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Introduction: Therapeutic plasma exchange (TPE), with solvent/detergent (S/D)-treated plasma as replacement fluid, is an extracorporeal blood purification technique with major impact on both coagulation and lipids. Our previous in vitro study showed that S/D-plasma enhances thrombin generation by lowering intact protein S (PS) levels., Aims: To evaluate the impact of altered lipid balance on coagulation phenotype during heparin-anticoagulated TPE with S/D-plasma, and to investigate whether the lowered intact PS levels with concomitant procoagulant phenotype, are recapitulated in vivo., Methods: Coagulation biomarkers, thrombin generation with Calibrated Automated Thrombogram (CAT), and lipid levels were measured before and after the consecutive 1st, 3rd and 5th episodes of TPE performed to six patients with Guillain-Barré syndrome or myasthenia gravis. The effects of in vitro dilution of S/D-plasma on thrombin generation were explored with CAT to mimic TPE., Results: Patients did not have coagulation disorders, except elevated FVIII. Intact PS, lipoproteins, especially LDL, Apolipoprotein CIII (ApoC3) and ApoB/ApoA1 ratio declined (p < 0.05). In contrast, VLDL and triglyceride levels stayed intact. CAT lag time shortened (p < 0.05). In vitro dilution of S/D plasma with co-transfused Ringer's lactate and 4% albumin partially reduced its procoagulant phenotype in CAT, which is mainly seen as peak thrombin, and modestly shortened lag time., Conclusions: After the five settings of TPE using S/D-plasma in vivo, which associated with heparinization and reduced coagulation factor activities, our observations of declining natural anticoagulant intact PS and apolipoproteins refer to rebalance of the hemostatic and lipid profiles., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Infections are the most common non-cardiovascular cause of death among dialysis patients. Earlier studies have shown similar or higher risk of infectious complications in peritoneal dialysis (PD) compared to hemodialysis (HD) patients, but comparisons to home HD patients have been rare. We investigated the risk of severe infections after start of continuous ambulatory PD (CAPD) and automated PD (APD) as compared to home HD., Methods: All adult patients (n = 536), who were on home dialysis at day 90 from starting kidney replacement therapy (KRT) between 2004 and 2017 in Helsinki healthcare district, were included. We defined severe infection as an infection with C-reactive protein of 100 mg/l or higher. Cumulative incidence of first severe infection was assessed considering death as a competing risk. Hazard ratios were estimated using Cox regression with propensity score adjustment., Results: The risk of getting a severe infection during the first year of dialysis was 35% for CAPD, 25% for APD and 11% for home HD patients. During five years of follow-up, the hazard ratio of severe infection was 2.8 [95% CI 1.6-4.8] for CAPD and 2.2 [95% CI 1.4-3.5] for APD in comparison to home HD. Incidence rate of severe infections per 1000 patient-years was 537 for CAPD, 371 for APD, and 197 for home HD patients. When excluding peritonitis, the incidence rate was not higher among PD than home HD patients., Conclusions: CAPD and APD patients had higher risk of severe infections than home HD patients. This was explained by PD-associated peritonitis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Finne has received honoraria for lectures from Baxter, AstraZeneca and Boehringer-Ingelheim, and he is a member in an advisory board of Baxter. Dr. Rauta has received honoraria for lectures from Baxter, Fresenius and AstraZeneca, and research funding (not for this project) from Business Finland; and she is a board member in Finnish Society of Nephrology. Dr. Honkanen has received honoraria for lectures from AstraZeneca and Fresenius Medical Care. The findings, results, and conclusions in this report are those of the authors and are independent from the funding sources., (Copyright: © 2023 Bitar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Mortality prediction is critical on long-term kidney replacement therapy (KRT), both for individual treatment decisions and resource planning. Many mortality prediction models already exist, but as a major shortcoming most of them have only been validated internally. This leaves reliability and usefulness of these models in other KRT populations, especially foreign, unknown. Previously two models were constructed for one- and two-year mortality prediction of Finnish patients starting long-term dialysis. These models are here internationally validated in KRT populations of the Dutch NECOSAD Study and the UK Renal Registry (UKRR)., Methods: We validated the models externally on 2051 NECOSAD patients and on two UKRR patient cohorts (5328 and 45493 patients). We performed multiple imputation for missing data, used c-statistic (AUC) to assess discrimination, and evaluated calibration by plotting average estimated probability of death against observed risk of death., Results: Both prediction models performed well in the NECOSAD population (AUC 0.79 for the one-year model and 0.78 for the two-year model). In the UKRR populations, performance was slightly weaker (AUCs: 0.73 and 0.74). These are to be compared to the earlier external validation in a Finnish cohort (AUCs: 0.77 and 0.74). In all tested populations, our models performed better for PD than HD patients. Level of death risk (i.e., calibration) was well estimated by the one-year model in all cohorts but was somewhat overestimated by the two-year model., Conclusions: Our prediction models showed good performance not only in the Finnish but in foreign KRT populations as well. Compared to the other existing models, the current models have equal or better performance and fewer variables, thus increasing models' usability. The models are easily accessible on the web. These results encourage implementing the models into clinical decision-making widely among European KRT populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Haapio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Several studies have shown superior survival of patients on home haemodialysis (HD) compared with peritoneal dialysis (PD), but patients on automated PD (APD) and continuous ambulatory PD (CAPD) have not been considered separately. As APD allows larger fluid volumes