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scoping review on the Immunological aspects of early pre-eclampsia

The role of angiogenic factors in the onset of clinical manifestations of preeclampsia was demonstrated in 2003 by the implication of sFlt-1, PlGF and VEGF, and in 2006 by the implication of soluble endoglin. Placental ischemia and inflammation observed in preeclampsia alter both the production and progression of angiogenic factors during pregnancy. During the first trimester, the combination of PlGF with clinical, biophysical and biological factors results in a better test than the conventional one. However, the clinical value of this method remains to be confirmed. During the second and third trimesters, the sFlt-1/PlGF ratio may be used, with or without pre-existing renal disease, for short-term prediction, diagnosis, and prognosis, and to evaluate the effectiveness of preeclampsia treatment. While a sFlt-1/PlGF ratio 665 and>205, respectively, is a good short-term predictor of adverse outcomes of early and late-onset preeclampsia. These values could be incorporated into future guidelines for better clinical management of preeclampsia.

Background Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area. Methods We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area. Results In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at Conclusions This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia.

Introduction Les patients dialyses presentent un risque important de forme severe de COVID-19 avec une mortalite elevee a la phase initiale. Cependant, les consequences a long terme de cette pathologie dans cette population sont peu decrites. Nous rapportons ici le suivi a long terme des patients en hemodialyse, touches par le COVID-19. Description Il s’agit d’une etude retrospective sur patients dialyses affectes par le COVID-19 dans 19 centres de la region parisienne. Methodes L’analyse concerne la description de la presentation clinique et du suivi a long terme de ces patients. Resultats Dans cette cohorte de 248 patients avec un taux de mortalite initial de 18 %, l’âge, les comorbidites, la dyspnee et un traitement immunosuppresseur anterieur etaient associes au deces dans les 30 premiers jours. Parmi les 203 patients survivants apres la phase aigue, le suivi a long terme (mediane 180 jours) etait disponible pour 189 (93 %) patients. Des complications majeurs (cardiovasculaires, infections severes ou tout autre evenement menant a une hospitalisation) sont survenues chez 30 (16 %) patients au cours du suivi, dont 12 deces (6 %) apres une mediane de 78 jours a compter de l’apparition des symptomes. Un âge plus avance, un taux d’albumine plus faible au moment du diagnostic et des comorbidites cardiovasculaires presentaient des tendances d’association avec le deces a long terme. Dans l’ensemble, les evenements cardiovasculaires, les infections et les hemorragies gastro-intestinales ont ete les principales complications. Une cachexie post-COVID-19 a ete observee chez 25/189 (13 %) patients. Une albuminemie initiale plus faible etait significativement associee a ce syndrome. Aucune reinfection par le SARS-CoV-2 n’a ete observee sur la periode de 6 mois. Conclusion Ce travail montre les consequences a long terme du COVID-19 chez les patients dialyses, mettant en evidence la severite initiale et a long terme de la maladie, associe notamment a une cachexie chez 13 % des patients.

The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract

Introduction La pandémie de COVID-19 a été à l’origine d’une crise sanitaire sans précédent. Nous décrivons la présentation clinique, l’évolution et les facteurs pronostiques au sein d’une vaste cohorte de patients hémodialysés. Description/Méthodes Il s’agit d’une étude rétrospective de l’ensemble des patients COVID-19 diagnostiqués par PCR ou imagerie compatible dans dix-neuf centres de dialyse en Île-de-France entre le 5 février et le 1er mai 2020. Nous rapportons l’évolution des patients à un mois. Les facteurs de risque de mortalité à la fin du suivi ont été déterminés par une régression logistique multivariée et l’effet des traitements a été analysé par score de propension. Résultats Une maladie COVID-19 a été diagnostiquée chez 248 patients (hommes 66 %, âge 67 ± 15 ans, ancienneté en dialyse de 5 ± 5 ans, suivi moyen de 39 ± 20 jours). La présentation clinique incluait fièvre (n = 152 ; 61 %), toux (n = 121 ; 49 %) et asthénie (n = 101 ; 41 %). Une diarrhée aiguë était présente dans 12 % des cas (n = 29). Cent quarante-deux patients (57 %) ont été hospitalisés et 46 sont décédés (mortalité globale 18 %, mortalité des hospitalisés 30 %). En analyse multivariée, un traitement immunosuppresseur (OR = 7,54 [2,39–24,96] ; p

