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.

Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.

BACKGROUND: There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. CASE PRESENTATION: A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. CONCLUSION: We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.

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.

[Suspected allergy to COVID-19 vaccines: A retrospective study of 320 patients]. / Suspicion d'allergie aux vaccins anti COVID-19 : étude rétrospective sur 320 patients.

Introduction: The health context with COVID-19 pandemic has led to fast development of many vaccines against the SarS-Cov-2 virus. Four of them are currently available in France and contain polyethylene glycol (PEG) or polysorbate 80 as excipients, already described as causing anaphylaxis. French recommendations have been suggested by allergology authorities and proposed a course of action in the event of a suspected allergy to these vaccines. Thus, allergies to excipients were the only contraindication to COVID-19 vaccination. Our main objective was to determine the impact of these allergology vaccine recommendations on the management of these patients. Our secondary objective was to determine prevalence of true allergies to these vaccines. Materials and methods: We conducted a unicentric descriptive retrospective study with all patients over 18 years of age referred for an allergological opinion before or after an injection of one of the anti-COVID-19 vaccines. Nineteen patients were classified into different interest groups, based on french recommendations. Results: The vast majority of patients did not require a pre-vaccination allergological assessment. Indeed, only 25 patients received skin tests prior to vaccination. The rest of patients were able to be vaccinated without allergological assessment. Patients not vaccinated due to allergy to excipients represent less than 1% of the population (n = 3/320). Conclusion: French recommendations made it possible to vaccinate the vast majority of patients included in our study. Allergy to PEG, polysorbate or their derivatives, the only contraindication to anti-COVID vaccination, according to the recommendations of February 2021, remains rare. Today, several authors propose tolerance inductions allowing the vaccination of patients allergic to PEGs or their derivatives with good tolerance.

Reconsidering adsorption in hemodialysis: is it just an epiphenomenon? A narrative review.

Since the first attempt at extracorporeal renal replacement therapy, renal replacement therapy has been constantly improved. In the field of hemodialysis, substantial efforts have been made to improve toxin removal and biocompatibility. The advent of hemodiafiltration (HDF) and, more recently, of mid cut-off membranes have contributed to management of patients with end-stage renal disease (ESRD). Although several uremic toxins have been discovered, we know little about the clinical impact of their clearance in hemodialysis patients. In addition, a great deal of progress has been made in the areas of filtration and diffusion, but the adsorptive properties of hemodialysis membranes remain under-studied. The mechanism of action of adsorption is based on the attraction between the polymer of the dialysis membrane and the solutes, through hydrophobic interactions, ionic or electrostatic forces, hydrogen bonds or van der Waals forces. Adsorption on the dialysis membrane depends on the membrane surface, pore size, structure and electric load. Its involvement in toxin removal and biocompatibility is significant, and is not just an epiphenomenon. Diffusive and convective properties cannot be improved indefinitely and high permeability membranes, despite their high performance in the clearance of many toxins, have several limitations for long-term use in hemodialysis. This review will discuss why adsorption should be reconsidered and better characterized to improve efficiency and adequacy of dialysis.

Prolonged hemodialysis for acute kidney injury in myeloma patients.

OBJECTIVE: Cast nephropathy, due to free light chain (FLC) toxicity, is the main cause of acute kidney injury in multiple myeloma, with about 10% of patients requiring dialysis. In these patients, in addition to chemotherapy that prevents FLC production, daily hemodialysis using high cutoff or adsorptive membranes, showed promising results by decreasing quickly toxic serum FLC concentrations. CASE HISTORY: We report here the case of 2 patients presenting with acute kidney injury and high FLC serum concentration and M-components one with IgG Kappa and the other with IgD lambda. Both were treated with bortezomib and dexamethasone and received a 24-h continuous hemodialysis using a high and sharp cutoff (around 35,000 Daltons) polysulfone membrane (ultraflux® HD 1000, Fresenius Medical Care GmbH, Bad Homburg, Germany) with citrate regional anticoagulation using a safe and dedicated device (multi filtrate Ci-Ca®). CONCLUSION: Despite similar range of depuration, serum plasma FLC decreased importantly in the patient with the kappa type who recovered but was unchanged in the lambda type patient who remained under maintenance dialysis. Further studies are needed to confirm this new approach therapy.

Acute renal and splenic infarctions: a review.

