Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) program: the teachers' perspective.

The N-PATH (Nephrology Partnership for Advancing Technology in Healthcare) program concluded with the 60th European Renal Association 2023 Congress in Milan, Italy. This collaborative initiative aimed to provide advanced training in interventional nephrology to young European nephrologists. Funded by Erasmus+ Knowledge Alliance, N-PATH addressed the global burden of chronic kidney disease (CKD) and the shortage of nephrologists. CKD affects >850 million people worldwide, yet nephrology struggles to attract medical talent, leading to unfilled positions in residency programs. To address this, N-PATH focused on enhancing nephrology education through four specialized modules: renal expert in renal pathology (ReMAP), renal expert in vascular access (ReVAC), renal expert in medical ultrasound (ReMUS) and renal expert in peritoneal dialysis (RePED). ReMAP emphasized the importance of kidney biopsy in nephrology diagnosis and treatment, providing theoretical knowledge and hands-on training. ReVAC centred on vascular access in haemodialysis, teaching trainees about different access types, placement techniques and managing complications. ReMUS recognized the significance of ultrasound in nephrology, promoting interdisciplinary collaboration and preparing nephrologists for comprehensive patient care. RePED addressed chronic peritoneal dialysis, offering comprehensive training in patient selection, prescription, monitoring, complications and surgical techniques for catheter insertion. Overall, N-PATH's strategy involved collaborative networks, hands-on training, mentorship, an interdisciplinary approach and the integration of emerging technologies. By bridging the gap between theoretical knowledge and practical skills, N-PATH aimed to revitalize interest in nephrology and prepare proficient nephrologists to tackle the challenges of kidney diseases. In conclusion, the N-PATH program aimed to address the shortage of nephrologists and improve the quality of nephrology care in Europe. By providing specialized training, fostering collaboration and promoting patient-centred care, N-PATH aimed to inspire future nephrology professionals to meet the growing healthcare demands related to kidney diseases and elevate the specialty's status within the medical community.

Temporal trends in the quality of deceased donor kidneys and kidney transplant outcomes in Europe: an analysis by the ERA-EDTA Registry.

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.

Author Correction: Kinesiologist-guided functional exercise in addition to intradialytic cycling program in end-stage kidney disease patients: a randomised controlled trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Association of Uremic Toxins and Inflammatory Markers with Physical Performance in Dialysis Patients.

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), ß2-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.

Citrate Anticoagulation in Tandem Membrane Plasma-Exchange or Immunoadsorption and Hemodialysis in Patients With Immunological Diseases and Dialysis-Dependence.

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.

Comparison of the Pharmacological Effects of Paricalcitol Versus Calcitriol on Secondary Hyperparathyroidism in the Dialysis Population.

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.

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

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.

From registry data collection to international comparisons: examples of haemodialysis duration and frequency.

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.

Platelet (dys)function and plasma plasminogen levels in hemodialysis patients.

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.

The study of anaemia-related haemostasis impairment in haemodialysis patients by in vitro closure time test.

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.

Utility of in vitro closure time test for evaluating platelet-related primary hemostasis in dialysis 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.

Continuous renal replacement therapy and plasma exchange in newborns and infants.

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.