KEY POINTS:Far infrared radiation did not improve the proportion of interventions in arteriovenous fistulas in patients on hemodialysis after 12 months of treatment. No difference was seen between treatment groups in time to intervention, number of thrombosed fistulas, and change in access flow. This study does not support the effect of far infrared radiation on fistula survival as proposed in previous vascular access guidelines. INTRODUCTION:In patients on hemodialysis, the risk of arteriovenous fistula (AVF) failure is unacceptably high. Up to 67% of AVFs need an intervention within 1 year after placement. There are no effective treatments to prolong AVF longevity. Far infrared radiation (FIR) treatment has been suggested to enhance AVF survival. The present trial investigated the effect of FIR on the proportion of interventions in the AVF. METHODS:In a multicenter, randomized, controlled trial, patients were allocated to receive FIR treatment or no FIR. Eligible patients were patients on chronic hemodialysis with a well-functioning AVF. The FIR group received FIR above the skin of their AVF for 40 minutes at every hemodialysis session for 1 year. The primary outcome was the difference in the proportion of patients with at least one intervention (thrombectomy or percutaneous transluminal angioplasty) after 12 months. The chi-squared test analyzed the difference. Secondary outcomes included differences in the number of thrombosed AVFs, intervention rate, access flow at various time points, and time to first intervention between groups. RESULTS:A total of 115 patients were randomized to the FIR group ( n =58) or the control group ( n =57). Baseline characteristics were similar in both groups. There was no significant difference in the proportion of patients with interventions between the FIR and control groups (19% versus 28%, P = 0.25) or in the proportion with thrombosed AVFs (5% versus 3%, P = 0.26). Time to first intervention was 164 (interquartile range, 86-272) days in the FIR group and 127 (interquartile range, 44-164) days in the control group ( P = 0.26). No differences in the change of access flow occurred ( P = 0.86). CONCLUSION:During 12 months of treatment, FIR did not affect the overall patency of the AVF. No difference was found in the number of patients with interventions or in any of the secondary endpoints (Clinicaltrials.gov: NCT04011072 ). CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Clinicaltrials.gov: NCT04011072.

Introduction: The age and number of comorbidities in the hemodialysis population has increased over time. This may influence the construction and survival of the arteriovenous fistula (AVF). The present study explored the incidence and survival of AVFs over a period of 39 years. Methods: A retrospective cohort study was conducted based on Danish registries. Incident hemodialysis patients between 1977 and 2015 were included. The incidence of AVF and factors associated with the construction of an AVF were described. Risk factors for AVF survival and repair were explored by Kaplan Meier and Cox proportional hazard analysis. Results: The total number of arteriovenous accesses (AVF and arteriovenous grafts) were 10,187 and there were 4201 central venous catheters (CVC). No significant difference in the proportion of AVFs during the 39 years was seen. Age and renal diagnosis did not influence the proportion of AVFs. Patients with CVCs were found to have a significantly higher prevalence of comorbidities (p < 0.01). AVF survival remained stable during the 39 years. The first constructed AVF had the best survival, 35% still functioning after 15 years. Factors such as brachiocephalic AVF, female sex, and diabetic nephropathy increased the risk of AVF failure (Odds Ratio (OR): 2.46, 95% Confidence Interval (CI) (2.29-2.65), 1.17 (1.10-1.25), and 1.21 (1.12-1.3)), respectively. Conclusion: Despite an older dialysis population, the proportion and survival of the AVF in the Danish dialysis population has not changed, probably because of increased awareness of AVF as the first choice of vascular access and improved surveillance, surgery, and repair.

