoring data from 184 patients prior to and from 193 patients following specific instructions not to put their arm on top of the pillow was examined. RESULTS Following the instructions, the percentage of patients with 'excessive' nocturnal dipping in blood pressure decreased (excessive systolic dipping 17.4 versus 8.8%, P = 0.014; excessive diastolic dipping 37 versus 24.4%, P = 0.01). Consistent with an increase in the ratio of nocturnal/day pressures, there was an increase in the percentage of patients with inadequate nocturnal dipping (< 10% decrease in night/day blood pressure; systolic dipping 33.7 versus 45.6%, P = 0.02; diastolic dipping 13.0 versus 31.6%, P < 0.001) CONCLUSION Instructing patients to avoid resting their arm on a pillow at night has a substantial effect on the classification of nocturnal dipping status. Patients need clear instructions not to place their arm on a pillow at night during blood pressure monitoring.

Background Evidence suggests that high dose haemodialysis (HD) may be associated with better health outcomes and even cost savings (if conducted at home) versus conventional in-centre HD (ICHD). Home-based regimens such as peritoneal dialysis (PD) are also associated with significant cost reductions and are more convenient for patients. However, the financial impact of increasing the use of high dose HD at home with an increased tariff is uncertain. A budget impact analysis was performed to investigate the financial impact of increasing the proportion of patients receiving home-based dialysis modalities from the perspective of the England National Health Service (NHS) payer. Methods A Markov model was constructed to investigate the 5 year budget impact of increasing the proportion of dialysis patients receiving home-based dialysis, including both high dose HD at home and PD, under the current reimbursement tariff and a hypothetically increased tariff for home HD (£575/week). Five scenarios were compared with the current England dialysis modality distribution (prevalent patients, 14.1% PD, 82.0% ICHD, 3.9% conventional home HD; incident patients, 22.9% PD, 77.1% ICHD) with all increases coming from the ICHD population. Results Under the current tariff of £456/week, increasing the proportion of dialysis patients receiving high dose HD at home resulted in a saving of £19.6 million. Conducting high dose HD at home under a hypothetical tariff of £575/week was associated with a budget increase (£19.9 million). The costs of high dose HD at home were totally offset by increasing the usage of PD to 20–25%, generating savings of £40.0 million – £94.5 million over 5 years under the increased tariff. Conversely, having all patients treated in-centre resulted in a £172.6 million increase in dialysis costs over 5 years. Conclusion This analysis shows that performing high dose HD at home could allow the UK healthcare system to capture the clinical and humanistic benefits associated with this therapy while limiting the impact on the dialysis budget. Increasing the usage of PD to 20-25%, the levels observed in 2005-2008, will totally offset the additional costs and generate further savings.

Hyperkalemia in hemodialysis patients is associated with high mortality, but prescription of low dialysate potassium concentrations to decrease serum potassium levels is associated with a high incidence of sudden cardiac arrest or sudden death. Improved clinical outcomes for these patients may be possible if rapid and substantial intradialysis decreases in serum potassium concentration can be avoided while maintaining adequate potassium removal. Data from kinetic modeling sessions during the HEMO Study of the dependence of serum potassium concentration on time during hemodialysis treatments and 30 minutes postdialysis were evaluated using a pseudo one-compartment model. Kinetic estimates of potassium mobilization clearance (K(M)) and predialysis central distribution volume (V(pre)) were determined in 551 hemodialysis patients. The studied patients were 58.8 ± 14.4 years of age with predialysis body weight of 72.1 ± 15.1 kg; 306 (55.4%) of the patients were female and 337 (61.2%) were black. K(M) and V(pre) for all patients were non-normally distributed with values of 158 (111, 235) (median [interquartile range]) mL/min and 15.6 (11.4, 22.8) L, respectively. K(M) was independent of dialysate potassium concentration (P 0.2), but V(pre) was lower at higher dialysate potassium concentration (R = -0.188, P 0.001). For patients with dialysate potassium concentration between 1.6 and 2.5 mEq/L (N = 437), multiple linear regression of K(M) and V(pre) demonstrated positive association with predialysis body weight and negative association with predialysis serum potassium concentration. Potassium kinetics during hemodialysis can be described using a pseudo one-compartment model.

