Antibody Responses after Two Doses of COVID-19 mRNA Vaccine in Dialysis and Kidney Transplantation Patients Recovered from SARS-CoV-2 Infection.

Background and Objectives: Hemodialysis patients (HD) and kidney transplant recipients (KTRs) have been heavily impacted by COVID-19, showing increased risk of infection, worse clinical outcomes, and higher mortality rates than the general population. Although mass vaccination remains the most successful measure in counteracting the pandemic, less evidence is available on vaccine effectiveness in immunodepressed subjects previously infected and recovered from COVID-19. Materials and Methods: This study aimed at investigating the ability to develop an adequate antibody response after vaccination in a 2-dose series against SARS-CoV-2 in HD patients and KTR that was administered after laboratory and clinical recovery from COVID-19. Results: Comparing SARS-CoV-2 S1/S2 IgG levels measured before and after 2 doses of mRNA vaccine (BNT162b2 vaccine, Comirnaty, Pfizer-BioNTech or mRNA-1273 vaccine, Spikevax, Moderna), highly significant increases of antibody titers were observed. The antibody peak level was reached at 3 months following second dose administration, regardless of the underlying cause of immune depression and the time of pre-vaccine serology assessment after negativization. Conclusions: Our data indicate that HD patients and KTR exhibit a satisfying antibody response to a 2-dose series of mRNA vaccine, even in cases when infection-induced humoral immunity was poor or rapidly fading. Further studies are needed to evaluate the role of booster doses in conferring effective and durable protection in weak patient categories.

Physical activity and renal function in the Italian kidney transplant population.

BACKGROUND: The well-documented benefits of physical activity (PA) are still poorly characterized in long-term kidney transplant outcome. This study analyzed the impact over a 10-year follow-up of PA on graft function in Italian kidney transplant recipients (KTRs). METHODS: Since 2002, the Italian Transplant-Information-System collected donor and recipient baseline and transplant-related parameters in KTRs. In 2015, 'penchant for PA' (PA ≥ 30-min, 5 times/week) was added. Stable patients aged ≥18 years at the time of first-transplantation were eligible. KTRs with at least 10-year follow-up were also analyzed. Mixed-effect regression models were used to compare eGFR changes over time in active versus non-active patients. RESULTS: PA information was available for 6,055 KTRs (active 51.6%, non-active 48.4%). Lower penchant for PA was found in overweight and obese patients (OR = 0.84; OR = 0.48, respectively), in those with longer dialysis vintage (OR = 0.98 every year of dialysis), and older age at transplant. Male subjects showed greater penchant for PA (OR = 1.25). A slower decline of eGFR over time was observed in active KTRs compared to non-active, and this finding was confirmed in the subgroup with at least 10-year follow-up (n = 2,060). After applying the propensity score matching to reduce confounding factors, mixed-effect regression models corroborated such better long-term trend of graft function preservation in active KTRs. CONCLUSIONS: Penchant for PA is more frequent among male and younger KTRs. Moreover, in our group of Italian KTRs, active patients revealed higher eGFR values and preserved kidney function over time, up to 10-years of follow-up.

Sodium Prescription in the Prevention of Intradialytic Hypotension: New Insights into an Old Concept.

BACKGROUND: Sodium prescription in patients with intradialytic hypotension remains a challenge for the attending nephrologist, as it increases dialysate conductivity in hypotension-prone patients, thereby adding to dietary sodium levels. METHODS: New sodium prescription strategies are now available, including the use of a mathematical model to compute the sodium mass to be removed during dialysis as a physiological controller. RESULTS: This review describes the sodium load of patients with end-stage renal disease on chronic hemodialysis (HD) and discusses 2 strategies to remove excess sodium in patients prone to intradialytic hypotension, namely, Profiled HD and the hemodiafiltration Aequilibrium System. CONCLUSION: The Profiled HD and Aequilibrium System trial both proved effective in counteracting intradialytic hypotension.

Removal of free light chains in hemodialysis patients without multiple myeloma: a crossover comparison of three different dialyzers.