Chronic kidney diseases imply an ongoing need to remove toxins, with hemodialysis as the preferred treatment modality. We derive analytical expressions for phosphate clearance during dialysis, the single pass (SP) model corresponding to a standard clinical hemodialysis and the multi pass (MP) model, where dialysate is recycled and therefore makes a smaller clinical setting possible such as a transportable dialysis suitcase. For both cases we show that the convective contribution to the dialysate is negligible for the phosphate kinetics and derive simpler expressions. The SP and MP models are calibrated to clinical data of ten patients showing consistency between the models and provide estimates of the kinetic parameters. Immediately after dialysis a rebound effect is observed. We derive a simple formula describing this effect which is valid both posterior to SP or MP dialysis. The analytical formulas provide explanations to observations of previous clinical studies.

Hyperphosphatemia in patients with renal failure is associated with increased vascular calcification and mortality. Hemodialysis is a conventional treatment for patients with hyperphosphatemia. Phosphate kinetics during hemodialysis may be described by a diffusion process and modeled by ordinary differential equations. We propose a Bayesian model approach for estimating patient-specific parameters for phosphate kinetics during hemodialysis. The Bayesian approach allows us to both analyze the full parameter space using uncertainty quantification and to compare two types of hemodialysis treatments, the conventional single-pass and the novel multiple-pass treatment. We validate and test our models on synthetic and real data. The results show limited identifiability of the model parameters when only single-pass data are available, and that the Bayesian model greatly reduces the relative standard deviation compared to existing estimates. Moreover, the analysis of the Bayesian models reveal improved estimates with reduced uncertainty when considering consecutive sessions and multiple-pass treatment compared to single-pass treatment.

INTRODUCTION:There is a substantial risk of developing stenosis and dysfunction in the arteriovenous fistula (AVF) in patients on hemodialysis (HD). Far infrared radiation (FIR) is a non-invasive local intervention with a potentially beneficial effect on AVF patency. The underlying mechanism is not clear. It was hypothesized that a single FIR treatment reduces factors of inflammation and promotes endothelial vasodilators in the AVF. METHODS:Forty HD patients with an AVF were included in an open-label intervention study. Patients were randomized to receive either FIR (FIR group) or no FIR (control group). Blood samples were drawn directly from the AVF and from a peripheral vein in the non-AVF arm before (T0) and 40 min after (T40) treatment during a HD session. The changes [median (interquartile range)] in circulating factors of inflammation, endothelial function and vasoreactivity during FIR were measured. RESULTS:In the AVF a single FIR treatment during dialysis resulted in a significantly diminished decrease in soluble vascular cell adhesion molecule, sVCAM [-31.6 (-54.3; 22.1) vs -89.9 (-121.6; -29.3), P = .005] and soluble intercellular adhesion molecule, sICAM [-24.2 (-43.5; 25.3) vs -49 (-79.9; -11.6), P = .02] compared with the control group. Other factors, such as interleukins, nitrite, nitrate and tumor necrosis factor 1, also declined during dialysis, but with no significant differences related to FIR in either the AVF or the non-AVF arm. CONCLUSION:A single FIR treatment attenuated the decrease in sVCAM and sICAM in the AVF compared with a control group during HD. Findings do not support the hypothesis of a vaso-protective effect of FIR. The long-term effects of FIR on the AVF are unknown.

Background Chronic kidney disease (CKD) is a global challenge. CKD prevalence estimation is central to management strategies and prevention. It is necessary to predict end stage kidney disease (ESKD) and, subsequently, the burden for healthcare systems. In this study we characterize CKD stage 3–5 prevalence and incidence in a cohort covering the majority of the Region of Southern Denmark and investigate individuals’ demographic, socioeconomic, and comorbidity status. Methods We used data from the Kidney Disease Cohort (KidDiCo) combining laboratory data from Southern Denmark with Danish national databases. Chronic kidney disease was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Results The prevalence varied between 4.83 and 4.98% and incidence rate of CKD was 0.49%/year. The median age was 76.4 years. The proportion of individuals with CKD stage 3–5 in the entire population increased consistently with age. The percentage of women in the CKD 3–5 group was higher than in the background population. Diabetes mellitus, hypertension and cardiovascular disease were more prominent in patients with CKD. CKD stage 5 and ESKD were more frequent as incident CKD stages in the 18–49 year olds when compared to older individuals. CKD patients tended to have a lower socioeconomic status. Conclusion Chronic kidney disease stage 3–5 is common, especially in the elderly. Patients with CKD stage 3–5 are predominantly female. The KidDiCo data suggests an association between lower socioeconomic status and prevalence of CKD.