and may be more efficient than CAPD, we primarily compared patient survival between APD and home HD., Methods: All adult patients who started kidney replacement therapy (KRT) between 2004 and 2017 in the district of Helsinki-Uusimaa in Finland and who were on one of the home dialysis modalities at 90 days from starting KRT were included. We used intention-to-treat analysis. Survival of home HD, APD and CAPD patients was studied using Kaplan-Meier curves and Cox regression with adjustment for propensity scores that were based on extensive data on possible confounding factors., Results: The probability of surviving 5 years was 90% for home HD, 88% for APD and 56% for CAPD patients. After adjustment for propensity scores, the hazard ratio of death was 1.1 [95% confidence interval (CI) 0.52-2.4] for APD and 1.6 (95% CI 0.74-3.6) for CAPD compared with home HD. Censoring at the time of kidney transplantation (KTx) or at transfer to in-centre HD did not change the results. Characteristics of home HD and APD patients at the start of dialysis were similar, whereas patients on CAPD had higher median age and more comorbidities and received KTx less frequently., Conclusions: Home HD and APD patients had comparable characteristics and their survival appeared similar., Competing Interests: P.F. has received honoraria for lectures and membership in advisory board from Baxter. V.R. has received honoraria for lectures from Baxter and Fresenius and research funding (not for this project) from Business Finland. The findings, results and conclusions in this report are those of the authors and are independent from the funding sources., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Acute kidney injury (AKI) is often diagnosed based on plasma creatinine (Cr) only. Adjustment of Cr for cumulative fluid balance due to potential dilution of Cr and subsequently missed Cr-based diagnosis of AKI has been suggested, albeit the physiological rationale for these adjustments is questionable. Furthermore, whether these adjustments lead to a different incidence of AKI when used in conjunction with urine output (UO) criteria is unknown., Methods: This was a post hoc analysis of the Finnish Acute Kidney Injury study. Hourly UO and daily plasma Cr were measured during the first 5 days of intensive care unit admission. Cr values were adjusted following the previously used formula and combined with the UO criteria. Resulting incidences and mortality rates were compared with the results based on unadjusted values., Results: In total, 2044 critically ill patients were analyzed. The mean difference between the adjusted and unadjusted Cr of all 7279 observations was 5 (±15) µmol/L. Using adjusted Cr in combination with UO and renal replacement therapy criteria resulted in the diagnosis of 19 (1%) additional AKI patients. The absolute difference in the incidence was 0.9% (95% confidence interval [CI]: 0.3%-1.6%). Mortality rates were not significantly different between the reclassified AKI patients using the full set of Kidney Disease: Improving Global Outcomes criteria., Conclusion: Fluid balance-adjusted Cr resulted in little change in AKI incidence, and only minor differences in mortality between patients who changed category after adjustment and those who did not. Using adjusted Cr values to diagnose AKI does not seem worthwhile in critically ill patients., (© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Comorbidities are associated with increased mortality among patients receiving long-term kidney replacement therapy (KRT). However, it is not known whether primary kidney disease modifies the effect of comorbidities on KRT patients' survival., Methods: An incident cohort of all patients (n = 8696) entering chronic KRT in Finland in 2000-2017 was followed until death or end of 2017. All data were obtained from the Finnish Registry for Kidney Diseases. Information on comorbidities (coronary artery disease, peripheral vascular disease, left ventricular hypertrophy, heart failure, cerebrovascular disease, malignancy, obesity, underweight, and hypertension) was collected at the start of KRT. The main outcome measure was relative risk of death according to comorbidities analyzed in six groups of primary kidney disease: type 2 diabetes, type 1 diabetes, glomerulonephritis (GN), polycystic kidney disease (PKD), nephrosclerosis, and other or unknown diagnoses. Kaplan-Meier estimates and Cox regression were used for survival analyses., Results: In the multivariable model, heart failure increased the risk of death threefold among PKD and GN patients, whereas in patients with other kidney diagnoses the increased risk was less than twofold. Obesity was associated with worse survival only among GN patients. Presence of three or more comorbidities increased the age- and sex-adjusted relative risk of death 4.5-fold in GN and PKD patients, but the increase was only 2.5-fold in patients in other diagnosis groups., Conclusions: Primary kidney disease should be considered when assessing the effect of comorbidities on survival of KRT patients as it varies significantly according to type of primary kidney disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock., Results: P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71-150) pmol/mL and 138 (84-214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1-4.4, p = 0.03] and 2.8 [95% CI 1.2-6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria < 0.5 mL/kg/h for > 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p < 0.001). However, the biomarkers provided best discrimination for mortality when measured at 24 h. Identified cut-offs of P-PENK 24h  > 105.7 pmol/L and P-NGAL 24h  > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1-10.7, p < 0.001) and 5.2 (95% CI 2.8-9.8, p < 0.001) for 90-day mortality. The association remained significant despite adjustments with AKI and two risk scores for mortality in cardiogenic shock., Conclusions: High levels of P-PENK and P-NGAL at baseline were independently associated with AKI in cardiogenic shock patients. Furthermore, oliguria before study inclusion was associated with worse outcomes only if combined with high baseline levels of P-PENK or P-NGAL. High levels of both P-PENK and P-NGAL at 24 h were found to be strong and independent predictors of 90-day mortality., Trial Registration: NCT01374867 at www.clinicaltrials.gov , registered 16 Jun 2011-retrospectively registered.