BACKGROUND: Renal and splenic infarctions are close entities, with few data concerning their clinical, biological and radiological features. AIM: The aim of this study was to compare the clinical presentations, etiologies and outcomes of acute renal infarctions (RI) and splenic infarctions (SI). DESIGN: A retrospective multicentric cohort study included patients of the 6 university hospitals in Lyon with RI, SI, or associated RI-SI infarctions was conducted. METHODS: All consecutive cases diagnosed by CT imaging, between January 2013 and October 2016, were included. The exclusion criteria were causes of infarction that did not require additional investigations. RESULTS: A total of 161 patients were selected for analysis: 34 patients with RI, 104 patients with SI and 23 patients with both RI-SI. Mean ± SD age of patients was 63.2 ± 16.6 years; 59.6% were male. Only 5/161 (3.1%) were healthy prior to the event. The main symptoms were diffuse abdominal pain (26.4%), followed by nausea/vomiting (18.3%) and fever (16.4%).The causes of RI or SI varied significantly within the three groups. Hypercoagulable state was associated with SI, and embolic disease and arterial injury were associated with RI. Extensive (i.e.>2/3 of organ volume) (OR 6.22, 95%CI 2.0119.22) and bilateral infarctions (OR 15.05, 95%CI 1.79-126.78) were significantly associated with hemodynamic shocks. The survival at 1 month follow-up did not significantly differ between the three groups. CONCLUSION: Acute RI and SI are heterogenous entities in regards to their clinical presentation, etiology, associated venous or arterial thrombosis, but prognoses were not different at short term follow-up.

Thesaurus for off-label indications for systemic antifungal agents.

OBJECTIVES: Following the removal of temporary treatment protocol procedures, we developed a thesaurus for off-label indications for systemic antifungals at our facility to update clinical practices and to control off-label prescriptions. MATERIALS AND METHODS: Clinical practice guidelines and literature data were analyzed. This work was part of an antifungal stewardship program. RESULTS: Off-label wording (prophylaxis, preemptive, empirical, curative) and corresponding antifungals and references were validated by the multidisciplinary group for antifungal agents under the aegis of the Commission for the use of drugs and sterile medical devices and of the anti-infective committee. CONCLUSION: Considering the complexity of invasive fungal infection management, this thesaurus needs to be shared and used as a helping tool to review off-label situations.

[Role of networks in the screening and management of chronic kidney disease]. / Impact des réseaux sur les pratiques et les résultats de la prise en charge de la maladie rénale chronique.

Whatever the health care system, the prevention of chronic renal failure is at present limited by an insufficient use of available screening and treatment methods for chronic kidney disease. Consequently, most patients with chronic kidney disease remain exposed to an otherwise avoidable progression towards end-stage renal disease, an emergency start of dialysis, and increased cardiovascular risk. The coordination of care within a multiprofessional network including appropriate guidelines, continuous medical education and practice assessment, and patient information and therapeutic education, may radically change the prognosis of chronic kidney disease, and the burden of care.

Large Middle Molecule and Albumin Removal: Why Should We Not Rest on Our Laurels?

Large middle molecules (LMM) are an important subclass of uremic toxins. Many of them have been linked with poor outcomes in hemodialysis (HD) patients. The onset of high-flux membranes and convective techniques allowed to dramatically improve their clearance but without a clear and undebatable reduction of mortality in HD patients. Despite the real effect on the removal of selected toxins, little is known about the influence of modern HD techniques on the global removal of uremic toxins. Mostly explained by a lack of knowledge and selective assays, LMM removal is not evaluated appropriately. The development of highly sensitive and widespread detection techniques such as mass spectrometry could increase our knowledge about the real state of their removal in HD. Nevertheless, these techniques remain cost effective and are difficult to handle. On the contrary, the improvement of LMM removal raises the question of a tolerable albumin removal. Indeed, increasing membrane permeability can significantly increase LMM removal accompanied by a higher albumin loss. However, in chronic kidney disease and particularly in HD patients, albumin can be modified, and it subsequently exerts detrimental effects. This could be avoided by the clearance of the modified forms in HD, but future efforts should be done to investigate the real impact of their removal.

Interactions cardiorénales.

Hypertension is common in patients with chronic renal disease particularly those with diabetes. It is sometimes resistant to the pharmacological treatment. The mineralocorticoid receptor antagonist spironolactone may be indicated here. The mineralocorticoid receptor antagonists have a Class 1, Level A indication for the treatment of heart failure with reduced ejection fraction. There is an associated risk of worsening renal function and of hyperkalemia which does not hinder their clinical benefit. However, an appropriate biological monitoring is warranted, along with potential dose adaptations. Cardiorenal syndrome significantly worses the prognosis of congestive heart failure. The use of ultrafiltration can be effective when conventional treatments failed. Its place in the front line needs to be evaluated.

Microaneurysms in renal angiomyolipomas: Can clinical and computed tomography features predict their presence and size?

