"Eculizumab First" in the Management of Posttransplant Thrombotic Microangiopathy.

Introduction: Posttransplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3% to 14% of kidney transplants (KTs), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first 3 months after transplant and can be a manifestation of de novo disease or the recurrence of previous atypical hemolytic uremic syndrome (aHUS). Abnormalities in complement regulation genes could explain the increased susceptibility of some patients to PT-TMA. Eculizumab is a humanized monoclonal antibody that inhibits the formation of the membrane attack complex C5b-9. The aim of this study is to evaluate the efficacy of eculizumab as treatment for PT-TMA. Methods: We retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA. Results: Kidney biopsy was performed in 91.1% of patients, and complement genetic study was performed in 64.4%. Of the kidney biopsies, 85.4% showed signs of TMA; genetic analysis revealed 1 pathogenetic variant, 2 variants of uncertain significance, 1 likely benign variant, 8 risk polymorphisms, and 27 risk haplotypes. After 2 weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After 6 months, 28.8% of patients had a complete renal recovery whereas 44.4% had a partial recovery. Conclusion: This is, to our knowledge, the largest series of KT patients with PT-TMA treated with eculizumab. These data suggest that eculizumab is associated with a normalization of hemolysis indices and an important and progressive improvement of graft function.

Estimated glomerular filtration rate in observational and interventional studies in chronic kidney disease.

Estimated glomerular filtration rate is considered the principal measure of kidney function and, together with albuminuria, is a relevant prognostic factor for the development of end-stage kidney disease. Due to the strong association between estimated glomerular filtration rate and clinical events, such as commencement of dialysis, cardiovascular outcomes and all-cause death, estimated glomerular filtration rate is crucial for clinical decision-making in terms of scheduling follow-up and pharmacological interventions, and planning renal replacement therapies in advanced chronic kidney disease. In this review we discuss the available methods for measuring glomerular filtration rate and for estimating it through mathematical equations developed over the last few decades. We summarize the prognostic association of different percentages of estimated glomerular filtration rate decline and the main clinical outcomes, and how treatments modify estimated glomerular filtration rate decline and the risk of future endpoints. We also examine the role of pre-clinical trial slope and that of estimated glomerular filtration rate as a useful biomarker when evaluating patients for inclusion into both observational and interventional studies.

Renal Benefits of CO2 as a Contrast Media for EVAR Procedures: New Perspectives on 1 Year Outcomes.

BACKGROUND AND OBJECTIVES: Endovascular aneurism repair (EVAR) is a minimally invasive alternative to open surgery for the treatment of abdominal aortic aneurysm. Iodine contrast medium (ICM) is considered the gold standard, at the high price of related nephrotoxicity and allergic reactions. Carbon dioxide (CO2) has been suggested as an alternative non-nephrotoxic contrast media agent. We aimed to evaluate the safety and the renal impact of the administration of CO2, compared with ICM in EVAR procedures. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively reviewed data of patients who underwent EVAR at the Vascular Surgery Department of the Sant'Orsola Hospital in Bologna. Estimated glomerular filtration rate (eGFR) was evaluated before intervention, immediately after and at 12 months. RESULTS: In total, 22 patients received CO2 and low-dose ICM (CO2 Group) and 22 received standard ICM (Control Group), matched for clinical characteristics and renal function at the time of procedure. Pre and post-operative renal function values (eGFR) were compared between the two groups: in the immediate post-operative the group treated with CO2 and low-dose ICM globally showed a slight improvement in renal function (mean eGFR +5.10%±3.2), meanwhile the group treated with standard dose of ICM presented a significant worsening of renal function compared with pre-procedure values (mean eGFR -9.65%±4). Incidence of post-contrast acute kidney injury (PC-AKI) was 9% in the CO2 group vs 27% in the Control group. At 12 months, the renal impairment was significantly greater in the ICM group than in the CO2 group (mean eGFR decrease -19.2%±11.1 and -7.40%±3.5, respectively). CONCLUSIONS: Administration of either CO2 alone or along with low-dose ICM showed to be safer than full-dose ICM alone, lowering the incidence of PC-AKI in patients undergoing EVAR. Unexpectedly, our study revealed also a significant worsening of renal function in patients treated with standard dose of ICM in 1-year follow-up, introducing the concept that acute renal damage caused by ICM could elicit a chronic injury process that affect long-term renal outcomes. CLINICAL IMPACT: Evaluating the safety and the renal impact of the administration of CO2, compared to Iodinate Contrast Medium, in EVAR procedures represents a first step in order to further tayloring medical procedures on patients characteristics. Our findings can guide the clinicians and surgeons in the procedures choice, not considering only the immediate effect of ICM on renal function but also the potential long-term effects.

Anti-Inflammatory Approach in Chronic Dialysis Patients with SARS-CoV-2: ATA or PMMA Dialyzers?

