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Fibrillary glomerulonephritis belongs to a group of disorders characterized by pathogenic deposition of fibrils in glomeruli. This glomerulopathy tends to progress to end-stage kidney disease, and there currently are no treatments of proven benefit, including corticosteroids and cytotoxic agents. Because the glomerular deposits contain an immunoglobulin component, it was postulated that anti-B-cell therapy with rituximab, an anti-CD20 monoclonal antibody, may be effective in the treatment of patients with fibrillary glomerulonephritis. We describe 3 patients with fibrillary glomerulonephritis who were treated with rituximab for nephrotic-range proteinuria. Each patient also received standard antiproteinuria therapy, including blockade of the renin-angiotensin system and strict blood pressure control. All patients showed a decrease in proteinuria to less than 1.5 g/d of protein by 27 months, and kidney function was preserved throughout the duration of therapy and follow-up. No adverse effects were seen with rituximab. These outcomes suggest that treatment with rituximab may be a promising approach to the management of fibrillary glomerulonephritis, an entity previously considered refractory to therapy. [ABSTRACT FROM AUTHOR]

Background: Real-world data for patients with chronic kidney disease (CKD), specifically pertaining to clinical management, metabolic control, treatment patterns, quality of life (QoL) and dietary patterns, are limited. Understanding these gaps using real-world, routine care data will improve our understanding of the challenges and consequences faced by patients with CKD, and will facilitate the long-term goal of improving their management and prognosis., Methods: DISCOVER CKD follows an enriched hybrid study design, with both retrospective and prospective patient cohorts, integrating primary and secondary data from patients with CKD from China, Italy, Japan, Sweden, the UK and the USA. Data will be prospectively captured over a 3-year period from >1000 patients with CKD who will be followed up for at least 1 year via electronic case report form entry during routine clinical visits and also via a mobile/tablet-based application, enabling the capture of patient-reported outcomes (PROs). In-depth interviews will be conducted in a subset of ∼100 patients. Separately, secondary data will be retrospectively captured from >2 000 000 patients with CKD, extracted from existing datasets and registries., Results: The DISCOVER CKD program captures and will report on patient demographics, biomarker and laboratory measurements, medical histories, clinical outcomes, healthcare resource utilization, medications, dietary patterns, physical activity and PROs (including QoL and qualitative interviews)., Conclusions: The DISCOVER CKD program will provide contemporary real-world insight to inform clinical practice and improve our understanding of the epidemiology and clinical and economic burden of CKD, as well as determinants of clinical outcomes and PROs from a range of geographical regions in a real-world CKD setting., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb) < 10 g/dL, the CIF at 12 months for any anemia medication was 40%, and 28% for ESAs. Patients with TSAT < 20% had a CIF of 26% and 6% for oral and IV iron, respectively. Heart failure was associated with earlier initiation of anemia medications. IV iron was prescribed to < 10% of patients with iron deficiency. Only 40% of patients with Hb < 10 g/dL received any anemia medication within a year. Discontinuation of anemia treatment was very common. Anemia treatment is initiated in a limited number of NDD-CKD patients, even in those with guideline-based indications to treat. Hemoglobin trajectory and a history of heart failure appear to guide treatment start. These results support the concept that anemia is sub-optimally managed among NDD-CKD patients in the real-world setting.

Background: We explored the association of anemia severity in patients with chronic kidney disease (CKD) and anemia treatment with work productivity in China., Methods: Cross-sectional survey data from Chinese physicians and their CKD patients were collected in 2015. Physicians recorded demographics, disease characteristics, and treatment. Patients completed the Work Productivity and Activity Impairment questionnaire. Data were stratified by dialysis-dependence, hemoglobin (Hb) level, and anemia treatment., Results: Based on data from 1,052 patients (704 non-dialysis-dependent [NDD] and 348 dialysis-dependent [DD] patients), prescribed anemia treatment differed significantly across Hb levels ( P < 0.001). In NDD patients, anemia treatment also differed significantly by on-treatment Hb level ( P < 0.001). In treated NDD patients with Hb < 10 g/ dL, Hb 10 to 12 g/dL, and Hb > 12 g/dL, 31%, 59%, and 38% of patients, respectively, were prescribed oral iron, and 34%, 19%, and 0% of patients, respectively, were prescribed oral iron with erythropoiesis-stimulating agents (ESA). NDD patients were less likely to be prescribed any anemia treatment, and ESA specifically, than DD patients. When treated, 67% and 45% of NDD and DD patients, respectively, had Hb ≥ 10 g/dL ( P < 0.001). Overall work and activity impairment differed significantly across Hb levels in NDD and DD patients, with the least impairment observed at the highest Hb level., Conclusion: Approximately 40% of NDD patients and 60% of DD patients receiving anemia treatment had Hb < 10 g/dL. Compared with mild anemia patients, severe anemia patients were more likely to be treated for anemia and have impaired work productivity. Chinese CKD patients could benefit from improved anemia treatment.