ABSTRACT Background Data on the referral rate of chronic kidney disease (CKD) patients to specialists are sparse. Investigating referral rates and characterizing patients with kidney disease not followed by a nephrologist are relevant for future measures in order to optimize public health and guideline implementation. Methods Data were extracted from the Kidney Disease Cohort of Southern Denmark (KidDiCo). Referral rates for all incident CKD patients below 60 mL/min/1.73 m² and referral rates according to the KDIGO guidelines based on glomerular filtration rates below 30 mL/min/1.73 m² were calculated. Information on contact with one of the nephrologist outpatient clinics in the Region of Southern Denmark was collected from the Danish National Patient Registry. The individual follow-up time for nephrology contact was 12 months. Additional data were accessed via the respective national databases. CKD patients on dialysis and kidney transplanted patients were excluded. Results A total of 3% of patients with an eGFR <60 mL/min/1.73 m²–16% of patients with an eGFR <30 mL/min/1.73 m² and 35% of patients with an eGFR <15 mL/min/1.73 m² were in contact with a nephrologist in the outpatient settings. Younger age, male sex, diabetes, hypertension, higher education and proximity to a nephrology outpatient clinic increased the chance of nephrology follow-up. Conclusion Only a small fraction of CKD patients are followed by a nephrologist. More studies should be performed in order to find out which patients will profit the most from renal referral and how to optimize the collaboration between nephrologists and general practitioners.

Abstract BACKGROUND AND AIMS Severe volume overload in peritoneal dialysis (PD) patients is associated with an elevated risk of technique failure [including death and transfer to hemodialysis (HD)] compared to moderate volume overload, euvolemia and volume depletion (Vrtovsnik et al., 2021 Clin Kidney J). Severe volume overload is often defined by a single cut-off value. However, such dichotomization of continuous variables in analytical models has shortcomings, especially when a nonlinear association is likely to be present. The aim of the present analysis was to investigate whether the association of volume overload to technique failure was nonlinear in nature. METHOD The IPOD-PD study enrolled incident patients, on either continuous ambulatory PD or automated PD. Besides regular documentation of demographic, medical and laboratory data, body composition data from measurements employing the Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany) were recorded. In contrast to the previously published analysis (Vrtovsnik et al., 2021 Clin Kidney J), a competing risk analysis (kidney transplantation as competing risk) with cubic spline analysis was applied to take the continuous nature of the parameter fluid overload into account. Of 1054 incident PD patients from the IPOD-PD patient cohort (Van Biesen et al., 2019 CJASN), after excluding those who terminated the study before month 6, 719 patients were included in the present analysis. The ‘starting point’ of the follow-up was month 6 on PD, and technique failure (composite endpoint of change to HD and death) in the next 12 months was recorded as the outcome. The association of relative fluid overload with technique failure was estimated using penalized cubic splines regression, with kidney transplantation as competing risk. The model was adjusted for same variables as in previous study, including age, percentage of PD patients in the center, and number of incident PD patients in the last 2 years in the center, which were derived from backward selection based on Akaike's information criteria. RESULTS The patients included in the present analysis (n = 719) were in average 58.4 ± 14.9 years old, and 57% were male. Mean relative fluid overload was 9.7% at baseline, and 8.0% at month 6. With the means of cubic spline analysis, the course of subdistributional hazard (SDH) over the range of relative fluid overload as measured in our patient cohort was illustrated. Whereas SDH was rather constant in the range of fluid overload representing euvolemia, it increased strongly at more elevated relative fluid overload levels, which could accordingly be considered as overhydration (Fig. 1). Of covariates included in the model, increasing age was significantly associated with an elevated risk of technique failure and being treated in a center with a high versus low proportion of PD patients (≥ versus < 56.5% of the patients on PD) was significantly associated with a lower risk of technique failure. CONCLUSION An analytical approach considering the continuous nature of the parameter fluid overload allows to visualize a differentiated nonlinear pattern of associations to technique failure.

