[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.

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.

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.

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.

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.

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.

Dyslipidemia in chronic kidney disease: are statins still indicated in reduction cardiovascular risk in patients on dialysis treatment?

BACKGROUND: Chronic kidney disease (CKD) is an increasingly health disease all around the world with a high burden of mortality and cardiovascular (CV) morbidity rate. Even when renal replacement therapy is reached, more than half patients die, mainly for CV causes due either to uremia-related cardiovascular risk factors (such as anemia, hyperhomocysteinemia, mineral bone disease-CKD with hyperparathyroidism, oxidative stress, hypoalbuminemia, chronic inflammation, prothrombotic factors) or to traditional ones (age, male gender, diabetes, obesity, hypertension, smoking, insulin levels, family history, dyslipidemia). Among the latter causes dyslipidemia represents one of the major, potentially correctable risk factor. METHODS AND RESULTS: Statins have demonstrated to effectively and safely reduce cholesterol levels in CKD patients. Here we will examine the effects of statins on CV risk factors in CKD patients and particularly in patients on dialysis treatment, in the light of the unfavorable results of the large trials 4D and AURORA, recently published, underlining the role of malnutrition/inflammation as confounding factor. Probably it will be that only with a real prevention, starting statins even in the early stages of CKD, as indicated by post hoc analysis of large trials, that we will reach results in reducing the mortality rate in CKD patients. In the meanwhile, all the other remediable CV risk factors have to be at the same time corrected.

Quality of water, dialysate and infusate.

Great improvements in water treatment technology and the spread of ultrafiltration for cold sterilization have been the basic support for the development and diffusion of on-line dialysis treatments. Some 20 years ago, nephrologists recognized that the official standards for dialysis fluids were insufficient with respect to these new treatment modalities, and ultrapure water (bacteria <0.1 CFU/ml; endotoxin <0.03 EU/ml) was proposed as a reference. Today, ultrapure water is included in most guidelines and recommended standards, but there remains a need for harmonization between standards. To achieve and ensure these levels of purity, technology must be supported by commitment of resources to an active quality assurance programme with adequate maintenance, monitoring, cleaning, sanitizing and problem analysis procedures.

Biofilm on artificial surfaces.

Biofilms are microbial communities quite different from planktonic cells and most of common microbiological concepts had to be updated in recent years. The peculiar capacity to resist to disinfectants and antibiotics results in biofilms being a public health problem mainly when modern medical devices are used. All artificial surfaces used in medicine may be prone to biofilm attachment and could therefore represent a cause of acute or chronic infectious diseases. Uremic patients are at higher risk from biofilms as not only traditional causes, such as indwelling catheters, but also hemodialysis apparatuses contribute to bacterial exposure. Chemical or physical disinfections have been demonstrated partially active on sessile microorganisms and biofilm avoidance remains the goal to assure an adequate quality of dialytic treatment.

A validated model of disease progression in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the general population. There is accumulating evidence that immunosuppressive treatment is efficacious in IgAN. However, it is critical to define appropriate indicators for this therapy especially in the wake of potentially deleterious side effects to immunosuppressives. METHODS: This study retrospectively reviewed IgAN cases collected since 1981 to identify clinical and/or histological parameters for disease progression; 310 patients with biopsy proven IgAN, diagnosed from January 1981 to March 2004, were included. RESULTS: We defined a clinical prognostic index (CPI) using multivariate analysis, which incorporated these clinical/ histological parameters. Semiquantitative scores were assigned as follows: 2 points if creatinine (Cr) was >1.4 mg/dL, 1 point if proteinuria was >1 g/24 hr, 1 point if a patient was affected by hypertension, and 1 point if a patient was older than 30 yrs. Dividing our population into two groups (scores 0-2 = low CPI group; scores 3-5 = high CPI group), we demonstrated a significantly different 10-yr renal survival rate; in the low CPI group, renal survival since time of biopsy at 10 yrs was 91.7%; in the high CPI group the renal survival at 10 yrs was 35%. We validated the CPI in an independent sample from Verona (validation group) and demonstrated similar results for the CPI. CONCLUSIONS: The CPI is convenient to use for defining the risk of disease progression.

Water treatment for hemodialysis: a 2005 update.

Water for dialysis represents an additive risk factors to the chronic inflammatory state documented in patients on ESRD. The possibility of sustaining proinflammatory cytokines through microbial derived products, coming from dialysate or infused solutions, is enhanced by biofilm presence on piping and on water treatment system or monitor components. Spread use of reverse osmosis, loop distribution system and pre-treatment components tailored to local raw water characteristics have greatly contributed to a general improvement in final water quality. Notwithstanding these contributions literature still reports fatal accidents or significant percentage of dialysis units not complying to the water quality standards. Technological improvement lowers chemical contamination but microbial quality relays more on quality assurance programs than on technology. Optimal water quality represents part of the anti-inflammatory strategies we need to assure to our dialysis patients to improve outcome.