Background. The KDIGO work group recommends increasing dialytic phosphorus removal in Stage 5D chronic kidney disease patients with persistent hyperphosphatemia; however, optimal prescriptions to enhance phosphorus removal by hemodialysis (HD) therapies have not yet been established. This study evaluated whether phosphorus kinetic modeling based on a pseudo one-compartment model could provide practical clinical guidance for predicting changes in predialysis serum phosphorus concentration after altering the HD prescription. Methods. Patient-specific phosphorus kinetic parameters determined from thrice weekly HD treatments on 774 patients in the HEMO Study were used to predict changes in predialysis serum phosphorus concentration after altering the HD prescription from thrice weekly to short daily and long nocturnal HD therapies. The effect of changes in the oral phosphorus binder prescription on predicted changes in the predialysis serum phosphorus concentration was also illustrated using the concept of equivalent phosphorus binder dose. Results. Decreases in predialysis serum phosphorus concentration from thrice weekly HD to short daily and long nocturnal HD prescriptions demonstrated strong associations with the predialysis serum phosphorus concentration during thrice weekly HD that were relatively independent of patient-specific phosphorus kinetic parameters. Thus, the percent decrease in predialysis serum phosphorus concentration was approximately the same among patients for a given alteration in the HD prescription. Both increased weekly treatment time and frequency resulted in a reduction in the predialysis serum phosphorus concentration; however, the effect of treatment time was more influential. Simultaneous reduction in the effective phosphorus binder dose blunted the decrease in the predialysis serum phosphorus concentration. Conclusions. This study demonstrated that a simplified form of phosphorus kinetic modeling based on a pseudo onecompartment model can provide practical clinical guidance for predicting changes in predialysis serum phosphorus concentration after altering the HD prescription. Prospective validation of this approach in future studies is warranted.

Objective To investigate the cost-effectiveness of high-dose hemodialysis (HD) versus conventional in-center HD (ICHD), over a lifetime time horizon from the UK payer's perspective. Methods We used a Markov modeling approach to compare high-dose HD (in-center or at home) with conventional ICHD using current and hypothetical home HD reimbursement tariffs in England. Sensitivity analyses tested the robustness of the results. The main outcome measure was the incremental cost-effectiveness ratio (ICER) expressed as a cost per quality-adjusted life-year (QALY). Results Over a lifetime, high-dose HD in-center (5 sessions/wk) is associated with higher per-patient costs and QALYs (increases of £108,713 and 0.862, respectively) versus conventional ICHD. The corresponding ICER (£126,106/QALY) indicates that high-dose HD in-center is not cost-effective versus conventional ICHD at a UK willingness-to-pay threshold of £20,000 to £30,000. High-dose HD at home is associated with lower total costs (£522 less per patient) and a per-patient QALY increase of 1.273 compared with ICHD under the current Payment-by Results reimbursement tariff (£456/wk). At an increased home HD tariff (£575/wk), the ICER for high-dose HD at home versus conventional ICHD is £17,404/QALY. High-dose HD at home had a 62% to 84% probability of being cost-effective at a willingness-to-pay threshold of £20,000 to £30,000/QALY. Conclusions Although high-dose HD has the potential to offer improved clinical and quality-of-life outcomes over conventional ICHD, under the current UK Payment-by Results reimbursement scheme, it would be considered cost-effective from a UK payer perspective only if conducted at home.

Patients with progressive renal insufficiency (PRI) who start renal replacement therapy (RRT) within 4 months of seeing a nephrologist ( late referral) have increased morbidity, mortality, and health care costs. We performed an economic evaluation of early versus late referral of patients with PRI to a multidisciplinary clinic. A decision analysis was performed from the perspective of the health care provider, using a Markov model to simulate progression of PRI and survival of patients on RRT. Our simulated patient cohort comprised 1,000 patients with PRI and estimated creatinine clearance of 20 mL/min. The study time horizon was 5 years. Clinical and cost data were taken from published Canadian and U.S. data, where available. Where published data were lacking, we used data from our prospectively maintained database. The study intervention was attendance at a PRI clinic where patients receive treatment to slow the rate of renal progression, receive treatment of complications of PRI, and are prepared for RRT. Endpoints were total cost of patient care, patient life-years, patient life-years free of RRT, and hospital admission days. Early referral resulted in cost savings and improved patient survival along with more life-years free of RRT and fewer hospital inpatient days. Cost-effectiveness was unaffected by univariate sensitivity analyses. Cost-effectiveness decreased as rates of renal function loss for patients referred early versus late approximated each other. In conclusion, early referral of patients with PRI to a multidisciplinary clinic appears cost-effective. © 2001 by the National Kidney Foundation, Inc.

