Diagnosis and management of pruritus associated with chronic kidney disease in hemodialyzed patients / Diagnostic et prise en charge du prurit associé à la maladie rénale chronique chez les patients hémodialysés

Chronic kidney disease-associated pruritus (CKD-aP) is a disabling symptom which is frequent and often underestimated. Pa-MRC has a negative impact on quality of life, and is frequently accompanied by sleep disorders and depression. The approval of difelikefalin ­ a kappa opioid receptor agonist ­ in this indication requires updated recommendations. As a first step, secondary causes of pruritus without skin lesions must be ruled out, and general measures taken (emollients, psychological support, optimization of dialysis, normalization of serum calcium, phosphate and PTH in the range proposed by the KGIDO guidelines, treatment of iron deficiency). A therapeutic test with a non-sedating oral antihistamine may be proposed. If this test is negative, Pa-MRC must be strongly suspected, and its intensity (WI-NRS scale) and impact on quality of life assessed. In the case of mild Pa-MRC (WI-NRS ≤ 3), only general measures are implemented. If Pa-MRC is moderate to severe (WI-NRS ≥ 4), specific treatment with difelikefaline can be initiated for 6 months in addition to general measures. At 3 months, if the response is complete (WI-NRS score ≤ 1) or partial (decline ≥ 3 points), treatment is continued. At 6 months, if the response is complete, treatment may be discontinued with the patient's agreement; treatment is maintained if the response is partial. At 3 or 6 months, if response is insufficient (decline < 3 points) and/or in the event of intolerance, treatment is discontinued and an alternative treatment (e.g., gabapentinoids, UVB) may be considered after dermatological consultation.

Le prurit associé à la maladie rénale chronique (Pa-MRC) est un symptôme invalidant qui est fréquent et souvent sous-estimé. Le Pa-MRC a des conséquences négatives sur la qualité de vie et s'accompagne fréquemment de troubles du sommeil et de dépression. L'approbation de la difélikéfaline ­ agoniste des récepteurs opioïdes kappa ­ dans cette indication nécessite l'actualisation des recommandations. Les causes secondaires de prurit sans lésions cutanées doivent être exclues et des mesures générales doivent être prises (émollients, aide psychologique, optimisation de la dialyse, équilibre phosphocalcique avec parathormone [PTH] dans la cible KDIGO [Kidney Disease: Improving Global Outcomes], traitement de la carence martiale). Une épreuve thérapeutique avec un antihistaminique oral non sédatif peut être proposée. En cas de test négatif, il faut fortement suspecter un Pa-MRC et évaluer son intensité (échelle WI-NRS [Worst Itch Numeric Rating Scale]) et son impact sur la qualité de vie. En cas de Pa-MRC léger (WI-NRS ≤ 3), seules les mesures générales sont mises en œuvre. Si le Pa-MRC est modéré à sévère (WI-NRS ≥ 4), un traitement spécifique par difélikéfaline peut être instauré pour 6 mois en plus des mesures générales. À 3 mois, si la réponse est complète (score WI-NRS ≤ 1) ou partielle (baisse ≥ 3 points), le traitement est poursuivi. À 6 mois, si la réponse est complète, l'arrêt du traitement peut être envisagé avec l'accord du patient ; il est maintenu en cas de réponse partielle. À 3 ou 6 mois, en cas de réponse insuffisante (baisse < 3 points) et/ou d'intolérance, le traitement est interrompu et un autre traitement (par exemple, gabapentinoïdes, ultraviolet de type B [UVB]) peut être envisagé après avis dermatologique.

[Contribution of hemostatic dressings in the hemostasis of arteriovenous fistula? A quality improvement program in our center]. / Évaluation de nos pratiques professionnelles : apport des pansements hémostatiques dans l'hémostase de la fistule artério-veineuse ?