Patients with end-stage kidney disease (ESKD) have different options to replace the function of their failing kidneys. The "integrated care" model considers treatment pathways rather than individual renal replacement therapy (RRT) techniques. In such a paradigm, the optimal strategy to plan and enact transitions between the different modalities is very relevant, but so far, only limited data on transitions have been published. Perspectives of patients, caregivers, and health professionals on the process of transitioning are even less well documented. Available literature suggests that poor coordination causes significant morbidity and mortality.This review briefly provides the background, development, and scope of the INTErnational Group Research Assessing Transition Effects in Dialysis (INTEGRATED) initiative. We summarize the literature on the transition between different RRT modalities. Further, we present an international research plan to quantify the epidemiology and to assess the qualitative aspects of transition between different modalities., (Copyright © 2019 International Society for Peritoneal Dialysis.)

Telehealth and remote monitoring of a patient's health status has become more commonplace in the last decade and has been applied to conditions such as heart failure, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease. Conversely, uptake of these technologies to help engender and support home RRTs has lagged. Although studies have looked at the role of telehealth in RRT, they are small and single-centered, and both outcome and cost-effectiveness data are needed to inform future decision making. Furthermore, alignment of payer and government (federal and state) regulations with telehealth procedures is needed along with a better understanding of the viewpoints of the various stakeholders in this process (patients, caregivers, clinicians, payers, dialysis organizations, and government regulators). Despite these barriers, telehealth has great potential to increase the acceptance of home dialysis, and improve outcomes and patient satisfaction while potentially decreasing costs. The Kidney Health Initiative convened a multidisciplinary workgroup to examine the current state of telehealth use in home RRTs as well as outline potential benefits and drawbacks, impediments to implementation, and key unanswered questions., (Copyright © 2017 by the American Society of Nephrology.)

Background: Remote monitoring (RM) is defined as the surveillance of device-transmitted outpatient data. RM is expected to enable better management of chronic diseases. The objective of this research was to identify public policies concerning RM in four European countries., Methods: Searches of the medical literature, the Internet, and Ministry of Health websites for the United Kingdom (UK), Germany, Italy, and Spain were performed in order to identify RM policies for chronic diseases, including end stage renal disease (ESRD), chronic pulmonary obstructive disease (COPD), diabetes, heart failure, and hypertension. Searches were first performed in Q1 2014 and updated in Q4 2015. In addition, in depth interviews were conducted with payers/policymakers in each country. Information was obtained on existing policies, disease areas and RM services covered and level of reimbursement, other incentives such as quality indicators, past/current assessments of RM technologies, diseases perceived to benefit most from RM, and concerns about RM., Results: Policies on RM and/or telemedicine were identified in all four countries. Pilot projects (mostly in diabetes, COPD, and/or heart failure) existed or were planned in most countries. Perceived value of RM was moderate to high, with the highest rating given for heart failure. Interviewees expressed concerns about sharing of medical information, and the need for capital investment. Patients recently discharged from hospital, and patients living remotely, or with serious and/or complicated diseases, were believed to be the most likely to benefit from RM. Formal reimbursement is scarce, but more commonly available for patients with heart failure., Conclusions: In the four European countries surveyed, RM has attracted considerable interest for its potential to increase the efficiency of healthcare for chronic diseases. Although rare at this moment, incentives to use RM technology are likely to increase in the near future as the body of evidence of clinical and/or economic benefit grows.

