The impact of age and body composition on the agreement between estimated and measured GFR in heart transplant recipients.

Background Estimated GFR (eGFR) has shown poor agreement with measured GFR (mGFR) in several populations. We investigated the impact of age and body composition on the accuracy and precision of eGFR in heart transplant (HTx) recipients. Methods In a longitudinal, observational, retrospective study-design, patients receiving first-time HTx with at least one registered mGFR value within 15 months after HTx and a corresponding plasma creatinine were included. GFR was measured by 51Cr-EDTA and eGFR calculated by creatinine-based CKD-EPI formula. Results 150 patients with a total of 723 mGFR measurements were included. During the first year after HTx, mean weight increased by 4.2 kg (CI:3.2-5.1) followed by an annual decrease of 0.35 kg/year (Cl:-0.05-0.74). mGFR increased by 7.5 ml/min (Cl:3.2-11.8) the first year but was stable hereafter (0.0 ml/min/year CI:-1.0-1.0). The initial weigh gain and increase in mGFR were most pronounced in patients <45 years. Neither eGFR adjusted nor unadjusted for BSA detected the initial increase in mGFR. At one year after HTx, limits of agreement on the Bland-Altman plot were -37.2-33.1 ml/min with a bias of -2.1 ml/min (Cl:-5.0-0.9). In patients <45 years, eGFR significantly overestimated mGFR by 7.1 ml/min (Cl:1.0-13.2) and showed a significant lower precision than patients >45 years. There was no effect of BMI class, weight, BSA or change in BMI class on the difference between eGFR and mGFR. Conclusion eGFR is, on average, accurate but imprecise in HTx patients. The agreement is affected by age, but not body composition.

The validity of pathology codes for biopsy-confirmed kidney disease in the Danish National Patobank.

Background: This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments and prognosis of kidney diseases. Methods: Kidney biopsy reports from 1 January 1998 to 31 December 2018 were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values and Cohen's kappa coefficient for the retrieved SNOMED codes were calculated. Results: A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease (n = 368), tubulointerstitial disease (n = 67), renal vascular disease (n = 51), diabetic nephropathy (n = 51) and various renal disorders (n = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%) and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%) and other renal disorders (17%) showed lower PPV. Conclusions: SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research.

Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A-C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) compared with both individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] min) compared with individuals with cirrhosis (5.7 [5.2;6.3] min, P = 0.002) and control individuals (5.7 [5.2;6.3] min, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, CKD, but not liver cirrhosis, leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.

Renal Disease in Metabolic Syndrome: the Hidden Role of Intrarenal Ischemia.

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project. Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m2; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease. Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) (P = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P < 0.05). These vascular changes were independent of differences in age. Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health.

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial.

INTRODUCTION: Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit. METHODS AND ANALYSIS: The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient. ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.

Coronary angiography in patients with kidney dysfunction and myocardial injury: A retrospective cohort study on management of myocardial injury in hospitalized patients with kidney disease.