INTRODUCTION: In haemodialysis patients the length of bleeding times after fistula cannulation is an easy and fairly used method of monitoring vascular access. In the most cases, compression is performed manually by nurses and the use of haemostatic dressing is common. As data in the literature are scares, we have decided to develop a quality improvement program in our hemodialysis center to manage this issue. MATERIAL AND METHODS: After informed consent, 35 hemodialysis outpatients were selected in order to study the bleeding time using haemostatic dressing or not during two weeks in a cross over schema. The dialysis schedule was unchanged and comparative analysis of parameters such as blood flow rate or anticoagulant treatment were done between the groups. RESULTS: Compression times with and without hemostatic dressing were not different (12.6 min and 12.9 min, respectively). Patients with an anticoagulation during the dialysis session greater than 0.35 IU/kg/session had a longer bleeding time (12.75 min vs 11.75 min; P=0.008). CONCLUSION: In our evaluation, the use of haemostatic dressings is not associated with a real shorter bleeding time. Their use generate an additional cost estimated on average at 164 euros/year/patient. Patients and team realized that compression time is important for fistula monitoring and using compresses does not really increase this time.

Idiopathic nephrotic syndrome relapse following COVID-19 vaccination: a series of 25 cases.

Background: Several cases of idiopathic nephrotic syndrome (INS) relapse following the administration of coronavirus disease 2019 (COVID-19) vaccines have recently been reported, raising questions about the potential relationship between the immune response to COVID-19 vaccination and INS pathogenesis. Methods: We performed a retrospective multicentre survey describing the clinical and biological characteristics of patients presenting a relapse of INS after COVID-19 vaccination, with an assessment of outcome under treatment. Results: We identified 25 patients (16 men and 9 women) presenting a relapse within 1 month of a COVID-19 vaccine injection. The glomerular disease was of childhood onset in half of the patients and most patients (21/25) had received at least one immunosuppressive drug in addition to steroids for frequently relapsing or steroid-dependent nephrotic syndrome (NS). All patients were in a stable condition at the time of injection and 11 had no specific treatment. In five patients, the last relapse was reported >5 years before vaccine injection. The Pfizer-BioNTech (BNT162b2) vaccine was used in 80% of the patients. In 18 cases, INS relapse occurred after the first injection, a mean of 17.5 days after vaccination. A second injection was nevertheless administered in 14 of these patients. Five relapses occurred after administration of the second dose and two relapses after the administration of the third dose. All but one of the patients received steroids as first-line treatment, with an additional immunosuppressive agent in nine cases. During follow-up, complete remission was achieved in 21 patients, within 1 month in 17 cases. Only one patient had not achieved at least partial remission after 3 months of follow-up. Conclusions: This case series suggests that, in rare patients, COVID-19 vaccination may trigger INS relapse that is generally easy to control. These findings should encourage physicians to persuade their patients to complete the COVID-19 vaccination schedule.

ANCA-Negative Pauci-immune Necrotizing Glomerulonephritis: A Case Series and a New Clinical Classification.

RATIONALE & OBJECTIVE: Pauci-immune necrotizing glomerulonephritis (PING) is usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a minority (2%-3%) of patients with PING do not have detectable ANCA. We assessed the clinical spectrum and outcome of patients with ANCA-negative PING. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 74 patients with ANCA-negative PING diagnosed in 19 French nephrology centers between August 2006 and December 2018 were included in the series. Patients' medical files were reviewed, and kidney biopsies were centrally reexamined by pathologists who were masked to the diagnosis. FINDINGS: Median age at diagnosis was 69 (IQR, 61-76) years. The clinical and pathological features were remarkable for a high frequency of extrarenal manifestations (54%), nephrotic syndrome (32%), and endocapillary hypercellularity (31%). Three main subtypes of ANCA-negative PING were observed: infection-associated (n=9[12%]), malignancy-associated (n=6[8%]), and primary (n=57[77%]). For patients with primary PING, induction treatment included mainly corticosteroids (n=56[98%]), cyclophosphamide (n=37[65%]), and rituximab (n=5[9%]). Maintenance treatment consisted mainly of corticosteroids (n=42[74%]), azathioprine (n=18[32%]), and mycophenolate mofetil (n=11[19%]). After a median follow-up period of 28 months, 28 (38%) patients had died and 20 (27%) developed kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2). Eleven (21%) patients (9 with primary and 2 with malignancy-associated PING) relapsed. LIMITATIONS: Retrospective study and limited number of patients; electron microscopy was not performed to confirm the absence of glomerular immune deposits. CONCLUSIONS: Within the spectrum of ANCA-negative PING, infection and malignancy-associated forms represent a distinct clinical subset. This new clinical classification may inform the management of ANCA-negative PING, which remains a severe form of vasculitis with high morbidity and mortality rates despite immunosuppressive treatments.

