[West Nile Infection and Kidney Disease: Description of Two Clinical Cases in Peritoneal Dialysis Patients].

The West Nile Virus (WNV), an RNA arbovirus, has been transmitted by wild birds and conveyed by ticks and mosquitoes, with wide diffusion all over the world; it is not transmitted from human to human. It can give clinical symptoms only in a minority of infected subjects such as fever, headache, muscle tiredness, visual disturbances, drowsiness, convulsions and muscle paralysis; in the most serious cases even potentially fatal encephalitis. In the literature there are few reports on WNV infection in patients with kidney diseases: here we report our experience on two patients on peritoneal dialysis infected by WNV with a revision of the literature.

Primary membranous nephropathy in the Italian region of Emilia Romagna: results of a multicenter study with extended follow-up.

BACKGROUND: Since primary membranous nephropathy is a heterogeneous disease with variable outcomes and multiple possible therapeutic approaches, all 13 Nephrology Units of the Italian region Emilia Romagna decided to analyze their experience in the management of this challenging glomerular disease. METHODS: We retrospectively studied 205 consecutive adult patients affected by biopsy-proven primary membranous nephropathy, recruited from January 2010 through December 2017. The primary outcome was patient and renal survival. The secondary outcome was the rate of complete remission and partial remission of proteinuria. Relapse incidence, treatment patterns and adverse events were also assessed. RESULTS: Median (IQR) follow-up was 36 (24-60) months. Overall patient and renal survival were 87.4% after 5 years. At the end of follow-up, 83 patients (40%) had complete remission and 72 patients (35%) had partial remission. Among responders, less than a quarter (23%) relapsed. Most patients (83%) underwent immunosuppressive therapy within 6 months of biopsy. A cyclic regimen of corticosteroid and cytotoxic agents was the most commonly used treatment schedule (63%), followed by rituximab (28%). Multivariable analysis showed that the cyclic regimen significantly correlates with complete remission (odds ratio 0.26; 95% CI 0.08-0.79) when compared to rituximab (p < 0.05). CONCLUSIONS: In our large study, both short- and long-term outcomes were positive and consistent with those published in the literature. Our data suggest that the use of immunosuppressive therapy within the first 6 months after biopsy appears to be a winning strategy, and that the cyclic regimen also warrants a prominent role in primary membranous nephropathy treatment, since definitive proof of rituximab superiority is lacking.

Peritoneal videodialysis: first Italian audit.

Conceived and developed since 2001 at the Alba Center, Videodialysis (VD) was used initially to prevent dropout in prevalent PD patients by guiding them in performing dialysis (VD-Caregiver). Subsequently, its use was extended to the clinical follow-up of critical patients (VD-Clinical), problems relating to transport to the Center (VD-Transport), and since 2016 for training/retraining all patients (VD-Training). Since 2017 other Centers have employed VD using modalities analyzed in this paper. Methods: the paper reports the findings of an Audit (February 2021) of the Centers using VD on 31-12-2020. The Centers provided the following information: the characteristics of the patients using VD; the main and secondary reasons for using VD, considering nursing home (VD-NH) patients separately; VD outcomes: duration, drop-out, peritonitis, patient/caregiver satisfaction (minimum: 1 - maximum: 10). Results: VD, which began between 09-2017 and 12-2019, has been used in 6 Centers for 54 patients at 31-12-2020 (age:71.8±12.6 years - M:53.7% - CAPD:61.1% - Assisted PD:70.3%). The most frequent reason has been VD-Training (70.4%), followed by VD-Caregiver (16.7%), VD-NH (7.4%), VD-Clinical (3.7%), and VD-Transport (1.9%), with differences between Centers. VD-Training is used most with self-care patients (93.8% - p<0.05), while with patients on Assisted PD it is associated with secondary reasons (95.7% - p<0.02). VD-Training (duration: 1-4 weeks) has always been completed successfully. No peritonitis was reported; satisfaction was 8.4±1.4. Conclusion: videodialysis is a flexible, effective, safe, and valued tool that can be employed using various modalities depending on the choice of the Center and the complexity of the patient.

