A pragmatic approach for implementation of value-based healthcare in Amsterdam UMC, the Netherlands.

BACKGROUND: The emphasis on implementation of value-based healthcare (VBHC) has increased in the Dutch healthcare system. Yet, the translation of the theoretical principles of VBHC towards actual implementation in daily practice has been rarely described. Our aim is to present a pragmatic step-by-step approach for VBHC implementation, developed and applied in Amsterdam UMC, to share our key elements. The approach may inspire others and can be used as a template for implementing VBHC principles in other hospitals. METHODS: The local approach is developed in a major academic hospital in the Netherlands, based at two locations with 15,000 employees in total. Experience-based co-design is used, building on our learning experiences from implementing VBHC for 14 specific patient groups. The described steps and activities devolved from iterative and participative co-design sessions with various experienced stakeholders involved in the implementation of one or more VBHC pathways. RESULTS: The approach includes five phases; preparation, design (team introduction, outcome selection, action agenda), building (outcome set integration in daily practice), implementation (training, outcome registration and implementation) and the continuous improvement cycle. We described two cases for illustration of the approach; the Cleft Lip and Palate and the Chronic Kidney Disease patient groups. For a good start, involvement of a clinical leader as driving force, ensuring participation of patient representatives and sufficient resources are needed. CONCLUSION: We have experienced that several defining features of the development and implementation of this approach may have contributed to its completeness and applicability. Key elements for success have been organisational readiness and clinical leadership. In conclusion, the approach has provided a first step towards VBHC in our hospital. Further research is needed for evaluation of its effectiveness including impact on value for patients.

The effect of natriuretic C-type peptide and its change over time on mortality in patients on haemodialysis or haemodiafiltration.

BACKGROUND: C-type natriuretic peptide (CNP) and its co-product N-terminal proCNP (NTproCNP) have been associated with beneficial effects on the cardiovascular system. In prevalent dialysis patients, however, a relation between NTproCNP and mortality has not yet been investigated. Furthermore, as a middle molecular weight substance, its concentration might be influenced by dialysis modality. METHODS: In a cohort of patients treated with haemodialysis (HD) or haemodiafiltration (HDF), levels of NTproCNP were measured at baseline and 6, 12, 24 and 36 months. The relation between serum NTproCNP and mortality and the relation between the 6-month rate of change of NTproCNP and mortality were analysed using Cox regression models. For the longitudinal analyses, linear mixed models were used. RESULTS: In total, 406 subjects were studied. The median baseline serum NTproCNP was 93 pmol/L and the median follow-up was 2.97 years. No relation between baseline NTproCNP or its rate of change over 6 months and mortality was found. NTproCNP levels remained stable in HD patients, whereas NTproCNP decreased significantly in HDF patients. The relative decline depended on the magnitude of the convection volume. CONCLUSIONS: In our study, levels of NTproCNP appear strongly elevated in prevalent dialysis patients. Second, while NTproCNP remains unaltered in HD patients, its levels decline in individuals treated with HDF, with the decline dependent on the magnitude of the convection volume. Third, NTproCNP is not related to mortality in this population. Thus NTproCNP does not seem to be a useful marker for mortality risk in dialysis patients.

Influence of exogenous growth hormone administration on circulating concentrations of α-klotho in healthy and chronic kidney disease subjects: a prospective, single-center open case-control pilot study.