INTRODUCTION: High-flux hemodialysis membranes may modulate the cytokine storm of SARS-CoV-2, but their impact on chronic hemodialysis (CHD) patients is unknown. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers and clinical outcomes in CHD patients with SARS-CoV-2. METHODS: A prospective, observational study on CHD patients with SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021. Pre- and postdialysis C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) were determined at each session. Patients who underwent on-line hemodiafiltration (OLHDF) with a PMMA dialyzer were compared with those treated with OLHDF with a ATA dialyzer. The primary endpoint was the differences in the reduction ratio per session (RR) of CRP, PCT, IL-6, and IL-6 RR >25%. RESULTS: We consecutively enrolled 74 CHD patients with COVID-19, 48 were treated with ATA membrane, and 26 with PMMA. Median IL-6 RR was higher in the ATA group compared to PMMA (17.08%, IQR -9.0 to 40.0 vs. 2.95%, IQR -34.63 to 27.32). Median CRP RR was 7.77% (IQR 2.47-13.77) in the ATA group versus 4.8% (IQR -2.65 to 11.38) in the PMMA group (p = 0.0017). Median PCT-RR% was 77.38% (IQR 70.92-82.97) in ATA group versus 54.59% (IQR 42.62-63.16) in the PMMA group (p < 0.0001). A multiple logistic regression analysis with IL-6 RR >25% as the outcome including the membrane employed, pre-dialysis IL-6, CRP, PCT, and ferritin showed that ATA led to a higher probability to reach the outcome (OR 1.891, 95% CI 1.273-2.840, p = 0.0018) while higher CRP favors the risk of lower IL-6 RR values (OR 0.910, 95% CI 0.868-0.949, p ≤ 0.0001). CONCLUSIONS: In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile, regarding IL-6 RR, compared to PMMA.

Acute Kidney Injury and Blood Purification Techniques in Severe COVID-19 Patients.

Although most patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) experience respiratory manifestations, multi-organ dysfunction is frequent. Almost 20% of hospitalized patients with SARS-CoV-2 infection develop acute kidney injury (AKI). The pathophysiology of AKI is a result of both the direct and indirect effects of SARS-CoV-2 infection, including systemic inflammatory responses, the activation of the renin-angiotensin-aldosterone system (RAAS), and endothelial and coagulative dysfunction. Underlying SARS-CoV-2 infection-associated AKI, an immunological hyper-response with an unbalanced innate and adaptative response defined as a "cytokine storm" has emerged. Numerous agents have been tested in an effort to mitigate the cytokine storm, and a range of extracorporeal cytokine removal techniques have been proposed as potential therapeutic options. In the present review, we summarize the main pathogenetic mechanisms underlying COVID-19-related AKI in order to provide an appropriate individual therapeutic strategy to improve clinical outcomes and limit the progression of early disease.

Precision Nephrology in Patients with Diabetes and Chronic Kidney Disease.

Diabetes is the leading cause of kidney failure and specifically, diabetic kidney disease (DKD) occurs in up to 30% of all diabetic patients. Kidney disease attributed to diabetes is a major contributor to the global burden of the disease in terms of clinical and socio-economic impact, not only because of the risk of progression to End-Stage Kidney Disease (ESKD), but also because of the associated increase in cardiovascular (CV) risk. Despite the introduction of novel treatments that allow us to reduce the risk of future outcomes, a striking residual cardiorenal risk has been reported. This risk is explained by both the heterogeneity of DKD and the individual variability in response to nephroprotective treatments. Strategies that have been proposed to improve DKD patient care are to develop novel biomarkers that classify with greater accuracy patients with respect to their future risk (prognostic) and biomarkers that are able to predict the response to nephroprotective treatment (predictive). In this review, we summarize the principal prognostic biomarkers of type 1 and type 2 diabetes and the novel markers that help clinicians to individualize treatments and the basis of the characteristics that predict an optimal response.

Safety of Intradialytic Bamlanivimab/Etesevimab Administration in Two COVID-19 Dialysis Outpatients.

Chronic hemodialysis patients are at high risk of severe COVID-19 disease and death related to the infection. Anti-spike monoclonal antibodies administration reduces risk of disease progression and hospitalization in high-risk subjects but no clear data on end-stage renal disease are available. We report 2 cases of Bamlanivimab/Etesevimab administration to two not hospitalized chronic hemodialysis patients with SARS-CoV2 infection. Since they are large molecules (human immunoglobulin G1) with molecular weight of 146,000 Da, administration was conducted during the second hour of the dialysis session with no adverse reaction. Conclusions: Intradialytic administration of Bamlanivimab/Etesevimab could be considered safe and may allow adequate clinical observation time without hospital-stay prolongation.

Sickle Cell Trait and SARS-CoV-2-Induced Rhabdomyolysis: A Case Report.

BACKGROUND Rhabdomyolysis is a syndrome characterized by muscle necrosis and the subsequent release of intracellular muscle constituents into the bloodstream. Although the specific cause is frequently evident from the history or from the immediate events, such as a trauma, extraordinary physical exertion, or a recent infection, sometimes there are hidden risk factors that have to be identified. For instance, individuals with sickle cell trait (SCT) have been reported to be at increased risk for rare conditions, including rhabdomyolysis. Moreover, there have been a few case reports of SARS-CoV-2 infection-related rhabdomyolysis. CASE REPORT We present a case of a patient affected by unknown SCT and admitted with SARS-CoV-2 pneumonia, who suffered non-traumatic non-exertional rhabdomyolysis leading to acute kidney injury (AKI), requiring acute hemodialysis (HD). The patients underwent 13 dialysis session, of which 12 were carried out using an HFR-Supra H dialyzer. He underwent kidney biopsy, where rhabdomyolysis injury was ascertained. No viral traces were found on kidney biopsy samples. The muscle biopsy showed the presence of an "open nucleolus" in the muscle cell, which was consistent with virus-infected cells. After 40 days in the hospital, his serum creatinine was 1.62 mg/dL and CPK and Myoglobin were 188 U/L and 168 ng/mL, respectively; therefore, the patient was discharged. CONCLUSIONS SARS-CoV-2 infection resulted in severe rhabdomyolysis with AKI requiring acute HD. Since SARS-CoV-2 infection can trigger sickle-related complications like rhabdomyolysis, the presence of SCT needs to be ascertained in African patients.