Objective: Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis. Methods: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 mg/ daily, n = 61) or placebo (n = 62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1 + 2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher's exact test or Pearson's Chi-Squared test. Results: A between-group difference at 52 weeks was observed for PIVKA-II (P < .001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P = .04), and no between-group differences in adverse events and serious adverse events. Conclusion: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.

Background. Arterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients. Methods. In a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized to vitamin K [menaquinone-7 (MK-7), 360 mu g daily] or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aortic calcification (AAC) were used to assess arterial calcification. Results. Thirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40% lower after vitamin K supplementation compared with placebo {mean dp-ucMGP difference: -1380 pmol/L [95% confidence interval (CI) -2029 to -730]}. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95% CI -0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95% CI -554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences. Conclusions. Vitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients.

AIMS:The relevance of adherence to established dietary guidelines is repeatedly challenged. We hypothesised that non-adherence to established dietary guidelines is associated with an excess risk of cardiovascular, non-cardiovascular and all-cause mortality.METHODS:We studied 100,191 white adult Danes aged 20-100 years recruited in 2003-2015 and followed up until December 2018. During follow-up equalling 865,600 person-years, 9273 individuals died. Participants' diets were assessed at baseline by a food frequency questionnaire focusing on key foods defining a healthy diet according to Danish dietary guidelines. Individuals were divided into five categories ranging from very high to very low adherence to dietary guidelines and studied with Cox and Fine-Gray regression models. At study inclusion, we collected demographic and lifestyle characteristics by questionnaire, made a physical examination and took a blood sample.RESULTS:Cardiovascular, non-cardiovascular and all-cause mortality increased gradually with increasing non-adherence to dietary guidelines. Cardiovascular mortality was 30% higher (95% confidence interval 7-57%), non-cardiovascular mortality 54% higher (32-79%) and all-cause mortality 43% higher (29-59%) in individuals with very low adherence to dietary guidelines compared with those with very high adherence after adjustments for age, sex, education, income, smoking, leisure time physical activity and alcohol intake. Mortality risk estimates were similar in all strata of adjusted variables.CONCLUSION:Non-adherence to Danish food-based dietary guidelines is associated with up to 43% increased all-cause mortality in a dose-response manner. The mortality excess was seen for both cardiovascular and non-cardiovascular causes. The public has good reasons to have confidence in and to adhere to established dietary guidelines.

Nutritional status of maintenance dialysis patients: Low lean body mass index and obesity is common, protein-energy wasting is uncommon Abstract Background and aims: Maintenance dialysis patients are at increased risk of abnormal nutritional status due to numerous causative factors, both nutritional and non-nutritional. The present study assessed the current prevalence of protein-energy wasting, low lean body mass index and obesity in maintenance dialysis patients, and compared different methods of nutritional assessment. Methods: In a cross-sectional study conducted in 2014 at Roskilde Hospital, Denmark, we performed anthropometry (body weight, skinfolds, mid-arm, waist, and hip circumferences), and determined plasma albumin and normalized protein catabolic rate in order to assess the prevalence of protein-energy wasting, low lean body mass index and obesity in these patients. Results: Seventy-nine eligible maintenance dialysis patients participated. The prevalence of protein-energy wasted patients was 4% (95% CI: 2-12) as assessed by the coexistence of low lean body mass index and low fat mass index. Low lean body mass index was seen in 32% (95% CI: 22-44). Obesity prevalence as assessed from fat mass index was 43% (95% CI: 32-55). Coexistence of low lean body mass index and obesity was seen in 10% (95% CI: 5-19). The prevalence of protein-energy wasting and obesity varied considerably, depending on nutritional assessment methodology. Conclusions: Our data indicate that protein-energy wasting is uncommon, whereas low lean body mass index and obesity are frequent conditions among patients in maintenance dialysis. A focus on how to increase and preserve lean body mass in dialysis patients is suggested in the future. In order to clearly distinguish between shortage, sufficiency and abundance of protein and/or fat deposits in maintenance dialysis patients, we suggest the simple measurements of lean body mass index and fat mass index.