BACKGROUND: Immunoglobulin light chains are classified as middle molecule uremic toxins able to interact with B lymphocyte membranes leading to the activation of transmembrane signaling. The ensuing impairment of neutrophil function can contribute to the chronic inflammation state of uremic patients, and the increased risk of bacterial infections or vascular calcifications. The aim of this crossover observational study was to assess the difference in free light chain removal by three different hemodialysis filters in patients not affected by multiple myeloma. METHODS: Free light chain removal was compared in the polymethylmethacrylate (PMMA) membrane Filtryzer BK-F, the polyphenylene HFR17 filter and the conventional polysulfone filter F7HPS. Twenty chronic hemodialysis patients were enrolled: mean age was 67.7 ± 17.0 years, M/F = 14/6, dialysis vintage (months) 25.5 ± 32.0. The patients were randomized into two groups of treatment lasting 6 weeks each. The dialysis sessions checked were the midweek sessions and the blood was drawn at times 0, 120' and 240'. Kappa (k) and lambda (λ) light chain levels, ß2microglobulin (ß2M), C reactive protein (CRP) and albumin were checked. RESULTS: K light chain levels were 345.0 ± 100.0 mg/L, λ light chains were 121.4 ± 27.0 mg/L. The values of k light chains at times 120' and 240' were significantly lower with PMMA and HFR17 than those obtained with F7. The reduction ratio per session (RRs) for k light chains was 44.1 ± 4.3% with HFR17, 55.3 ± 3.4% with PMMA, 25.7 ± 8.3% with F7 (p = 0.018). The RRs for λ light chains was 30.3 ± 2.9% with HFR17, 37.8 ± 17.3% with PMMA, 14.0 ± 3.9% with F7 (p = 0.032). As to ß2M, RRs was 42.4 ± 3.2% with HFR17 vs. 33.9 ± 2.8% with PMMA vs. 6.3 ± 1.9% with F7 (p = 0.022). The three filters tested showed no differences in CRP or albumin levels. CONCLUSION: In terms of light chain and ß2M removal, the PMMA and on-line HFR filters are similar and both are significantly more effective than the F7 filter in chronic dialysis patients. TRIAL REGISTRATION: The present trial was registered retrospectively ( NCT02950389 , 31/10/2016).

[New Perspectives in Post-Surgical Acute Kidney Injury During Sepsis].

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. Sepsis is a common complication in patients undergoing surgery and is a major risk factor for the development of acute kidney injury (SA-AKI). Prevention of AKI in surgery patients is largely based on identification of high baseline risk, monitoring, and reduction of nephrotoxic insults. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches.

Identification of palliative care needs and prognostic factors of survival in tailoring appropriate interventions in advanced oncological, renal and pulmonary diseases: a prospective observational protocol.

INTRODUCTION: It is estimated that of those who die in high-income countries, 69%-82% would benefit from palliative care with a high prevalence of advanced chronic conditions and limited life prognosis. A positive response to these challenges would consist of integrating the palliative approach into all healthcare settings, for patients with all types of advanced medical conditions, although poor clinician awareness and the difficulty of applying criteria to identify patients in need still pose significant barriers. The aim of this project is to investigate whether the combined use of the NECPAL CCOMS-ICO and Palliative Prognostic (PaP) Score tools offers valuable screening methods to identify patients suffering from advanced chronic disease with limited life prognosis and likely to need palliative care, such as cancer, chronic renal or chronic respiratory failure. METHODS AND ANALYSIS: This multicentre prospective observational study includes three patient populations: 100 patients with cancer, 50 patients with chronic renal failure and 50 patients with chronic pulmonary failure. All patients will be treated and monitored according to local clinical practice, with no additional procedures/patient visits compared with routine clinical practice. The following data will be collected for each patient: demographic variables, NECPAL CCOMS-ICO questionnaire, PaP Score evaluation, Palliative Performance Scale, Edmonton Symptom Assessment System, Eastern Cooperative Oncology Group Performance Status and data concerning the underlying disease, in order to verify the correlation of the two tools (PaP and NECPAL CCOMS-ICO) with patient status and statistical analysis. ETHICS AND DISSEMINATION: The study was approved by local ethics committees and written informed consent was obtained from the patient. Findings will be disseminated through typical academic routes including poster/paper presentations at national and international conferences and academic institutes, and through publication in peer-reviewed journals.

[Discovering uncommon nephropathies: a case of acute kidney damage from malaria].