BACKGROUND: Although kidney insufficiency has been shown to be associated with increased risk of myocardial injury, benefit of coronary angiography (CAG) and revascularization remains uncertain, with implications on management strategies and outcomes. We aimed to compare rates of CAG and revascularization and subsequent risk of cardiovascular and kidney outcomes in hospitalized patients with myocardial injury and kidney dysfunction. METHODS: Retrospective cohort study encompassing hospitalized patients with myocardial injury i.e. elevated troponin I or T and an eGFR ≤60 ml/min/1.73 m2 identified between 2011 and 2021 in Danish national registers. 30-day odds for CAG were computed across granular eGFR-categories based on multiple logistic regression. Standardized one-year risks of cardiovascular and kidney outcomes including mortality were determined based on hazards obtained in multiple Cox regression. RESULTS: A total of 52,798 patients with myocardial injury were identified. CAG was performed in 14.3 % (n = 7549). 30-day odds ratios for CAG were 0.64 [0.60-0.68], 0.38 [0.34-0.42], 0.18 [0.14-0.22], and 0.35 [0.30-0.40] in patients with eGFR 31-45 ml/min/1.73 m2, eGFR 15-30 ml/min/1.73 m2 for eGFR<15 ml/min/1.73 m2 and chronic dialysis, respectively (eGFR 46-60 ml/min/1.73 m2 as reference). Median follow-up was 4.1 years. One-year mortality risk differences associated with CAG and revascularization (no CAG as reference) were -7.8 [-7.0; -8.7] and -9.1 [-8.4; -9.9] for eGFR 46-60 ml/min/1.73 m2; -7.0 [-5.7;-8-3] and -8.0 [-6.6; -9.5] for eGFR 31-45 ml/min/1.73 m2; -5.4 [-3.0; -7.2] and -5.2 [-2.2; -8.3] for eGFR 15-30 ml/min/1.73 m2; -8.8 [-3.1; -13.7] and -5.4 [3.1; -13.4] for eGFR<15 ml/min/1.73 m2; and -4.9 [-0.1; -9.7] and -4.2 [1.5; -9.2] for chronic dialysis, respectively. CONCLUSION: Probability of CAG following myocardial injury declined with progressive kidney dysfunction. Overall, CAG was associated with lower mortality irrespective of kidney function and subsequent revascularization.

International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Intravascular volumes and the influence on anemia assessed by a carbon monoxide rebreathing method in patients undergoing maintenance hemodialysis.

INTRODUCTION: Fluid overload is a major challenge in hemodialysis patients and might cause hypervolemia. We speculated that hemodialysis patients reaching dry weight could have undetected hypervolemia and low hemoglobin (Hb) concentration (g/dL) due to hemodilution. METHODS: The study included hemodialysis patients (n = 22) and matched healthy controls (n = 22). Blood volume, plasma volume, red blood cell volume, and total Hb mass were determined using a carbon monoxide (CO)-rebreathing method in hemodialysis patients reaching dry weight and controls. Blood volume measurements were also obtained by a dual-isotope labeling technique in a subgroup for validation purposes. FINDINGS: In the hemodialysis group, the median specific blood volume was 89.3 mL/kg (interquartile range [IQR]: 76.7-95.4 mL/kg) and was higher than in the control group (79.9 mL/kg [IQR: 70.4-88.0 mL/kg]; p < 0.037). The median specific plasma volume was 54.7 mL/kg (IQR: 47.1-61.0 mL/kg) and 44.0 mL/kg (IQR: 38.7-49.5 mL/kg) in the hemodialysis and control groups, respectively (p < 0.001). Hb concentration was lower in hemodialysis patients (p < 0.001), whereas no difference in total Hb mass was observed between groups (p = 0.11). A correlation was found between blood volume measured by the CO-rebreathing test and the dual-isotope labeling technique in the control group (r = 0.83, p = 0.015), but not the hemodialysis group (r = 0.25, p = 0.60). DISCUSSION: The hemodialysis group had increased specific blood volume at dry weight due to high plasma volume, suggesting a hypervolemic state. However, correlation was not established against the dual-isotope labeling technique underlining that the precision of the CO-rebreathing test should be further validated. The total Hb mass was similar between hemodialysis patients and controls, unlike Hb concentration, which emphasizes that Hb concentration is an inaccurate marker of anemia among hemodialysis patients.