Acute kidney injury, a common and severe complication in hospitalized patients during the COVID-19 pandemic.

INTRODUCTION: Acute respiratory failure (ARF) is the main clinical sign of coronavirus disease-2019 (COVID-19), but little is known about the outcome of acute kidney injury (AKI) associated with ARF. STUDY DESIGN: Retrospective cohort study on clinical features of adult patients hospitalized with COVID-19 between March 1st and April 30th, 2020 in the district of Piacenza (Italy). RESULTS: Among 1894 hospitalized patients, 1701 affected by COVID-19 underwent at least two serum creatinine evaluations. According to KDIGO definitions, 233 of 1,701 patients (13.7%) developed AKI: 159, 34, and 40 had stage 1, 2 and 3 AKI, respectively. Patients with AKI were older (mean age 73.5 ± 14 years, range 24-95) than those without AKI (72 ± 14 years, range 20-102). In-hospital mortality was high in COVID patients (567/1701 patients, 33%), which almost doubled among AKI patients (132/233 patients, 57%), compared with those without AKI (p < 0.01). Risk factors for AKI included older age, male gender, diabetes and need for ventilation. Fourteen patients with stage 3 AKI underwent renal replacement therapy (RRT). CONCLUSIONS: Hospitalized COVID-19 patients with AKI associated with ARF have poor chances of survival. Diagnosing and preventing the progression of renal damage is fundamental in order to delay initiating RRT, especially when resources are limited.

A Rare Case of Coronavirus Disease 2019 Survival in an Elderly Patient With Atheroembolic Renal Disease.

Atheroembolic renal disease (AERD) is a life-threatening illness. Coronavirus disease 2019 (COVID-19) has a high mortality rate in older patients with comorbidities. We report the case of severe-type COVID-19 in an 82-year-old female with AERD. She was treated with hydroxychloroquine-based therapy and overcame COVID-19. To our knowledge, this is the first report of a patient with AERD and COVID-19 pneumonia who overcame the infection and remains alive and well nine months following infection.

What can a home hemodialysis program offer to patients in a nursing home setting? A case series and feasibility analysis.

INTRODUCTION: Over the last decades, the number of elderly patients on dialysis has rapidly grown on account of increased life expectancy, improved care and reduced mortality rate. Therefore, cooperation between geriatricians and nephrologists has become mandatory for co-managing kidney disease in these patients. Based on renewed interest in home hemodialysis (HHD), elderly patients may benefit from not being transported from their home for therapy. METHODS: Here, we report our experience with HHD involving three elderly patients who were followed-up over a 15-months period in a nursing home. FINDINGS: Our experience demonstrates that hospitalization abruptly dropped from 40 days to zero days, the need for erythropoietin stimulating agents (ESAs) diminished, transportation-related costs for home treatments decreased, and quality of life (QoL) improved. This was confirmed by a questionnaire administered to our patients at the start and again after 6 months of HHD which evaluated the Physical Health Component Score (PCS) and the Mental Health Component Score (MCS). DISCUSSION: Home hemodialysis may represent an important way to improve social, mental, and physical recovery, while also eliminating the cost of transportation and the discomfort of abandoning their "homes" and daily habits. Home hemodialysis is an effective alternative to in-center HD or peritoneal dialysis (PD) that should be offered to elderly patients when a home caregiver is not available, nonetheless, nursing assistance is required. Moreover, HHD allows patients to stay at home, thereby avoiding several weekly trips to the dialysis center, and may be useful in reducing infections, especially in times of the COVID-19 pandemic, as demonstrated by our experience.

Observational Retrospective Study on Patient Lifestyle in the Pretransplantation and Post-transplantation Period in the Emilia-Romagna Region.