Elevated serum uric acid is a frequent finding in patients with kidney disease and cardiovascular disease. Intrarenal ischaemia, induced by hypertension, increased sympathetic nervous system activity, and hyperinsulinaemia have all been implicated in reduced renal clearance of urate. This frequently results in elevated serum uric acid levels. The association of hyperuricaemia with cardiovascular disease remains controversial. Current evidence suggests that serum uric acid may provide additional prognostic information in patients with essential hypertension. However, there has been no test of the hypothesis that a reduction in serum uric acid would prevent cardiovascular disease. Furthermore, a critical review of the current literature does not support a causal role of serum uric acid in the development of cardiovascular disease. Serum uric acid probably reflects and integrates different risk factors and their possible interactions.

the hemoglobin levels used todefine a chronic kidney disease (CKD) patient as anemic arebased on gender-specific values under the 5th percentile foran age of more than 18 years. The data are taken from thethird National Health and Nutrition Examination Survey(NHANES III) data set of the US population, 1988–1994

Clinical Practice Guidelines for the management of anemia associated with chronic kidney disease Braden J. Manns, Colin T. White, Francois Madore, Louise M. Moist, Scott W. Klarenbach, Brendan J. Barrett, Rob N. Foley, Bruce F. Culleton and Marcello Tonelli Division of Nephrology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Division of Nephrology, Department of Pediatrics, Faculty of Medicine, British Columbia Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada; Division of Nephrology, Department of Medicine, Hopital du Sacre-Cœur de Montreal, Universite de Montreal, Montreal, Quebec, Canada; Department of Medicine, University of Western Ontario, London, Ontario, Canada; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, Memorial University, St John’s, Newfoundland and Labrador, Canada and Minneapolis Medical Research Foundation, Minneapolis, Minnesota, USA

Glucose-containing peritoneal dialysis solutions may exacerbate metabolic abnormalities and increase cardiovascular risk in diabetic patients. Here, we examined whether a low-glucose regimen improves metabolic control in diabetic patients undergoing peritoneal dialysis. Eligible patients were randomly assigned in a 1:1 manner to the control group (dextrose solutions only) or to the low-glucose intervention group (IMPENDIA trial: combination of dextrose-based solution, icodextrin and amino acids; EDEN trial: a different dextrose-based solution, icodextrin and amino acids) and followed for 6 months. Combining both studies, 251 patients were allocated to control (n=127) or intervention (n=124) across 11 countries. The primary endpoint was change in glycated hemoglobin from baseline. Mean glycated hemoglobin at baseline was similar in both groups. In the intention-to-treat population, the mean glycated hemoglobin profile improved in the intervention group but remained unchanged in the control group (0.5% difference between groups; 95% confidence interval, 0.1% to 0.8%; P=0.006). Serum triglyceride, very-low-density lipoprotein, and apolipoprotein B levels also improved in the intervention group. Deaths and serious adverse events, including several related to extracellular fluid volume expansion, increased in the intervention group, however. These data suggest that a low-glucose dialysis regimen improves metabolic indices in diabetic patients receiving peritoneal dialysis but may be associated with an increased risk of extracellular fluid volume expansion. Thus, use of glucose-sparing regimens in peritoneal dialysis patients should be accompanied by close monitoring of fluid volume status.

There is limited information about the clinical and prognostic significance of patient-reported recovery time.Prospective cohort study.6,040 patients in the DOPPS (Dialysis Outcomes and Practice Patterns Study).Answer to question "How long does it take you to recover from a dialysis session?" categorized as follows: fewer than 2, 2-6, 7-12, or longer than 12 hours.Cross-sectional and longitudinal associations between recovery time and patient characteristics, hemodialysis treatment variables, health-related quality of life (HRQoL), and hospitalization and mortality.32% reported recovery time shorter than 2 hours; 41%, 2-6 hours; 17%, 7-12 hours; and 10%, longer than 12 hours. Using proportional odds (ordinal) logistic regression, shorter recovery time was associated with male sex, full-time employment, and higher serum albumin level. Longer recovery time was associated with older age, dialysis vintage, body mass index, diabetes, and psychiatric disorder. Greater intradialytic weight loss, longer dialysis session length, and lower dialysate sodium concentration were associated with longer recovery time. In facilities that used uniform dialysate sodium concentrations for ≥90% of patients, the adjusted OR of longer recovery time, comparing dialysate sodium concentration140 vs 140 mEq/L, was 1.72 (95% CI, 1.37-2.16). Recovery time was correlated positively with symptoms of kidney failure and kidney disease burden score and inversely with HRQoL mental and physical component summary scores. Using Cox regression, adjusting for potential confounders not influenced by recovery time, it was associated positively with first hospitalization and mortality (adjusted HRs for recovery time12 vs 2-6 hours 1.22 [95% CI, 1.09-1.37] and 1.47 [95% CI, 1.19-1.83], respectively).Answers are subjective and not supported by physiologic measurements.Recovery time can be used to identify patients with poorer HRQoL and higher risks of hospitalization and mortality. Interventions to reduce recovery time and possibly improve clinical outcomes, such as increasing dialysate sodium concentration, need to be tested in randomized trials.

