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In the current paper, we will focus on requirements to ensure big data can advance the outcomes of our patients suffering from kidney disease. The associated ethical question is whether and how we as a nephrology community can and should encourage the collection of big data of our patients. We identify some ethical reflections on the use of big data, and their importance and relevance. Furthermore, we balance advantages and pitfalls and discuss requirements to make legitimate and ethical use of big data possible. The collection, organization and curation of data come upfront in the pipeline prior to any analyses. Great care must therefore be taken to ensure quality of the data at this stage, to avoid the garbage in garbage out problem and suboptimal patient care as a consequence of such analyses. Access to the data should be organized so that correct and efficient use of data is possible. This means that data must be stored safely, so that only those entitled to do so can access them. At the same time, those who are entitled to access the data should be able to do so in an efficient way, so as not to hinder relevant research. Analysis of observational data is itself prone to many errors and biases. Each of these biases can finally result in provision of low-quality medical care. Secure platforms should therefore also ensure correct methodology is used to interpret the available data. This requires close collaboration of a skilled workforce of experts in medical research and data scientists. Only then will our patients be able to benefit fully from the potential of AI and big data., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

With the increasing frequency and severity of disasters and the increasing number of patients living with kidney disease, on dialysis and with transplants around the world, the need for kidney care in humanitarian settings is increasing. Almost all humanitarian emergencies pose a threat to kidney health because all treatments are highly susceptible to interruption, and interruption can be deadly. Providing support for people requiring dialysis in humanitarian settings can be complex and is associated with many trade-offs. The global kidney care community must become familiar with the ethics, principles and duties essential to meeting the overarching goals of ethical and effective disaster relief. Ethics principles and values must be considered on the individual, public health and global levels. The wellbeing of a single patient must be considered in the context of the competing needs of many others, and optimal treatment may not be possible due to resource constraints. Public health ethics principles, including considerations of triage and resource allocation, maximization of benefit and feasibility, often become directly relevant at the bedside. Individuals delivering humanitarian relief must be well trained, competent, respectful and professional, while involved organizations need to uphold the highest professional and ethical standards. There may be dissonance between ethical guidance and practical realities in humanitarian settings, which for inexperienced individuals may present significant challenges. Sustaining dialysis care in emergencies brings these issues starkly to the fore. Preparedness for dialysis in emergencies is an ethical imperative that mandates multisectoral stakeholder engagement and action, development of surge response plans, clinical and ethics guidance, and transparent priority setting. This manuscript outlines common ethics challenges and considerations that apply in all humanitarian actions, and illustrates their relevance to kidney care as a whole, using examples of how these may apply to dialysis and kidney disaster relief efforts in humanitarian settings., Competing Interests: All authors declare no conflicts of interest with relevance to this work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: We investigated 10-year trends in deceased donor kidney quality expressed as the kidney donor risk index (KDRI) and subsequent effects on survival outcomes in a European transplant population., Methods: Time trends in the crude and standardized KDRI between 2005 and 2015 by recipient age, sex, diabetic status and country were examined in 24 177 adult kidney transplant recipients in seven European countries. We determined 5-year patient and graft survival probabilities and the risk of death and graft loss by transplant cohort (Cohort 1: 2005-06, Cohort 2: 2007-08, Cohort 3: 2009-10) and KDRI quintile., Results: The median crude KDRI increased by 1.3% annually, from 1.31 [interquartile range (IQR) 1.08-1.63] in 2005 to 1.47 (IQR 1.16-1.90) in 2015. This increase, i.e. lower kidney quality, was driven predominantly by increases in donor age, hypertension and donation after circulatory death. With time, the gap between the median standardized KDRI in the youngest (18-44 years) and oldest (>65 years) recipients widened. There was no difference in the median standardized KDRI by recipient sex. The median standardized KDRI was highest in Austria, the Netherlands and the Basque Country (Spain). Within each transplant cohort, the 5-year patient and graft survival probability were higher for the lowest KDRIs. There was no difference in the patient and graft survival outcomes across transplant cohorts, however, over time the survival probabilities for the highest KDRIs improved., Conclusions: The overall quality of deceased donor kidneys transplanted between 2005 and 2015 has decreased and varies between age groups and countries. Overall patient and graft outcomes remain unchanged., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Association of higher serum levels of uremic toxins and inflammatory markers with poorer physical performance is understudied. We measured the six-minute walk test (6MWT), 10 repetition sit-to-stand test (STS-10), handgrip strength (HGS), and Human Activity Profile (HAP) questionnaire score in 90 prevalent hemodialysis patents, with low comorbidity to reduce the potential confounding of concomitant disease. Midweek pre-dialysis serum levels of asymmetric dimethyl-arginine (ADMA), β2-microglobulin (B2M), high-sensitivity C-reactive protein (hs-CRP), indoxyl sulfate (IS), insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6), myostatin, and urea were analyzed as predictor parameters of physical performance measures in adjusted models. Serum levels of most measured toxins were not significantly related to performance, except for ADMA, which was significantly related to poorer performance in the STS-10 test (B = 0.11 ± 0.03 s, p < 0.01). Higher hs-CRP was associated with poorer results in the 6MWT (B = -2.6 ± 0.97 m, p < 0.01) and a lower HAP score (B = -0.36 ± 0.14, p = 0.01). There were no other significant associations found. We conclude that inflammation may be a more important pathway to physical impediment than uremic toxemia. This suggests that there is a large physical rehabilitation potential in non-inflamed uremic patients.