Introduction: CT is the primary imaging option for acute abdominal pain in adults. Intravenous (IV) contrast media use improves CT quality but may cause post-contrast acute kidney injury (PC-AKI). Retrospective studies show no association between reduced baseline renal function and IV contrast CT, but, to our knowledge, no data from randomised controlled trials exist., Methods and Analysis: The INCARO (INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn) trial is a multicentre, open-label, parallel group, superiority, individually randomised controlled trial comparing IV contrast-enhanced CT to native CT in patients requiring emergency abdominal or body CT with impaired renal function defined as an estimated glomerular filtration rate (eGFR) of 15 to 45 mL/min/1.73 m 2 . The primary outcome is a composite of all-cause mortality or renal replacement therapy (RRT) within 90 days from CT. Secondary outcomes are AKI measured by KDIGO (The Kidney Disease: Improving Global Outcomes) criteria within 72 hours from CT, organ dysfunction defined by mSOFA (modified Sequential Organ Failure Assessment) criteria after 48 hours from CT, alive and hospital-free days within 90 days after CT, and time from imaging to definitive treatment. All-cause mortality, need for RRT and renal transplant in long-term follow-up are also measured. The calculated sample size is 994 patients. Patient recruitment is estimated to take 3 years., Ethics and Dissemination: The Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals., Trial Registration Number: NCT04196244., Competing Interests: Competing interests: AL has received funding from Helsinki University Hospital research funds. PR has received a research grant from Orion Research foundation. VS reports grants from the Vatsatautien Tutkimussäätiö Foundation, Mary and Georg Ehrnrooth’s Foundation, Martti I Turunen Foundation, Helsinki University Hospital research funds, the Finnish Surgical Society, Finska Läkaresällskapet, Finnish Gastroenterological Society, Cancer Foundation, and Academy of Finland, personal lecturing fees from City of Vantaa, Finnish Gastroenterological Society, Novartis, and University of Helsinki, and non-financial support from Astellas outside of the submitted work. STV has received funding for Clinical Researchers (317061) from the Academy of Finland., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is released from kidney tubular cells under stress as well as from neutrophils during inflammation. It has been suggested as a biomarker for acute kidney injury (AKI) in critically ill patients with sepsis. To evaluate clinical usefulness of urine NGAL (uNGAL), we post-hoc applied recently introduced statistical methods to a sub-cohort of septic patients from the prospective observational Finnish Acute Kidney Injury (FINNAKI) study. Accordingly, in 484 adult intensive care unit patients with sepsis by Sepsis-3 criteria, we calculated areas under the receiver operating characteristic curves (AUCs) for the first available uNGAL to assess discrimination for four outcomes: AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, severe (KDIGO 2-3) AKI, and renal replacement therapy (RRT) during the first 3 days of intensive care, and mortality at day 90. We constructed clinical prediction models for the outcomes and used risk assessment plots and decision curve analysis with predefined threshold probabilities to test whether adding uNGAL to the models improved reclassification or decision making in clinical practice., Results: Incidences of AKI, severe AKI, RRT, and mortality were 44.8% (217/484), 27.7% (134/484), 9.5% (46/484), and 28.1% (136/484). Corresponding AUCs for uNGAL were 0.690, 0.728, 0.769, and 0.600. Adding uNGAL to the clinical prediction models improved discrimination of AKI, severe AKI, and RRT. However, the net benefits for the new models were only 1.4% (severe AKI and RRT) to 2.5% (AKI), and the number of patients needed to be tested per one extra true-positive varied from 40 (AKI) to 74 (RRT) at the predefined threshold probabilities., Conclusions: The results of the recommended new statistical methods do not support the use of uNGAL in critically ill septic patients to predict AKI or clinical outcomes.