Evidence on clinical relevance of cardiovascular risk evaluation in the general population using cardio-specific biomarkers.

In recent years, the formulation of some immunoassays with high-sensitivity analytical performance allowed the accurate measurement of cardiac troponin I (cTnI) and T (cTnT) levels in reference subjects. Several studies have demonstrated the association between the risk of major cardiovascular events and cardiac troponin concentrations even for biomarker values within the reference intervals. High-sensitivity cTnI and cTnT methods (hs-cTn) enable to monitor myocardial renewal and remodelling, and to promptly identify patients at highest risk ofheart failure. An early and effective treatment of individuals at higher cardiovascular risk may revert the initial myocardial remodelling and slow down heart failure progression. Specific clinical trials should be carried out to demonstrate the efficacy and efficiency of the general population screening by means of cost-benefit analysis, in order to better identify individuals at higher risk for heart failure (HF) progression with hs-cTn methods.

Dialysis Reimbursement: What Impact Do Different Models Have on Clinical Choices?

Allowing patients to live for decades without the function of a vital organ is a medical miracle, but one that is not without cost both in terms of morbidity and quality of life and in economic terms. Renal replacement therapy (RRT) consumes between 2% and 5% of the overall health care expenditure in countries where dialysis is available without restrictions. While transplantation is the preferred treatment in patients without contraindications, old age and comorbidity limit its indications, and low organ availability may result in long waiting times. As a consequence, 30⁻70% of the patients depend on dialysis, which remains the main determinant of the cost of RRT. Costs of dialysis are differently defined, and its reimbursement follows different rules. There are three main ways of establishing dialysis reimbursement. The first involves dividing dialysis into a series of elements and reimbursing each one separately (dialysis itself, medications, drugs, transportation, hospitalisation, etc.). The second, known as the capitation system, consists of merging these elements in a per capita reimbursement, while the third, usually called the bundle system, entails identifying a core of procedures intrinsically linked to treatment (e.g., dialysis sessions, tests, intradialyitc drugs). Each one has advantages and drawbacks, and impacts differently on the organization and delivery of care: payment per session may favour fragmentation and make a global appraisal difficult; a correct capitation system needs a careful correction for comorbidity, and may exacerbate competition between public and private settings, the latter aiming at selecting the least complex cases; a bundle system, in which the main elements linked to the dialysis sessions are considered together, may be a good compromise but risks penalising complex patients, and requires a rapid adaptation to treatment changes. Retarding dialysis is a clinical and economical goal, but the incentives for predialysis care are not established and its development may be unfavourable for the provider. A closer cooperation between policymakers, economists and nephrologists is needed to ensure a high quality of dialysis care.

Where Are You Going, Nephrology? Considerations on Models of Care in an Evolving Discipline.

Nephrology is a complex discipline, including care of kidney disease, dialysis, and transplantation. While in Europe, about 1:10 individuals is affected by chronic kidney disease (CKD), 1:1000 lives thanks to dialysis or transplantation, whose costs are as high as 2% of all the health care budget. Nephrology has important links with surgery, bioethics, cardiovascular and internal medicine, and is, not surprisingly, in a delicate balance between specialization and comprehensiveness, development and consolidation, cost constraints, and competition with internal medicine and other specialties. This paper proposes an interpretation of the different systems of nephrology care summarising the present choices into three not mutually exclusive main models ("scientific", "pragmatic", "holistic", or "comprehensive"), and hypothesizing an "ideal-utopic" prevention-based fourth one. The so-called scientific model is built around kidney transplantation and care of glomerulonephritis and immunologic diseases, which probably pose the most important challenges in our discipline, but do not mirror the most common clinical problems. Conversely, the pragmatic one is built around dialysis (the most expensive and frequent mode of renal replacement therapy) and pre-dialysis treatment, focusing attention on the most common diseases, the holistic, or comprehensive, model comprehends both, and is integrated by several subspecialties, such as interventional nephrology, obstetric nephrology, and the ideal-utopic one is based upon prevention, and early care of common diseases. Each model has strength and weakness, which are commented to enhance discussion on the crucial issue of the philosophy of care behind its practical organization. Increased reflection and research on models of nephrology care is urgently needed if we wish to rise to the challenge of providing earlier and better care for older and more complex kidney patients with acute and chronic kidney diseases, with reduced budgets.

