[Semaglutide in Chronic Kidney Disease: Great Enthusiasm. But How Does It Work?] / La Semaglutide nella Malattia Renale Cronica: tanto entusiasmo. Ma come funziona?

Chronic Kidney Disease (CKD) is a clinical condition characterized by the progressive loss of kidney function. 10% of the world's population is affected by this condition, which represents the fifth leading cause of death globally. Furthermore, CKD is associated with increased risk of fatal and non-fatal cardiovascular events, and progression to end-stage renal disease. Over the last twenty years, an exponential growth in its prevalence and incidence has been observed. For this reason, various drugs have been developed and implemented in clinical practice, with various mechanisms, with the aim of reducing and minimizing this dramatic "cardio-renal" risk. These include SGLT2 inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists. However, a large proportion of CKD patients do not respond sufficiently to these treatments. GLP-1 receptor agonists represent a class of antidiabetic and nephroprotective drugs that are very promising in improving the prognosis of patients with CKD, especially if associated with one of the above-mentioned classes. In this article, we discuss the direct and indirect mechanisms through which one of the GLP-1 agonists, semaglutide, ensures nephro- and cardioprotection in patients with CKD and type 2 diabetes.

Improving Kidney Disease Care: One Giant Leap for Nephrology.

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence have prompted the development and implementation of novel drugs in clinical practice with the aim of treating the 'specific cause' of kidney disease (including chronic kidney disease, glomerular disease, and genetic kidney disorders) and the main immunological complications following kidney transplantation. Herein, we provide an overview of the principal emerging drug classes with proved efficacy in the context of the aforementioned clinical conditions. This can represent a simplified guide for clinical nephrologists to remind them of the vast and heterogeneous armamentarium of drugs that should be used in the present and the future to improve the management of patients suffering from kidney disease.

Validation of GeneFinder COVID-19 Ag Plus Rapid Test and Its Potential Utility to Slowing Infection Waves: A Single-Center Laboratory Evaluation Study.

Diagnostic laboratory tools are essential to keep everyone safe and track newly emerging variants; on the other hand, "filter" screening tests recognizing positivity are valuable tools to avoid hectic laboratory work that, besides COVID-19, are also part of the routine. Therefore, complementary assays, such as rapid antigen tests (RATs), are essential in controlling and monitoring virus spread within the community, especially in the asymptomatic population. A subset of nasopharyngeal swab specimens resulted in SARS-CoV-2 positive and investigated for genomic characterization were used for RAT validation. RATs were performed immediately after sampling, following the manufacturer's instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimens' collection. Out of 603 patients, 145 (24.05%) tested positive by RT-PCR and RAT and 451 (74.79%) tested negative by both methods; discordant results (RT-PCR+/RAT- or RT-PCR-/RAT+) were obtained in 7 patients (1.16%). RATs' overall specificity and sensitivity were 96.03% (95%CI: 91.55-98.53%) and 99.78% (95%CI: 98.77-99.99%), respectively, taking RT-PCR as the reference. Overall, RAT negative predictive value was 98.69% (95%CI 97.17-99.40%). The GeneFinder COVID-19 Ag Plus Rapid Test performed well as a screening test for early diagnosis of COVID-19, especially in asymptomatic subjects. The data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAT are unlikely to be infectious. GeneFinder COVID-19 Ag Plus Rapid Test also works on variants of concern (VOC) delta and omicron BA.1 and BA.2.

NFKB1 promoter polymorphism: A new predictive marker of cytomegalovirus infection after kidney transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection represents a common cause of morbidity and mortality in kidney transplant recipients (KTR). The NF-kB signaling pathway is highly involved in the pathogenesis of CMV infection. The -94ins/delATTG functional polymorphism in the promoter of NFKB1 has been associated with low intracellular levels of the protein and high incidence of inflammatory and autoimmune disease. In this study, we evaluated the association of this NFKB1 polymorphism with the risk of CMV infection. METHODS: CMV infection was defined as virus isolation or detection of viral antigens or nucleic acid in any body fluid or tissue specimen. Using Cox regression and survival analysis, we analyzed the association between the polymorphism and CMV infection as well as recurrence in the first 12 months after transplantation. RESULTS: We analyzed the -94ins/delATTG NFKB1 polymorphism of 189 KTRs. The 65% of CMV infections occurred in ins/ins group. Survival free from CMV infection was 54.7% for ins/ins group and 79.4% for deletion carriers one year after transplantation (P < 0.0001). At multivariate regression, deletion carriers showed a lower risk of CMV infection and recurrence with respect to ins/ins KTRs (HR = 0.224 P = 0.0002; HR = 0.307, P = 0.012, respectively). CONCLUSIONS: In conclusion, pretransplantation screening for NFKB1 -94ins/delATTG polymorphism may predict CMV infection and improve the management of patients at higher risk of infection in the post-transplant period.