Background: Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)•insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk®., Methods: Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers., Results: Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs < 0.700. The combination uCHI3L1•TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk® cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk® cutoff of 0.3., Conclusions: We found that uCHI3L1 and NephroCheck Risk® had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.

Background: Mortality rates associated with acute kidney injury (AKI) vary among critically ill patients. Outcomes are often not corrected for severity or duration of AKI. Our objective was to analyse whether a new variable, AKI burden, would outperform 1) presence of AKI, 2) highest AKI stage, or 3) AKI duration in predicting 90-day mortality., Methods: Kidney Diseases: Improving Global Outcomes (KDIGO) criteria using creatinine, urine output and renal replacement therapy were used to diagnose AKI. AKI burden was defined as AKI stage multiplied with the number of days that each stage was present (maximum five), divided by the maximum possible score yielding a proportion. The AKI burden as a predictor of 90-day mortality was assessed in two independent cohorts (Finnish Acute Kidney Injury, FINNAKI and Simple Intensive Care Studies I, SICS-I) by comparing four multivariate logistic regression models that respectively incorporated either the presence of AKI, the highest AKI stage, the duration of AKI, or the AKI burden., Results: In the FINNAKI cohort 1096 of 2809 patients (39%) had AKI and 90-day mortality of the cohort was 23%. Median AKI burden was 0.17 (IQR 0.07-0.50), 1.0 being the maximum. The model including AKI burden (area under the receiver operator curve (AUROC) 0.78, 0.76-0.80) outperformed the models using AKI presence (AUROC 0.77, 0.75-0.79, p = 0.026) or AKI severity (AUROC 0.77, 0.75-0.79, p = 0.012), but not AKI duration (AUROC 0.77, 0.75-0.79, p = 0.06). In the SICS-I, 603 of 1075 patients (56%) had AKI and 90-day mortality was 28%. Median AKI burden was 0.19 (IQR 0.08-0.46). The model using AKI burden performed better (AUROC 0.77, 0.74-0.80) than the models using AKI presence (AUROC 0.75, 0.71-0.78, p = 0.001), AKI severity (AUROC 0.76, 0.72-0.79. p = 0.008) or AKI duration (AUROC 0.76, 0.73-0.79, p = 0.009)., Conclusion: AKI burden, which appreciates both severity and duration of AKI, was superior to using only presence or the highest stage of AKI in predicting 90-day mortality. Using AKI burden or other more granular methods may be helpful in future epidemiological studies of AKI.

Background: Studies reporting renal and overall survival after acute kidney injury (AKI) treated exclusively with intermittent modalities of renal replacement therapy (IRRT) are rare. This study focused on outcomes of AKI patients treated with IRRT both in intensive care units (ICUs) and non-ICU dialysis units., Methods: This prospective observational study was carried on during a 5-month period in 17 ICUs and 17 non-ICUs. ICU and non-ICU patients (total n = 138; 65 ICU, 73 non-ICU) requiring RRT for AKI and chosen to receive IRRT were included. Patient and RRT characteristics as well as outcomes at 90 days, 1 year, and 3 years were registered., Results: Characteristics of ICU and non-ICU patients differed markedly. Pre-existing chronic kidney disease (CKD) and chronic heart failure were significantly more common among non-ICU patients. At 1 year, RRT dependence was significantly more common in the non-ICU group. At 3 years, there was no significant difference between the groups either in RRT dependence or mortality., Conclusion: Outcome of AKI patients treated with IRRT is dismal with regard to 3-year kidney function and mortality. Although pre-existing CKD emerged as a major risk factor for end-stage renal disease after AKI, the poor kidney survival was also seen in patients without prior CKD., (© 2018 The Acta Anaesthesiologica Scandinavica Founzdation. Published by John Wiley & Sons Ltd.)

