Protocol of comparison of the effects of single plasma exchange and double filtration plasmapheresis on peripheral lymphocyte phenotypes in patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: a monocentric prospective study with single-case experimental design.

BACKGROUND: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare disorder affecting young adults, causes gradual weakness of the limbs, areflexia and impaired sensory function. New CIDP phenotypes without pathogenic antibodies but with modified cell profiles have been described. Treatments include corticotherapy, intravenous immunoglobulins, and plasmapheresis but the latter's action mechanisms remain unclear. Plasmapheresis supposedly removes toxic agents like antibodies from plasma but it is uncertain whether it has an immune-modulating effect. Also, the refining mechanisms of the two main plasmapheresis techniques-single plasma exchange and double filtration plasmapheresis (DFPP) - are different and unclear. This study aims to compare the evolution of peripheral lymphocyte profiles in patients with CIDP according to their treatment (single centrifugation plasmapheresis or DFPP) to better grasp the action mechanisms of both techniques. METHOD: In this proof-of-concept, monocentric, prospective, Single-Case Experimental Design study, 5 patients are evaluated by alternating their treatment type (single plasma exchange or DFPP) for 6 courses of treatment after randomization to their first treatment type. Each course of treatment lasts 2-4 weeks. For single plasma exchange, 60 ml/kg plasma will be removed from the patient and replaced with albumin solutes, with a centrifugation method to avoid the immunological reaction caused by the membrane used with the filtration method. For DFPP, 60 ml/kg plasma will be removed from the patient with a plasma separator membrane, then processed via a fractionator membrane to remove molecules of a greater size than albumin before returning it to the patient. This technique requires no substitution solutes, only 20 g of albumin to replace what would normally be lost during a session. The primary outcome is the difference between the two plasmapheresis techniques in the variation of the TH1/TH17 ratio over the period D0H0-D0H3 and D0H0-D7. Secondary outcomes include the variation in lymphocyte subpopulations at each session and between therapeutic plasmapheresis techniques, the clinical evolution, tolerance and cost of treatments. DISCUSSION: Understanding the action mechanisms of single plasma exchange and DFPP will help us to offer the right treatment to each patient with CIPD according to efficacy, tolerance and cost. TRIAL REGISTRATION: ClinicalTrials.gov under the no. NCT04742374 and date of registration 10 December 2020.

Tandem hemodialysis and DFPP: Procedure, safety and cost-effectiveness in patients requiring chronic hemodialysis and lipid apheresis.

INTRODUCTION: Certain patients require simultaneous lipoprotein apheresis (LA) and intermittent hemodialysis (HD). Instead of undergoing 2 consecutive treatment sessions, a double filtration plasmapheresis (DFPP) and HD tandem procedure could be offered to reduce treatment times and costs. Our study evaluated the performance, safety and cost of this tandem procedure. MATERIAL AND METHODS: Three patients underwent 168 HD and DFPP tandem sessions in a tertiary center from August 2018 to November 2020, using a Fresenius 5008 generator for HD and an InfomedHF440 for DFPP. The system's efficacy was assessed by lipid subtraction performance for DFPP. Efficacy of 2 blood line connection configurations (parallel or sequential) was compared in terms of Kt/V and matched against an HD control session for each patient. Clinical and biological safety and the differential cost between tandem and consecutive procedures were evaluated. RESULTS: Throughout the tandem sessions, DFPP lasted 85 to 120 minutes, overlapping the 240-minute HD. Blood flow for HD and Kt/V were significantly lower during the tandem procedure with a parallel configuration compared to sequential or control paired HD. DFPP efficacy was comparable between all groups: over 60% reduction in cholesterol and over 50% for triglycerides. Symptomatic hypotension depended on the patients, not the procedure. The tandem procedure revealed an acceptable benefit-cost ratio. CONCLUSION: HD-DFPP tandem with a sequential blood line connecting system (derivation installed on the HD venous line) is effective and well-tolerated with a good cost-benefit ratio. Tandem reduces hospitalization and treatment session times and can be offered to patients requiring simultaneous HD and DFPP.

Not only disease activity but also chronic hypertension and overweight are determinants of pregnancy outcomes in patients with systemic lupus erythematosus.