BackgroundLow 25‐hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. Methods and ResultsWe conducted a systematic review and individual participant meta‐analysis to examine the effect of vitamin D supplementation on flow‐mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo‐controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial‐level meta‐analysis was performed using random‐effects models; individual participant meta‐analyses used a 2‐stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial‐level meta‐analysis, and 24 trials (2051 participants) contributed to individual‐participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial‐level meta‐analysis showed no significant effect of supplementation on macrovascular measures (flow‐mediated dilatation, 0.37% [95% confidence interval, −0.23 to 0.97]; carotid‐femoral pulse wave velocity, 0.00 m/s [95% confidence interval, −0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial‐level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. ConclusionsVitamin D supplementation had no significant effect on most markers of vascular function in this analysis.

OBJECTIVETo better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined.METHODSWe performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability.RESULTSTwo studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified.CONCLUSIONBy providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

NephrologyVolume 23, Issue 7 p. 706-707 Correspondence Rituximab better for idiopathic membranous nephropathy? Peter Marckmann, Peter Marckmann orcid.org/0000-0002-7458-8172 Department of Internal Medicine, Section of Nephrology, Zealand University Hospital, Roskilde, Roskilde, DenmarkSearch for more papers by this author Peter Marckmann, Peter Marckmann orcid.org/0000-0002-7458-8172 Department of Internal Medicine, Section of Nephrology, Zealand University Hospital, Roskilde, Roskilde, DenmarkSearch for more papers by this author First published: 24 July 2018 https://doi.org/10.1111/nep.13121Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume23, Issue7July 2018Pages 706-707 RelatedInformation

Elevated plasma phosphate is considered a major risk factor for cardiovascular disease and mortality in patients with chronic kidney disease. 1 Adeney K.L. Siscovick D.S. Ix J.H. et al. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol. 2009; 20: 381-387 Crossref PubMed Scopus (339) Google Scholar 2 Block G.A. Klassen P.S. Lazarus J.M. Ofsthun N. Lowrie E.G. Chertow G.M. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004; 15: 2208-2218 Crossref PubMed Scopus (2212) Google Scholar Hyperphosphatemia is caused by excessive intake of phosphate-containing foods and other sources of phosphate, whereas the renal phosphate excretion is reduced. 3 Levin A. Bakris G.L. Molitch M. et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007; 71: 31-38 Abstract Full Text Full Text PDF PubMed Scopus (1153) Google Scholar Phosphate-Containing Prescription Medications Contribute to the Daily Phosphate Intake in a Third of Hemodialysis PatientsJournal of Renal NutritionVol. 27Issue 2PreviewHyperphosphatemia is associated with all-cause mortality in hemodialysis (HD) patients and is managed by restricting dietary phosphate. Many patients are unable to adhere to the recommended dietary phosphate limit. We sought to quantify the additional phosphate burden from prescription medication in a hemodialysis population. Full-Text PDF

Background and AimsMaintenance dialysis patients are at increased risk of abnormal nutritional status due to numerous causative factors, both nutritional and non-nutritional. The present study assessed the current prevalence of protein-energy wasting, low lean body mass index and obesity in maintenance dialysis patients, and compared different methods of nutritional assessment.MethodsIn a cross-sectional study conducted in 2014 at Roskilde Hospital, Denmark, we performed anthropometry (body weight, skinfolds, mid-arm, waist, and hip circumferences), and determined plasma albumin and normalized protein catabolic rate in order to assess the prevalence of protein-energy wasting, low lean body mass index and obesity in these patients.ResultsSeventy-nine eligible maintenance dialysis patients participated. The prevalence of protein-energy wasted patients was 4% (95% CI: 2-12) as assessed by the coexistence of low lean body mass index and low fat mass index. Low lean body mass index was seen in 32% (95% CI: 22-44). Obesity prevalence as assessed from fat mass index was 43% (95% CI: 32-55). Coexistence of low lean body mass index and obesity was seen in 10% (95% CI: 5-19). The prevalence of protein-energy wasting and obesity varied considerably, depending on nutritional assessment methodology.ConclusionsOur data indicate that protein-energy wasting is uncommon, whereas low lean body mass index and obesity are frequent conditions among patients in maintenance dialysis. A focus on how to increase and preserve lean body mass in dialysis patients is suggested in the future. In order to clearly distinguish between shortage, sufficiency and abundance of protein and/or fat deposits in maintenance dialysis patients, we suggest the simple measurements of lean body mass index and fat mass index.