Combining intra-dialytic exercise and nutritional supplementation in malnourished older haemodialysis patients: Towards better quality of life and autonomy.

Protein-energy wasting (PEW), defined as a loss of body protein mass and fuel reserves, is a powerful predictor of adverse outcomes in haemodialysis (HD) patients. Robust arguments suggest that intra-dialytic exercise, combined with oral/parenteral nutrition, enhances the effect of nutritional interventions in HD patients. This pilot randomized controlled trial investigated the feasibility and the effects of a 6 month intra-dialytic cycling program combined to a nutritional support on PEW, physical functioning (gait, balance, muscle strength) and quality of life (QoL) in older HD patients (mean age 69.7 ± 14.2 years).Twenty-one patients fulfilling diagnostic criteria of PEW were randomly assigned to Nutrition-Exercise group (GN-Ex , n = 10) or Nutrition group (GN , n = 11). Both groups received nutritional supplements in order to reach recommended protein and energy intake goals. In addition GN-Ex completed a cycling program. No significant difference between groups was found in the number of patients having reached remission of PEW. Likewise, no change was observed in serum-albumin, -prealbumin, C-reactive protein, body mass index, lean- and fat-tissue index, or quadriceps force. Interestingly, we found positive effects of exercise on physical function and QoL for the GN-Ex , as evidenced by a significant improvement in the 6-min walk test (+22%), the absence of decline in balance (unlike the GN ), and a noteworthy increase in QoL (+53%). Combining intra-dialytic exercise and nutrition in HD patients is feasible, and well accepted, improves physical function and QoL but it appears not to have the potential to reverse PEW.

[Conservative management option in elderly patients]. / Choisir de ne pas dialyser les patients très âgés.

"Conservative management" is as an alternative care pathway offered to patients who elect not to start dialysis often because of a heavy burden of comorbid illness and advanced ages. Our research, characterized by a transdisciplinary medical and social investigation and based on a case by case analysis, intends to understand the reasons and the context in which this choice has to be made. On the first hand, the results show that all the studied cases can be explained by two variables, the latter can be combined: when the patient is suffering from important clinical pathologies; when the patient lives with this renal failure as a trouble linked to the age. On the second hand, two important questions are raised: the first one is about the medical practices and stems from the influence of criteria always present in the decisions to take (the paramedical exams and the clinical information from the interview, the patient's examination and the discussion with his/her close family member). The second one is about the patient's autonomy and can be analyzed regarding to his/her capacity to express his/her choices and share it with his close family. But also, to live in according to his age, that is to say the relation he/she has with his/her edged body and to the limits of his/her existence. The key notion of shared decision-making renewed is to refer in the consultation and the choices to take to the question of the advantages/drawbacks for the patient's life and not only to the question of the connection between the results and the medical risks, in order to exchange view with the patient on his/her future life and not only on the condition of his failed organ.

Isonatric Dialysis Biofeedback in Hemodiafiltration with Online Regeneration of Ultrafiltrate in Hypertensive Hemodialysis Patients: A Randomized Controlled Study.