INTRODUCTION: Pregnancies in women with lupus nephritis are at high-risk of complications, while scarcity of scientific knowledge on prognostic factors impedes a fair medical counseling. We aimed to identify determinants associated with maternal and fetal complications. MATERIALS: We retrospectively reviewed medical charts of pregnancies that lasted more than 22 weeks in 66 patients with pre-existing lupus nephritis between 2004 and 2013 in France. Univariate and multivariate analyses were conducted to identify determinants for maternal complications, lupus renal flare and fetal prematurity or death. RESULTS: Eighty-four pregnancies were identified. A maternal complication occurred in 31 pregnancies (36.9%): mostly preeclampsia (17 pregnancies, 20.2%) and renal flares (12 pregnancies, 14.3%). Overall fetal survival was 94.0% (79/84). Maternal pregnancy complications were independently associated with prepregnancy body mass index >25 kg/m2 (OR 3.81, 95% CI 1.03-14.09) and immunological activity (positive anti-dsDNA antibodies or Farr assay lupus) (OR 4.95, 95% CI 1.33-18.43). Renal lupus flares were independently associated with maternal age (OR 1.50, 95% CI 1.12-2.01) and prepregnancy immunological activity (OR 15.99, 95% CI 1.57-162.68) while a remission time >12 months had a protective effect (OR 0.17, 95% CI 0.04-0.68). Three parameters were associated with a higher risk of fetal prematurity or death: a prepregnancy body mass index >25 kg/m2 (HR 3.58, 95% CI 1.45-8.83), hypertension (HR 8.97, 95% CI 3.32-24.25), and immunological activity (HR 3.34, 95% CI 1.30-8.63). CONCLUSION: Maternal age, prepregnancy hypertension, body mass index >25 kg/m2 and lupus immunological activity may be considered as the main determinants for fetal and maternal complications. A remission time above 12 months for patients with lupus nephritis could be associated with a reduced risk of renal flare during pregnancy.

Rate of renal graft function decline after one year is a strong predictor of all-cause mortality.

The slope of GFR associates with an increased risk for death in patients with native CKD but whether a similar association exists in kidney transplantation is not known. We studied an inception cohort of 488 kidney transplant recipients (mean follow-up of 12 ± 4 years) for whom GFR was longitudinally measured by inulin clearance (mGFR) at 1 year and then every 5 years. Association of mGFR at 1 year posttransplant and GFR slope after the first year with all-cause mortality was studied with a Cox regression model and a Fine and Gray competing risk model. While in Crude analysis, the mGFR value at 1 year posttransplant and the rate of mGFR decline were both associated with a higher risk of all-cause mortality, only the slope of mGFR remained a significant and strong predictor of death in multivariate analysis. Factors independently associated with a more rapid mGFR decline were feminine gender, higher HLA mismatch, retransplantation, longer duration of transplantation, CMV infection during the first year and higher rate of proteinuria. Our data suggest that the rate of renal graft function decline after 1 year is a strong predictor of all-cause mortality in kidney transplantation.

Management of anticancer treatment in patients under chronic dialysis: results of the multicentric CANDY (CANcer and DialYsis) study.

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.

Increased time exposure to tenofovir is associated with a greater decrease in estimated glomerular filtration rate in HIV patients with kidney function of less than 60 ml/min/1.73 m2.

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 ± 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 ± 11.7 years, mean eGFR at baseline of 53.0 ± 0.8 (ml/min/1.73 m(2)) and eGFR slope of 0.46 ± 0.07 ml/min/1.73 m(2)/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope ± standard error of the mean: 1.1 ± 0.1, 0.5 ± 0.1, -0.07 ± 0.08 and -0.87 ± 0.06 ml/min/1.73 m(2)/year for no time exposure, <34, 34-67 and ≥67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline.

Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma?

BACKGROUND: The growth factor Angiotensin-2 signals through Angiotensin receptor type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2 receptor (AT2-R) in a more restricted group of cell types. Although numerous forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2-R by human renal clear-cell carcinoma (RCCC) is not well understood. In this study, the expression of both angiotensin receptors was quantified in a retrospective series of RCCC and correlated with prognostic factors. METHODS: Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour tissues by immunohistochemistry (IHC), western blot and quantitative reverse transcriptase PCR (qRT-PCR). IHC results were correlated to Fuhrman's grade and patient progression-free survival (PFS). RESULTS: A total of 84 RCCC were analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade tumours (AT1-R: P<0.001, AT2-R: P<0.001). Univariate analysis showed a correlation between PFS and AT1-R or AT2-R expression (P=0.001). By multivariate analysis, only AT2-R expression correlated with PFS (HR 1.021, P=0.006) and cancer stage (P<0.001). By western blot, AT1-R and AT1-R were also found to be overexpressed in higher Fuhrman's grade (P<0.01 and P=0.001 respectively). By qRT-PCR, AT1-R but not AT2-R mRNA were downregulated (P=0.001 and P=0.118, respectively). CONCLUSION: Our results show that AT1-R and AT2-R proteins are overexpressed in the most aggressive forms of RCCC and that AT2-R expression correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel directions for anti-RCCC therapy.