Malaria is one of the most common infectious diseases in the world with a high prevalence in developing countries. Renal impairment occurs in 40% of Plasmodium falciparum infections; glomeruli, tubules or interstitium can be involved with different pathophysiological mechanisms. We describe a case of severe acute renal failure caused by P. falciparum malaria in a young woman from the Ivory Coast. Renal biopsy revealed severe and widespread acute tubular necrosis and the presence of blackish pigment granules in the glomerular and peritubular capillaries, negative for iron histochemical staining; in electron microscopy we found rounded-oval-shaped structures containing cytoplasmic organelles, electrondensic granules and cellular debris, likely of infectious origin, within monocyte-macrophages located in the tubular lumen. Specific Antigen for P. falciparum and malarial parasite in blood were positive, with very rare trophozoites and gametocytes compatible with Plasmodium falciparum. Steroid therapy and specific antiparasitic therapy were set up with progressive functional improvement until complete recovery. This case highlights the importance of paying maximum attention to low incidence pathologies in our country, considering the continuous migratory movements of these years that can cause an increase in these diseases; anamnestic data are essential for a timely diagnosis which can contribute to a rapid remission avoiding severe complications.

Renal Thrombotic Microangiopathy in Concurrent COVID-19 Vaccination and Infection.

We report on the development of nephrotic proteinuria and microhematuria, with histological features of renal thrombotic microangiopathy (TMA), following the first dose of BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) and COVID-19 diagnosis. A 35-year-old previously healthy man was admitted at our hospital due to the onset of foamy urine. Previously, 40 days earlier, he had received the first injection of the vaccine, and 33 days earlier, the RT-PCR for SARS-CoV-2 tested positive. Laboratory tests showed nephrotic proteinuria (7.9 gr/day), microhematuria, serum creatinine 0.91 mg/dL. Kidney biopsy revealed ultrastructural evidence of severe endothelial cell injury suggestive of a starting phase of TMA. After high-dose steroid treatment administration, complete remission of proteinuria was achieved in a few weeks. The association of COVID-19 with renal TMA has been previously described only in patients with acute renal injury. Besides, the correlation with COVID-19 vaccine has not been reported so far. The close temporal proximity (7 days) between the two events opens the question whether the histological findings should be ascribed to COVID-19 itself or to vaccine injection.

Persistence of Antibody Responses to the SARS-CoV-2 in Dialysis Patients and Renal Transplant Recipients Recovered from COVID-19.

Nephropathic subjects with impaired immune responses show dramatically high infection rates of coronavirus disease 2019 (COVID-19). This work evaluated the ability to acquire and maintain protective antibodies over time in 26 hemodialysis patients and 21 kidney transplant recipients. The subjects were followed-up through quantitative determination of circulating SARS-CoV-2 S1/S2 IgG and neutralizing antibodies in the 6-month period after clinical and laboratory recovery. A group of 143 healthcare workers with no underlying chronic pathologies or renal diseases recovered from COVID was also evaluated. In both dialysis and transplanted patients, antibody titers reached a zenith around the 3rd month, and then a decline occurred on average between the 270th and 300th day. Immunocompromised patients who lost antibodies around the 6th month were more common than non-renal subjects, although the difference was not significant (38.5% vs. 26.6%). Considering the decay of antibody levels below the positivity threshold (15 AU/mL) as "failure", a progressive loss of immunisation was found in the overall population starting 6 months after recovery. A longer overall antibody persistence was observed in severe forms of COVID-19 (p = 0.0183), but within each group, given the small number of patients, the difference was not significant (dialysis: p = 0.0702; transplant: p = 0.1899). These data suggest that immunocompromised renal patients recovered from COVID-19 have weakened and heterogeneous humoral responses that tend to decay over time. Despite interindividual variability, an association emerged between antibody persistence and clinical severity, similar to the subjects with preserved immune function.

COVID-19 Infection: Viral Clearance and Antibody Response in Dialysis Patients and Renal Transplant Recipients.