Management of secondary hyperparathyroidism (SHPT) in dialysis population includes the use of active vitamin D forms, among which paricalcitol was shown to be more effective at reducing parathyroid hormone (PTH) concentrations. A prospective randomized study comparing the effectiveness and safety of peroral paricalcitol and calcitriol in suppressing PTH concentrations in 20 hemodialysis patients was performed comparing the influence of agents on PTH suppression, calcium (Ca) and phosphate (P) level and calcium-phosphorus product (C×P). The study was performed in an "intent to treat" manner with primary end point in reduction of PTH level in the target area of 150 > PTH < 300 ng/L after 3 months. At the time point 3 months after therapy induction paricalcitol and calcitriol were equally efficient at correcting PTH levels, with paricalcitol showing significantly less calcemic effect than calcitriol., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

In 1996 we performed tandem membrane plasma exchange-hemodialysis in a 3-year-old girl and tandem immunoadsorption-hemodialysis with citrate as the only anticoagulant in a patient with Goodpasture's syndrome. In the present study, we evaluated the feasibility, efficacy and safety of 24 tandem plasma exchange/immunoadsorption hemodialysis procedures in four different circuit setups with citrate as the only anticoagulant. In two setups, the tandem procedures were connected in series (plasma exchange hemodialysis and immunoadsorption hemodialysis), while in the other two setups they were in parallel (plasma exchange hemodialysis with independent blood circuits and plasma exchange hemodialysis with independent arterial blood lines, but with a common return line). All tandem procedures were feasible, efficient and safe. No serious side-effects were recorded. The most elegant setup was the procedure with independent, parallel blood circuits. However, serial tandem procedures provided for the elimination of citrate and normalization of electrolytes before blood was returned to the patient., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time., Methods: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency., Results: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively., Conclusions: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Hemostasis impairment and iron deficiency are relatively frequent in hemodialysis patients. Both conditions may contribute to anemia. The aim of our study was to explore possible associations between hemostasis impairment and iron deficiency by employing recently introduced methods for measurement of both conditions. Sixty-three hemodialysis patients were studied, with 30 age-matched, healthy controls. Hemostasis impairment was detected by in vitro closure time tests (collagen/epinephrine cartridge: CEPI; collagen/adenosine diphosphate (ADP) cartridge: CADP), whereas (functional) iron deficiency was measured by reticulocyte hemoglobin content (CHr) and the percentage of hypochromic red cells (HRC). We found that the patient group (N=14) with functional iron deficiency (CHr<29) had significantly delayed in vitro closure times in comparison to the patients (N=49) without functional iron deficiency. Furthermore, both types of closure time (CEPI and CADP) correlate highly significantly with CHr (P=0.002, and P=0.001). Such an association was not observed between in vitro closure time and HRC. We found a significant correlation between hemostasis impairment (measured by in vitro closure time) and iron deficiency (measured by CHr) in hemodialysis patients. This correlation has not previously been reported. It seems that in hemodialysis patients the hemostasis impairment affects (functional) iron deficiency, most likely by facilitating excessive blood loss and consequent iron deficiency. Thus, it appears that a delayed in vitro closure time along with decreased CHr may identify hemodialysis patients who suffer (occult) blood loss and/or excessive blood loss during hemodialysis procedure. The clinical value of this finding should be tested in larger studies., (© 2010 The Authors. Therapeutic Apheresis and Dialysis © 2010 International Society for Apheresis.)