Abstract BACKGROUND AND AIMS Troponin is the preferred biomarker for diagnosing acute myocardial infarction (AMI). The new generations of high-sensitive troponin (hs-cTnI) assays are now the most commonly used including ultra-sensitive assays. If, or how, haemodialysis influences troponin is still under debate. Failure to interpret troponin values correctly during dialysis may lead to overlooked AMI´s thus putting patients’ lives at risk. The aim of this systematic review is to examine the literature regarding the effect hemodialysis has on hs-cTnI. METHOD A systematic review was performed. Inclusion criteria: measurement of hs-cTnI before and after dialysis in asymptomatic patients. Full text articles only were eligible. Exclusion criteria: posters, abstracts and articles in other languages than English. JK and MH screened 1745 publications. In cases of conflict, FB was contacted as a referee. A total of 153 articles were eligible for full text screening. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS2) score was used in terms of risk of bias and quality assessment. RESULTS Seven articles met the inclusion criteria (see Table 1). The sample size of the included studies ranged from n = 13 to n =100 and n =310 in total. Two articles investigated exclusively ultra-sensitive cTnI. One article examined both ultra-sensitive cTnI and hs-cTnI. Three articles examined the effect of haemodiafiltration (HDF) on hs-cTnI. In general, dialysis modalities were rarely described in detail. Only one article showed an increase in hs-cTnI after four hours haemodialysis (HD)/haemodiafiltration (HDF); however, hs-cTnI decreased significantly after 8 h. One study showed no change in the control group in patients who were exposed to remote ischemic preconditioning, although, a statistically insignificant 10% change in the background population was displayed. Of the studies that found a decrease in hs-cTnI, the range was from –3.4% to –36% with a significant decrease in four studies after 4 h HD/HDF. Hs-cTnI concentrations were corrected differently in three articles using either haematocrit concentration, total protein and albumin, or weight change after dialysis. Corrections might make sense in the trial setting, but pose a challenge regarding how to interpret troponin after dialysis in real life, where blood samples are not corrected following dialysis. The use of mean, median and different concentration corrections made sub-analysis and meta-analysis impossible. CONCLUSION Most publications included in the review showed a decrease of hs-cTnI after dialysis. Diagnosing AMI is based on typical symptoms, signs of ischemia in the ECG and a significant change of troponin (cTn) with at least one value above the 99th percentile. A decrease of hs-cTnI during HD/HDF can alter the diagnostic validity of troponin. The level of significance of the decreased troponin is influenced by sample size, which was low in general. However, it is very important to underline that one size does not fit all. Further studies with larger sample sizes are needed for sub-analysis for gender and age. Additionally, dialysis details could impact the outcome of the influence of haemodialysis on troponin.

Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease, including acute myocardial infarction. However, whether this risk is only associated with severe kidney disease or is also related to mildly impaired kidney function is still under debate. The incidence rate and risk factors of incident acute myocardial infarction (AMI) in patients with CKD are sparse. Potential differences in risk factor profiles between CKD patients with incident AMI and CKD patients with a prior AMI have not been sufficiently investigated. Furthermore, important factors such as albuminuria and socio-economic factors are often not included. The primary aim of this study was to establish the incidence rate of AMI after CKD debut. Secondly, to evaluate the importance of different CKD stages and the risk of having an AMI. Finally, to identify individuals at risk for AMI after CKD debut adjusted for prevalent AMI. Based on data from the kidney disease cohort of Southern Denmark (KidDiCo), including 66,486 CKD patients, we established incidence rates and characteristics of incident AMI among patients within a 5-year follow-up period after CKD debut. A Cox regression was performed to compute the cause-specific hazard ratios for the different risk factors. The incidence rate for CKD stage G3–5 patients suffering acute myocardial infarction is 2.5 cases/1000 people/year. In patients without a previous myocardial infarction, the risk of suffering a myocardial infarction after CKD debut was only significant in CKD stage G4 (HR = 1.402; (95% CI: 1.08–1.81); p-value = 0.010) and stage G5 (HR = 1.491; (95% CI: 1.01–2.19); p-value = 0.042). This was not the case in patients who had suffered an acute myocardial infarction prior to their CKD debut. In this group, a previous myocardial infarction was the most critical risk factor for an additional myocardial infarction after CKD debut (HR = 2.615; (95% CI: 2.241–3.05); p-value < 0.001). Irrespective of a previous myocardial infarction, age, male sex, hypertension, and a low educational level were significant risk factors associated with an acute myocardial infarction after CKD debut. The incidence rate of AMI in patients with CKD stage G3–5 was 2.5 cases/1000 people/year. Risk factors associated with incident AMI in CKD stage G3–5 patients were CKD stage, age, and hypertension. Female sex and higher educational levels were associated with a lower risk for AMI. Prior AMI was the most significant risk factor in patients with and without previous AMI before fulfilling CKD stage G3–5 criteria. Only age, sex, and a medium-long educational level were significant risk factors in this group.

Background Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI. Methods Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality. Results First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD. Conclusions First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a “free” choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes.

Identifying acute myocardial infarction in patients with renal disease is notoriously difficult, due to atypical presentation and chronically elevated troponin. The aim of this study was to identify a specific troponin T/troponin I cut-off value for diagnosis of acute myocardial infarction in patients with renal impairment via meta-analysis. Two investigators screened 2590 publications from MEDLINE, Embase, PubMed, Web of Science, and the Cochrane library. Only studies that investigated alternative cut-offs according to renal impairment were included. Fifteen articles fulfilled the inclusion criteria. Six studies were combined for meta-analysis. The manufacturer's upper reference level for troponin T is 14 ng/L. Based on the meta-analyses, cut-off values for troponin in patients with renal impairment with myocardial infarction was 42 ng/L for troponin I and 48 ng/L for troponin T. For patients on dialysis the troponin T cut-off is even higher at 239 ng/L. A troponin I cut-off value for dialysis patients could not be established due to lack of data. The 15 studies analyzed showed considerable diversity in study design, study population, and the definition of myocardial infarction. Further studies are needed to define a reliable troponin cut-off value for patients with kidney disease, especially in dialysis patients, and to allow necessary subanalysis.

For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. We included all children aged <15 years starting KRT 2007–2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression. Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007–2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007–2009 or 2010–2012 (adjusted HR: 0.98, 95% CI:0.71–1.35). We found a stable incidence and increasing prevalence of European children on KRT 2007–2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.

Objective: The nutritional status of patients on peritoneal dialysis (PD) is influenced by patient- and disease-related factors and lifestyle. This analysis evaluated the association of PD prescription with body composition and patient outcomes in the prospective incident Initiative for Patient Outcomes in Dialysis–Peritoneal Dialysis (IPOD-PD) patient cohort. Design and Methods: In this observational, international cohort study with longitudinal follow-up of 1,054 incident PD patients, the association of PD prescription with body composition was analyzed by using the linear mixed models, and the association of body composition with death and change to hemodialysis (HD) by means of a competing risk analysis combined with a spline analysis. Body composition was regularly assessed with the body composition monitor, a device applying bioimpedance spectroscopy. Results: Age, time on PD, and the use of hypertonic and polyglucose solutions were significantly associated with a decrease in lean tissue index (LTI) and an increase in fat tissue index (FTI) over time. Competing risk analysis revealed a U-shaped association of body mass index (BMI) with the subdistributional hazard ratio (HR) for risk of death. High LTI was associated with a lower subdistributional HR, whereas low LTI was associated with an increased subdistributional HR when compared with the median LTI as a reference. High FTI was associated with a higher subdistributional HR when compared with the median as a reference. Subdistributional HR for risk of change to HD was not associated with any of the body composition parameters. The use of polyglucose or hypertonic PD solutions was predictive of an increased probability of change to HD, and the use of biocompatible solutions was predictive of a decreased probability of change to HD. Conclusion: Body composition is associated with non-modifiable patient-specific and modifiable treatment-related factors. The association between lean tissue and fat tissue mass and death and change to HD in patients on PD suggests developing interventions and patient counseling to improve nutritional markers and, ultimately, patient outcomes. Study Registration: The study has been registered at Clinicaltrials.gov (NCT01285726).