Introduction: Mortality risk of patients with end-stage renal disease (ESRD) is highly elevated. Methods to estimate individual mortality risk are needed to provide individualized care and manage expanding ESRD populations. Many mortality prediction models exist but have shown deficiencies in model development (data comprehensiveness, validation) and in practicality. Therefore, our aim was to design 2 easy-to-apply prediction models for 1- and 2-year all-cause mortality in patients starting long-term renal replacement therapy (RRT)., Methods: We used data from the Finnish Registry for Kidney Diseases with complete national coverage of RRT patients. Model training group included all incident adult patients who started long-term dialysis in Finland in 2000 to 2008 (n = 4335). The external validation cohort consisted of those who entered dialysis in 2009 to 2012 (n = 1768). Logistic regression with stepwise variable selection was used for model building., Results: We developed 2 prognostic models, both of which only included 6 to 7 variables (age at RRT start, ESRD diagnosis, albumin, phosphorus, C-reactive protein, heart failure, and peripheral vascular disease) and showed sufficient discrimination (c-statistic 0.77 and 0.74 for 1- and 2-year mortality, respectively). Due to a significantly lower mortality in the newer cohort, the models, to a degree, overestimated mortality risk., Discussion: Mortality prediction algorithms could be more widely implemented into management of ESRD patients. The presented models are practical with only a limited number of variables and fairly good performance.

Myasthenia gravis (MG) is the most common neuromuscular transmission disorder, causing weakness of skeletal muscles on exertion. The course of the disease is highly variable, symptoms and signs may change rapidly due to infection or pregnancy. MG is classified using serological, electrophysiological and pharmaceutical tools. A precise diagnosis allows for the choice of right treatment, predicts the course of disease and hence helps with the follow-up. In this review we present Finnish guidelines for diagnostics, treatment and follow-up of MG patients.

Background: Interleukin-18 (IL-18) is a pro-inflammatory protein, which mediates ischaemic tubular injury, and has been suggested to be a sensitive and specific biomarker for acute kidney injury (AKI). The predictive value of IL-18 in the diagnosis, evolution, and outcome of AKI in critically ill patients is still unclear., Methods: We measured urine IL-18 from critically ill patients at intensive care unit (ICU) admission and 24 h. We evaluated the association of IL-18 with developing new AKI, renal replacement therapy (RRT), and 90-day mortality. We calculated areas under receiver operating characteristics curves (AUCs), best cut-off values, and positive likelihood ratios (LR+) for IL-18 concerning these endpoints. Additionally, we compared the predictive value of IL-18 at ICU admission to that of urine neutrophil gelatinase-associated lipocalin (NGAL)., Results: In this study population of 1439 patients the highest urine IL-18 during the first 24 h in the ICU associated with the development of AKI with an AUC [95% confidence interval (CI)] of 0.586 (0.546-0.627) and with the development of Stage 3 AKI with an AUC (95% CI) of 0.667 (0.591-0.774). IL-18 predicted the initiation of RRT with an AUC (95% CI) of 0.655 (0.572-0.739), and 90-day mortality with an AUC (95% CI) of 0.536 (0.497-0.574)., Conclusions: IL-18 had poor-to-moderate ability to predict AKI, RRT, or 90-day mortality in this large cohort of critically ill patients. Thus, it should be used with caution for diagnostic or predictive purposes in the critically ill., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: To examine use and changes of medication in the three years before start of chronic renal replacement therapy (RRT) among patients with type 1 diabetes, and the association between predialytic medication and survival on RRT., Methods: We recorded medication of 496 patients with type 1 diabetes before and after start of RRT in 2000-2006 and followed up until death or end of 2009. Data were retrieved from the Finnish Registry for Kidney Diseases and from the FinDM diabetes database. We evaluated the use of renin-angiotensin system (RAS) blockers, calcium channel blockers, β-blockers, statins, vitamin D, erythropoiesis-stimulating agents, and phosphate binders over three years. The association between predialytic medication and survival was assessed using Cox proportional hazards regression., Results: Medication increased markedly with progressing renal insufficiency. Almost 70% of the patients used calcium channel blockers and β-blockers before initiating RRT. Use of calcium channel blockers (RR 0.72, 95% CI 0.53-0.95) and vitamin D (RR 0.70, 95% CI 0.52-0.94) at start of RRT were associated with better survival when adjusted for age and sex, but after further adjustment the association lost statistical significance., Conclusions: Among type 1 diabetes patients in the predialysis phase, use of medication is abundant. Use of medication appears to keep patients at an equal survival level to those without the same medication. However, due to the observational nature of our study, conclusions regarding the effect of medication on survival must be made with caution., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background/aims: End-stage renal disease (ESRD) is one of the most serious complications of type 1 diabetes, but scarcely studied. Our aim was to estimate the association between biochemical variables and survival among these patients., Methods: This was an incident cohort study of patients with type 1 diabetes entering chronic renal replacement therapy (RRT) in Finland 2000-2011 (n = 834). Biochemical variables were measured before the initiation of RRT. Adjusted relative risk of death according to biochemical variables was estimated by Cox regression., Results: When adjusted for age, sex, comorbidities, and initial treatment modality of RRT, the most important predictors of death were low creatinine and albumin and high C-reactive protein., Conclusion: Among type 1 diabetes patients entering chronic RRT, biochemical variables independently associated with survival are creatinine, albumin and C-reactive protein. They reflect the nutritional status, proteinuria, liver function, and ongoing inflammatory process. Treatment of these might improve survival., (© 2014 S. Karger AG, Basel.)