Background: The purpose of this study was to investigate haemodialysis (HD) dose practice patterns in different European countries in the light of the European Best Practice Guidelines (EBPG) and to study the associations of patient characteristics and country with weekly dialysis duration., Methods: Renal registries in Europe were asked to contribute to the study with individual patient data on weekly HD duration, number of HD sessions a week and last measured Kt/V. Additional items were age, sex, date of first renal replacement therapy (RRT), dry weight, height, HD modality, HD technique, diabetes status and vascular access type. Multivariate logistic regression was used to study the probability of receiving HD for <12 h per week., Results: Seven registries contributed data on 26 136 patients on HD on 31 December 2005. Eighty-three percent of the patients received HD for at least 12 h per week as recommended by the EBPG (range 49.0-97.3% across countries). Multivariate analysis showed significant differences across countries concerning the risk of receiving <12 h. Other risk factors included age (older), sex (female), BMI (low) and duration of RRT (shorter). Diabetes was associated with longer total HD duration., Conclusion: This study shows a great international variability in weekly HD duration and some discrepancies between current practices and the EBPG. It also points out the difficulty of obtaining and comparing Kt/V values under current registry practices.

The factors contributing to platelet dysfunction in hemodialysis patients are still not completely known. We explored whether the fibrinolytic system influences platelet function in hemodialysis patients. We measured standard fibrinolytic parameters and markers of fibrinolysis/coagulation activation, and correlated them to platelet aggregation in 15 hemodialysis patients. Fifteen healthy age-matched volunteers served as controls. Hemodialysis patients had significantly decreased levels of plasminogen (0.76 [0.64-0.86] vs. 0.98 [0.87-1.08] rel, P < 0.001), and increased levels of fibrinogen (4.6 [3.9-5.5] vs. 4.0 [3.4-4.6] g/L, P < 0.05), whereas tissue-type plasminogen activator antigen and plasminogen activator inhibitor (PAI)-1 antigen and PAI activity were comparable to controls. Furthermore, elevated levels of markers of fibrinolysis/coagulation were found in hemodialysis patients: D-dimer (280 [170-460] vs. 135 [120-150] ng/mL, P < 0.01), prothrombin fragments 1 + 2 (1.7 [1.4-1.9] vs. 1.1 [1.0-1.2] nmol/L, P < 0.001), and thrombin-antithrombin complexes (5.2 [4.2-17.7] vs. 0 [0-4.2]microg/L, P < 0.01). The aggregation of platelets (induced by adenosine diphosphate) was slightly impaired in patients compared to controls (72 [43-79] vs. 83 [73-88]%, P = 0.08). Analysis showed that platelet aggregation positively correlated with plasminogen levels (r = 0.48, P < 0.01). No correlation with other fibrinolytic parameters or markers of activation was found. In hemodialysis patients platelet (dys)function appears to be associated with both the fibrinolytic and coagulation systems. We found that platelet aggregation significantly correlates with plasma plasminogen levels. This relation, which has not been hitherto described, seems to be causal and clinically important. Further exploration of this may help us to better understand the mechanisms of platelet dysfunction in hemodialysis patients.