Peritonitis is a significant complication of peritoneal dialysis (PD), contributing to mortality and technique failure. Suboptimal disinfection and/or a loose connection at the catheter adapter-transfer set junction are forms of touch contamination that can compromise the integrity of the sterile fluid path and lead to peritonitis. Proper use of the right disinfectants for connections at the PD catheter adapter-transfer set interface can help eliminate bacteria at surface interfaces, secure connections, and prevent bacteria from entering into the sterile fluid pathway. Three studies were conducted to assess the antibacterial effects of various disinfecting agents and procedures, and ensuing security of the catheter adapter-transfer set junction. An open-soak disinfection procedure with 10% povidone iodine improves disinfection and tightness/security of catheter adapter-transfer set connection., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Unlabelled: ♦, Background: In recent years, results from clinical studies have changed the focus of peritoneal dialysis (PD) adequacy from small solute clearance to volume control, resulting in continued efforts to improve fluid and sodium removal in PD patients. We used a modified 3-pore model to theoretically predict fluid and solute removal using glucose-based and icodextrin solutions for a wide range of transport characteristics with automated PD (APD) and continuous ambulatory PD (CAPD) therapies. ♦, Methods: Simulations were performed for the day (APD: 15-hr, 2.27% glucose and 7.5% icodextrin; CAPD: 3x5-hr, 1.36% and 2.27% glucose) and night (APD: 9-hr, 1.36% glucose; CAPD: 9-hr, 2.27% glucose and 7.5% icodextrin) dialysis periods separately. During APD, the number of night exchanges (N) was varied from 3 to 7. Ultrafiltration (UF), sodium removal (NaR), total carbohydrate absorption (CHO), UF efficiency (UFE), and sodium removal efficiency (NaRE) were calculated. Typical patients in fast (i.e. high, H), average (high-average, HA; low-average, LA), and slow (low, L) transport groups with no residual kidney function were considered. ♦, Results: The effective dwell times varied between 1.0 and 14.7 hours depending on the number of exchanges. With glucose-based solutions, differences in UF and NaR between H and L transport patients ranged from 140 mL and 2 mmol (APD night, n = 7) to 778 mL and 56.4 mmol (CAPD day, 2.27%). With icodextrin, differences in UF and NaR ranged from 1 mL and 1.1 mmol (CAPD night) to 59 mL and 6.1 mmol (APD day). The use of icodextrin resulted in greater CHO than 2.27% glucose (APD: 27.1 - 35.6 g more; CAPD: 17.1 - 17.5 g more). The UFE and NaRE were greater for all patients with icodextrin than with glucose-based solution in both therapy modalities, except for slow transport patients in CAPD. ♦, Conclusion: This modeling study shows that the dependence of UF and NaR on patient transport type observed with glucose-based solutions can be minimized using icodextrin during the long dwells of APD and CAPD. While this approach simplifies the PD prescription by minimizing the dependencies of ultrafiltration and sodium removal on patient transport type when using icodextrin, it improves fluid and sodium removal efficiencies in fast and average transport patients without any added glucose exposure., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Introduction: We measured serum creatinine concentrations in 17 male athletes of the Italian national rugby team., Methods: Blood was obtained before the start of training and during the competitive season. Serum creatinine level was measured by Jaffé reaction at 4 time points during the season, with a formal measure of creatinine clearance in midseason., Results: The values of estimated glomerular filtration rate (eGFR) calculated with the Cockcroft-Gault (CG) equation were higher than those calculated with the Modification of Diet in Renal Disease (MDRD) Study formula (p<0.001). This difference was significantly decreased but still present when the MDRD formula was corrected for body surface area (BSA). When compared with measured creatinine clearance (CrCl), the MDRD underestimates the CrCl by 51 ml/min (95% confidence interval [95% CI], 36-67 ml/min, p<0.0001). When corrected for BSA, this difference falls to 27 ml/min (95% CI, 13-44 ml/min, p=0.001). The CG eGFR gave a better estimate of CrCl, differing by 1 ml/min (95% CI, -16 to +17 ml/min, p=NS)., Conclusions: The MDRD formula underestimates the CrCl in rugby players, even when corrected for BSA. Conversely, the CG formula more closely approximates the actual CrCl measurement. The equations to estimate GFR should be used with caution in subjects having atypical anthropometric characteristics.