Techniques to Assess the Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Blood Volume in Patients with Diabetic Kidney Disease.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a kidney protective effect in patients with diabetic kidney disease. Several mechanisms have been proposed, but why precisely SGLT2 inhibition has a kidney protective effect is incompletely understood. Clinical trials using SGLT2 inhibitors have found them to induce a rapid weight loss likely due to loss of sodium and subsequently fluid. While SGLT2 inhibitors are reported to increase hematocrit, it remains unknown whether the natriuretic and aquaretic effect reduces patient's blood volume and whether this could partly explain its kidney protective effects. A blood volume reduction could induce several beneficial effects with reduction in arterial and venous blood pressure as two central mechanisms. The aim of this paper was to review current techniques for assessing patient blood volume that could enhance our understanding of SGLT2 inhibitors' physiological effects. SUMMARY: Changes induced by SGLT2 inhibitors on erythrocyte volume and plasma volume can be assessed by tracer dilution techniques that include radioisotopes, indocyanine green (ICG) dye, or carbon monoxide (CO). Techniques with radioisotopes can provide direct estimates of both erythrocyte volume and plasma volume but are cumbersome procedures and the radiation exposure is a limitation for repeated measures in clinical studies. Methods more suitable for repeated assessment of erythrocyte and plasma volume include dilution of injected ICG dye or dilution of inhaled CO. ICG dye requires higher precision with timed blood samples and provides only a direct estimate of plasma volume wherefrom erythrocyte volume is estimated. Inhalation of CO is a time-effective and automated method that provides measure of the total hemoglobin mass wherefrom erythrocyte and plasma volumes are estimated. KEY MESSAGES: A kidney protective effect has been observed in clinical trials with SGLT2 inhibitors, but the underlying mechanisms are not fully understood. Significant weight loss within weeks has been reported in the SGLT2 inhibitor trials and could be related to a reduction in blood volume secondary to increased natriuresis and aquaresis. Alterations in blood volume compartments can be quantified by tracer dilution techniques and further improve our understanding of kidney protection from SGLT2 inhibitors.

Predicting type 2 diabetes risk before and after solid organ transplantation using polygenic scores in a Danish cohort.

Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves. Patients were assessed pre-transplant and in three post-transplant periods: 0-45, 46-365 and >365 days. A higher PRS was significantly associated with increased odds of pre-transplant T2DM. However, no improvement was observed for pre-transplant T2DM prediction when comparing PRS combined with non-genetic risk scores to using non-genetic risk scores alone. This was also true for predictions of PTDM in all three post-transplant periods. This study demonstrated that polygenic risk was only associated with the risk of T2DM among SOT recipients prior to transplant and not for PTDM. Combining PRS with a clinical model of non-genetic risk scores did not significantly improve the predictive ability, indicating its limited clinical utility in identifying patients at high risk for T2DM before transplantation, suggesting that non-genetic or different genetic factors may contribute to PTDM.

Non-adherence, medication beliefs and symptom burden among patients receiving hemodialysis -a cross-sectional study.

BACKGROUND: Non-adherence to medication is a common and complex issue faced by individuals undergoing hemodialysis (HD). However, more knowledge is needed about modifiable factors influence on non-adherence. This study investigated the prevalence of non-adherence, medication beliefs and symptom burden and severity among patients receiving HD in Denmark. Associations between non-adherence, medications beliefs and symptom burden and severity were also explored. METHOD: A cross-sectional questionnaire-based multisite study, including 385 participants. We involved patient research consultants in the study design process and the following instruments were included: Medication Adherence Report Scale, Beliefs about Medication Questionnaire and Dialysis Symptom Index. Logistic regression analysis was performed. RESULTS: The prevalence of non-adherence was 32% (95% CI 27-37%) using a 23-point-cut-off. Just over one third reported being concerned about medication One third also believed physicians to overprescribe medication, which was associated with 18% increased odds of non-adherence. Symptom burden and severity were high, with the most common symptoms being tiredness/ lack of energy, itching, dry mouth, trouble sleeping and difficulties concentrating. A high symptom burden and/or symptom severity score was associated with an increased odd of non-adherence. CONCLUSION: The study found significant associations between non-adherence and, beliefs about overuse, symptom burden and symptom severity. Our results suggest health care professionals (HCP) should prioritize discussion about medication adherence with patients with focus on addressing patient-HCP relationship, and patients' symptom experience. Future research is recommended to explore the effects of systematically using validated adherence measures in clinical practice on medication adherence, patient-HCP communication and trust. Additionally, studies are warranted to further investigate the relationship between symptom experience and adherence in this population. TRIAL REGISTRATION: NCT03897231.