CKD-EPI equation: A suitable Glomerular Filtration Rate estimate for drug dosing in HIV-infected patients.

OBJECTIVES: To evaluate concordance between glomerular filtration rate (GFR) estimates (Cockcroft and Gault, modification of diet in renal diseases, chronic kidney disease epidemiology study group equations) for drug dosing in HIV-infected patients. PATIENTS AND METHODS: We performed a monocentric study. GFR was measured using the gold standard method (plasma clearance of iohexol) in 230 HIV-infected patients. Concordance rate was evaluated between measured GFR (mGFR) and estimated GFR (eGFR) for different GFR categories (GFR>90 mL/min, GFR<90 mL/min, GFR>70 mL/min, and GFR<70 mL/min). MDRD and CKD-EPI were used with and without indexation to body surface area (BSA). RESULTS: Mean age was 48±10 years, mean mGFR was 101±26 mL/min. Concordance between mGFR and eGFR estimated with CG, CKD-EPI (indexed and not indexed to BSA), or MDRD equations (not indexed to BSA) was similar (73%, 73%, 74%, and 73% respectively) for a breakpoint value of 90 mL/min for GFR. At this value, the concordance rate between mGFR and MDRD indexed to BSA was significantly lower (65%, P<0.05). Using 70 mL/min of GFR as the breakpoint value, all equations had similar concordance rates with mGFR (with or without indexation to BSA). CONCLUSION: CKD-EPI equation has the same concordance with GFR and with CG when used for drug dosing.

French peritoneal dialysis registry (RDPLF): outline and main results.

The Registre de Dialyse Péritonéale de Langue Française (RDPLF Registry) is a non-profit association that has been set up to assist physicians and nurses in evaluating their practical experience and results regarding peritoneal dialysis (PD). Five French-speaking and two Spanish-speaking countries have participated in this initiative (which includes 21 000 patients). In France, 82% of all PD patients are included in the registry and the main results for the period from 1995 to January 2006 form the basis of this report: of 11 744 incident patients with a median age of 71 years, 21.5% were over 80 years of age and 56% were not able to perform PD treatment at home without assistance. Eighty-six percent of the latter group received external assistance from a private nurse and 14% were aided by their family. The overall average rate of peritonitis was one episode every 29 months. The probability of being peritonitis-free appeared to be better for patients on automated PD (59.4% at 2 year) than for those on continuous ambulatory PD (55.3%), but this finding requires further validation. The average waiting time before transplantation was about 2 years. In patients who had undergone transplantation, the peritonitis rate was one episode per 42 months before transplantation compared to one episode per 29 months for patients who had not received a transplant. Eighty-three percent of patients had a hemoglobin level greater than 11 g%. Catheter survival was 92% at 2 years post-insertion and 85% at 5 years, with 94% being implanted by experienced surgeons. In conclusion, the RDPLF results demonstrate that PD may be successfully prescribed for older patients who receive assistance either from their family or from a nurse. Further, a larger number of younger patients should also be prescribed this technique in France. Patients eligible for transplantation and on short-term PD have the lowest risk of developing peritonitis; PD before transplantation may help prolong residual renal function, and initial treatment by PD may also help to preserve vascular access for the future.

[Calcific arteriolopathy (Calciphylaxis)]. / Artériolopathie calcique (Calciphylaxie).

PURPOSE: Calcific arteriolopathy (CA), also known as " Calciphylaxis " describes a phenomenon of necrosis, mainly cutaneous and sometimes systemic, due to the obliteration of the arteriole's lumen. Initially there are under-intimal calcium deposits, and then the thrombosis occurs leading to the necrosis. CA affects mainly the renal insufficient hemodialysed patient, but not exclusively. We present 4 cases which illustrate well the etiologic spectrum of CA: terminal renal insufficiency, neoplasia, primary hyperparathyroidism, proteinuria, vitamin K inhibitors. We describe the AC's epidemiology, its cutaneous and systemic clinical presentations, its treatment. We make the hypothesis that CA is a strong risk marker in matter of cardiac mortality and we discuss this point. CURRENT KNOWLEDGE AND KEY POINTS: In this article we describe the numerous breakthroughs that have been made in matter of research about calcification over the past few years: inhibitors of calcium phosphate deposition, vitamin D and PTH1R, protein-calcium complexes, cell death, induction of bone formation. These data are analysed from a clinical point of view with practical purposes. We present CA not only as a cutaneous disease but as a systemic pathology. FUTURE PROSPECTS AND PROJECTS: The CA epidemiology is an incentive to more diagnosis suspicion in front of organ infarct involving a patient likely to be concerned by CA. The scientific and therapeutic breakthroughs in matter of calcification enable a better prevention of the disease. Nevertheless it remains very difficult to cure when installed.