Background: Intermittent peritoneal dialysis (IPD) is an old strategy that has generally been eclipsed, in the home setting, by daily peritoneal therapies. However, for a select group of patients with exhausted vascular access or inability to receive PD at home, in-center IPD may remain an option or may serve as an incremental strategy before initiation of full-dose PD. We investigated the residual kidney clearance requirements necessary to allow thrice-weekly IPD regimens to meet current adequacy targets., Methods: The 3-pore model of peritoneal transport was used to examine 2 thrice-weekly IPD dialysis modalities: 5 - 6 dwells with 10 - 12 L total volume (low-dose IPD), and 50% tidal with 20 - 24 L total volume (high-dose IPD). We assumed an 8-hour dialysis duration and 1.5% dextrose solution, with a 2-L fill volume, except in tidal mode. The PD Adequest application (version 2.0: Baxter Healthcare Corporation, Deerfield, IL, USA) and typical patient kinetic parameters derived from a large dataset [data on file from Treatment Adequacy Review for Gaining Enhanced Therapy (Baxter Healthcare Corporation)] were used to model urea clearances. The minimum glomerular filtration rate (GFR) required to achieve a total weekly urea Kt/V of 1.7 was calculated., Results: In the absence of any dialysis, the minimum residual GFR necessary to achieve a weekly urea Kt/V of 1.7 was 9.7 mL/min/1.73 m(2). Depending on membrane transport type, the low-dose IPD modality met urea clearance targets for patients with a GFR between 6.0 mL/min/1.73 m(2) and 7.6 mL/min/1.73 m(2). Similarly, the high-dose IPD modality met the urea clearance target for patients with a GFR between 4.7 mL/min/1.73 m(2) and 6.5 mL/min/1.73 m(2)., Conclusions: In patients with residual GFR of at least 7.6 mL/min/1.73 m(2), thrice-weekly low-dose IPD (10 L) achieved a Kt/V urea of 1.7 across all transport types. Increasing the IPD volume resulted in a decreased residual GFR requirement of 4.7 mL/min/1.73 m(2) (24 L, 50% tidal). In patients with residual kidney function and dietary compliance, IPD may be a viable strategy in certain clinical situations.

The term obesity cardiomyopathy has previously been used to describe a clinical syndrome in obese patients typically consisting of eccentric left ventricular hypertrophy with preserved ejection fraction and diastolic dysfunction and is often associated with right ventricular dysfunction independent of the presence of the obstructive sleep apnea syndrome. Although several publications have described the early stages of this syndrome, little is known about the end stages of the disease. The authors conducted a retrospective study of a subset of edematous obese patients with multiple common medical comorbidities who present with a clinical syndrome in the setting of physiologic stress or infection. Under severe physiologic stress these patients developed pulmonary hypertension, right-sided volume overload, decreased effective arterial blood volume, and renal failure. Often, these findings were in the setting of obstructive sleep apnea. This retrospective study focuses on an obesity-related cardiorenal syndrome but also serves to provide a foreground for acknowledging the broad spectrum of cardiovascular pathology, including pulmonary hypertension, diastolic dysfunction, and sleep apnea, seen in the obese.

Infection is the Achilles heel of peritoneal dialysis. Exit site mupirocin prevents Staphylococcus aureus peritoneal dialysis (PD) infections but does not reduce Pseudomonas aeruginosa or other Gram-negative infections, which are associated with considerable morbidity and sometimes death. Patients from three centers (53% incident to PD and 47% prevalent) were randomized in a double-blinded manner to daily mupirocin or gentamicin cream to the catheter exit site. Infections were tracked prospectively by organism and expressed as episodes per dialysis-year at risk. A total of 133 patients were randomized, 67 to gentamicin and 66 to mupirocin cream. Catheter infection rates were 0.23/yr with gentamicin cream versus 0.54/yr with mupirocin (P = 0.005). Time to first catheter infection was longer using gentamicin (P = 0.03). There were no P. aeruginosa catheter infections using gentamicin compared with 0.11/yr using mupirocin (P < 0.003). S. aureus exit site infections were infrequent in both groups (0.06 and 0.08/yr; P = 0.44). Peritonitis rates were 0.34/yr versus 0.52/yr (P = 0.03), with a striking decrease in Gram-negative peritonitis (0.02/yr versus 0.15/yr; P = 0.003) using gentamicin compared with mupirocin cream, respectively. Gentamicin use was a significant predictor of lower peritonitis rates (relative risk, 0.52; 95% confidence interval, 0.29 to 0.93; P < 0.03), controlling for center and incident versus prevalent patients. Gentamicin cream applied daily to the peritoneal catheter exit site reduced P. aeruginosa and other Gram-negative catheter infections and reduced peritonitis by 35%, particularly Gram-negative organisms. Gentamicin cream was as effective as mupirocin in preventing S. aureus infections. Daily gentamicin cream at the exit site should be the prophylaxis of choice for PD patients.