BACKGROUND/AIMS: The coronavirus disease 2019 (CO-VID-19) pandemic is the major current health emergency worldwide, adding a significant burden also to the community of nephrologists for the management of their patients. Here, we analyzed the impact of COVID-19 infection in renal patients to assess the time to viral clearance, together with the production and persistence of IgG and IgM antibody response, in consideration of the altered immune capacity of this fragile population. METHODS: Viral clearance and antibody kinetics were investigated in 49 renal patients recovered from COVID-19 infection: 7 of them with chronic decompensated renal failure, 31 under dialysis treatment, and 11 kidney transplant recipients. RESULTS: The time span between the diagnosis of infection and recovery based on laboratory testing (2 negative nasopharyngeal swabs in consecutive days) was 31.7 ± 13.3 days. Three new positive cases were detected from 8 to 13 days following recovery. At the first serological determination after swab negativization, all the patients developed IgG and IgM antibodies. The semiquantitative analysis showed a progressive increase in IgG and a slow reduction in IgM. DISCUSSION/CONCLUSION: In subjects with decompensated chronic kidney disease, under dialysis and in transplant recipients, viral clearance is lengthened compared to the general population. However, in spite of their common status of immunodepression, all of them were able to produce specific antibodies. These data might provide useful insights for monitoring and planning health-care activities in the weak category of patients with compromised renal function recovered from COVID-19.

Bloodstream infections and patient survival with tunneled-cuffed catheters for hemodialysis: A single-center observational study.

BACKGROUND: In hemodialysis patients, a tunneled-cuffed permanent catheter is mandatory when the arteriovenous fistula is not feasible. The major risks of the use of tunneled-cuffed permanent catheter are bloodstream infections. The aim of this study is to analyze bloodstream infections from tunneled-cuffed permanent catheter in hemodialysis patients. METHODS: An observational prospective study was carried out and 79 hemodialysis patients with tunneled-cuffed permanent catheter were enrolled. Patients were divided into those with bloodstream infections from tunneled-cuffed permanent catheter and those without. Their clinical and laboratory characteristics were compared. An original tunneled-cuffed permanent catheter lock therapy sequence was carried out combined with systemic antibiotic therapy. In case of antibiotic resistance, the tunneled-cuffed permanent catheter was removed. RESULTS: The patients affected by bloodstream infections from tunneled-cuffed permanent catheter were 16/79 (20.3%). The bloodstream infection from tunneled-cuffed permanent catheter's incidence rate was 0.52 per 1000 catheter days. Twenty-three bloodstream infections from tunneled-cuffed permanent catheter were found in 16/79 patients who used tunneled-cuffed permanent catheter. Staphylococcus aureus was the cause of bloodstream infection from tunneled-cuffed permanent catheter in 35% of the cases and Staphylococcus epidermidis in 30% of the cases. Risk factors were infection located in other organs and the presence of peripheral obstructive arterial disease. CONCLUSION: The enrolled cohort showed a reduced bloodstream infection from tunneled-cuffed permanent catheter incidence rate in comparison with the reference value (1 per 1000 catheter days). To reduce the number of bloodstream infections from tunneled-cuffed permanent catheter, hand hygiene and asepsis management of the tunneled-cuffed permanent catheter during the connection to the extracorporeal circuit and an original tunneled-cuffed permanent catheter lock therapy sequence seem to be the most efficient measures. Infections of other organs and the presence of peripheral obstructive arterial disease are the most important risk factors for bloodstream infections from tunneled-cuffed permanent catheter.

[Resilience in COVID-19 times: general considerations on the recovery of a 93-year-old patient on haemodialysis treatment].

We report the case of a 93-year-old woman on haemodialysis treatment for more than 30 months and with multiple comorbidities who recovered from a Covid-19 infection without any significant clinical problems. The patient has shown a delay in viral clearance with swab test negativization (confirmed) after 33 days; after testing positive again, she has resulted persistently negative, (confirmed after 49 days). After the first negative swab, IgG and IgM antibodies have been found; these have remained persistently positive after a month. As well as highlighting an unexpected resilience in an extremely fragile context, the analysis of this case draws attention to patients' management and, potentially, to the need to arrange dialysis treatments in isolation for some time after their "laboratory recovery".

Promotion of Pre- and Post-Transplant Physical Exercise in the Emilia-Romagna Region: The Network of the Program "Transplantation, Physical Activity, and Sport".