BACKGROUND: The CKD-associated decline in soluble α-Klotho (α-Klotho) levels is considered detrimental. Some studies suggest a direct induction of α-Klotho concentrations by growth hormone (GH). In the present study, the effect of exogenous GH administration on α-Klotho concentrations in a clinical cohort with mild chronic kidney disease (CKD) and healthy subjects was studied. METHODS: A prospective, single-center open case-control pilot study was performed involving 8 patients with mild CKD and 8 healthy controls matched for age and sex. All participants received subcutaneous GH injections (Genotropin®, 20 mcg/kg/day) for 7 consecutive days. α-Klotho concentrations were measured at baseline, after 7 days of therapy and 1 week after the intervention was stopped. RESULTS: α-Klotho concentrations were not different between CKD-patients and healthy controls at baseline (554 (388-659) vs. 547 (421-711) pg/mL, P = 0.38). Overall, GH therapy increased α-Klotho concentrations from 554 (405-659) to 645 (516-754) pg/mL, P < 0.05). This was accompanied by an increase of IGF-1 concentrations from 26.8 ± 5.0 nmol/L to 61.7 ± 17.7 nmol/L (P < 0.05). GH therapy induced a trend toward increased α-Klotho concentrations both in the CKD group (554 (388-659) to 591 (358-742) pg/mL (P = 0.19)) and the healthy controls (547 (421-711) pg/mL to 654 (538-754) pg/mL (P = 0.13)). The change in α-Klotho concentration was not different for both groups (P for interaction = 0.71). α-Klotho concentrations returned to baseline levels within one week after the treatment (P < 0.05). CONCLUSIONS: GH therapy increases α-Klotho concentrations in subjects with normal renal function or stage 3 CKD. A larger follow-up study is needed to determine whether the effect size is different between both groups or in patients with more severe CKD. TRIAL REGISTRATION: This trial is registered in EudraCT ( 2013-003354-24 ).

Left ventricular geometric patterns in end-stage kidney disease: Determinants and course over time.

INTRODUCTION: While concentric left ventricular hypertrophy (cLVH) predominates in non-dialysis-dependent chronic kidney disease (CKD), eccentric left ventricular hypertrophy (eLVH) is most prevalent in dialysis-dependent CKD stage 5 (CKD5D). In these patients, the risk of sudden death is 5× higher than in individuals with cLVH. Currently, it is unknown which factors determine left ventricular (LV) geometry and how it changes over time in CKD5D. METHODS: Data from participants of the CONvective TRAnsport Study who underwent serial transthoracic echocardiography were used. Based on left ventricular mass (LVM) and relative wall thickness (RWT), 4 types of left ventricular geometry were distinguished: normal, concentric remodeling, eLVH, and cLVH. Determinants of eLVH were assessed with logistic regression. Left ventricular geometry of patients who died and survived were compared. Long-term changes in RWT and LVM were evaluated with a linear mixed model. FINDINGS: Three hundred twenty-two patients (63.1 ± 13.3 years) were included. At baseline, LVH was present in 71% (cLVH: 27%; eLVH: 44%). Prior cardiovascular disease (CVD) was positively associated with eLVH and ß-blocker use inversely. None of the putative volume parameters showed any relationship with eLVH. Although eLVH was most prevalent in non-survivors, the distribution of left ventricular geometry did not vary over time. DISCUSSION: The finding that previous CVD was positively associated with eLVH may result from the permanent high cardiac output and the strong tendency for aortic valve calcification in this group of long-term hemodialysis patients, who suffer generally also from chronic anemia and various other metabolic derangements. No association was found between eLVH and parameters of fluid balance. The distribution of left ventricular geometry did not alter over time. The assumption that LV geometry worsens over time in susceptible individuals, who then suffer from a high risk of dying, may explain these findings.

Myocardial contrast echocardiography in mice: technical and physiological aspects.

Myocardial contrast echocardiography (MCE) offers the opportunity to study myocardial perfusion defects in mice in detail. The value of MCE compared with single-photon emission computed tomography, positron emission tomography, and computed tomography consists of high spatial resolution, the possibility of quantification of blood volume, and relatively low costs. Nevertheless, a number of technical and physiological aspects should be considered to ensure reproducibility among research groups. The aim of this overview is to describe technical aspects of MCE and the physiological parameters that influence myocardial perfusion data obtained with this technique. First, technical aspects of MCE discussed in this technical review are logarithmic compression of ultrasound data by ultrasound systems, saturation of the contrast signal, and acquisition of images during different phases of the cardiac cycle. Second, physiological aspects of myocardial perfusion that are affected by the experimental design are discussed, including the anesthesia regimen, systemic cardiovascular effects of vasoactive agents used, and fluctuations in body temperature that alter myocardial perfusion. When these technical and physiological aspects of MCE are taken into account and adequately standardized, MCE is an easily accessible technique for mice that can be used to study the control of myocardial perfusion by a wide range of factors.