The role of angiogenic factors in the onset of clinical manifestations of preeclampsia was demonstrated in 2003 by the implication of sFlt-1, PlGF and VEGF, and in 2006 by the implication of soluble endoglin. Placental ischemia and inflammation observed in preeclampsia alter both the production and progression of angiogenic factors during pregnancy. During the first trimester, the combination of PlGF with clinical, biophysical and biological factors results in a better test than the conventional one. However, the clinical value of this method remains to be confirmed. During the second and third trimesters, the sFlt-1/PlGF ratio may be used, with or without pre-existing renal disease, for short-term prediction, diagnosis, and prognosis, and to evaluate the effectiveness of preeclampsia treatment. While a sFlt-1/PlGF ratio38 and≤33, respectively, rules out the short-term onset and diagnosis of preeclampsia, a sFlt-1/PlGF ratio≥85 between 20 and 34 weeks of pregnancy and≥110 beyond 34 weeks of pregnancy confirms a diagnosis of preeclampsia. Angiogenic and non-angiogenic preeclampsia are identified by a sFlt-1PlGF≥85 and85, respectively, with the risk of maternal and fetal complications at two weeks differing between the two. Similarly, a sFlt-1/PlGF ratio665 and205, respectively, is a good short-term predictor of adverse outcomes of early and late-onset preeclampsia. These values could be incorporated into future guidelines for better clinical management of preeclampsia.

Purpose Our aim was to evaluate the safety and effectiveness of the IRIS® bandage (Nephrokit®) on post-puncture bleeding compared to conventional manual compression. Methods Sixty-four patients, hemodialyzed with an arteriovenous fistula, were enrolled in a 3-week prospective study. Conventional manual compression was used during the first week, the IRIS® bandage during the second week and conventional manual compression again during the third week. The outcomes analyzed were the persistence or absence of bleeding 3 minutes post-puncture with IRIS® device compared to conventional manual compression. The safety of the IRIS® bandage was also evaluated. Results Rates of persistent bleeding 3 minutes post-puncture at arterial sites were 53±6% and 56±5%, respectively, during the first and third weeks (conventional compression) versus 18±5% during the second week (IRIS® bandage). Similarly, rates of persistent bleeding 3 minutes post-puncture at venous sites were 45±6% and 45±6%, respectively, with conventional compression versus 23±5% with the IRIS® bandage. The difference between the IRIS® device and conventional compression therefore proved highly statistically significant (pConclusions Post-puncture bleeding time at arteriovenous fistula sites is significantly shortened by the IRIS® bandage in comparison with conventional manual compression.

The purpose of the study is to assess the impact of cinacalcet on calcium and bone remodeling, in post-renal transplanted patients with persistent hypercalcaemia secondary to hyperparathyroidism. Thirteen renal-transplanted adult recipients with a glomerular filtration rate over 30 ml/min/1.73 m(2), a total serum calcium>2.60 mmol/l with ionized calcium>1.31 mmol/l and a parathyroid hormone serum level over 70 pg/ml, were treated with cinacalcet for 4 months followed by a 15-day wash out. The results show that cinacalcet lowers significantly total and ionized calcium respectively from 2,73 (2,67-2,86) to 2,31 (2,26-2,37) mmol/l (P