Purpose: We aimed to determine the incidence, risk factors and outcome of acute kidney injury (AKI) in Finnish ICUs., Methods: This prospective, observational, multi-centre study comprised adult emergency admissions and elective patients whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. We defined AKI first by the Acute Kidney Injury Network (AKIN) criteria supplemented with a baseline creatinine and second with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We screened the patients' AKI status and risk factors for up to 5 days., Results: We included 2,901 patients. The incidence (95 % confidence interval) of AKI was 39.3 % (37.5-41.1 %). The incidence was 17.2 % (15.8-18.6 %) for stage 1, 8.0 % (7.0-9.0 %) for stage 2 and 14.1 % (12.8-15.4 %) for stage 3 AKI. Of the 2,901 patients 296 [10.2 % (9.1-11.3 %)] received renal replacement therapy. We received an identical classification with the new KDIGO criteria. The population-based incidence (95 % CI) of ICU-treated AKI was 746 (717-774) per million population per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease were independent risk factors for AKI. Hospital mortality (95 % CI) for AKI patients was 25.6 % (23.0-28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9-36.5 %). All AKIN stages were independently associated with 90-day mortality., Conclusions: The incidence of AKI in the critically ill in Finland was comparable to previous large multi-centre ICU studies. Hospital mortality (26 %) in AKI patients appeared comparable to or lower than in other studies.