A closer look at the trajectory of physical functioning in chronic hemodialysis.

Background: in chronic hemodialysis, physical functioning (PF) is known to be poor. We set out to assess to what extent chronic dialysis patients are able to maintain a good physical condition over time and what the influence of age is on the trajectory of PF. Methods: we used data form 714 prevalent hemodialysis patients, enrolled in the CONvective TRAnsport STudy (CONTRAST). The PF subscale of the KDQOL SF-36 was assessed at baseline (n = 679) and during 2 years of follow-up (n = 298). Baseline PF score (0-100) was categorized into tertiles (good, intermediate and low). Change of PF of ≥ 5 points was considered clinically relevant. A regression model was applied to assess factors related to 'decline of PF (≥5 points)/low PF (0-33) at follow-up'. Results: during follow-up, only 15.3 % (1 out of 6) of patients succeeded in maintaining a good physical condition, the remainder deteriorated or died. Of the older patients (≥75) only 3.6% remained in a good physical condition. Factors related to decline/low PF were increasing age (odds ratio [OR] = 1.96 [95% CI: 1.03-3.72] for 65-74 years and OR = 2.38 [95%CI: 1.17-4.84] for ≥75 years compared to <65 years) and albumin (OR = 1.10 [95%CI: 1.01-1.18] per g/L decrease). Conclusion: very few hemodialysis patients maintain a good physical condition over a 2-year time span. Especially in older patients, physical performance is poor and decline is faster than in the healthy population. These findings should be taken into account when considering dialysis in older patients and more emphasis should be placed to attempts for improving physical condition.

Serum sclerostin: relation with mortality and impact of hemodiafiltration.

BACKGROUND: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated. METHODS: In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl. RESULTS: The mean (±standard deviation) age of 396 test subjects was 63.6 (±13.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P = 0.01)]. Stratified models showed a stable sScl in patients treated with HD (Δ +2.9 pmol/L/year, 95% CI -0.5 to +6.3, P = 0.09) and a decreasing concentration in those treated with HDF (Δ -4.5 pmol/L/year, 95% CI -8.0 to -0.9, P = 0.02). The relative change in the latter group was related to the magnitude of the convection volume. CONCLUSIONS: (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume.

Renal Effects of DPP-4 Inhibitor Sitagliptin or GLP-1 Receptor Agonist Liraglutide in Overweight Patients With Type 2 Diabetes: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To investigate effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) sitagliptin or glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide treatment on renal hemodynamics, tubular functions, and markers of renal damage in overweight patients with type 2 diabetes without chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: In this 12-week, randomized, double-blind trial, 55 insulin-naïve patients with type 2 diabetes (mean ± SEM: age 63 ± 7 years, BMI 31.8 ± 4.1 kg/m2, glomerular filtration rate [GFR] 83 ± 16 mL/min/1.73 m2; median [interquartile range]: albumin-to-creatinine ratio (ACR) 1.09 mg/mmol [0.47-3.31]) received sitagliptin (100 mg/day), liraglutide (1.8 mg/day), or matching placebos. GFR (primary end point) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid clearance, respectively. Intrarenal hemodynamic variables were estimated. Absolute and fractional excretions of sodium (FENa), potassium, and urea (FEU) and renal damage markers (ACR, neutrophil gelatinase-associated lipocalin [NGAL], and kidney injury molecule-1 [KIM-1]) were measured. Plasma renin concentration (PRC) and glycated hemoglobin (HbA1c) were assessed. At weeks 2 and 6, estimated GFR and fractional electrolyte excretions were determined. RESULTS: At week 12, GFR was not affected by sitagliptin (-6 mL/min/1.73 m2 [95% CI -14 to 3], P = 0.17) or liraglutide (+3 mL/min/1.73 m2 [-5 to 11], P = 0.46), compared with placebo. Sitagliptin modestly reduced estimated glomerular hydraulic pressure (PGLO; P = 0.043). ERPF, other intrarenal hemodynamic variables, renal damage markers, and PRC did not change for both treatments. Both agents reduced HbA1c. Only at week 2, sitagliptin increased FENa and FEU (P = 0.005). CONCLUSIONS: Twelve-week treatment with sitagliptin or liraglutide does not affect measured renal hemodynamics. No sustained changes in tubular functions or alteration in renal damage markers were observed. The validity and clinical relevance of the slight sitagliptin-induced PGLO reduction remains speculative.

Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating α-Klotho Concentrations.

The CKD-associated decline in soluble α-Klotho levels is considered detrimental. Some in vitro and in vivo animal studies have shown that anti-oxidant therapy can upregulate the expression of α-Klotho in the kidney. We examined the effect of anti-oxidant therapy on α-Klotho concentrations in a clinical cohort with mild tot moderate chronic kidney disease (CKD). We performed a post-hoc analysis of a prospective randomized trial involving 62 patients with mild to moderate CKD (the ATIC study), all using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for 12 months. On top of that, the intervention group received anti-oxidative therapy consisting of the combination of pravastatin (40 mg/d) and vitamin E (α-tocopherol acetate, 300 mg/d) while the placebo was not treated with anti-oxidants. α-Klotho concentrations were measured at baseline and after 12 months of anti-oxidant therapy. Data were analysed using T-tests and Generalized Estimating Equations, adjusting for potential confounders such as vitamin D, parathyroid hormone, fibroblast-growth-factor 23 (FGF23) and eGFR. The cohort existed of 62 patients with an eGFR (MDRD) of 35 ± 14 ml/min/1.72 m2, 34 were male and mean age was 53.0 ± 12.5 years old. Anti-oxidative therapy did successfully reduce oxLDL and LDL concentrations (P <0.001). α-Klotho concentrations did not change in patients receiving either anti-oxidative therapy (476.9 ± 124.3 to 492.7 ± 126.3 pg/mL, P = 0.23) nor in those receiving placebo 483.2 ± 142.5 to 489.6 ± 120.3 pg/mL, P = 0.62). Changes in α-Klotho concentrations were not different between both groups (p = 0.62). No evidence was found that anti-oxidative therapy affected α-Klotho concentrations in patients with mild-moderate CKD.

Comparing Tests Assessing Protein-Energy Wasting: Relation With Quality of Life.

OBJECTIVE: Protein-energy wasting (PEW), a state of decreased bodily protein and energy fuels, is highly prevalent among hemodialysis patients. The best method to determine PEW, however, remains debated. As an independent, negative association between PEW and quality of life (QOL) has been demonstrated, establishing which nutrition-related test correlates best with QOL may help to identify how PEW should preferably be assessed. DESIGN AND METHODS: Data were used from CONTRAST, a cohort of end-stage kidney disease patients. At baseline, Subjective Global Assessment (SGA), Malnutrition Inflammation Score (MIS), Geriatric Nutritional Risk Index, composite score on protein-energy nutritional status, normalized protein nitrogen appearance, body mass index, serum albumin, and serum creatinine were determined. QOL was assessed by the Kidney Disease Quality of Life Short Form 1.3. The present study reports on 2 general and 11 kidney disease-specific QOL scores. Spearman's rho (ρ) was calculated to determine correlations between nutrition-related tests and QOL domains. Twelve months after randomization, a sensitivity analysis was performed to test the robustness of the results. RESULTS: Of 714 patients, 489 representative subjects were available for analysis. All tests correlated with the Physical Component Score, except body mass index. Only SGA and MIS correlated significantly with the Mental Component Score. SGA correlated significantly with 10 of 11 kidney disease-specific QOL domains. The MIS not only correlated significantly with all (11) kidney disease-specific QOL domains but also with higher correlation coefficients. CONCLUSION: Of the 8 investigated nutrition-related tests, only MIS correlates with all QOL domains (13 of 13) with the strongest associations.