[Medicine in Vanuatu: a voyage to the end of the earth to Espiritu Santo Island]. / La médecine au Vanuatu: voyage au bout du monde sur l'île d'Espiritu Santo.

INTRODUCTION: The republic of Vanuatu, which was previously termed the Hebrides, has been independant since 1981. Colonization by both France and England has left its numerous marks on this country over the years. The authors spent the year 1997 on the Espiritu Santo Island and report their experience as practitioners at the northern district hospital. CURRENT KNOWLEDGE AND KEY POINTS: As Vanuatu is a developing country, medical practice is subject to changes in government, development aid provided by foreign countries and socio-economical conditions. Numerous chronic diseases with historical complications and malpractice are encountered. As well, numerous infectious diseases such as tuberculosis and malaria are still endemic. Means of fighting and preventing infections are great problems, with, for example, deficiencies in immunization programs. Though medical structures are well organized, due to its immature governments and assistance rather than cooperation policies of various helping countries, latitudinarianism is important and medical practice is not continuously organized. FUTURE PROSPECTS AND PROJECTS: Several objectives should be considered: epidemiological studies in order to reconstitute diseases profiles in this archipelago and, most of all, cooperation that would aim at training and education.

[Important elevation of uric acid associated with vomiting at the third trimester of pregnancy: report of five cases with favorable outcome]. / Elévation majeure de l'uricémie associée à des vomissements au cours du troisième trimestre de la grossesse: cinq cas avec issue favorable.

We report five cases of vomiting associated with a very important increase of maternal plasma uric acid (> 595 mmol/l, 100 mg/l) at the third trimester of pregnancy. In all cases, elevation was transitory and regressive with rehydratation. Pregnancies proceeded normally to term and delivered healthy babies. An important rise of plasmatic uric acid during pregnancy can be found in severe hypertensive disorders (preeclampsia, HELLP syndrome, acute fatty liver). Nevertheless, it can be related to transient renal insufficiency without any severe pathology. In our five observations, digestive disorders seem to be the reason for this phenomenon and spontaneous prognosis was excellent in all cases.

[Leptospirosis in Espiritu Santo, Vanuatu, 8 case reports]. / La leptospirose à Espiritu Santo (Vanuatu), à propos de 8 cas.

Our review of the literature on leptospirosis in Vanatu turned up only one previous report describing 3 cases at the Central Port Vila Hospital in 1992. The purpose of this report is to describe 8 cases of leptospirosis in patients admitted to the North District Hospital on Espiritu Santo Island in 1997. There were 6 men and 2 women with a mean age of 45 +/- 16 years. At the onset of the disease patients presented fever, myalgia, and diarrhea. After an average of four days initial symptoms were followed by visceral involvement with severe jaundice in all cases. Kidney failure occurred in 6 cases and neurological manifestations in 5. Subconjunctival hemorrhage was observed in 2 cases. Laboratory studies demonstrated hyperleukocytosis in 6 cases and liver enzyme abnormalities in 6 cases. Three patients presented Weil syndrome. Microscopic agglutination testing performed more than a week after the onset of disease was positive at 1/800 in 6 cases and at 1/200 with typical clinical abnormalities and positive serum PCR in 2 cases. All patients responded favorably to antimicrobial therapy using penicillin IV and symptomatic treatment. The estimated incidence of leptospirosis in the North District of the Island of Espiritu Santo, in 1997 was 40/100,000 person-year but this was probably an underestimation because of unawareness of the disease, poor access to medical care, and underdiagnosis.

[Positive Pneumocystis jirovecii PCR in immunocompromised patients with a systemic disease: infection or colonisation?]. / PCR Pneumocystis jirovecii positive chez les patients atteints de maladie auto-immune: pneumocystose pulmonaire ou simple colonisation?