Points essentiels Le debit de filtration glomerulaire (DFG) est la variable quantitative definissant le mieux la fonction renale. La creatinine plasmatique est le parametre le plus simple d’estimation du DFG. La standardisation du dosage de la creatininemie est en cours et garantit une comparaison plus fiable des resultats. Il est l’outil de reference de diagnostic et de suivi de l’insuffisance renale aigue. Le diagnostic et le suivi de la maladie renale chronique necessite en revanche une evaluation du DFG a partir des formules d’estimation du DFG derivees de la creatininemie. Les performances de la formule issue de l’etude Modified diet in renal disease (MDRD) sont superieures a celle de la formule de Cockcroft, dans la quasi-totalite des situations cliniques et des patients. Il n’y a donc plus d’indication a utiliser la formule de Cockcroft qui doit desormais etre abandonnee au profit de la formule MDRD. Une mesure directe du DFG par traceur exogene doit etre proposee quand la precision de la valeur obtenue par estimation est inferieure a celle necessaire pour prendre une decision medicale. Cela necessite donc dans chaque situation et pour un patient donne de definir parallelement la precision souhaitee et la precision que l’on peut attendre des formules.

Preeclampsia still represents the leading cause of feto-maternal morbi-mortality in developed countries. The reason for the persistence of such gravity results to a large extent from the lack of clear knowledge concerning the pathophysiology of this disease and consequently the lack of adequate therapy apart from placental extraction. Preeclampsia is the clinical result of a generalized maternal systemic endothelial dysfunction secondary to an abnormal placental development. The close mechanisms of the abnormal placental development remain elusive. Currently, only epidemiologic risk factors and some immuno-genetic dysfunctions have been identified to favour abnormal placentation and preeclampsia. On the other hand, the identification of two circulating anti-angiogenic proteins, the soluble-fms-like tyrosine kinase-1 and the soluble endoglin, produced in excess by the placenta during the preeclampsia, allow us now to connect clearly abnormal placentation to an endothelial dysfunction. The excessive production of these two anti-angiogenic proteins induces an endothelial dysfunction by inhibiting circulating proangiogenic factors such as the placental growth factor, the vascular endothelial growth factor but also the transforming growth factor-beta. So far, numerous placental factors have been proposed, however none has been able to induce a real typical phenotype of preeclampsia. This discovery has two potential medical impacts. Firstly, the potential possibility, in the future, to measure these surrogate markers in the blood or urine to predict the onset of preeclampsia before its clinical manifestations. Secondly the theoretical possibility to reverse the angiogenic imbalance state of preeclamspsia and consequently to correct the maternal syndrome transiently by adding exogenous proangiogenic factor.

International audience; Dialysis patients exhibit an inverse, L- or U-shaped association between blood pressure and mortality risk, in contrast to the linear association in the general population. We prospectively studied 9333 hemodialysis patients in France, aiming to analyze associations between predialysis systolic, diastolic, and pulse pressure with all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular endpoints for a median follow-up of 548 days. Blood pressure components were tested against outcomes in time-varying covariate linear and fractional polynomial Cox models. Changes throughout follow-up were analyzed with a joint model including both the time-varying covariate of sequential blood pressure and its slope over time. A U-shaped association of systolic blood pressure was found with all-cause mortality and of both systolic and diastolic blood pressure with cardiovascular mortality. There was an L-shaped association of diastolic blood pressure with all-cause mortality. The lowest hazard ratio of all-cause mortality was observed for a systolic blood pressure of 165 mm Hg, and of cardiovascular mortality for systolic/diastolic pressures of 157/90 mm Hg, substantially higher than currently recommended values for the general population. The 95% lower confidence interval was approximately 135/70 mm Hg. We found no significant correlation for either systolic, diastolic, or pulse pressure with myocardial infarction or nontraumatic amputations, but there were significant positive associations between systolic and pulse pressure with stroke (per 10-mm Hg increase: hazard ratios 1.15, 95% confidence interval 1.07 and 1.23; and 1.20, 1.11 and 1.31, respectively). Thus, whereas high pre-dialysis blood pressure is associated with stroke risk, low pre-dialysis blood pressure may be both harmful and a proxy for comorbid conditions leading to premature death.