INTRODUCTION: Despite the well-known benefits of exercise during the pretransplantation and post-transplantation phases, adherence to active lifestyles is still reduced. The aim of the present study is to evaluate how many patients who have received organ transplants and candidates for organ transplantation carry out physical or sports activities in order to increase adherence to an active lifestyle. METHODS: The patients who agreed to participate in the study were interviewed about their lifestyle habits by the staff at the nephrology, dialysis, and hepatology units of the Emilia-Romagna region. The interview investigated the patient's lifestyle (active or sedentary) and type of physical activity (walking, cycling, gardening, gym at least 3 to 40 minutes, 2 to 3 times per week) or sport (training > 2 times per week) routinely practiced. RESULTS: We collected 1138 interviews from patients on the waiting list (n = 159) for organ transplant, those with kidney transplants (n = 756), and those with liver transplants (n = 223) monitored in the Emilia-Romagna hospitals (regional patients 67%, extraregional 33%). Eighty-four patients on the waiting list for a transplant (kidney) were sedentary, 75 practiced physical activity, and 10 of 75 physically active patients practiced sport. Four hundred fifteen patients with kidney transplants were sedentary, 341 practiced physical activity, and 31 of 341 physically active patients practiced sport. Among patients with liver transplants, 56 were sedentary, 167 practiced physical activity, and 20 of 167 physically active patients played sport. CONCLUSIONS: In-line with the general population, we confirmed a high tendency toward a sedentary lifestyle (44% of respondents) among patients with organ transplants and those on waiting lists for organ transplants. Including a prescription for physical exercise as part of the therapeutic regimen can be useful for changing lifestyles during the pre- and post-transplantation period.

Covid-19 and its impact on nephropathic patients: the experience at Ospedale "Guglielmo da Saliceto" in Piacenza.

Roberto Scarpioni and colleagues recount their experience with the Covid-19 epidemic at the Nephrology and Dialysis Center of the "Guglielmo da Saliceto" Hospital in Piacenza, where everybody is still fighting to this moment to contain the spread of the disease and face an increasingly unsustainable clinical situation. Piacenza is only 15 km away from the main cluster of cases in the country (Codogno, in the Lodi province) and, after the closure of the Hospital in Codogno, saw an escalation in the number of patients testing positive to Covid-19. The authors describe their efforts and the practices they adopted to contain the spread of the disease among inpatients visiting the hospital's Hemodialysis Clinic. They also reflect on some of the data available on the 25/03/2020, such as the number of patients testing positive and the mortality rate, unfortunately very high. Their aim is to help all colleagues that have yet to face this epidemic in its full force.

The PIRP project (Prevenzione Insufficienza Renale Progressiva): how to integrate hospital and community maintenance treatment for chronic kidney disease.

Chronic kidney disease (CKD) represents a global health burden with great economic impact on healthcare and therefore it requires appropriate interventions by Health Care Systems. The PIRP (Prevenzione Insufficienza Renale Progressiva) project is endorsed and funded by the Emilia-Romagna Regional Health Board and involves all the Nephrology Units of the Emilia-Romagna Region (Italy). The project has a predominantly clinical purpose and is expected to bring about a continuous quality improvement in the treatment of patients with CKD. Its aims are to intercept patients in an early phase of CKD, to delay their illness progression and to prevent cardiovascular complications. An integrated care pathway involving nephrologists, general practitioners (GPs) and other specialists has been created to identify patients to whom ambulatory care targeted on effective, efficient pharmaceutical and dietary treatment as well as on lifestyle modifications is subsequently provided. With the cooperation of GPs, in its 13 years of activity the project identified and followed up more than 25,000 CKD patients, who attended the Nephrology units with more than 100,000 visits. The effects of a closer and joint monitoring of CKD patients by GPs and nephrologists can be quantified by the reduction of the mean annual GFR decline (average annual CKD-EPI change: - 0.34 ml/min), and by the decrease in the overall incidence of patients who annually started dialysis in the Emilia-Romagna Region, that dropped from 218.6 (× million) in 2006 to 197.5 (× million) in 2016, corresponding to about 100 cases.

[Challenges and results of the PIRP project (Prevenzione della Insufficienza Renale Progressiva) of the Emilia-Romagna Region].