UNLABELLED: Dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR) could help to improve arterial hypertension. We evaluated the impact of isonatric HFR (HFR-iso) on hypertension control compared to conventional HFR. Forty-seven hemodialysis patients were included and randomized (ratio 2/1) HFR-iso versus HFR during 24 dialysis sessions. In the HFR-iso group (32 patients, 768 dialysis sessions), the predialytic systolic blood pressure (BP) decreased from S1 to S24 of 9 ± 20 mm Hg and increased of 5 ± 24 mm Hg in the HFR group (15 patients, 360 dialysis sessions), variation that differed between the 2 groups (x0394;S1-S24, p = 0.035; interaction group*time, p = 0.012). The diastolic BP (HFR-iso -3 ± 14 mm Hg vs. HFR 5 ± 13 mm Hg; p = 0.088), the DDD of antihypertensive treatment and the dry weight did not vary significantly during the study. Number of sessions complicated by symptomatic hypotension was similar in the 2 groups. HFR-iso improved BP control without increasing dialysis hypotension episodes. SHORT SUMMARY: In this multicenter, open-label, controlled, randomized study, we evaluated the impact of dialysis biofeedback in HFR on arterial hypertension compared to conventional HFR. We observed that HFR-iso improved arterial BP control without increasing dialysis hypotension episodes.

The effect of hemodialysis session on postural strategies in older end-stage renal disease patients.

Patients suffering from end-stage renal disease experience multiple disabilities, such as muscle wasting, weakness, higher postural sway, and fall rates compared with healthy population, which has a negative effect on physical functioning and autonomy. The vital treatment of hemodialysis is recognized to induce important post-hemodialysis fatigue, hypotension, cramps, and headache due to the rapid fluid redistribution, among others. Nevertheless, even the well-known negative effect of aforementioned consequences of hemodialysis treatment, its effect on physical function, especially postural balance, is unclear. Thus, this study hypothesized the adverse effect of hemodialysis treatment on postural sway in 12 end-stage renal disease patients (mean age 63.3 ± 11 years) through the analysis of center-of-pressure (COP) trajectories recorded before and immediately after hemodialysis session. Evident postural alterations were observed at post-hemodialysis balance assessment for COP position-based (Fs < 7.7, P < 0.02) and COP velocity-based variables (Fs > 2.33, P < 0.05), without changes in complexity of COP time series in anteroposterior and mediolateral directions. These results suggest that period after hemodialysis treatment is particularly unsafe, as evidenced by important disability in postural control, and highlight the importance of the medical support and falls-related prevention strategies of these older frail patients after hemodialysis treatment.

Implicit postural control strategies in older hemodialysis patients: an objective hallmark feature for clinical balance assessment.

Elderly patients with end stage renal diseases (ESRD) undergoing hemodialyis (HD) present poorer physical function and higher accident falls than healthy elderly population. Therefore, the aim of this study was to examine the HD-related changes in postural sway in ESRD patients, as an objective hallmark of their functional abilities. We hypothesized that the ESRD symptoms (i.e. uremic syndrome) and the HD therapy affected the postural control, evidenced by higher bounding limits of center-of-pressure (COP) velocity dynamics. Fifty-five participants, including 28 HD patients and 27 age, body mass index and gender-matched healthy participants HS (70.42 ± 13.69 years; 23.46 ± 4.67 kg/m(2); 35.7% women vs. 73.62 ± 6.59 years; 25.09 ± 3.54 kg/m(2); 37% women), were asked to maintain quiet stance on force platform, with eyes open and eyes closed. COP parameters were mean and standard deviation (SD) of position, velocity and average absolute maximal velocity (AAMV) in antero-posterior and medio-lateral directions. The results revealed a significant main effect of group on velocity-based variables, highlighting that mean velocity, SD velocity and AAMV (p<0.01) were higher for HD as compared to HS. These findings identified the bounding limits of COP velocity as an objective hallmark feature of HD-related changes in postural sway. The clinical assessment of this active control of COP velocity dynamics could be useful to examine the effects of targeted intradialytic exercise programs on functional performances and for early detection of increased fall risk in HD patients.

Mortality in a cohort of cement workers in a plant of Central Italy.