6. Mallek R, Mostbeck GH, Kain R, Sunder-Plassmann G,Helbich T, Tscholakoff D. Polyetiology of renal allograftdysfunction. Does calculation of the resistive index still makesense? Acta Radiol 1992; 33: 434–4397. Scholbach T, Girelli E, Scholbach J. Dynamic tissue perfusionmeasurement: a novel tool in follow-up of renal transplants.Transplantation 2005; 79: 1711–17168. Nankivell BJ, Chapman JR, Gruenewald SM. Detection ofchronic allograft nephropathy by quantitative doppler imaging.Transplantation 2002; 74: 90–969. Jakobsen JA, Oyen R, Thomsen HS, Morcos SK. Safety ofultrasound contrast agents. Eur Radiol 2005; 15: 941–94510. Albrecht T, Blomley M, Bolondi L et al. Guidelines for the useof contrast agents in ultrasound. Ultraschall Med 2004; 25:249–25611. Korosoglou G, Hansen A, Hoffend J et al. Comparison of real-time myocardial contrast echocardiography for the assessmentof myocardial viability with fluorodeoxyglucose-18 positronemission tomography and dobutamine stress echocardiography.Am J Cardiol 2004; 94: 570–57612. Lindner JR, Villanueva FS, Dent JM, Wei K, Sklenar J, Kaul S.Assessment of resting perfusion with myocardial contrastechocardiography: theoretical and practical considerations.Am Heart J 2000; 139(2 Pt 1): 231–240Received for publication: 9.5.06Accepted in revised form: 28.6.06Nephrol Dial Transplant (2006) 21: 2696–2702doi:10.1093/ndt/gfl448Advance Access publication 5 August 2006

Background One million people worldwide benefit from chronic dialysis, with an increased rate in Western countries of 5% yearly. Owing to increased incidence of cancer in dialyzed patients, the management of these patients is challenging for oncologists/nephrologists. Patients and methods The CANcer and DialYsis (CANDY) retrospective multicenter study included patients under chronic dialysis who subsequently had a cancer (T0). Patients were followed up for 2 years after T0. Prescriptions of anticancer drugs were studied with regard to their renal dosage adjustment/dialysability. Results A total of 178 patients from 12 institutions were included. The mean time between initiation of dialysis and T0 was 30.8 months. Fifty patients had received anticancer drug treatment. Among them, 72% and 82% received at least one drug needing dosage and one drug to be administered after dialysis sessions, respectively. Chemotherapy was omitted or prematurely stopped in many cases where systemic treatment was indicated or was often not adequately prescribed. Conclusions Survival in dialysis patients with incident cancer was poor. It is crucial to consider anticancer drug treatment in these patients as for non-dialysis patients and to use current available specific drug management recommendations in order to (i) adjust the dose and (ii) avoid premature elimination of the drug during dialysis sessions.

Background The increased incidence of malignancies in patients with chronic renal failure has been discussed since the mid-70s. On the other hand, the high frequency of chronic renal insufficiency among cancer patients has been recently assessed in the Insuffisance Renale et Medicaments Anticancereux Study which demonstrated a prevalence as high as 50%–60% of the patients for all stages of kidney disease. Furthermore, the incidence of end-stage renal disease is growing worldwide and so is the number of patients on chronic dialysis, hemodialysis (HD) for the large majority of them. As a result, the question of cytotoxic drug handling in those patients in terms of dosage adjustment and time of administration regarding the dialysis sessions needs to be addressed to optimize cytotoxic drug therapy in those patients. Methods We reviewed the international literature on the pharmacokinetics, efficacy, tolerance and dosage adjustment of cytotoxic drugs used to treat solid tumor patients and when available, specific literature on HD cancer patients. Results From these data, dosing recommendations are given for the most prescribed cytotoxic drugs in clinical practice. Conclusions Dosage adjustments are often necessary in HD cancer patients. These adaptations have to be carefully carried out to optimize drug exposure, ensure efficacy and reduce the risk of side-effects.