PURPOSE: To evaluate clinical and multidetector computed tomography (MDCT) features associated with the presence and size of microaneurysms in renal angiomyolipomas (AMLs). MATERIALS AND METHODS: The MDCTs and digital subtraction angiographies (DSAs) of 31 patients who had further percutaneous arterial embolization of AMLs were retrospectively reviewed. They were 22 women and 9 men (mean age, 47.7±27.7 years). The medical files of the included patients were reviewed for age, gender and clinical features. MDCT and DSA images were analyzed by two readers working in consensus. RESULTS: Of the 31 patients, 15 had tuberous sclerosis complex (TSC) or lymphangioleiomyomatosis (LAM). In total, the 31 patients had 54 AMLs (5 ruptured). On DSA, 28 clusters of microaneurysms were found in 17 patients (21 AMLs). Four of the five ruptured AMLs had microaneurysms. None of the 12 AMLs≤40mm and 21 of the 42 AMLs>40mm had microaneurysms. Among AMLs>40mm, history of TSC/LAM (P=0.5), RENAL score (P=0.7) and relative volume of fat (P=0.11) did not significantly predict the presence of microaneurysms. Microaneurysms were significantly larger in ruptured (9.5±5.7mm) than non-ruptured (3.9±1.9mm, P=0.02) AMLs. No associations were found between the size of microaneurysms and the size of AMLs. CONCLUSION: Microaneurysms were found in no AML ≤40mm and in 50%of AMLs>40mm. In AMLs >40mm, history of TSC/LAM, RENAL score and relative volume of fat did not significantly predict the presence of microaneurysms.

[Renal AA amyloidosis secondary to bronchiectasis: a report of two cases (including one with Mounier-Kuhn syndrome)]. / Amylose rénale AA secondaire à des bronchectasies.

INTRODUCTION: We describe 2 patients with AA renal amyloidosis secondary to bronchiectasis (one patient had tracheobronchomegaly or Mounier-Kuhn syndrome). CASE REPORTS: The time period between the diagnosis of bronchiectasis and the development of renal amyloidosis was 40 years and 30 years respectively. Both patients evolved to end-stage renal failure requiring dialysis. CONCLUSION: Although the incidence of renal amyloidosis secondary to bronchectasis has declined, it remains a dreadful complication.

Is renal allograft dysfunction a risk factor for severe infection in kidney transplant recipients?

The ANTICIPE study is a cross-sectional, multicenter, French study. The aim of this study was to describe clinical and biological parameters observed in a cohort of 1446 stable renal transplant recipients, according to the stage of chronic kidney disease. Severe infection was defined as an infection necessitating ≥ 7 days of hospital stay. We observed a negative correlation between declining glomerular filtration rate and occurrence of severe infection (P < .0001). In multivariate analysis, severe infection was associated with age, female gender, chronic kidney disease stage (Kidney Disease Outcomes Quality Initiative classification), and number of acute rejection episodes. Our study suggested that renal allograft function is a predictor not only of cardiac death and cardiovascular complications, but also of severe infections.

Kidney volume quantification using contrast-enhanced in vivo X-ray micro-CT in mice.

The present study sought to establish a standard in vivo imaging procedure for mouse kidney anatomy evaluation using contrast-enhanced high-resolution X-ray microtomography (micro-CT). Micro-CT estimation of kidney volume was compared with ex vivo measurement by micro-CT and water displacement. Control values were obtained in four strains (BALB/c, C3H/HeN, 129/Sv and C57BL/6J) of healthy male and female mice aged 22 +/- 2 weeks. An excellent correlation was found between in vivo and ex vivo kidney volumes (n = 26 mice; 52 kidneys; r = 0.96). In vivo measurement systematically overestimated ex vivo kidney volume by 28 +/- 4%, while there was no significant difference between the ex vivo micro-CT value and the true kidney volume on water displacement (2.3 +/- 2.1%). In vivo kidney volume also correlated strongly with kidney weight and in vivo kidney length (n = 52 mice; 104 kidneys; r = 0.84, r = 0.92 respectively). Differences between strains were observed for kidney volume when comparing either kidney volume or kidney weight to body weight. In conclusion, this study demonstrated that contrast-enhanced micro-CT enables accurate in vivo measurement of kidney volume, length and thickness in mice. Reference parameters are reported for four strains. The technique provides a useful follow-up research tool for mouse phenotyping and renal disease studies.

Effects of recombinant growth factors on energy expenditure in maintenance hemodialysis patients.