How to improve duration and efficiency of the antiproteinuric response to Ramipril: RamiPROT-a prospective cohort study.

BACKGROUND: The antiproteinuric pharmacokinetics of Ramipril in response to different doses and modalities of administration has been poorly investigated so far. STUDY DESIGN: Prospective, open-label and not placebo controlled study. SETTING AND PARTICIPANTS: 40 Caucasian adult patients having GFR ≥ 50 mL/min, proteinuria 1-3 g/day; SBP/DBP ≤ 150/90 mmHg were recruited between June 2014 and November 2014. FACTOR AND OUTCOME: Impact on 24 h proteinuria and fractioned proteinuria of Ramipril given at different dosages (2.5 mg/day or Ramipril 5 mg/day or Ramipril 10 mg/day) and with different daily administration modalities (single or two divided doses) for cycles of 10 days. MEASUREMENTS: At the end of each cycle, 24 h and fractioned proteinuria on three timed urinary collections (morning, afternoon and night) were measured. RESULTS: Compared to baseline, Ramipril significantly reduced 24 h proteinuria at each dose and modality of administration. In particular, the greatest effects were evident with the higher and divided dose of the drug. The analysis of the fractioned proteinuria showed that the greatest reduction was obtained in the night urinary collection by administering Ramipril 10 mg/day in two divided doses. LIMITATIONS: Small sample size. CONCLUSIONS: Ramipril reduces proteinuria at any of the tested doses. Although the using of high and divided doses seems to maximize the antiproteinuric effect of the drug, possibly due to a better pharmacological coverage of the nocturnal period.

[Is it feasible to improve the duration and the efficiency of Ramipril anti-proteinuric response?]. / È possibile migliorare la durata e l'efficacia della risposta anti-proteinurica di Ramipril?

BACKGROUND: Ramipril administered once daily is characterized by an attenuation of its pharmacological activity in the following 24 hours, whose effects on antiproteinuric activity have not yet been investigated. METHODS: The antiproteinuric efficacy of Ramipril has been evaluated in a cross-over study in 20 patients with renal disease, proteinuria and hypertension (GFR50 mL / min, proteinuria <3 g / day; SBP/DBP 150/90 mmHg). Proteinuria was measured over 24 hours on three consecutive urine collections (morning, afternoon and night) in the absence of antiproteinuric drugs and after ten days of treatment with single morning administration of Ramipril 2.5 mg or Ramipril 10 mg. RESULTS: At baseline: mean proteinuria was not significantlychanged over the course of the three urinary collections (88 7.2 mg/h in the morning of 80 10.5 mg/h in the afternoon and 81 10.1 mg/hr during the night). After Ramipril 2.5 mg/day: slight reduction in mean proteinuria, with no significant differences between collections (80 11 mg/h in the morning, 69 7.4 mg/h in the afternoon and 75 9.1 mg/h during the night). After Ramipril 10 mg/day: afternoon and night values of proteinuria were significantly reduced compared to baseline; noctural proteinuria was significantly lower than morning value (51 7.5 mg/h vs. 81 10 mg/h, p <0.05). CONCLUSION: The antiproteinuric effectiveness of Ramipril tends to decrease significantly over the 24hours after a single daily administration. An increase and/or division of Ramipril dose might help to stabilize and to maximizeits antiproteinuric effectiveness.

An uncommon presentation of an uncommon nephropathy: the karyomegalic interstitial nephritis.

Karyomegalic interstitial nephritis (KIN) is a rare and certainly underdiagnosed nephropathy. It is characterized by a peculiar histological picture of interstitial nephritis associated with the presence of hyperchromatic, abnormally enlarged nuclei of tubular epithelial cells. KIN has an uncertain etiology, but should be suspected in young patients in the second or third decade of life presenting with progressive renal failure, proteinuria and/or hematuria and a history of recurrent respiratory infections. In these cases, the diagnosis should be suspected and confirmed by a renal biopsy. Herein, we report a case of KIN with atypical clinical presentation in a young patient with progressive kidney failure without proteinuria or hematuria or history of recurrent respiratory infections.

Coupled plasma filtration adsorption for the treatment of a patient with acute respiratory distress syndrome and acute kidney injury: a case report.

Coupled plasma filtration adsorption (CPFA) is an extracorporeal blood purification therapy based on non-specific pro- and anti-inflammatory mediator adsorption on a special resin cartridge coupled with continuous veno-venous haemofiltration or continuous veno-venous haemodiafiltration and is one of the emerging treatments for septic patients. However, in the literature, there are limited data about its efficacy in treating patients with acute diseases but without the traditional criteria for sepsis. We describe the case of a 43-year-old male who developed acute respiratory distress syndrome secondary to pneumonia and acute kidney injury, whose clinical conditions rapidly improved after early CPFA therapy.