BACKGROUND: Following the positive experience of the national project "A transplant...and now it's time for sport," the Transplant Reference Center of the Emilia-Romagna Region has pursued the promotion of pre- and post-transplant physical exercise by developing a network. METHODS: The path involved the transplant centers and operative units (UU.OO) who wanted to target transplant and waiting list patients, who are clinically stable, to perform personalized exercise through a program (supervised or not) prescribed by a specialist in sports medicine. With the collaboration of the Collective Prevention and Public Health Service, the network was established, consisting of the sports medicine centers and the gyms that promote health for adapted physical activity (PS-AMA). To implement the network, training courses for all the professionals involved (doctors, nurses, exercise specialists) and operational meetings in the transplant centers-nephrology units with patients' associations have been organized. RESULTS: To date, there are 14 transplant centers and UU.OO, 9 sports medicine centers, and 45 PS-AMA involved in this network. Seven training courses were organized with the participation of 193 health professionals. Since January 2016, there have been 65 transplanted patients and 5 patients on the waiting list who practice the prescribed exercise. Of these, 45 carry out supervised exercise in PS-AMA; 25 perform autonomous exercise. Each patient is monitored every 6 months. No problems related to the exercise performance were recorded. CONCLUSIONS: The development of a network of professionals and associations is the key element to raise awareness of physical activity among transplanted and waiting-for-transplant patients, reducing the pathologies associated with a sedentary lifestyle.

[Membranous glomerulonephritis (MGN), ongoing studies]. / Glomerulonefrite membranosa, ongoing studies.

The membranous nephropathy (MN) is the major cause of nephrotic syndrome in in the adult, account for 20% of cases with annual incidence is 1 in 100.000. In the past 10 years, the role of podocytes has been identified; environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes (receptor of phospholipase A2, thrombospondin type 1) that become targets of specific autoantibodies with subsequent complement activation. The discovery of this mechanisms has opened new horizons in the therapy of MN and novel drugs are available with more specific mechanism of action. Rituximab, a monoclonal antibody directed against CD20 expressed by lymphocytes B, has been used in several trials and appears able to induce remission of nephrotic syndrome in 60% of patients (GEMRITUX trial) with similar risk profile. Nowadays it remains to define the most effective therapeutic pattern. In MN, the concept of targeting disease control, has permit novel therapies with specific blocking mechanisms (belimumab) and non-specific (ACTH) and new therapeutic options, such as ofatumumab, bortezomib and eculizumab, that have allowed to recognize pathological processes involved in the glomerular diseases.

Incidence and predictors of postoperative atrial fibrillation in kidney transplant recipients.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a complication of cardiothoracic and noncardiothoracic surgery. Kidney transplant recipients bear several known risk factors and may have a higher incidence of POAF. We retrospectively studied kidney and kidney/liver transplant recipients to estimate their POAF incidence and identify relevant risk factors. We also adapted a clinical score originally designed to predict thromboembolic risk in atrial fibrillation (AF; CHA2DS2-VASc) for assessing transplant patients. METHODS: We reviewed the clinical charts of kidney or kidney/liver transplant recipients from January 2005 to December 2008 at St. Orsola University Hospital Kidney Transplant Centre. Patients with and without POAF were compared on a number of clinical, laboratory, and instrumental data. RESULTS: The POAF incidence in kidney transplant recipients was 8.2%. Risk factors for POAF identified in univariate analyses included older recipient age, history of myocardial infarction, history of AF, liver/kidney transplantation, arterial stiffness, atherosclerotic plaques in the aorta or lower limbs, and diabetes mellitus. In a multivariate analysis, age, myocardial infarction history and combined liver/kidney transplantation were significant independent predictors of POAF. The modified CHA2DS2-VASc score proved to have a better predictive validity that the original CHA2DS2-VASc (area under the curve=0.71, 95% confidence interval=0.63-0.79 vs. area under the curve=0.62, 95% confidence interval=0.52-0.73, respectively). CONCLUSION: AF is a notable complication of kidney, and particularly simultaneous liver/kidney, transplant surgery. Age, previous myocardial infarction, and simultaneous liver/kidney transplant independently predicted POAF. The modified CHA2DS2-VASc score could be useful to predict POAF risk in kidney transplant candidates.