Background: Associations between mode of renal replacement therapy and employment rate have not been well characterized., Study Design: Cross-sectional registry analysis., Setting & Participants: The employment status of all prevalent 15- to 64-year-old dialysis and kidney transplant patients in Finland at the end of 2007 (N = 2,637) was analyzed by combining data from the Finnish Registry for Kidney Diseases with individual-level employment statistics of the Finnish government., Predictor: Prevalence rate ratios (PRRs) of employment according to treatment modality with adjustment for age, sex, cause of end-stage renal disease (ESRD), duration of ESRD, and comorbid conditions were estimated using Cox regression with a constant time at risk., Outcome: Employment status of patients on dialysis therapy or after transplant., Measurements: Clinical data were collected from the Finnish Registry for Kidney Diseases, and employment data were acquired from Statistics Finland., Results: 19% of hemodialysis patients, 31% of peritoneal dialysis patients, and 40% of patients with a functioning transplant were employed; the overall employment rate for the Finnish population aged 15-64 years is 67%. Home hemodialysis patients and those treated with automated peritoneal dialysis had employment rates of 39% and 44%, respectively. In adjusted analysis, patients on home hemodialysis therapy (PRR, 1.87), on automated peritoneal dialysis therapy (PRR, 2.14), or with a kidney transplant (PRR, 2.30) had higher probabilities of employment than in-center hemodialysis patients. Patients with type 1 or 2 diabetes as the cause of ESRD had the lowest probability of employment (PRR, 0.48-0.60 compared with glomerulonephritis). Patients aged 25-54 years more frequently were employed than those younger than 25 or older than 54 years. Sex did not predict employment. For transplant recipients, longer time since transplant was associated with higher employment in addition to the mentioned factors., Limitations: Cross-sectional design., Conclusions: Employment rate of home dialysis patients was similar to that of transplant recipients and higher than that of in-center hemodialysis patients. Patients with diabetes were less likely to be employed., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Estimated glomerular filtration rate (eGFR) is widely used in follow-up and assessment of patients before start of chronic renal replacement therapy (RRT). Reported data on impact of eGFR decline pattern during pre-dialysis phase on consequent survival on RRT are, however, non-existent., Methods: Using the database of the Finnish Registry for Kidney Diseases, we conducted a cohort study of all incident adult patients (n = 457) entering chronic RRT in Finland in 1998, with follow-up until 31 December 2008. We included those (n = 319) with three serum creatinine measurements (at ∼12 and 3 months and 1 to 2 weeks prior to RRT start) and calculated their slopes of eGFR using the modification of diet in renal disease formula. According to eGFR slopes (in mL/min/1.73m(2)/year), patients were divided into tertiles: most rapid (>8.5, n = 107), intermediate (3.4-8.5, n = 107) and slowest decline (<3.4, n = 105)., Results: Median survival time was 5.6 (95% confidence interval 4.2-7.0) years. Compared to the patient group with the slowest eGFR decline, age- and gender-adjusted relative risk of death was 1.1 (0.8-1.5) in the intermediate group and 1.7 (1.2-2.4, P = 0.002) in the most rapid decline group. When further adjusting for kidney disease diagnosis, comorbidities, use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, body mass index, blood haemoglobin and serum albumin, the association was no longer significant., Conclusions: Rapid decline in eGFR before entering chronic RRT associates with increased mortality on RRT. The elevated mortality appears to be caused by known risk factors for death on RRT.

Objective: Assessment of fluid status in chronic peritoneal dialysis (PD) patients is complex. Clinical evaluation based solely on body weight, blood pressure, volume of ultrafiltration (UF) and peripheral edema is insufficient. A non-invasive test, bioelectrical impedance analysis (BIA) might be of potential benefit., Aim: To test whether BIA correlates with other ancillary markers of extracellular fluid volume, namely B-type natriuretic peptide (BNP), residual renal function (RRF) and UF, and whether BIA provides complementary information in categorizing PD patients vis-à-vis hydration status., Methods: A cross-sectional study of 61 out-patients on chronic PD. Single-frequency BIA measurements of resistance/height were divided into tertiles (lowest: <253 Ω/m; middle: >253 Ω/m and <316 Ω/m; highest: >316 Ω/m)., Results: Compared to patients in the highest tertile of BIA (least fluid), patients in the lowest tertile (most fluid) had highest BNP, RRF and UF (93.5 vs. 55.0 pg/ml, p = 0.029; 850 vs. 300 ml/day, p = 0.05; and 1.75 vs. 1.21 l/day, p = 0.023, respectively)., Conclusions: BIA tertiles categorized PD patients who differed in BNP, RRF and UF in a stepwise pattern, suggesting BIA may better inform hydration status, and serve as an additional clinical tool in management of chronic PD patients., (Copyright © 2012 S. Karger AG, Basel.)

Most poisonings that have resulted in hospitalization in Finland are alcohol, drug or mixed poisonings of adults. If the quantity of the drug or the poison is high or organ injury is anticipated, the patients may require extracorporeal blood purification in order to eliminate the substance or its metabolic products from the circulation. Hemodialysis or hemodiafiltration are used as the treatment, if the substance having caused the poisoning is water-soluble, binds to proteins only to a small extent, and has a low molecular weight and small distribution of volume. Fat-soluble substances are eliminated by using hemoperfusion, those having bound to proteins by using albumin dialysis.