Background An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis treatment. After creation many of the AVFs will never mature or if functioning will need an intervention within 1 year due to an AVF stenosis. Studies investigating possible therapies that improves the AVF maturation and survival are scarce. Far infrared therapy (FIR) has shown promising results. In minor single centre and industry supported trials FIR has shown improved AVF maturation and survival. There is a need of a randomized multicentre controlled trial to examine the effect of FIR on the AVF maturation and survival and to explore the possible AVF protective mechanism induced by the FIR treatment. Methods This investigator initiated, randomized, controlled, open-labeled, multicenter clinical trial will examine the effect of FIR on AVF maturation in patients with a newly created AVF (incident) and AVF patency rate after 1 year of treatment in patients with an existing AVF (prevalent) compared to a control group. The intervention group will receive FIR to the skin above their AVF three times a week for 1 year. The control group will be observed without any treatment. The primary outcome for incident AVFs is the time from surgically creation of the AVF to successful cannulation. The primary outcome for the prevalent AVFs is the difference in number of AVFs without intervention and still functioning in the treatment and control group after 12 months. Furthermore, the acute changes in inflammatory and vasodilating factors during FIR will be explored. Arterial stiffness as a marker of long term AVF patency will also be examined. Discussion FIR is a promising new treatment modality that may potentially lead to improved AVF maturation and survival. This randomized controlled open-labelled trial will investigate the effect of FIR and its possible mechanisms. Trial registration Clinicaltrialsgov NCT04011072 (7th of July 2019).

