The New Nordic Renal Diet Induces a Pronounced Reduction of Urine Acid Excretion and Uremic Toxins in Chronic Kidney Disease Patients (Stage 3 and 4).

OBJECTIVE: Metabolic acidosis and the uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with increased risks of kidney disease progression, muscle catabolism, cardiovascular disease, and mortality in patients with chronic kidney disease (CKD). The New Nordic Renal Diet (NNRD) is a plant-focused meal pattern, with reduced phosphorus and protein content compared to an average Danish diet. Due to a higher amount of plant-based products, we hypothesized that NNRD would reduce renal excretion of acids and uremic toxins. Thus, we evaluated the effects of NNRD on metabolic acidosis and uremic toxins in patients with moderate CKD, stages 3-4. DESIGN AND METHODS: This post hoc analysis is based on a randomized controlled crossover trial comparing 1 week of the NNRD to a control 1-week period of an average Danish diet, in patients with CKD stages 3 and 4. Urine pH and urine excretion of bicarbonate, ammonium, titratable acids, IS, and PCS alongside plasma total CO2 (tCO2) were measured at days 1, 4, and 7 in 18 patients. RESULTS: After 7 days on NNRD 24-hour urine net acid excretion was decreased by 80% (P < .001), 24-hour urine excretion of ammonium and bicarbonate decreased by 34% (P < .001), and increased by 678% (P < .001), respectively, compared with the control period. Plasma tCO2 was increased by 8% (P = .005). Moreover, 24-hour urine excretion of PCS and IS were reduced by 31% (P = .018) and 29% (P < .001), respectively. CONCLUSION: One week of NNRD in patients suffering from moderate CKD effectively improved metabolic acidosis with a marked reduction in urine net acid excretion that included a large increase in urine bicarbonate excretion. In addition, NNRD reduced urinary excretion of the uremic toxins PCS and IS. These results encourage further investigations of the long-term effects of NNRD on renal protection in patients with CKD.

Associations Between Albuminuria, Estimated GFR and Cardiac Phenotype in a Cohort with Chronic Kidney Disease: The CPH-CKD ECHO Study.

OBJECTIVE: Echocardiographic findings in chronic kidney disease (CKD) vary. We sought to estimate the prevalence of abnormal cardiac structure and function in patients with CKD and their association to estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR). METHODS: We prospectively enrolled 825 outpatients with non-dialysis-dependent CKD, mean age 58± 13 yrs, and 175 matched healthy controls, mean age 60±12 yrs. Echocardiography included assessment of left ventricular (LV) hypertrophy, LV ejection fraction (LVEF), global longitudinal strain (GLS) and diastolic dysfunction according to ASE/EACVI guidelines. RESULTS: LV hypertrophy was found in 9% of patients vs. 1.7% of controls (p=0.005) was independently associated with UACR (p=0.002). Median LVEF was 59.4% (IQR 55.2, 62.8) in patients vs. 60.8% (57.7, 64.1) in controls (p=0.002). GLS was decreased in patients with eGFR <60ml/min/1.73m² (-17.6%±3.1%) vs. patients with higher eGFR (19.0%±2.2%, p<0.001), who were similar to controls. Diastolic dysfunction was detected in 55% of patients and in 34% of controls. LIMITATIONS: Non-random sampling, cross-sectional analysis. CONCLUSIONS: We report lower prevalence of hypertrophy than previous studies, but similar measurements of systolic and diastolic function. Cardiac remodeling in CKD may be influenced by treatment modalities, demographics, comorbidities and renal pathology.

Outcome of Dialysis-Requiring Acute Kidney Injury in Patients With Infective Endocarditis: A Nationwide Study.