The PIRP project was conceived in 2004; with the aim to face the increased prevalence of chronic kidney disease (CKD) associated with the aging and increased survival of the population. The first phase of the project consisted of training primary care physicians to identify people at risk of CKD and to implement intervention strategies that proved to be effective in preventing CKD it or delaying its progression once it is established. In the second phase of the project, dedicated ambulatories were opened in the nephrology units of Emilia-Romagna hospitals to provide an in-depth assessment and personalized care to CKD patients, following them up until renal failure or death or referring them back to general practitioners, according to the study protocol. A web-based registry was implemented to collect demographic and clinical data on PIRP patients. As of 30 June 2018, the registry included 26.211 CKD patients, with a median follow-up of 24.5 months. Over the 14 years of the PIRP the mean age of incident patients increased from 71.0 years to 74.2 years and the mean eGFR increased from 30.56 to 36.52 mL/min/1.73 m ², proving that the project was successful in recruiting older patients with a better renal function. At 5 years, the percentage of patients still active in the project was =45%.The implementation of the project has seen a reduction in the number of patients arriving every year to the dialysis treatment in E-R (about 100 units less from 2006 to 2016). The PIRP cohort is the largest in Italy and in Europe, which makes it ideal for research based on international comparisons and as a model for national registries.

Interaction between Albuminuria and Treatment Group Outcomes for Patients with Renal Artery Stenosis: The NITER Study.

PURPOSE: To perform a post-hoc analysis of the Nephropathy Ischemic Therapy (NITER) trial, which enrolled patients with atherosclerotic renal artery stenosis, to evaluate whether medical therapy plus stent placement is superior to medical therapy alone in patients without elevated albuminuria. MATERIALS AND METHODS: Data from 51 patients were analyzed and stratified into 2 cohorts by median urinary albumin (UAlb) levels: cohort 1 ("low albuminuria," UAlb ≤0.04 g/24h) and cohort 2 ("high albuminuria," UAlb >0.04g/24h). Interaction effect between treatment arms and UAlb cohorts was calculated using Cox regression analysis. Survival analysis was followed by test for effect size, power analysis, and construction of a Kaplan-Meier survival table. RESULTS: At study completion, 13 patients had an outcome event: 6 (23%) from cohort 1 and 7 (28%) from cohort 2. Patients in cohort 1 had event-free survival of 83% at 3.9 ± 0.3 years from the primary endpoints of all-cause mortality, dialysis, and cardiovascular events when treated with interventional therapy, compared to 45% when treated with medical therapy alone (P = .501), which showed a 62% treatment effect for stent placement. In cohort 2, event-free survival rates were 64% for medical therapy versus 52% for medical plus interventional therapy (P = .64). Using Cox regression analysis, the interaction effect between treatment arms and UAlb cohorts was not significant (P = .32). The power of the study to detect an interaction effect, if one existed, was only 15%. CONCLUSIONS: Inference cannot be drawn for similar populations because of inadequate sample size, but, in this sample, patients treated with stent placement who had low albuminuria had better outcomes than patients treated with medical therapy alone.

Renal involvement in autoinflammatory diseases and inflammasome-mediated chronic kidney damage.

Unprovoked activation of innate immune pathways and increased secretion of interleukin (IL)-1ß and IL-18 are responsible for the protean clinical manifestations and the marked inflammatory response that characterise most hereditary autoinflammatory disorders. The kidney is a major target organ of this inflammatory process. The deposition of the acute-phase reactant serum amyloid A (SAA) as amyloid causes progressive glomerular and vascular damage and leads to organ failure. In this review we focus on the potential impact of hereditary autoinflammatory diseases on renal function, provide red flags that may guide the clinical suspicion of amyloid kidney damage and discuss the relevance of close renal monitoring for early diagnosis and prompt treatment. Moreover, NLRP3 inflammasome activation is increasingly recognised to play a key causative role in the pathogenesis of several chronic kidney diseases in which activation of caspase-1 and the proteolytic cleavage of IL-1ß and IL-18 into their biologically active forms mediate glomerular and tubulointerstitial damage. Although much of the knowledge about the role of the inflammasome in kidney injury has been mostly gathered in experimental models, inhibition of IL-1 is also becoming an attractive potential therapeutic target in a variety of chronic renal disorders with a substantial inflammatory component.