The purpose of the study is to assess the impact of cinacalcet on calcium and bone remodeling, in post-renal transplanted patients with persistent hypercalcaemia secondary to hyperparathyroidism. Thirteen renal-transplanted adult recipients with a glomerular filtration rate over 30 ml/min/1.73 m(2), a total serum calcium2.60 mmol/l with ionized calcium1.31 mmol/l and a parathyroid hormone serum level over 70 pg/ml, were treated with cinacalcet for 4 months followed by a 15-day wash out. The results show that cinacalcet lowers significantly total and ionized calcium respectively from 2,73 (2,67-2,86) to 2,31 (2,26-2,37) mmol/l (P0.05) and from 1,39 (1,37-1,47) to 1,21 (1,15-1,22) mmol/l (P0.05) with no alteration of the 24-hour urine calcium/creatinine ratio and no significant expected PTH serum level suppression (153 [115-214,9] and 166 [122-174] pg/ml). On the other hand, fasting urine calcium was significantly decreased from 0,61 (0,27-1,02) to 0,22 (0,15-0,37) (P0.05) and bone-specific alkaline phosphatases increased from 20,5 (13-46,6) to 33,8 (12-58,9) ng/ml, upon cinacalcet treatment. After its discontinuation, all these effects were reversible. In conclusion, cinacalcet normalizes total and ionized calcium in renal-transplanted recipients with hypercalcemia secondary to hyperparathyroidism through a mechanism that could be independent of PTH serum level suppression. The increase in bone-specific alkaline phosphatases, biochemical markers of bone accretion and the significant decrease in fasting urine calcium suggest the possibility of a beneficial impact of cinacalcet on bone remodeling.

The glomerular filtration rate (GFR) is the best indicator of renal function. Measurement of the plasma creatinine level is the simplest laboratory test for estimating GFR. The plasma creatinine assay is currently being standardized, which will improve its reproducibility. It remains the best indicator for the diagnosis and follow-up of acute renal failure. Conversely, diagnosis and follow-up of chronic kidney disease are based on the GFR value, which is routinely estimated from formulas derived from plasma creatinine levels. The formula developed from the MDRD study performs better than the Cockcroft formula for nearly all patients and clinical situations and should replace it. GFR should be measured directly, by the urinary clearance of exogenous markers, in any situation in which the precision of the formula used is insufficient for medical decision-making. This requires defining for any given patient and situation both the desired precision and that expected from the formulas.

Understanding of the maternal syndrome of pre-eclampsia has greatly improved over the past 5 years. Specifically, the notion has emerged that the placenta is a source of antiangiogenic factors, such as soluble fms-like tyrosine kinase 1, that can progressively impair the mother's vascular and glomerular function throughout pregnancy. This impairment can be harmless during normal pregnancy, but in cases of defective placentation, concentrations of antiangiogenic factors increase to a level that compromises vital vascular functions in the short term and jeopardizes long-term maternal and fetal outcomes. In both pre-eclamptic and healthy pregnancies, the transient imbalance between angiogenic and antiangiogenic factors elicited by pregnancy acts as a 'stress test' for the endothelium, particularly in the glomerular capillary bed. Women who do not pass this test (i.e. those who develop pre-eclampsia or gestational hypertension) should be screened for glomerular disease, and their cardiovascular risk should be carefully monitored throughout life.

Preeclampsia still represents the leading cause of feto-maternal morbi-mortality in developed countries. The reason for the persistence of such gravity results to a large extent from the lack of clear knowledge concerning the pathophysiology of this disease and consequently the lack of adequate therapy apart from placental extraction. Preeclampsia is the clinical result of a generalized maternal systemic endothelial dysfunction secondary to an abnormal placental development. The close mechanisms of the abnormal placental development remain elusive. Currently, only epidemiologic risk factors and some immuno-genetic dysfunctions have been identified to favour abnormal placentation and preeclampsia. On the other hand, the identification of two circulating anti-angiogenic proteins, the soluble-fms-like tyrosine kinase-1 and the soluble endoglin, produced in excess by the placenta during the preeclampsia, allow us now to connect clearly abnormal placentation to an endothelial dysfunction. The excessive production of these two anti-angiogenic proteins induces an endothelial dysfunction by inhibiting circulating proangiogenic factors such as the placental growth factor, the vascular endothelial growth factor but also the transforming growth factor-beta. So far, numerous placental factors have been proposed, however none has been able to induce a real typical phenotype of preeclampsia. This discovery has two potential medical impacts. Firstly, the potential possibility, in the future, to measure these surrogate markers in the blood or urine to predict the onset of preeclampsia before its clinical manifestations. Secondly the theoretical possibility to reverse the angiogenic imbalance state of preeclamspsia and consequently to correct the maternal syndrome transiently by adding exogenous proangiogenic factor.