BACKGROUND: Infective endocarditis (IE) may be complicated by acute kidney injury, yet data on the use of dialysis and subsequent reversibility are sparse. METHODS: Using Danish nationwide registries, we identified patients with first-time IE from 2000 to 2017. Dialysis-naïve patients were grouped into: those with and those without dialysis during admission with IE. Continuation of dialysis was followed 1 year postdischarge. Multivariable adjusted Cox proportional hazard analysis was used to examine 1-year mortality for patients surviving IE according to use of dialysis. RESULTS: We included 7307 patients with IE; 416 patients (5.7%) initiated dialysis treatment during admission with IE and these were younger, had more comorbidities and more often underwent cardiac valve surgery compared with nondialysis patients (47.4% vs 20.9%). In patients with both cardiac valve surgery and dialysis treatment (n = 197), 153 (77.7%) initiated dialysis on or after the date of surgery. The in-hospital mortality was 40.4% and 19.0% for patients with and without dialysis, respectively (P < .0001). Of those who started dialysis and survived hospitalization, 21.6% continued dialysis treatment within 1 year after discharge. In multivariable adjusted analysis, dialysis during admission with IE was associated with an increased 1-year mortality from IE discharge, hazard ratio = 1.64 (95% confidence interval, 1.21-2.23). CONCLUSION: In dialysis-naïve patients with IE, approximately 1 in 20 patients initiated dialysis treatment during admission with IE. Dialysis identified a high-risk group with an in-hospital mortality of 40% and an approximate 20% risk of continued dialysis. Those with dialysis during admission with IE showed worse long-term outcomes than those without.

Regional distribution and severity of arterial calcification in patients with chronic kidney disease stages 1-5: a cross-sectional study of the Copenhagen chronic kidney disease cohort.

BACKGROUND: Patients with chronic kidney disease (CKD) and arterial calcification are considered at increased risk of adverse cardiovascular outcomes. However, the optimal site for measurement of arterial calcification has not been determined. The primary aim of this study was to examine the pattern of arterial calcification in different stages of CKD. METHODS: This was an observational, cross-sectional study that included 580 individuals with CKD stages 1-5 (no dialysis) from the Copenhagen CKD Cohort. Calcification of the carotid, coronary and iliac arteries, thoracic and abdominal aorta was assessed using non-contrast multidetector computed tomography scans and quantified according to the Agatston method. Based on the distribution of Agatston scores in the selected arterial region, the subjects were divided into calcium score categories of 0 (no calcification), 1-100, 101-400 and > 400. RESULTS: Participants with CKD stages 3-5 had the highest prevalence of calcification and the highest frequency of calcium scores > 400 in all arterial sites. Calcification in at least one arterial site was present in > 90% of patients with CKD stage 3. In all five CKD stages prevalence of calcification was greatest in both the thoracic and abdominal aorta, and in the iliac arteries. These arterial sites also showed the highest calcium scores. High calcium scores (> 400) in all five arterial regions were independently associated with prevalent cardiovascular disease. In multivariable analyses, after adjusting for cardiovascular risk factors, declining creatinine clearance was associated with increasing calcification of the coronary arteries (p = 0.012) and the thoracic aorta (p = 0.037) only. CONCLUSIONS: Arterial calcification is highly prevalent throughout all five CKD stages and is most prominent in both the thoracic and abdominal aorta, and in the iliac arteries. Follow-up studies are needed to explore the potential of extracardiac calcification sites in prediction of cardiovascular events in the CKD population.

Short-term effect of the New Nordic Renal Diet on phosphorus homoeostasis in chronic kidney disease Stages 3 and 4.

BACKGROUND: The New Nordic Diet is a food concept favouring organically produced food items, fruits, vegetables, whole grains and fish. We investigated the short-term effects of a modified phosphorus-reduced New Nordic Renal Diet (NNRD) in chronic kidney disease (CKD) patients on important parameters of phosphorus homoeostasis. METHODS: The NNRD contained a total of 850 mg phosphorus/day. A total of 18 patients, CKD Stages 3 and 4 were studied in a randomized crossover trial comparing a 1-week control period of the habitual diet with a 1-week period of the NNRD. Data were obtained at baseline and during 1 week of dietary intervention (habitual diet versus NNRD) by collecting fasting blood samples and 24-h urine collections. The primary outcome was the difference in the change in 24-h urine phosphorus excretion from baseline to Day 7 between the NNRD and habitual diet periods. Secondary outcomes were changes in the fractional excretion of phosphorus, fibroblast growth factor 23 (FGF23) and plasma phosphate. RESULTS: As compared with the habitual diet, 24-h urine phosphorus excretion was reduced in the NNRD by 313 mg/day (P < 0.001). The mean baseline phosphorus was 875 ± 346 mg/day and was decreased by 400 ± 256 mg/day in the NNRD and 87 ± 266 mg/day in the habitual diet. The 24-h urine fractional excretion of phosphorus decreased by 11% (P < 0.001) and FGF23 decreased by 30 pg/mL (P = 0.03) with the NNRD compared with the habitual diet. Plasma phosphate did not change. CONCLUSION: This study demonstrates that dietary phosphorus restriction in the context of the NNRD is feasible and has positive effects on phosphorus homeostasis in CKD patients.

Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study.

BACKGROUND: We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011-2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. RESULTS: Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26-0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39-1.78), MI (HR: 0.45, 95% CI: 0.18-1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77-1.26). CONCLUSION: NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

Long-Term Effects of High-Protein Diets on Renal Function.

Chronic kidney disease (CKD) has a prevalence of approximately 13% and is most frequently caused by diabetes and hypertension. In population studies, CKD etiology is often uncertain. Some experimental and observational human studies have suggested that high-protein intake may increase CKD progression and even cause CKD in healthy people. The protein source may be important. Daily red meat consumption over years may increase CKD risk, whereas white meat and dairy proteins appear to have no such effect, and fruit and vegetable proteins may be renal protective. Few randomized trials exist with an observation time greater than 6 months, and most of these were conducted in patients with preexisting diseases that dispose to CKD. Results conflict and do not allow any conclusion about kidney-damaging effects of long-term, high-protein intake. Until additional data become available, present knowledge seems to substantiate a concern. Screening for CKD should be considered before and during long-term, high-protein intake.

The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis.

BACKGROUND: The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis. METHODS: Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models. RESULTS: One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996-2012 and 2002-2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70-4.10) at > 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02-1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54-3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78-5.77) at > 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death. CONCLUSION: All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population.

Renal Function and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation: An Observational Cohort Study.

BACKGROUND AND PURPOSE: We sought to determine the risk of stroke/thromboembolism and bleeding associated with reduced renal function in patients with atrial fibrillation and the risk of stroke and bleeding associated with warfarin treatment in specific estimated glomerular filtration rate (eGFR) groups. METHODS: We conducted a register-based cohort study and included patients discharged with nonvalvular atrial fibrillation from 1997 to 2011 with available eGFR. RESULTS: A total of 17 349 patients were identified with eGFR available at baseline. All levels of lower eGFR were associated with higher risk of stroke/thromboembolism and bleeding. Use of warfarin was associated with higher bleeding risk in all eGFR groups; hazard ratios 1.23 (95% confidence interval [CI], 0.97-1.56), 1.26 (95% CI, 1.14-1.40), 1.18 (95% CI, 1.07-1.31), 1.11 (95% CI, 0.87-1.42), 2.01 (95% CI, 1.14-3.54) in patients with eGFR ≥90, 60 to 89, 30 to 59, 15 to 29, and <15 mL/min per 1.73 m2, respectively. Use of warfarin was associated with lower risk of stroke/thromboembolism in patients with eGFR ≥15 mL/min per 1.73 m2; hazard ratios 0.57 (95% CI, 0.43-0.76), 0.57 (95% CI, 0.51-0.64), 0.48 (95% CI, 0.44-0.54), 0.60 (95% CI, 0.45-0.80) in patients with eGFR ≥90, 60 to 89, 30 to 59, and 15 to 29 mL/min per 1.73 m2, respectively. Use of warfarin was not associated with lower risk of stroke/thromboembolism in patients with eGFR<15 mL/min per 1.73 m2; hazard ratio 1.18 (95% CI, 0.58-2.40). CONCLUSIONS: In patients with atrial fibrillation, the risk of stroke and bleeding was associated with levels of renal function. Warfarin treatment was associated with higher risk of bleeding in all eGFR groups and lower risk of stroke in patients with eGFR≥15 mL/min per 1.73 m2.

Differences in survival on chronic dialysis treatment between ethnic groups in Denmark: a population-wide, national cohort study.