PURPOSE: Pneumocystis pneumonia is a serious opportunistic infection that frequently occurred in HIV-seropositive patients, prior to the advent of highly active antiretroviral therapy. This infection can also occur in patients with systemic diseases. The diagnostic value of a positive Pneumocystis jirovecii PCR in patients with systemic diseases has not yet been clearly defined. METHODS: We conducted a retrospective study of patients with a systemic disease who presented clinical symptoms consistent with Pneumocystis pneumonia to assess the diagnostic value of a positive P. jirovecii PCR in respiratory samples. RESULTS: During a 10-year period, 73 patients with respiratory symptoms underwent respiratory sampling with tests for the presence of P. jirovecii. P. jirovecii PCR was positive in 20 patients: Pneumocystis pneumonia was diagnosed in nine patients and for six of these nine patients, the microscopic examination was negative. Patients with Pneumocystis pneumonia differed from those who were solely colonized in that they had a lower CD4+ T lymphocyte count, were more likely to have received immunosuppressive treatment, and were not receiving primary prophylaxis against Pneumocystis pneumonia. Chronic pulmonary involvement was more frequent among colonized patients. CONCLUSION: A positive P. jirovecii PCR does not always indicate overt infection. However, in a context of severe immunosuppression and in the absence of prophylaxis against Pneumocystis pneumonia, a specific treatment should be considered.

Primary glomerulonephritis: an update on renal survival and determinants of progression.

BACKGROUND: Few epidemiological studies have investigated the long-term outcome of primary glomerulonephritis (GN) and its determinants in the decade since angiotensin-converting enzyme inhibitors entered widespread use. AIM: To study several traditional and less traditional risk factors for kidney disease progression in a cohort of patients with primary GN. DESIGN: Retrospective cohort study. METHODS: We included 536 patients with primary GN first diagnosed between 1994 and 2001: 283 IgA nephropathy (IgA), 129 membranous nephropathy (MN), and 124 focal and segmental glomerulosclerosis (FSGS). Adjusted hazard ratios (HR) or dialysis or preemptive transplantation for end-stage renal disease (ESRD) according to various characteristics were estimated with Cox proportional-hazard models. RESULTS: At diagnosis, mean patient age was 43 +/- 17 years, 74% were men, and the mean estimated glomerular filtration rate (eGFR) was 69 +/- 31 mL/mn/1.73m(2). After a mean follow-up of 7-years, 104 patients had started ESRD treatment and 14 had died before reaching ESRD. The 7-year renal survival rate was 69% for FSGS, 88% for MN, and 82% for IgAN (p < 0.01). In patients with FSGS, younger age was associated with a higher risk of ESRD. Baseline proteinuria, diabetes, and haemoglobin (Hb) concentration were strongly associated with shorter time to ESRD independent of baseline eGFR, but gender, hypertension and smoking were not. Adjusted HRs for ESRD were 2.6 [95% confidence interval, 1.2-5.8] for diabetes and 2.4 [1.3-4.5] for the lowest and 1.9 [1.0-3.6] for the intermediate Hb tertiles versus the highest. DISCUSSION: In patients with primary GN, renal survival is clearly lower for FSGS than for IgAN and MN. Independent predictors for progression were baseline diabetes and anaemia, as well as proteinuria, for all GN types, and younger age, for FSGS.

[Pregnancy and hemodialysis]. / Grossesse en hémodialyse chronique.

Pregnancy is a rare occurrence in patients on chronic hemodialysis (CHD). The rate of successful pregnancies amounts to almost 60%, thanks to modifications of the dialysis schedule and a specifically adapted obstetrical and neonatal management. We report on seven pregnancies occurring between 1995 and 2001 in six women with a mean age of 32 years (22-39 years), on HD for a mean period of 36 months (12-96 months). Maternal and fetal complications, and the long-term outcome of mothers and children are reported, and the collaborative approaches adopted by obstetrician, pediatrician and nephrologist are discussed. The frequency and length of HD was systematically increased. One patient chose to terminate her pregnancy at 20 weeks of gestation. The mean gestational age for the six other pregnancies was 31 weeks (24-34 weeks) with an average weight at birth of 1495 g (660-1920 g). One neonate born at 24 weeks died 2 days following delivery. One patient was treated with uterine artery embolization for post-partum haemorrhage. Pediatric evaluation of the five children, who were followed up for a period ranging between 2.5 to 5.5 years, showed a good long-term outcome. In conclusion, pregnancy needs not be counterindicated or systematically terminated in patients on CHD, particularly if transplantation is not possible, if the patient refuses it, or if she is relatively old and there is a long waiting period before transplantation.