Introduction. Acute kidney injury (AKI) is common in the intensive care unit (ICU) and associated with poor outcome. Plasma B-type natriuretic peptide (BNP) is a biomarker related to myocardial overload, and is elevated in some ICU patients. There is a high prevalence of both cardiac and renal dysfunction in ICU patients. Aims. To investigate whether plasma BNP levels in the first 48 hours were associated with AKI in ICU patients. Methods. We studied a cohort of 34 consecutive ICU patients. Primary outcome was presence of AKI on presentation, or during ICU stay. Results. For patients with AKI on presentation, BNP was statistically higher at 24 and 48 hours than No-AKI patients (865 versus 148 pg/mL; 1380 versus 131 pg/mL). For patients developing AKI during 48 hours, BNP was statistically higher at 0, 24 and 48 hours than No-AKI patients (510 versus 197 pg/mL; 552 versus 124 pg/mL; 949 versus 104 pg/mL). Conclusion. Critically ill patients with AKI on presentation or during ICU stay have higher levels of the cardiac biomarker BNP relative to No-AKI patients. Elevated levels of plasma BNP may help identify patients with elevated risk of AKI in the ICU setting. The mechanism for this cardiorenal connection requires further investigation.

Cardiorenal syndromes are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The pharmacological management of Cardiorenal syndromes may be complicated by unanticipated or unintended effects of agents targeting one organ on the other. Hence, a thorough understanding of the pathophysiology of these disorders is paramount. The treatment of cardiovascular diseases and risk factors may affect renal function and modify the progression of renal injury. Likewise, management of renal disease and associated complications can influence heart function or influence cardiovascular risk. In this paper, an overview of pharmacological management of acute and chronic Cardiorenal Syndromes is presented, and the need for high-quality future studies in this field is highlighted.

Purpose. Strategies for volume assessment of critically ill patients are limited, yet early goal-directed therapy improves outcomes. Central venous pressure (CVP), Bioimpedance Vectorial Analysis (BIVA), and brain natriuretic peptide (BNP) are potentially useful tools. We studied the utility of these measures, alone and in combination, to predict changing oxygenation. Methods. Thirty-four mechanically ventilated patients, 26 of whom had data beyond the first study day, were studied. Relationships were assessed between CVP, BIVA, BNP, and oxygenation index (O(2)I) in a cross-sectional (baseline) and longitudinal fashion using both univariate and multivariable modeling. Results. At baseline, CVP and O(2)I were positively correlated (R = 0.39; P = .021), while CVP and BIVA were weakly correlated (R = -0.38; P = .025). The association between slopes of variables over time was negligible, with the exception of BNP, whose slope was correlated with O(2)I (R = 0.40; P = .044). Comparing tertiles of CVP, BIVA, and BNP slopes with the slope of O(2)I revealed only modest agreement between BNP and O(2)I (kappa = 0.25; P = .067). In a regression model, only BNP was significantly associated with O(2)I; however, this was strengthened by including CVP in the model. Conclusions. BNP seems to be a valuable noninvasive measure of volume status in critical care and should be assessed in a prospective manner.

We examined association of inducible myocardial perfusion defects with cardiorenal biomarkers, and of diminished left ventricular ejection fraction (LVEF) with kidney injury marker plasma neutrophil gelatinase-associated lipocalin (NGAL). Patients undergoing nuclear myocardial perfusion stress imaging were divided into 2 groups. Biomarkers were analyzed pre- and poststress testing. Compared to the patients in the low ischemia group (n = 16), the patients in the high ischemia group (n = 18) demonstrated a significantly greater rise in cardiac biomarkers plasma BNP, NT-proBNP and cTnI. Subjects were also categorized based on pre- or poststress test detectable plasma NGAL. With stress, the group with no detectable NGAL had a segmental defect score 4.2 compared to 8.2 (P = .06) in the detectable NGAL group, and 0.9 vs. 3.8 (P = .03) at rest. BNP rose with stress to a greater degree in patients with detectable NGAL (10.2 vs. 3.5 pg/mL, P = .03). LVEF at rest and with stress was significantly lower in the detectable NGAL group; 55.8 versus 65.0 (P = .03) and 55.1 vs. 63.8 (P = .04), respectively. Myocardial perfusion defects associate with biomarkers of cardiac stress, and detectable plasma NGAL with significantly lower LVEF, suggesting a specific heart-kidney link.

Cardiorenal syndromes are disorders of the heart and kidneys whereby acute or long-term dysfunction in one organ may induce acute or long-term dysfunction of the other. The management of cardiovascular diseases and risk factors may influence, in a beneficial or harmful way, kidney function and progression of kidney injury. In this review, we assess therapeutic strategies and discuss treatment options for the management of patients with heart failure with decreased kidney function and highlight the need for future high-quality studies in patients with coexisting heart and kidney disease., (Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)