It is known that anaemia in haemodialysis patients could contribute to haemostasis impairment. However, the precise relation between the degree of anaemia and the degree of haemostasis impairment is not known, nor the optimal level of hematocrit above which anaemia no longer disturbs haemostasis. Our study addresses these clinically relevant questions by employing in vitro closure time test, a new method in which the process of platelet adhesion and aggregation following vascular injury is simulated in vitro in samples of whole blood. We studied 63 haemodialysis patients, with 30 age-matched, healthy controls. Results show that patients with hematocrit below 0.32 (N=28) had significantly impaired primary haemostasis, in contrast to patients with hematocrit above 0.32 (N=35), as measured by both types of closure time test. A significant negative association was found between hematocrit values and closure time (CEPI cartridges: rho=-0.41, p<0.001; CADP cartridges: rho=-0.47, p<0.001). A multiple logistic regression model for predicting prolonged closure time confirmed this finding. Nonparametric curve fitting enabled estimation of the level of hematocrit at which the values of in vitro closure time in haemodialysis patients do not differ from those in the controls at approximately 0.35. ROC analysis confirmed this to be the optimal threshold for predicting prolonged closure time for both cartridges. By using in vitro closure time test, we confirmed that anaemia correlates with the severity of haemostasis impairment. We estimated the target level of hematocrit above which anaemia no longer affects haemostasis to be about 0.35. These new results (and new assay) appear to have clinical value for treating haemodialysis patients.

Background: The platelet aggregation and skin bleeding time (SBT) tests currently used for assessment of hemostasis impairment in dialysis patients have important disadvantages. The authors explored the utility of a novel in vitro closure time test (PFA-100, platelet function analyzer) in which the process of platelet adhesion and aggregation after vascular injury is simulated in vitro in dialysis patients., Methods: Thirty-four long-term dialysis patients were included in the study with 30 healthy volunteers as the control group. In vitro closure time was compared with results from the platelet aggregation and SBT tests., Results: In vitro closure time identified more patients and fewer controls with hemostasis impairment. In the patient group, 60%, 40%, and 20%, and in the control group, 0%, 10% and 3% of persons were found to have hemostasis impairment as determined by in vitro closure time, platelet aggregation, and SBT, respectively. In addition, values for patients and controls were significantly different for in vitro closure time (P < 0.05) but not for platelet aggregation or SBT. Thus, closure time appears to be more sensitive and specific than the other 2 tests. No correlation was found between the 3 tests, either in patients or in controls. However, a high correlation (r = 0.73; P < 0.0001) was found between the 2 types of in vitro closure time test (collagen/epinephrine [CEPI] and collagen/adenosine diphosphate [CADP]) in patients and controls., Conclusion: These results indicate that in vitro closure time can be a useful test for detecting platelet-related primary hemostasis defects in dialysis patients.

The objective of our study was to present our experience in the treatment of small children with continuous renal replacement therapy (CRRT) and plasma exchange (PE). From March 1986 to April 2000, 21 critically ill children (14 newborns and 7 infants) with acute renal failure (ARF) and multiple organ failure were treated with CRRT and PE. In the newborn group, there were 8 males and 6 females, age 15.7 +/- 11.7 days, with body weights of 3,348 +/- 585 g. In the infant group, there were 4 males and 3 females, age 118 +/- 67 days, with body weights 5,186 +/- 734 g. The indications for the beginning of CRRT and/or PE were ARF with anuria and hyperhydration (17 patients), azotemia and anuria (1 patient), hemolytic uremic syndrome (1 patient), and hyperammonemia (2 patients). In all patients, peritoneal dialysis was considered inappropriate. PE and CRRT monitors were used, double lumen 5 Fr and 7 Fr hemodialysis catheters were the vascular access, low dose heparin and prostacyclin were anticoagulants, and lactate or bicarbonate buffered replacement solutions were used predilutionally. Side events were clotting within the extracorporeal circuit, catheter malfunction, serious hypotension (6 patients), and pulmonary edema (1 patient). Ten of 21 patients (47.6%) recovered renal function and 9 of 21 patients (42.9%) survived. Survivors had fewer failing organs (3.6 +/- 0.5) than nonsurvivors (4.8 +/- 0.9) (p = 0.0008). Pump driven CRRT and PE were feasible, efficient, and safe procedures in newborns and infants. Without CRRT, it is uncertain whether any of our patients would have the chance to survive.