Rheumatic disease is the dominant cause of amyloid A (AA) amyloidosis, but other chronic inflammatory diseases may have similar consequences. Hidradenitis suppurativa (HS) is a relatively common, but little known skin disease characterized by chronic inflammation. Here we present a case of chronic HS leading to biopsy-verified severe renal AA amyloidosis and dialysis dependency.

OBJECTIVE:Malnutrition is common in dialysis patients and is associated with adverse clinical outcomes. Despite an increased focus on improved nutrition in dialysis patients, it is claimed that the prevalence of malnutrition in this group of patients has not changed during the last decades. Direct historical comparisons of the nutritional status of dialysis patients have never been published. To directly compare the nutritional status of past and current dialysis patients, we implemented the methodology of a study from 1986 on a population of dialysis patients in 2014.DESIGN:Historical study comparing results of two cross-sectional studies performed in 1986 and 2014.SETTING:We compared the nutritional status of hemodialysis (HD) and peritoneal dialysis (PD) patients attending the dialysis center at Roskilde Hospital, Denmark, in February to June 2014, with that of HD and PD patients treated at the dialysis center at Fredericia Hospital, Denmark, in April 1986.SUBJECTS:Maintenance PD and HD patients (n = 64 in 2014 and n = 48 in 1986).METHODS:We performed anthropometry (body weight, triceps skinfold, and midarm muscle circumferences [MAMCs]) and determined plasma transferrin.MAIN OUTCOME MEASURE:Relative body weight, triceps skinfold, MAMC, body mass index, and prevalence of protein-caloric malnutrition as defined in the original study from 1986.RESULTS:Average relative body weight, triceps skinfold, MAMC, and body mass index were significantly higher in 2014 compared with 1986. The prevalence of protein-caloric malnutrition was significantly lower in 2014 (18%) compared with 1986 (52%).CONCLUSIONS:The nutritional status of maintenance dialysis patients has improved during the last 3 decades. The reason for this improvement could not be identified in the present study, but the most likely contributors are the higher prevalence of obesity in the general population, less predialytic malnutrition, and an improved focus on nutrition in maintenance dialysis patients.

Background. Kidney recipients receive immunosuppression to prevent graft rejection, and long-term outcomes such as post-transplant cancer and mortality may vary according to the different protocols of immunosuppression.Methods. A national register-based historical cohort study was conducted to examine whether post-transplant cancer and all-cause mortality differed between Danish renal transplantation centres using standard immunosuppressive protocols including steroids (Centres 2, 3, 4) or a steroid-free protocol (Centre 1). The Danish Nephrology Registry, the Danish Civil Registration System, the Danish National Cancer Registry and the Danish National Patient Register were used. A historical cohort of 1450 kidney recipients transplanted in 1995-2005 was followed up with respect to post-transplant cancer and death until 31 December 2011.Results. Compared with Center 1 the adjusted post-transplant cancer risk was 6-39% lower in Centre 3 [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.67-1.32], in Centre 2 (HR 0.72, 95% CI 0.52-0.98) and in Centre 4 (HR 0.61, 95% CI 0.44-0.83). Compared with Center 1, the adjusted post-transplant mortality was 21-55% higher in Centre 4 (HR 1.21, 95% CI 0.91-1.61), in Centre 3 (HR 1.35, 95% CI 0.98-1.86) and in Centre 2 (HR 1.55, 95% CI 1.17-2.05). On average, post-transplant cancer was associated with a 4-fold increase in the risk of death (HR 4.25, 95% CI 3.36-5.38).Conclusions. There was a tendency of a higher post-transplant cancer occurrence, but lower all-cause mortality, in the Danish transplantation centre that adhered to a standard steroid-free immunosuppressive protocol.

High-protein diets (i.e., protein content of more than 25% of energy or more than 2 g/kg body weight per day) based on meat and dairy products are repeatedly promoted for weight reduction and better health, but the evidence supporting these notions is quite dubious. As described in the present review, there is a reason to be concerned about adverse effects of such diets, including glomerular hyperfiltration, hypertensive effects of a concomitant increase in dietary sodium, and an increased risk of nephrolithiasis. These diet-induced physiological consequences might lead to an increase in the prevalence of chronic kidney disease in the general population without preexisting kidney disease. Accordingly, we find medical reasons to refrain from promoting high-protein diets, in particular those based on meat and dairy products, until clear-cut evidence for the safety and for the superiority of such diets on human health has been provided.