PURPOSE: Workers of cement production are exposed to alkaline dust with irritant effects on the respiratory system. Most previous studies have examined workers in cement/asbestos factories, but there is limited information of the effects of exposures to Portland cement alone. The present study examines the effects of cement dust in a cohort of Portland cement workers through the analyses of their mortality records. METHODS: Using the records of a cement plant, we reconstructed the work history of all 748 male employees between 1956 and 2006. SMRs were computed for overall mortality and for specific causes of death for the cohort compared with the reference population. The analysis was also performed by subdividing the cohort in low- and high-exposure groups on the basis of the task of the worker and the length of his exposure. RESULTS: The overall mortality of the cohort (SMR = 0.87) as well as the mortality from all cancers (SMR = 0.64) and from cancers of the respiratory system (SMR = 0.56) was significantly lower compared to the reference population. Workers of the cement plant with higher exposures did not have an increased mortality risk from any cause. The only significantly elevated risk observed among these workers was for cancer of the respiratory system (SMR = 2.86), exclusively in the small subgroup of 39 workers with previous exposure to a cement/asbestos plant. CONCLUSIONS: Portland cement workers had a statistically significant reduced risk of overall mortality and of all cancers mortality probably due to the healthy workers effect. The study confirmed an increased risk of respiratory system cancer only in the subgroup with previous work exposure in a cement/asbestos plant.

Reduction of free immunoglobulin light chains using adsorption properties of hemodiafiltration with endogenous reinfusion.

In this work we investigated the acute effects of hemodiafiltration with endogenous reinfusion (HFR therapy) on the removal of free immunoglobulin light chains (FIgLCs), which may be considered members of the family of uremic toxins. In two groups of patients - group 1 (polyclonal FIgLCs production) and group 2 (monoclonal plasma cell proliferative disorders), we analyzed the pre- and postdialysis levels of kappa- and lambda-chains. In group 1 we observed a significant reduction of FIgLCs (p < 0.01). A similar trend was found in patients of group 2 only for kappa-chains. The FIgLCs removal ratio was significantly higher for kappa- than lambda-chains in the two patient groups. In vitro data showed affinity of macroporous resin to binding FIgLCs. Our results show that the HFR therapy could be effective in removing FIgLCs, particularly kappa-chains in dialysis patients with polyclonal and monoclonal FIgLCs production.

Regional discrepancies in peritoneal dialysis utilization in France: the role of the nephrologist's opinion about peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is underused in France compared with other countries. In addition, there are tremendous regional discrepancies concerning the utilization rate of PD. This study was carried out to evaluate the opinion of French nephrologists regarding the optimal rate of PD utilization and to determine which factors limit PD development in France. METHODS: Of the 22 French regions, 2 regions with a high rate of PD utilization (prevalence >15%) and 3 regions with a low rate of PD utilization (prevalence <10%) were selected. In June 2007, nephrologists from the five regions were surveyed by questionnaire. Responses were compared between 'low-prevalence' and 'high-prevalence' groups. RESULTS: The response rate was 70% and there was no significant difference between the two groups regarding the response rate. In the two groups, a majority of nephrologists were in charge of PD patients (30/34 in 'high-prevalence' group versus 61/80 in 'low-prevalence' group, P = 0.14). Information about PD in the predialysis clinics was provided by nephrologists from high- and low-prevalence regions (32/34 versus 65/80, P = 0.08). Opinions on the optimal rate of PD for prevalent and incident dialysis patients were significantly different between 'high-prevalence' and 'low-prevalence' groups [31 +/- 15% versus 25 +/- 14% (P < 0.03) and 25 +/- 14% versus 19 +/- 9% (P < 0.02)]. There was a significant difference concerning the optimal rate of PD in incident dialysis patients between nephrologists working in public centres (29 +/- 15%), those working in non- profit clinics (27 +/- 12%) and nephrologists working in the private sector (14 +/- 8%). Lack of nurses available for the patient care (48%), low reimbursement of PD (25%), limited training (23%) and hospital care facilities (23%) were the main barriers limiting PD utilization. CONCLUSIONS: In France, like in other countries, there are factors limiting PD development; however, regional discrepancies regarding PD utilization seem to be linked to the nephrologist's opinion.