We compared the metabolic effects of recombinant human (rh) insulin-like growth factor (IGF)-1 or a combination of rhIGF-1 + rh growth hormone (GH) on resting energy expenditure (REE) in 8 maintenance hemodialysis (MHD) patients. Seven males and 1 female (aged 41.6 +/- (SD) 12.4) with no evidence of malnutrition (BMI 21.6 +/- 2.2 kg/m2, serum albumin 45 +/- 2 g/l, serum IGF-1 359 +/- 165 microg/l) received either rhIGF-1 (80 microg/kg/day) or rhIGF-1 (80 microg/kg/day) + rhGH (50 microg/kg/day) for 3 days in a random crossover design. REE and the respiratory quotient (RQ) were measured at rest before and after the 3-day treatment. The results confirmed that MHD patients have a REE not different from normal individuals. REE was strongly correlated with lean body mass but not with fat mass. rhIGF-1 treatment did not modify REE despite doubling serum IGF-1 values, whereas a combined rhIGF1 + rhGH treatment significantly increased REE by 11% (p < 0.001). There was no change in RQ under both treatments, in response to a proportionate increase in VCO2 and VO2. These results show that energy expenditure is mainly dependent upon lean body mass in well-nourished MHD patients. The metabolic effects of rhIGF-1 and rhGH on energy expenditure may differ in response to their opposite effects on lipid oxidation and insulin regulation.

Acute leptin regulation in end-stage renal failure: the role of growth hormone and IGF-1.

BACKGROUND: Leptin, a recently discovered peptide involved in nutrient intake and energy expenditure, has been shown to be abnormally regulated in certain conditions such as obesity. In chronic renal failure, leptin appears to be increased. However, little is known about leptin regulation during chronic renal failure (CRF). METHODS: We measured serum leptin in eight well nourished, chronic hemodialysis patients (seven males, one female) receiving anabolic factors for three days as either recombinant insulin-like growth factor-1 (rhIGF-1) or a combination of recombinant growth hormone (rhGH) plus recombinant IGF-1, in a random cross-over trial. RESULTS: Serum leptin values were in the range of normal volunteers matched for body mass index. As reported in other conditions, serum leptin was strongly correlated with patients dry body wt (P = 0.01) and body fat (P = 0.0001). Both treatments affected serum leptin in a rapid and opposite manner. RhIGF-1 decreased serum leptin from 11.2+/-20.8 (SD) to 4.3+/-3.8 microg/liter (P = 0.011), whereas the combination of rhGH + rhIGF-1 increased serum leptin from 7.4+/-9.4 to 21.0+/-32.9 microg/liter (P = 0.011). Regression analyses indicated a linear regression between serum leptin and insulin variations after treatment. CONCLUSIONS: This study shows for the first time that both rhIGF-1 and rhGH acutely regulate serum leptin in dialysis patients. Whether leptin changes are explained by the concomitant insulin variation should be further studied under renal failure conditions.

Renal blood flow measurement by positron emission tomography using 15O-labeled water.

BACKGROUND: Only few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals. METHODS: RBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 microg. kg-1. min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng. kg-1. min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith. RESULTS: PET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL. min-1. 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 +/- 45 mL. min-1. 100 g-1 (mean +/- SD). CONCLUSION: To our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL. min-1. 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.

Peritoneal clearance of leptin in continuous ambulatory peritoneal dialysis.

Leptin is a 16-kd protein that increases energy expenditure and limits food intake. Serum leptin (S-leptin) is elevated in dialysis patients, and little data have been reported on leptin clearance (Cl) during dialysis. We analyzed the peritoneal dialysis (PD) Cl of leptin in 15 continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results to beta(2)-microglobulin (beta(2)-m), urea, and creatinine PD Cl. S-leptin was significantly elevated (Kruskal-Wallis, P < 0.005) in CAPD women (58.4 +/- 42.4 [SE] microg/L, n = 5) as compared with CAPD men (13.9 +/- 7.1, n = 10) and with healthy women (11.0 +/- 1.4, n = 13) and men (5.1 +/- 0. 9, n = 14). Correlations were found between percent of fat mass and S-leptin (P < 0.05); between S-leptin and the 24-hour PD leptin (P < 0.05); and between dialysate-to-plasma (D/P) beta(2)-m and D/P leptin (P < 0.01). PD leptin Cl (1.80 +/- 0.43 mL/min/1.73 m(2)) was higher than beta(2)-m Cl (1.22 +/- 0.31) (P < 0.01), but reduced as compared with urea Cl (8.84 +/- 1.20) (P < 0.005) and creatinine Cl (7.71 +/- 0.99) (P < 0.005). These results indicate that leptin is eliminated through the peritoneum membrane. However, peritoneal leptin clearance, as beta(2)-m, appears to be clearly restricted as compared with peritoneal transport of smaller molecules. Hence, leptin could use the same diffusion transport pathway as beta(2)-m. In addition, leptin, which has a higher molecular weight than beta(2)-m, was significantly more eliminated into the peritoneal dialysate. More studies are necessary to clarify whether this is an active leptin elimination process by peritoneal secretion or by a different restriction coefficient of diffusion through the peritoneum membrane.