Secondary amyloidosis in autoinflammatory diseases and the role of inflammation in renal damage.

The release of proinflammatory cytokines during inflammation represents an attempt to respond to injury, but it may produce detrimental effects. The inflammasome is a large, multiprotein complex that drives proinflammatory cytokine production in response to infection and tissue injury; the best-characterized inflammasome is the nod-like receptor protein-3 (NLRP3). Once activated, inflammasome leads to the active form of caspase-1, the enzyme required for the maturation of interleukin-1beta. Additional mechanisms bringing to renal inflammatory, systemic diseases and fibrotic processes were recently reported, via the activation of the inflammasome that consists of NLRP3, apoptosis associated speck-like protein and caspase-1. Several manuscripts seem to identify NLRP3 inflammasome as a possible therapeutic target in the treatment of progressive chronic kidney disease. Serum amyloid A (SAA), as acute-phase protein with also proinflammatory properties, has been shown to induce the secretion of cathepsin B and inflammasome components from human macrophages. SAA is a well recognised potent activator of the NLRP3. Here we will address our description on the involvement of the kidney in autoinflammatory diseases driven mainly by secondary, or reactive, AA amyloidosis with a particular attention on novel therapeutic approach which has to be addressed in suppressing underlying inflammatory disease and reducing the SAA concentration.

Excess mortality attributable to chronic kidney disease. Results from the PIRP project.

Although chronic kidney disease (CKD) has a high mortality rate, the estimation of CKD mortality burden in the general population may be challenging because CKD is not always listed as a cause of death in mortality registries. To overcome this limitation, relative survival was used to estimate the excess mortality attributable to CKD as compared to the general population using data of patients registered in the Prevenzione Insufficienza Renale Progressiva (PIRP) registry since 2005 and were followed up until 2013. Relative survival was the ratio of survival observed in CKD patients to the expected survival of the general population. Multivariate parametric survival analysis was used to identify factors predicting excess mortality. The relative survival of CKD patients at 9 years was 0.708. Survival was significantly lower in CKD patients with cardiovascular comorbidities, proteinuria, diabetes, anemia and high phosphate levels and in advanced CKD stages, males, older patients and those who underwent dialysis. Relative survival is a viable method to determine mortality attributable to CKD. Study limitations are that patients are representative only of CKD patients followed by nephrologists and that our follow-up duration may be relatively short as a model for mortality.

Identifying Patient Candidates for IL-1 Inhibition: Lessons From Real-World Cases.

A subgroup of patients with gouty arthritis have a chronic recurring form that is particularly difficult to treat. Such patients experience repeated flares and often have abundant tophi. Many also have underlying comorbidities, such as renal impairment, cardiovascular disease, gastrointestinal disorders, obesity, and hypertension, which contraindicate the use of standard anti-inflammatory medications. Five patients with difficult to treat gouty arthritis who were either candidates and/or treated with anti-IL therapy are described.

Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1ß monoclonal antibody canakinumab.

Muckle-Wells syndrome (MWS) is a rare hereditary autoinflammatory disorder characterized by recurrent urticaria-like skin rashes, arthralgias, conjunctivitis, hypoacusia, and risk of reactive AA amyloidosis due to the progressive accumulation of amyloid fibrils in different organs. Its genetic defect lies in mutations in the NLRP3 gene, encoding the cryopyrin protein, and resulting in interleukin (IL)-1ß oversecretion. Renal involvement, in terms of proteinuria or renal insufficiency, can be observed in up to 25% of patients. Herein, we describe our experience with two Caucasian patients, father and son, aged 52 and 26 years, respectively, heterozygous for both V198M and R260W NLRP3 mutations who had AA amyloid deposits on renal biopsy. The fully human monoclonal antibody canakinumab, providing selective and prolonged IL-1ß blockade, was administered in both patients every 60 days over a period of 18 months. This treatment allowed to obtain amazing results: a rapid disappearance of any clinical symptoms, the stable normalization of serum amyloid-A and, furthermore, a marked improvement of glomerular filtration rate and proteinuria with no adverse events. Our data, though limited to only two patients, emphasize that therapeutic intervention with canakinumab, suppressing both inflammation and IL-1ß-mediated manifestations, can contribute to improve kidney function in MWS with overt renal amyloidosis.