Serum Magnesium and Sudden Death in European Hemodialysis Patients.

Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77-94), the HR for cardiovascular mortality 0.73 (95% CI 0.62-0.85) and for sudden death 0.76 (95% CI 0.62-0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time.

Eccentric Left Ventricular Hypertrophy and Sudden Death in Patients with End-Stage Kidney Disease.

BACKGROUND/AIMS: Both all-cause and cardiovascular mortality risks are extremely high in patients with end-stage kidney disease (ESKD). Sudden death accounts for approximately one-quarter of all fatal events. Left ventricular hypertrophy (LVH) is a known risk factor for mortality and can be divided in 2 types: concentric and eccentric. This study evaluated possible differences in all-cause mortality, cardiovascular mortality and sudden death between prevalent ESKD patients with concentric and eccentric LVH. METHODS: Participants of the CONvective TRAnsport STudy (CONTRAST) who underwent transthoracic echocardiography (TTE) at baseline were analyzed. In patients with LVH, a relative wall thickness of ≤0.42 was considered eccentric and >0.42 was considered concentric hypertrophy. Cox proportional hazards models, adjusted for potential confounders, were used to calculate hazard ratios (HRs) of patients with eccentric LVH versus patients with concentric LVH for all-cause mortality, cardiovascular mortality and sudden death. RESULTS: TTE was performed in 328 CONTRAST participants. LVH was present in 233 participants (71%), of which 87 (37%) had concentric LVH and 146 (63%) eccentric LVH. The HR for all-cause mortality of eccentric versus concentric LVH was 1.14 (p = 0.52), 1.79 (p = 0.12) for cardiovascular mortality and 4.23 (p = 0.02) for sudden death in crude analyses. Propensity score-corrected HR for sudden death in patients with eccentric LVH versus those with concentric LVH was 5.22 (p = 0.03). CONCLUSIONS: (1) The hazard for all-cause mortality, cardiovascular mortality and sudden death is markedly increased in patients with LVH. (2) The sudden death risk is significantly higher in ESKD patients with eccentric LVH compared to subjects with concentric LVH.

The Effect of Online Hemodiafiltration on Infections: Results from the CONvective TRAnsport STudy.

BACKGROUND: Hemodialysis (HD) patients have a high risk of infections. The uremic milieu has a negative impact on several immune responses. Online hemodiafiltration (HDF) may reduce the risk of infections by ameliorating the uremic milieu through enhanced clearance of middle molecules. Since there are few data on infectious outcomes in HDF, we compared the effects of HDF with low-flux HD on the incidence and type of infections. PATIENTS AND METHODS: We used data of the 714 HD patients (age 64 ±14, 62% men, 25% Diabetes Mellitus, 7% catheters) participating in the CONvective TRAnsport STudy (CONTRAST), a randomized controlled trial evaluating the effect of HDF as compared to low-flux HD. The events were adjudicated by an independent event committee. The risk of infectious events was compared with Cox regression for repeated events and Cox proportional hazard models. The distributions of types of infection were compared between the groups. RESULTS: Thirty one percent of the patients suffered from one or more infections leading to hospitalization during the study (median follow-up 1.96 years). The risk for infections during the entire follow-up did not differ significantly between treatment arms (HDF 198 and HD 169 infections in 800 and 798 person-years respectively, hazard ratio HDF vs. HD 1.09 (0.88-1.34), P = 0.42. No difference was found in the occurrence of the first infectious event (either fatal, non-fatal or type specific). Of all infections, respiratory infections (25% in HDF, 28% in HD) were most common, followed by skin/musculoskeletal infections (21% in HDF, 13% in HD). CONCLUSIONS: HDF as compared to HD did not result in a reduced risk of infections, larger studies are needed to confirm our findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT00205556.

Treatment Time or Convection Volume in HDF: What Drives the Reduced Mortality Risk?