Abstract Background and Aims It has been suggested that, in patients with CKD stage 5, measured GFR (mGFR), defined as the mean of urea and creatinine clearance as measured by a 24-hour urine collection, is a better measure of renal function than estimated GFR (eGFR), based on the CKD-EPI formula. This could be due to reduced muscle mass in this group. Its use is recommended in the ERBP guidelines. Unplanned dialysis initiation (UDI) is associated with increased morbidity, mortality, and reduced modality choice. It is generally considered undesirable. We hypothesized that the ratio mGFR/eGFR (R) aids prediction of death and end stage kidney disease (ESKD), as defined by permanent dialysis requirement or transplantation. Method All 24-hour measurements of urea and creatinine excretion were extracted from the clinical biochemistry databases in Zealand. Data concerning renal diagnosis, comorbidity, biochemistry, medical treatment, mortality and date of ESKD, were extracted from patient notes, the National Patient Registry and the Danish Nephrology Registry. Patients were included if their eGFR was <30 ml/min/1.73m2. The last available value for each patient was included. Results 1265 patients were included. In 519, body surface area (BSA) was available, and the corrected ratio (RBSA) could be calculated. The urea clearance was 49 ±24% of creatinine clearance. R was median 0.88 (IQR 0.63-1.15), RBSA 0.87 (0.68-1.06). R was not related to eGFR. Comorbidity was associated with lower R, e.g. atherosclerosis (0.90 ±0.41 vs. 0.97 ±0.49*), heart failure (0.80 ±0.37 vs. 0.95 ±0.44*), pulmonary disease (0.80 ±0.37 vs. 0.94 ±0.44***), hepatic disease (0.67 ±0.41 vs. 0.92 ±0.43***), but not diabetes mellitus. It was related to albumin (r=0.24***), C-reactive protein (-0.22***) and biochemical markers of uraemia, e.g. bicarbonate (-0.19***). Medical treatment data was available in 137 patients. R was higher in patients treated with ACE inhibitors (1.20 ±0.50 vs. 1.01 ±0.36*) and diuretics (1.09 ±0.40 vs. 0.94 ±0.35*), but no other treatment groups. Patients were grouped as high R (H, >1.25), medium (M, 0.75-1.25) or low (L, <0.75). R was not associated with prognosis at one year, but L patients had a significantly higher ESKD and mortality incidence at 3 months. For patients with eGFR 10-15 ml/min/1.73m2, ESKD incidence was L 22%, M 15%, H 5%, mortality 19, 5, and 2% respectively. Similar findings were seen in other groups, e.g. eGFR 15-20 ml/min/1.73m2: ESKD 11, 2, and 0%; death 11, 5, and 1%. UDI was higher for L patients. For patients with eGFR 10-15 ml/min/1.73m2, UDI occurred in L: 47%, M:27%, H:25%. For patients with eGFR 10-15 ml/min/1.73m2 the figures were 51, 38 and 12% respectively. Findings for the subgroup of patients with RBSA measurements were similar. *:p<0.05; **:p<001;***:p<0.001 Conclusion A low mGFR/eGFR ratio is associated with comorbidity, malnutrition, inflammation and biochemical uraemia. It a marker of early ESKD, death and unplanned dialysis initiation, independently of eGFR. Particular attention paid to patients with a low R may lower the incidence of unplanned dialysis requirement.

Abstract Background It has been suggested that, in patients with CKD stage 5, measured GFR (mGFR), defined as the mean of urea and creatinine clearance, as measured by a 24-h urine collection, is a better measure of renal function than estimated GFR (eGFR), based on the CKD-EPI formula. This could be due to reduced muscle mass in this group. Its use is recommended in the ERBP guidelines. Unplanned dialysis initiation (DI) is associated with increased morbidity, mortality, and reduced modality choice and is generally considered undesirable. We hypothesized that the ratio mGFR/eGFR (M/E) aids prediction of death and DI. Methods All 24-h measurements of urea and creatinine excretion were extracted from the clinical biochemistry databases in Zealand. Data concerning renal diagnosis, comorbidity, biochemistry, medical treatment, mortality and date of DI, were extracted from patient notes, the National Patient Registry and the Danish Nephrology Registry. Patients were included if their eGFR was < 30 ml/min/1.73m2. The last available value for each patient was included. Follow-up was 12 months. Results One thousand two hundred sixty-five patients were included. M/E was median 0.91 ± 0.43. It was highly correlated to previous determinations. It was negatively correlated to eGFR, comorbidity, high age and female sex. It was positively related to albumin and negatively to C-reactive protein. M/E was higher in patients treated with ACE inhibitors and diuretics but no other treatment groups. On a multivariate analysis, M/E was negatively correlated with mortality and combined mortality/DI, but not DI. A post hoc analysis showed a negative correlation to DI at 3 months. For patients with an eGFR 10–15 ml/min/1.73m2, combined mortality and DI at 3 months was for low M/E (< 0.75) 36%, medium (0.75–1.25) 20%, high (> 1.25) 8%. A low M/E predicted increased need for unplanned DI. A supplementary analysis in 519 patients where body surface area values were available, allowing BSA-corrected M/E to be analyzed, revealed similar results. Conclusion A low mGFR/eGFR ratio is associated with comorbidity, malnutrition, and inflammation. It is a marker of early DI, mortality, and unplanned dialysis initiation, independently of eGFR, age and comorbidity. Particular attention paid to patients with a low M/E may lower the incidence of unplanned dialysis requirement.