Sir, The diagnosis of superimposed pre-eclampsia can be difficult when there is already pre-existing hypertension and a pre-existing glomerular kidney disease with significant proteinuria [1]. Case. We report the case of a 25-year-old woman, for whom a non-proliferative IgA nephropathy with a serum creatinine at 103 μmol/L, a nephrotic range proteinuria, no hypertension and no hyperuricaemia was discovered at the beginning of her first pregnancy. The evolution was characterized by the onset of hyperuricaemia at 19 weeks of gestation followed by an excess weight gain with oedema, hypertension and deterioration of the renal function with a serum creatinine value increasing to 140 µmol/L. To help us to distinguish superimposed pre-eclampsia from isolated worsening renal disease associated with hypertension and to better assess the evolution of the disease, circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) were measured serially by Quantikine immunoassays (R&D Systems) at 34 weeks plus 2 days, 34 weeks plus 6 days and 35 weeks. The high value of the first sample at 4193 pg/mL and the trend towards an increase with the second sample at 4446 pg/mL (even though the last value was at 3714 pg/mL) associated with concomitant threatening functional clinical manifestations of hypertension led us to perform delivery at 35 weeks by Caesarean section with the birth of a healthy baby weighing 2.5 kg. The post-partum period was characterized by a fall in circulating levels of sFlt-1, immediately after delivery, with values at 888, 667 and 123 pg/mL. Conversely, serum creatinine and uric acid remained unchanged, 30 days after delivery at 141 and 428 µmol/L, respectively. Comment. This case illustrates the difficulty in differentiating a superimposed pre-eclampsia from an isolated deterioration of a pre-existing renal disease during pregnancy. The increase in serum uric acid can be explained by a superimposed pre-eclampsia or by the impact of pregnancy in worsening pre-existing nephropathy, similar to the onset of hypertension. The high levels of circulating sFlt-1 found before delivery were in the same range as the mean serum level of 4382 pg/mL found by Levine et al. in the group of women with pre-eclampsia at a similar gestational age (as compared with 1643 pg/mL, in the control group of women with normal pregnancy) and strongly suggests an excess placental production related with superimposed pre-eclampsia [2,3]. Because of the possibility of false-positive values, histological placenta data would have been better to confirm the diagnosis [4]. Unfortunately, the latter was not preserved. However, these high levels of circulating sFlt-1 cannot account for the concomitant renal dysfunction. Indeed, renal failure is usually associated with a significant, but very moderate, increase in circulating sFlt-1 [5]. Moreover, in the present case, circulating levels of sFlt-1 fall rapidly after delivery despite the persistence of renal failure and hyperuricaemia. Variations of sFlt-1-circulating levels have been mainly studied among population groups of gestational women. The present case demonstrates that the results of several sFlt-1-circulating assays performed on the same patient can also assist better birth management in difficult situations. Conflict of interest statement. None declared.