Molecular imaging of atheroslerotic plaque with nuclear medicine techniques.

Atherosclerosis is a systemic disease of the vessel wall that mainly affects medium- and large-sized arteries, and accounts for 50% of all deaths in western countries. Imaging of atheromatous plaques has traditionally centered on assessing the degree of luminal narrowing. More recently it has become clear that it is of the utmost importance to identify the vulnerable atherosclerotic plaques responsible for the majority of life-threatening syndromes. Molecular imaging using nuclear medicine techniques such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET), has the potential to characterize the activity of atheromas. In the present review we summarize the results of radionuclide imaging in the detection of vulnerable atherosclerotic lesions.

[Crescentic glomerulonephritis]. / Glomérulonéphrites extracapillaires.

Crescentic glomerulonephritis are characterised by a crescent shaped cellular proliferation that may lead to glomerular destruction. Over 50% of at least 10 analysed glomeruli should be affected. The search for immune deposits by immunofluorescence is an important diagnostic step. Patients present with rapidly progressive glomerulonephritis (RPGN): renal failure, proteinuria and haematuria. Extra-renal symptoms may help diagnosis. Diseases are classified in three groups according to immunofluorescence studies. Group I is characterised by linear deposits along the glomerular basement membrane (GBM) with anti-GBM auto-antibodies responsible for Goodpasture's disease. Group II put together various diseases with immune complex deposits. In group III, no significant immune deposits are found. Those "pauci-immune" glomerulonephritis are secondary to anti-neutrophil cytoplasmic antibodies (ANCA) positive systemic vasculitis, mainly Wegener's granulomatosis and microscopic polyangiitis. Primary glomerulonephritis may also be associated with crescent formation. Treatment is urgently required. Diagnosis is suspected in the context of extra-renal symptoms or immunological abnormalities, and confirmed by a kidney biopsy, that also helps to define prognosis. Apart from some group II glomerulonephritis, the induction treatment is often an association of steroids and cyclophosphamide, with plasma exchange in case of Goodpasture's disease. After remission, a maintenance treatment is required for ANCA-positive vasculitis to prevent relapses. The high rate of opportunistic infections and cancer give the rational for searching less aggressive therapeutic options.

In vivo removal of high- and low-molecular-weight compounds in hemodiafiltration with on-line regeneration of ultrafiltrate.

BACKGROUND: Current methods of renal replacement therapy, combining convection and diffusion, are largely unsatisfactory in removing uremic toxins. Adsorption is a third mechanism that has been applied in extracorporeal therapy. This study evaluates the impact of hemodiafiltration with on-line regeneration of ultrafiltrate, a new two-step integrated sorbent system, on in vivo removal of a wide spectrum of solutes with different molecular weights. METHODS: Pre- and post-dialysis concentrations of small, medium-size, and large molecules were determined in ten patients undergoing regular hemodiafiltration treatments with on-line regeneration of the ultrafiltrate. We also analyzed, at different times of the same dialysis session, the inlet and outlet ultrafiltrate; the latter had been regenerated by the sorbent cartridge and was used as reinfusion liquid. The mean dialysis time was 260 +/- 21.2 min with a blood flow of 361 +/- 33.3 ml/min and a reinjection volume of 3.6 +/- 0.2 l/h. RESULTS: Urea, creatinine and phosphate reduction ratio were respectively 69.8 +/- 8.2, 61.9 +/- 5.5, and 40.2 +/- 17.3%. Removal of medium-size markers such as calcitonin, osteocalcin, beta2-microglobulin, cystatin C, myoglobin and prolactin varied between 24 and 60%. The percentage of reduction for retinol binding protein and alpha1-microglobulin was negligible and we were unable to demonstrate any removal of alpha1-acid glycoprotein, pre-albumin, and albumin in the regenerated ultrafiltrate. CONCLUSION: The hemodiafiltration with on-line regeneration of ultrafiltrate is a new hemodialysis system, which allows uremic toxin removal over a wide molecular-weight spectrum.