BACKGROUND: In Western countries, black and Asian dialysis patients experience better survival compared with white patients. The aim of this study is to compare the survival of native Danish dialysis patients with that of dialysis patients originating from other countries and to explore the association between the duration of residence in Denmark before the start of dialysis and the mortality on dialysis. METHODS: We performed a population-wide national cohort study of incident chronic dialysis patients in Denmark (≥18 years old) who started dialysis between 1995 and 2010. RESULTS: In total, 8459 patients were native Danes, 344 originated from other Western countries, 79 from North Africa or West Asia, 173 from South or South-East Asia and 54 from sub-Saharan Africa. Native Danes were more likely to die on dialysis compared with the other groups (crude incidence rates for mortality: 234, 166, 96, 110 and 53 per 1000 person-years, respectively). Native Danes had greater hazard ratios (HRs) for mortality compared with the other groups {HRs for mortality adjusted for sociodemographic and clinical characteristics: 1.32 [95% confidence interval (CI) 1.14-1.54]; 2.22 [95% CI 1.51-3.23]; 1.79 [95% CI 1.41-2.27]; 2.00 [95% CI 1.10-3.57], respectively}. Compared with native Danes, adjusted HRs for mortality for Western immigrants living in Denmark for ≤10 years, >10 to ≤20 years and >20 years were 0.44 (95% CI 0.27-0.71), 0.56 (95% CI 0.39-0.82) and 0.86 (95% CI 0.70-1.04), respectively. For non-Western immigrants, these HRs were 0.42 (95% CI 0.27-0.67), 0.52 (95% CI 0.33-0.80) and 0.48 (95% CI 0.35-0.66), respectively. CONCLUSIONS: Incident chronic dialysis patients in Denmark originating from countries other than Denmark have a better survival compared with native Danes. For Western immigrants, this survival benefit declines among those who have lived in Denmark longer. For non-Western immigrants, the survival benefit largely remains over time.

Metformin-associated risk of acute dialysis in patients with type 2 diabetes: A nationwide cohort study.

Recent guidelines governing anti-diabetic medications increasingly advocate metformin as first-line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug-naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1-year risk of acute dialysis was based on g-standardization of cause-specific Cox regression models for acute dialysis, end-stage renal disease and death. One-year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1-121.3) and 142.7 per 100 000 (95% CI, 118.3-168.0) for sulphonylurea and metformin, respectively. The metformin-associated 1-year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9-88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06-2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin.

The New Nordic Diet: phosphorus content and absorption.

PURPOSE: High phosphorus content in the diet may have adverse effect on cardiovascular health. We investigated whether the New Nordic Diet (NND), based mainly on local, organic and less processed food and large amounts of fruit, vegetables, wholegrain and fish, versus an Average Danish Diet (ADD) would reduce the phosphorus load due to less phosphorus-containing food additives, animal protein and more plant-based proteins. METHODS: Phosphorus and creatinine were measured in plasma and urine at baseline, week 12 and week 26 in 132 centrally obese subjects with normal renal function as part of a post hoc analysis of data acquired from a 26-week controlled trial. We used the fractional phosphorus excretion as a measurement of phosphorus absorption. RESULTS: Mean baseline fractional phosphorus excretion was 20.9 ± 6.6 % in the NND group (n = 82) and 20.8 ± 5.5 % in the ADD group (n = 50) and was decreased by 2.8 ± 5.1 and 3.1 ± 5.4 %, respectively, (p = 0.6) at week 26. At week 26, the mean change in plasma phosphorus was 0.04 ± 0.12 mmol/L in the NND group and -0.03 ± 0.13 mmol/L in the ADD group (p = 0.001). Mean baseline phosphorus intake was 1950 ± 16 mg/10 MJ in the NND group and 1968 ± 22 mg/10 MJ in the ADD group and decreased less in the NND compared to the ADD (67 ± 36 mg/10 MJ and -266 ± 45 mg/day, respectively, p < 0.298). CONCLUSION: Contrary to expectations, the NND had a high phosphorus intake and did not decrease the fractional phosphorus excretion compared with ADD. Further modifications of the diet are needed in order to make this food concept beneficial regarding phosphorus absorption.

Stroke and bleeding in atrial fibrillation with chronic kidney disease.

BACKGROUND: Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. METHODS: Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease. RESULTS: Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both. CONCLUSIONS: Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

Impact of the tumor necrosis factor receptor-associated protein 1 (Trap1) on renal DNaseI shutdown and on progression of murine and human lupus nephritis.