BACKGROUND/AIMS: Treatment time is associated with survival in hemodialysis (HD) patients and with convection volume in hemodiafiltration (HDF) patients. High-volume HDF is associated with improved survival. Therefore, we investigated whether this survival benefit is explained by treatment time. METHODS: Participants were subdivided into four groups: HD and tertiles of convection volume in HDF. Three Cox regression models were fitted to calculate hazard ratios (HRs) for mortality of HDF subgroups versus HD: (1) crude, (2) adjusted for confounders, (3) model 2 plus mean treatment time. As the only difference between the latter models is treatment time, any change in HRs is due to this variable. RESULTS: 114/700 analyzed individuals were treated with high-volume HDF. HRs of high-volume HDF are 0.61, 0.62 and 0.64 in the three models, respectively (p values <0.05). Confidence intervals of models 2 and 3 overlap. CONCLUSION: The survival benefit of high-volume HDF over HD is independent of treatment time.

A Comparison of 8 Nutrition-Related Tests to Predict Mortality in Hemodialysis Patients.

OBJECTIVE: Protein-energy wasting (PEW) describes a state of decreased protein and energy fuels and is highly prevalent in hemodialysis patients. As PEW is associated with mortality, it should be detected accurately and easily. This study investigated which nutrition-related test predicts mortality and morbidity best in hemodialysis patients. DESIGN AND SUBJECTS: Data were used from CONTRAST, a cohort of end-stage kidney disease patients. Subjective Global Assessment (SGA), Malnutrition Inflammation Score (MIS), Geriatric Nutritional Risk Index (GNRI), composite score of Protein-Energy Nutritional Status (cPENS), serum albumin, serum creatinine, body mass index, and normalized protein nitrogen appearance rate were assessed at baseline. End points were all-cause mortality, cardiovascular events, and infection. Discriminative value of every test was assessed with Harrell's C statistic and calibration tested using the Hosmer-Lemeshow goodness-of-fit test. Ultimately, in every test, 4 groups were created to compare (1) hazard ratios (HR; worst vs best group), (2) HR increase per group, and (3) HR of worst group versus other groups. RESULTS: In total, 489 patients were analyzed. Median follow-up was 2.97 years (interquartile range, 1.67-4.47 years). MIS, GNRI, albumin, and creatinine discriminated all-cause mortality equally. SGA, cPENS, body mass index, and normalized protein nitrogen appearance were inferior. cPENS and creatinine were inadequately calibrated. Of the remaining tests, GNRI predicted mortality less when comparing HRs. MIS and albumin predicted mortality equally well. In a subanalysis, these also predicted infection equally well, but MIS predicted cardiovascular events better. CONCLUSION: Of the 8 investigated nutrition-related tests, MIS and albumin predict mortality best in hemodialysis patients. As one has no added value over the other, we conclude that mortality is most easily predicted in hemodialysis patients by serum albumin.

A novel rat model of vitamin D deficiency: safe and rapid induction of vitamin D and calcitriol deficiency without hyperparathyroidism.

Vitamin D deficiency is associated with a range of clinical disorders. To study the mechanisms involved and improve treatments, animal models are tremendously useful. Current vitamin D deficient rat models have important practical limitations, including time requirements when using, exclusively, a vitamin D deficient diet. More importantly, induction of hypovitaminosis D causes significant fluctuations in parathyroid hormone (PTH) and mineral levels, complicating the interpretation of study results. To overcome these shortcomings, we report the successful induction of vitamin D deficiency within three weeks, with stable serum PTH and minerals levels, in Wistar rats. We incorporated two additional manoeuvres compared to a conventional diet. Firstly, the vitamin D depleted diet is calcium (Ca) enriched, to attenuate the development of secondary hyperparathyroidism. Secondly, six intraperitoneal injections of paricalcitol during the first two weeks are given to induce the rapid degradation of circulating vitamin D metabolites. After three weeks, serum 25-hydroxyvitamin D3 (25D) and 1,25-dihydroxyvitamin D3 (1,25D) levels had dropped below detection limits, with unchanged serum PTH, Ca, and phosphate (P) levels. Therefore, this model provides a useful tool to examine the sole effect of hypovitaminosis D, in a wide range of research settings, without confounding changes in PTH, Ca, and P.