Background/Aims: On-line hemodiafiltration (HDF) has been previously shown to result in modest reductions in predialysis serum phosphorus concentration compared with conventional hemodialysis (HD); however, understanding of phosphorus kinetics during these therapies remains limited. Methods: Previously published phosphorus kinetic data during HDF and HD were analyzed using a pseudo-one-compartment kinetic model. Phosphorus mobilization clearance (KM) and dialyzer phosphorus clearance (Kd) were simultaneously estimated from measured predialysis and postdialysis serum phosphorus concentrations and total removed phosphorus during each treatment. Results: KM varied among patients between 53 and 173 ml/min. Values of KM during HDF (105 ± 34, mean ± standard deviation, ml/min) and HD (112 ± 44 ml/min) were not different (p = 0.5); however, Kd during HDF (175 ± 23 ml/min) was higher (p = 0.01) than during HD (160 ± 14 ml/min). Conclusion: A pseudo-one-compartment kinetic model is useful for the analysis of phosphorus kinetic data during HDF. Lower predialysis serum phosphorus concentrations during HDF are likely due to increased extracorporeal phosphorus clearance.

The kinetics of plasma phosphorus concentrations during hemodialysis (HD) are complex and cannot be described by conventional one- or two-compartment kinetic models. It has recently been shown by others that the physiologic (or apparent distribution) volume for phosphorus (Vr-P) increases with increasing treatment time and shows a large variation among patients treated by thrice weekly and daily HD. Here, we describe the dependence of Vr-P on treatment time and predialysis plasma phosphorus concentration as predicted by a novel pseudo one-compartment model. The kinetics of plasma phosphorus during conventional and six times per week daily HD were simulated as a function of treatment time per session for various dialyzer phosphate clearances and patient-specific phosphorus mobilization clearances (K(M)). Vr-P normalized to extracellular volume from these simulations were reported and compared with previously published empirical findings. Simulated results were relatively independent of dialyzer phosphate clearance and treatment frequency. In contrast, Vr-P was strongly dependent on treatment time per session; the increase in Vr-P with treatment time was larger for higher values of K(M). Vr-P was inversely dependent on predialysis plasma phosphorus concentration. There was significant variation among predicted Vr-P values, depending largely on the value of K(M). We conclude that a pseudo one-compartment model can describe the empirical dependence of the physiologic volume of phosphorus on treatment time and predialysis plasma phosphorus concentration. Further, the variation in physiologic volume of phosphorus among HD patients is largely due to differences in patient-specific phosphorus mobilization clearance.

Background Sexual dysfunction is common in patients with end stage renal disease (ESRD) and treatment options are limited. Observational studies suggest that nocturnal hemodialysis may improve sexual function. We compared sexual activity and responses to sexual related questions in the Kidney Disease Quality of Life Short Form questionnaire among patients randomized to frequent nocturnal or thrice weekly conventional hemodialysis. Methods We performed a secondary analysis of data from an RCT which enrolled 51 patients comparing frequent nocturnal and conventional thrice weekly hemodialysis. Sexual activity and responses to sexual related questions were assessed at baseline and six months using relevant questions from the Kidney Disease Quality of Life Short Form questionnaire. Results Overall, there was no difference in sexual activity, or the extent to which people were bothered by the impact of kidney disease on their sex life between the two groups between randomization and 6 months. However, women and patients age Conclusions Our results suggest that frequent nocturnal hemodialysis is not associated with an improvement in sexual activity in all patients but might have an effect on the burden of kidney disease on sex life in women and patients less than 60 years of age. The validity of these subgroup findings require confirmation in future RCTs.

Objective More frequent dialysis may improve nutrition and remove dietary restrictions in hemodialysis (HD) patients. We present results from a trial comparing nutritional parameters between nocturnal hemodialysis (NHD) and conventional HD patients. Methods Patients were randomized to conventional thrice weekly HD or NHD for a 6-month study period. Dietary intake was recorded by patients using a 3-day food record at baseline and study exit. Results Of 51 patients, 23 completed baseline and exit food records and were included in the analysis. Although dietary intake of calcium, potassium, and lipids increased in the NHD group, serum levels of calcium and potassium remained within target limits. The majority of NHD subjects were able to reduce or discontinue their phosphate binders and maintain serum phosphate levels within target limits. Serum albumin improved among the NHD group (0.7 g/L) and declined for the conventional group (−1.6 g/L). None of the between group differences achieved statistical significance. Conclusions As compared with conventional dialysis, NHD was associated with a nonstatistically significant increase in dietary intake for some nutrients, with maintenance of serum levels for potassium, calcium, and phosphorus. Whether increased dietary intake translates into improvement in morbidity and mortality remains to be determined.