Recent findings show that transformation of mild glomerulonephritis into end-stage disease coincides with shutdown of renal DNaseI expression in (NZBxNZW)F1 mice. Down-regulation of DNaseI results in reduced chromatin fragmentation and deposition of extracellular chromatin fragments in glomerular basement membranes where they appear in complex with IgG antibodies. Here, we implicate the anti-apoptotic and survival protein, tumor necrosis factor receptor-associated protein 1 (Trap1) in the disease process, based on the observation that annotated transcripts from this gene overlap with transcripts from the DNaseI gene. Furthermore, we translate these observations to human lupus nephritis. In this study, mouse and human DNaseI and Trap1 mRNA levels were determined by real-time quantitative PCR and compared with protein expression levels and clinical data. Cellular localization was analyzed by immune electron microscopy, IHC, and in situ hybridization. Data indicate that silencing of DNaseI gene expression correlates inversely with expression of the Trap1 gene. Our observations suggest that the mouse model is relevant for the aspects of disease progression in human lupus nephritis. Acquired silencing of the renal DNaseI gene has been shown to be important for progression of disease in both the murine and human forms of lupus nephritis. Early mesangial nephritis initiates a cascade of inflammatory signals that lead to up-regulation of Trap1 and a consequent down-regulation of renal DNaseI by transcriptional interference.

High incidence of secondary hypertension in patients referred for renal denervation--the Copenhagen experience.

Percutaneous renal denervation is a new treatment option for patients with resistant hypertension and little is known about the eligibility of patients referred. 100 consecutive patients were referred for renal denervation from March 2011 through September 2012. Clinical data were prospectively extracted from letters and documents from referring clinics and from our physical examination. Of the 100 patients included, 68 were men and the mean age was 60 (± 12) years. Office blood pressure was 176 (± 28)/99 (± 19) mmHg and 24-h ambulatory blood pressure 156 (± 20)/88 (± 13) mmHg. The mean number of antihypertensive agents was 4.0 (± 1.6). Nearly four-fifths (82%) of the patients were categorized as having resistant hypertension based on the criteria stated by The American Heart Association's stated criteria. Nine patients declined interest in renal denervation before completing the clinical workup program. Thus, 91 patients were screened, and of those 51 were found to be candidates for renal denervation. Forty patients were not candidates, of which secondary hypertension was the most common cause (n = 10). Only 51% of patients referred for renal denervation were eligible for treatment. The prevalence of secondary hypertension was 10% of the referred population. Secondary hypertension should therefore be considered in the evaluation of candidates for renal denervation.

Less use of standard guideline-based treatment of myocardial infarction in patients with chronic kidney disease: a Danish nation-wide cohort study.

AIMS: The aim of this Danish nationwide study was to evaluate the treatment of myocardial infarction (MI) in patients with non-end-stage chronic kidney disease (CKD) and in patients requiring renal replacement therapy (RRT). Upgraded guidelines for the management of MI were implemented around 2004; hence, the treatment of MI in the time periods before and after 2004 was compared in order to evaluate the impact for patients with CKD. METHODS AND RESULTS: By linking nationwide registries by the personal registration number, we identified patients admitted to Danish hospitals with first time MI in the period 2000-09 (79 585 with no renal disease, 3144 with non-end-stage CKD, and 725 requiring RRT). Cox proportional hazards model was used to estimate the chance of invasive treatment within 60 days after MI and the chance of filling prescriptions on recommended post-MI drugs within 90 days before and after 2004. Significantly less use of relevant MI treatment in patients with non-end-stage CKD and patients requiring RRT compared with patients with no renal disease were seen; however, the absolute frequencies of invasive procedures and filled prescriptions on post-MI drugs increased after 2004 in all patients. CONCLUSIONS: After 2004, invasive and pharmacological treatment of first-time MI improved in patients with non-end-stage CKD and patients requiring RRT; however, all CKD patients were less treated with standard MI care compared with patients with no renal disease.

Oral anticoagulation for stroke prevention in atrial fibrillation and advanced kidney disease.