The approval of febuxostat, a non-purine analogue inhibitor of xanthine oxidase, by the European Medicines Agency and US Food and Drug Administration, heralds a new era in the treatment of gout [1]. The most commonly reported adverse drug reactions were liver function abnormalities, diarrhoea, headache, nausea, and dizziness and/or altered taste. Only one case of cutaneous leukocytoclastic vasculitis has been reported with febuxostat [2]. In this report, we provide the first case of anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immune glomerulonephritis (PIGN) during febuxostat treatment.

e12005 Background: Anemia in cancer patients (pts) on dialysis may result from both chemotherapy-induced anemia and renal anemia. Survival on dialysis has improved during the past years and dialysi...

e13562 Background: 1 million people worldwide benefit from chronic dialysis with an increased rate in Western countries of 5% yearly. Significant improvements of chronic renal replacement therapy have led to prolonged survival. Due to mean age and heightened incidence of many cancers in dialyzed pts, the management of pts who suffer from both cancer and end-stage renal disease is challenging for oncologists and nephrologists. Specific questions were addressed to assess the efficacy/toxicity ratio, namely life expectancy, toxicity/dialysis clearance/optimal timing of chemotherapy. Methods: Retrospective multicentre review of dialysis centre charts for pts under dialysis who subsequently had a cancer. Results: Among 178 patients (66% male, median age 69) from 12 institutions, 35% were GU, 23% GI, lung 14%, hematologic 10%, head and neck 8%, or various others 10%. Most common histologies were adenocarcinomas 47%, of hematologic origin 17% and urothelial carcinomas 12%. Physical status was 0 48%, 1 18%, 2 30%...

Sir, In our experience, 10% of renal allograft recipients develop sustained hyperparathyroidism and hypercalcaemia during the first year following renal transplantation. Persistent hypercalcaemia usually requires parathyroidectomy, which represents the only definitive treatment currently available. Cinacalcet, a calcimimetic drug, represents from now on an alternative therapy to avoid surgery. Recent studies have reported successful control of hypercalcaemia by this drug in this situation [1–3]. We report the case of a 25-year-old man, on peritoneal dialysis since 2003, who received a renal graft in November 2004 and developed after transplantation sustained hypercalcaemia at 3.35mmol/l (normal range, 2.2–2.6) with a high level of ionized calcium at 1.88mmol/l (normal range, 1.14–1.31) and an inappropriate plasmatic secretion of parathyroid hormone (PTH) at 607 pg/ml (normal range, 10–55). The glomerular filtration rate, assessed by creatinine clearance, was 73ml/min/1.73m. Treatment with cinacalcet was initiated, at 4 months post transplantation, in an attempt to avoid parathyroidectomy. Despite 2 months of treatment with increasing doses of oral cinacalcet (up to 120mg once daily), hypercalcaemia at 3.09mmol/l (ionized calcium, 1.61mmol/l) persisted with seric PTH concentration of 314 pg/ml. Interestingly hypercalciuria, which was not present in the early post transplantation period (urinary calcium, 4.6mmol/24 h), appeared upon cinacalcet treatment with value at 16mmol/24 h. Because of the persistent threatening high level of serum calcium (value at 3.36mmol/l) associated with hypercalciuria, a sub total parathyroidectomy was finally performed. The reasons for the resistance to cinacalcet need to be elucidated. Non observance of treatment can be excluded. A possible explanation could be a defect of sensitivity to extra cellular calcium or to the calcimimetic drug by the parathyroid cells. This observation also suggests, though not previously observed in studies, that cinacalcet could be responsible for a urinary calcium excretion increase by a direct effect on the calcium sensor located in the thick ascending limb of Henle [4,5]. Indeed, activating mutation of calcium sensor receptor could provide mechanism for the developments of Bartter’s syndrome, which is characterized by an increase in urinary calcium [6,7]. In conclusion, this case demonstrates a therapeutic failure of cinacalcet in a renal transplant patient presenting hypercalcaemia with inappropriate secretion of PTH. Furthermore increase of urinary calcium during cinacalcet treatment must be emphasized and needs to be clarified because it has not been observed in renal transplant recipients who respond successfully to cinacalcet [2,4]. Therefore, further studies, with larger numbers of patients, are required to better define which kind of patient could have resistance and to unravel the real effect of cinacalcet on urinary calcium tubular excretion.