Cardiac arrhythmia and hypoglycaemia in patients receiving haemodialysis with and without diabetes (the CADDY study): protocol for a Danish multicentre cohort study.

INTRODUCTION: Patients receiving haemodialysis are at increased risk of arrhythmias and sudden cardiac death, but data on arrhythmia burden and the pathophysiology remain limited. Among potential risk factors, hypoglycaemia is proposed as a possible trigger of lethal arrhythmias. The development of implantable loop recorders (ILR) and continuous glucose monitoring (CGM) enables long-term continuous ECG and glycaemic monitoring. The current article presents the protocol of a study aiming to increase the understanding of arrhythmias and risk factors in patients receiving haemodialysis. The findings will provide a detailed exploration of the burden and nature of arrhythmias in these patients including the potential association between hypoglycaemia and arrhythmias. METHODS AND ANALYSIS: The study is an investigator-initiated, prospective, multicentre cohort study recruiting 70 patients receiving haemodialysis: 35 with diabetes and 35 without diabetes. Participants are monitored with ILRs and CGM for 18 months follow-up. Data collection further includes a monthly collection of predialysis blood samples and dialysis parameters. The primary outcome is the presence of clinically significant arrhythmias defined as a composite of bradycardia, ventricular tachycardia, or ventricular fibrillation. Secondary outcomes include the characterisation of clinically significant arrhythmias and other arrhythmias, glycaemic characteristics, and mortality. The data analyses include an assessment of the association between arrhythmias and hypoglycaemia and hyperglycaemia, baseline clinical variables, and parameters related to kidney failure and the haemodialysis procedure. ETHICS AND DISSEMINATION: The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-20069767). The findings will be presented at national and international congresses as well as in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04841304.

Hepatic Fibrosis Evaluated in Patients with Type 2 Diabetes with and without Chronic Kidney Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population. METHODS: Cross-sectional study including patients with type 2 diabetes with CKD stages 3-5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) >0.675. RESULTS: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p < 0.0009 and p < 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007). CONCLUSION: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively.

Performance of Panel-Estimated GFR Among Hospitalized Older Adults.

RATIONALE & OBJECTIVE: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. STUDY DESIGN: Cross-sectional diagnostic test substudy of a randomized clinical trial. SETTING & PARTICIPANTS: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. TESTS COMPARED: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, ß-trace protein (BTP) and/or ß2-microglobulin (B2M). OUTCOME: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). RESULTS: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). LIMITATIONS: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. CONCLUSIONS: The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. FUNDING: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with registration number NCT03741283. PLAIN-LANGUAGE SUMMARY: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as ß-trace protein and ß2-microglobulin did not further improve accuracy.

Cardiovascular mortality in patients with advanced chronic kidney disease with and without diabetes: a nationwide cohort study.

BACKGROUND: Cardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels. METHODS: In a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m2 between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort. RESULTS: We included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6-10.0) and 7.4% (95% CI 7.3-7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1-3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes. CONCLUSIONS: Diabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD.

Endotrophin Levels Are Associated with Allograft Outcomes in Kidney Transplant Recipients.

Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation. P-ETP and U-ETP/Cr at D1 (P-ETP AUC = 0.86, p < 0.0001; U-ETP/Cr AUC = 0.70, p = 0.0002) were independent markers of delayed graft function (DGF) and P-ETP at D1 had an odds ratio of 6.3 (p < 0.0001) for DGF when adjusted for plasma creatinine. The results for P-ETP at D1 were confirmed in a validation cohort of 146 transplant recipients (AUC = 0.92, p < 0.0001). U-ETP/Cr at M3 was negatively associated with kidney graft function at M12 (p = 0.007). This study suggests that ETP at D1 can identify patients at risk of delayed graft function and that U-ETP/Cr at M3 can predict the future status of the allograft. Thus, measuring collagen type VI formation could aid in predicting graft function in kidney transplant recipients.