Background: The net benefit of oral anticoagulation (OAC) with vitamin K antagonists or direct oral anticoagulants in patients with advanced chronic kidney disease and atrial fibrillation remains uncertain. Objectives: We examined the use, efficacy, and safety of OAC in patients with estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m2 (including dialysis-treated patients) and atrial fibrillation. Methods: In a retrospective cohort study, patients diagnosed with atrial fibrillation and eGFR of <30 mL/min/1.73 m2 were identified in national Danish registers between 2010 and 2022. Initiation of OAC was identified based on redemption of a relevant prescription. One-year risks of thromboembolic event, major bleeding, and death associated with OAC and no treatment were computed and standardized to the distribution of risk factors in the sample based on hazards determined in multiple Cox regression models adjusted for age and sex. Results: A total of 3208 patients were included (mean age 80 years, 52.8% males, 20.9% chronic dialysis). OAC was initiated in 1375 (42.9%) patients, of whom 48.1% were vitamin K antagonists and 51.9% were direct oral anticoagulants. One-year risks in nontreated and anticoagulated patients were 4.8% (95% CI, 3.8%-5.7%) and 3.6% (95% CI, 2.8%-4.6%; P = .028) for thromboembolic event, 7.6% (95% CI, 6.6%-8.7%) and 10.5% (95% CI, 9.3%-12.1%; P < .001) for major bleeding, and 36.3% (95% CI, 34.2%-38.3%) and 29.6% (95% CI, 27.6%-31.6%; P < .001) for death, respectively. Conclusion: In a retrospective study on patients with advanced chronic kidney disease and atrial fibrillation, OAC was associated with overall decreased 1-year risk of thromboembolic event and death offset by increased 1-year risk of major bleeding.

Post-intervention Adherence to the New Nordic Renal Diet among patients with chronic kidney disease, stages 3 and 4.

The New Nordic Renal Diet (NNRD) is a meal pattern reduced in phosphorus, protein, and sodium for patients with moderate chronic kidney disease. The NNRD showed improvements in metabolic, and physiological outcomes after 26-weeks intervention. In the original study, participants were randomized to NNRD (n = 30), or control (habitual diet) (n = 30). The aim of this study was to explore adherence to the NNRD 3 months after cessation of intervention (follow-up). Fifty-seven participants completed the follow-up visit, which consisted of fasting blood samples and 24 h urine samples. At follow-up, there was no longer a significant reduction in 24 h urine phosphorus excretion in the NNRD group. From intervention to follow-up, 24 h urine phosphorus increased by 63 mg in the NNRD group, vs. -24.1 mg in the control group, between-group difference 87.1 mg (-10.1, 184.3, p = 0.08). Our findings show that more active intervention is needed to support adherence and maintain beneficial effects of the NNRD.

Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

BACKGROUND AND AIMS: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. METHODS: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. RESULTS: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2. CONCLUSIONS: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2.

The role of aetiology in cardiac manifestations of chronic kidney disease: the CPH-CKD ECHO study.

PURPOSE: We investigated the associations between cardiac parameters and aetiologies of CKD in an exploratory study. METHODS: The study population consisted of 883 participants, 174 controls and 709 patients with aetiologies of CKD including diabetic nephropathy/renovascular KD in diabetes mellitus, hypertensive/renovascular nephropathy, tubulointerstitial nephritis, glomerulonephritis/vasculitis, polycystic KD (PKD), and CKD of unknown origin. Echocardiographic measures included left ventricular (LV) ejection fraction, global longitudinal, area, and radial strain, E/e' ratio, and LV mass index. These were compared between each aetiological group and controls in unadjusted and adjusted analysis. RESULTS: In unadjusted analysis, patients with diabetic nephropathy/renovascular KD in diabetes mellitus, had impaired LV ejection fraction (Median [IQR]: 56% [49.9,60.69] vs. 60.8% [57.7,64.1]), global longitudinal (mean ± SD: 13.1 ± 3.5% vs. 15.5 ± 2.6%), area (24.1 ± 5.8% vs. 28.5 ± 4.2%), and radial strain (36.2 ± 11.2% vs. 44.1 ± 9.7%), and increased LV mass index (89.1 g/m2 [71.8,104.9] vs. 69,0 g/m2 [57.9,80.8]) and E/e' ratio (10.6 [8.5,12.6] vs. 7 [5.8,8.3], p < 0.001 for all) compared with controls. Associations were similar for CKD of unknown origin. Patients with hypertensive/renovascular nephropathy had impaired global longitudinal and area strain, and higher E/e' ratio. Patients with glomerulonephritis/vasculitis had higher LV mass index, while patients with PKD had better global longitudinal strain than controls. All findings remained significant in adjusted analysis, except for the impaired global longitudinal strain in hypertensive/renovascular nephropathy. CONCLUSION: Glomerulonephritis/vasculitis, hypertensive/renovascular nephropathy, CKD of unknown origin, and diabetic nephropathy/renovascular KD in diabetes mellitus were increasingly associated with adverse cardiac findings, while PKD and tubulointerstitial nephritis were not. Aetiology might play a role regarding the cardiac manifestations of CKD.