Objective: To determine the safety and efficacy of intravenous total dose iron (TDI) replacement in patients treated with home renal replacement therapy., Design: Prospective open-label study on end points in the population studied., Setting: Institutional outpatient home dialysis program., Patients: The study included 20 end-stage renal disease (ESRD) patients, performing chronic peritoneal or home hemodialysis, with iron deficiency defined as ferritin < 100 ng/mL and/or an iron saturation < 20%., Intervention: The total dose of iron dextran was calculated and infused at a rate not exceeding 6 mg/min. Hemoglobin, hematocrit, iron studies, and liver function tests (LFTs) were obtained before and 3 to 4 weeks after TDI infusion. Hematocrit of patients failing to achieve an increase in Hct over this period was re-examined 2 to 4 weeks later looking for a delayed response., Main Outcome Measures: Primary end points for efficacy were changes in Hct, ferritin, and iron saturation. Toxicity was measured as reported immediate and delayed symptoms and elevated transaminases and/or alkaline phosphatase levels., Results: A median iron dose of 1000 mg (range, 325-1500 mg) was administered. The infusions were generally well tolerated. Clinical adverse effects were seen in 2 patients weighing less than 50 kg. No increase in LFT results was seen. Hematocrit increased 2.2% (95% CI, 0.5%-3.9%) from 29.0% to 31.2% (p = 0.01) within 4 weeks of infusion. Significant increases also occurred in iron saturation (from 13% to 22%, p = 0.001) and ferritin (from 234 to 305 ng/mL, p = 0.008). Among the 9 patients who did not respond with a significant increase in Hct, 2 had a delayed response, increasing the overall response from 63% at 4 weeks to 71%, 8 weeks after TDI. Inadequate erythropoietin dosing and low-grade infectious/inflammatory disorders may have contributed to a poor response in several patients., Conclusion: Total dose iron is a safe and effective means of restoring iron and erythropoietic response in ESRD patients weighing more than 50 kg who receive their renal replacement therapy at home.

Patients with renal failure frequently manifest a hemorrhagic diathesis characterized by prolonged bleeding time (BT). Oral and intravenous estrogens have been shown to correct this abnormality, but both estrogens have real and potential disadvantages, especially for long-term use. We examined the effectiveness of transdermally applied 17 beta-estradiol on clinical bleeding and BT in renal failure patients. Six patients with renal insufficiency and prolonged BT were included in the study. Four patients had recurring gastrointestinal bleeding from telangiectasias. Two patients anticipated percutaneous renal biopsy. Transdermal estradiol 50 or 100 micrograms/24 hr was applied every 3.5 days for a period of 2 months. Bleeding times were measured just prior to estrogen administration (pre-estradiol) and again on cessation of clinical bleeding or prior to renal biopsy (post-estradiol). Differences were analyzed using a paired t-test. Erythrocyte transfusion requirement 2 months before and 2 months after estradiol application also was observed. Hemorrhage in all four actively bleeding patients ceased or improved, as reflected by the reduced need for transfusion. Bleeding time improved significantly (P = 0.008) when comparing before (day 0) with after (days 1 to 17) estradiol application. No adverse reactions associated with estradiol occurred over 2 months of therapy. In conclusion, transdermal application of 17 beta-estradiol is a safe and effective means to reduce BT and clinical hemorrhage in patients with renal failure and prolonged BT.

A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.

Purpose: To determine if the natural anticoagulant protein C plays a role in the pathogenesis of systemic calciphylaxis, a syndrome characterized by extensive vascular and soft tissue calcification and skin necrosis, which is similar to that seen in warfarin-induced skin necrosis., Patients and Methods: The study population included five patients with end-stage renal disease and systemic calciphylaxis undergoing hemodialysis, 12 patients without evidence of calciphylaxis undergoing dialysis, eight patients with nephrotic syndrome, and eight normal healthy volunteers. Protein C antigen levels were measured by rocket immunoelectrophoresis, and functional activity was quantitated by a chromogenic assay and an anticoagulant assay utilizing the venom of Agkistrodon contortrix., Results: Skin biopsy specimens of involved areas in three patients showed thrombotic occlusion of venules identical to that seen in warfarin-induced skin necrosis. Protein C antigen levels were normal in all groups. However, protein C activity was significantly reduced as measured by chromogenic (p less than 0.01) or anticoagulant assays (p less than 0.01) in patients with calciphylaxis compared with the other three groups., Conclusion: These findings suggest that hypercoagulability due to functional protein C deficiency may contribute to thrombosis, resulting in skin necrosis and digital gangrene in systemic calciphylaxis.