The influence of dialyzer membrane on the morbidity and mortality of patients with acute renal failure remains a matter of debate. The aim of the prospective randomized clinical study was to assess the influence of the flux of a synthetic dialyzer membrane on patients' survival rate, restitution of renal function, and duration of hemodialysis treatment of patients with acute renal failure as a part of multiorgan failure. Seventy-two patients treated in intensive care units of the University Medical Center Ljubljana were randomized according to the dialyzer used throughout the duration of hemodialysis treatment. There were 38 patients in the low-flux group (dialyzer F6, low-flux polysuphone, Fresenius, Bad Homburg, Germany) and 34 patients in the high-flux group (dialyzer Filtral 12, sulphonated high-flux polyacrylonitrile, Hospal, Industrie Meyzieu, France). Both groups were balanced in terms of sex, age, APACHE II score, oliguria before dialysis, cause of acute renal failure, inotropic support, mechanical ventilation, and the number of failing organs. The patients' survival rate was 18.7% in the low-flux group and 20.6% in the high-flux group. Ten patients (26.3%) recovered their renal function in the low-flux group and 8 (23.5%) in the high-flux group. Hemodialysis treatment lasted 11.2 days in the low-flux and 10.7 days in the high-flux group. An analysis of subgroups with a lower mortality rate (subgroup of patients without oliguria and subgroup of patients with less than 4 failed organ systems) did not show significant differences between the low-flux and high-flux groups in terms of survival rate, recovery of renal function, and duration of hemodialysis treatment. In conclusion, no significant differences were found in the results of low-flux versus high-flux synthetic membrane dialyzer treatment in patients with acute renal failure as a part of multiorgan failure in terms of survival rate, recovery of renal function, incidence of oliguria during hemodialysis, and duration of hemodialysis treatment. The number of failing organs seems to be the most important single factor determining the survival of patients with acute renal failure as a part of multiorgan failure.

Background: The clinical significance of vesicoureteric reflux (VUR) in renal transplant recipients remains controversial. Voiding urosonography (VUS), a new modality for detecting VUR, can be used in these patients. The sensitivity of X-ray and radionuclide cystography for detecting VUR may be improved with cyclic procedures. The aim of our study was to evaluate whether cyclic VUS is superior to the single-cycle procedure., Methods: Cyclic VUS was performed in 27 renal transplant recipients. Eight were children or adolescents and the remaining 19 recipients were adults. VUS was performed according to accepted guidelines. After the first micturition, the catheter was left in place and the entire procedure was repeated under the same conditions., Results: Both initial cycle and cyclic VUS detected 17 out of 27 (63%) VURs in the same patients. The sensitivity was not improved by cyclic VUS. However, there were differences between the initial cycle and cyclic VUS (P=0.028) when comparing the number of negative results and the grades of VURs detected. This difference was even more pronounced when analysing only positive results. In the initial cycle, five out of 17 (29%) VURs were grade III, compared with 10 out of 17 (59%) grade III VURs in the same patients using the cyclic procedure (P=0.008)., Conclusions: Cyclic VUS did not improve the detection sensitivity for VUR in our study. However, given that VUR grade may be important for the management of renal transplant recipients, the use of cyclic VUS may provide a useful diagnostic tool for these patients.