Treatment of dyslipidemia in chronic kidney disease: Effectiveness and safety of statins.

Several cardiovascular (CV) risk factors may explain the high rate of CV death among patients with chronic kidney disease (CKD). Among them both traditional and uremia-related risk factors are implicated and, moreover, the presence of kidney disease represents "per se" a multiplier of CV risk. Plasma lipid and lipoprotein profiles are changed in quantitative, but above all in qualitative, structural, and functional ways, and lipoprotein metabolism is influenced by the progressive loss of renal function. Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly, by reducing the lipid profile, or via pleiotropic effects; it is supposed to be able to reduce both the progression of CKD and also proteinuria. These observations derive from a post-hoc analysis of large trials conducted in the general population, but not in CKD patients. However, the recently published SHARP trial, including over 9200 patients, either on dialysis or pre-dialysis, showed that simvastatin plus ezetimibe, compared with placebo, was associated with a significant low-density lipoprotein cholesterol reduction and a 17% reduction in major atherosclerotic events. However, no benefit was observed in overall survival nor in preserving renal function in patients treated. These recent data reinforce the conviction among nephrologists to consider their patients at high CV risk and that lipid lowering drugs such as statins may represent an important tool in reducing atheromatous coronary disease which, however, represents only a third of CV deaths in patients with CKD. Therefore, statins have no protective effect among the remaining two-thirds of patients who suffer from sudden cardiac death due to arrhythmia or heart failure, prevalent among CKD patients. The safety of statins is demonstrated in CKD by several trials and recently confirmed by the largest SHARP trial, in terms of no increase in cancer incidence, muscle pain, creatine kinase levels, severe rhabdomyolysis, hepatitis, gallstones and pancreatitis; thus confirming the handiness of statins in CKD patients. Here we will review the latest data available concerning the effectiveness and safety of statin therapy in CKD patients.

Clinical outcomes after percutaneous revascularization versus medical management in patients with significant renal artery stenosis: a meta-analysis of randomized controlled trials.

BACKGROUND: We sought to systematically evaluate whether percutaneous revascularization is associated with additional clinical benefit in patients with renal artery stenosis (RAS) as compared with medical management alone. METHODS: We included randomized controlled trials that compared percutaneous revascularization in addition to medical therapy versus medical management alone in patients with RAS. Six trials with 1,208 patients were included. RESULTS: At a mean follow-up of 29 months, there was no change in systolic blood pressure (weighted mean difference [WMD] = 1.20 mm Hg, 95% CI -1.18 to 3.58 mm Hg) or diastolic blood pressure (WMD = -1.60 mm Hg, 95% CI -4.22 to 1.02 mm Hg) from baseline in the percutaneous revascularization arm compared with the medical management arm. There was a reduction in the mean number of antihypertensive medications (WMD = -0.26, 95% CI -0.39 to -0.13, P < .001), but not serum creatinine (WMD = -0.14 mg/dL, 95% CI -0.29 to 0.007 mg/dL), in the percutaneous revascularization arm at the end of follow-up. Percutaneous revascularization was not associated with a significant difference in all-cause mortality (relative risk [RR] = 0.96, 95% CI 0.74-1.25), congestive heart failure (RR = 0.79, 95% CI 0.56-1.13), stroke (RR = 0.86, 95% CI 0.50-1.47), or worsening renal function (RR = 0.91, 95% CI 0.67-1.23) as compared with medical management. CONCLUSIONS: In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use.