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BACKGROUND/OBJECTIVES: Comprehensive conservative management (CCM) is a viable treatment option for elderly patients with end-stage kidney disease (ESKD). However, it involves a significant change in dietary habits, such as adopting a low-protein diet. Therefore, it is crucial to understand its impact on the patient's quality of life (QoL), particularly when compared to hemodialysis (HD). The study aims to evaluate the differences in the QoL between patients undergoing CCM and HD. METHODS: The study included 50 patients over 75 with ESKD, with 25 patients in the CCM group and 25 in the HD group. The CCM group followed a personalized low-protein diet, while the HD group did not have protein restrictions. Various parameters were assessed, including demographic data, urine output, blood tests, comorbidity index, Visual Analog Scale (VAS), and hospitalization. The SF-12 questionnaire assessed the QoL, and the Physical Composite Score (PCS) and Mental Composite Score (MCS) were calculated. RESULTS: The study revealed no age and comorbidity index differences between CCM and HD patients. In contrast, CCM patients reported significantly better physical and mental well-being than HD patients. In univariate analysis, CCM (B 0.24, p = 0.001), protein intake (B -0.004, p = 0.008), hospitalization (B -0.18, p = 0.024), urine output (B 0.25, p = 0.001), and VAS (B -0.26, p < 0.001) influenced the PCS. At the same time, only the type of treatment (B = 0.15, p = 0.048), urine output (B 0.18, p = 0.02), and VAS (B -0.14, p = 0.048) influence the MCS. In contrast, in multivariate analysis, only CCM contributed to an improved PCS (B 0.19, p = 0.003) and MCS (B 0.16, p = 0.03), while a higher VAS worsened the PCS (B -0.24, p < 0.001) and MCS (B -0.157, p = 0.0024). CONCLUSIONS: In elderly patients with similar basal conditions, health-related QoL perception is better in CCM than in HD patients.

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Background: The possibility of keeping liver grafts viable and functioning until transplantation has been explored since the 1950s. However, the current modalities of Normothermic Machine Perfusion (NMP) have shown several limitations, such as the inability to correct electrolytes and pH derangements efficiently. Combining NMP with continuous kidney replacement therapy (CKRT) might provide a promising new model to overcome these issues. Methods: An NMP that covers the organ perfusion, oxygenation, carbon dioxide removal, and thermal balance was connected to a CKRT circuit to ensure physiological hydro-electrolytes, acid-base balance, and catabolite removal from the perfusate. Results: The integration of NMP and CKRT maintains a neoplastic liver in a perfusion system with physiological perfusate for 100 h. CKRT re-established and maintained the hydro-electrolyte and acid-base status throughout the 100 h of perfusion. Significant limitations were the need for frequent monitoring of electrolytes and acid-base disorders and the loss of low molecular weight nutrients, which have to be replenished by manual infusion into the system. Conclusions: This novel CKRT-NMP integrated system may represent a practical and versatile model to support organs' perfusion and extend preservation times. Further experiments are needed to fix monitoring and adjusting processes.

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In the evolving landscape of nephrology and kidney transplants, assessing renal functional reserve (RFR) in living kidney donors is essential for ensuring donor safety and successful transplantation. This study explores the use of the Intra-Parenchymal Renal Resistive Index Variation (IRRIV) test, a novel non-invasive method, to measure RFR in living donors. Our observational study included 11 participants undergoing living kidney donations, evaluated using the IRRIV-based Renal Stress Test (RST) before and 12 months post-nephrectomy. The study demonstrated significant changes in creatinine and eGFR CKD-EPI levels post-donation, with an average creatinine rise from 69 to 97 µmol/L and a reduction in eGFR from 104 to 66 mL/min/1.73 m2. These variations align with the expected halving of nephron mass post-nephrectomy and the consequent recruitment of RFR and hyperfiltration in the remaining nephrons. This pilot study suggests that the IRRIV-based RST is a practical, safe, and reproducible tool, potentially revolutionizing the assessment of RFR in living kidney donors, with implications for broader clinical practice in donor eligibility evaluation, even in borderline renal cases. Furthermore, it confirms the feasibility of RST in living kidney donors and allows us to assess the sample size in 48 donors for a future study.

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Regional Citrate Anticoagulation (RCA) is considered the first-line anticoagulation for Continuous Kidney Replacement Therapy (CKRT). The RCA requires strict protocols and trained staff to avoid unsafe use and ensure its benefit. We have analyzed all our CKRT prescriptions from December 2020 to April 2022 anonymously, collecting data on CKRT, lab tests, clinical conditions, and complications of RCA. In addition, in order to better detect citrate accumulation, we have performed an RCA protocol by reducing the CaTot/Ca2+ ratio cut-off from 2.50 to 2.40 and increasing the number of calcium checks according to its trend. Among the 374 patients in CKRT, 104 received RCA prescriptions, of which 11 (10.6%) were discontinued: 4 for the suspicion of citrate accumulation, 1 for the development of metabolic alkalosis, 1 for the shift to a different CKRT procedure due to the need for a higher bicarbonate dose, 4 for the elevation of hepatocytolysis indexes, and 1 due to a preemptive discontinuation following massive post-surgery bleeding. None of the patients have had citrate toxicity as indicated by a CaTot/Ca2+ greater than 2.50, and our protocol has allowed the early identification of patients who might develop clinical citrate toxicity.

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Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in PKHD1, a gene encoding fibrocystin/polyductin (FC1), a membrane-associated receptor-like protein involved in the regulation of tubular cell adhesion, proliferation and apoptosis. Although it is generally accepted that apoptosis is implicated in ARPKD, the question of whether increased apoptosis is a normal response to abnormal cell proliferation or, instead, it is a primary event, is still subject to debate. In support of the latter hypothesis, we hereby provide evidence that apoptosis occurs in the absence of hyper-proliferation of FC1-depleted kidney cells. In fact, a decrease in cell proliferation, with a concomitant increase in apoptotic index and caspase-3 activity was observed in response to FC1-depletion by PKHD1 siRNA silencing in HEK293 and 4/5 tubular cells. FC1-depletion also induced reduction in ERK1/2 kinase activation, upregulation of the pro-apoptotic protein p53 and activation of NF-kappaB, a transcription factor which reduces apoptosis in many organs and tissues. Interestingly, selective inactivation of NF-kappaB using either an NF-kappaB decoy or parthenolide, a blocker of IKK-dependent NF-kappaB activation, reduced, rather then increased, apoptosis and p53 levels in FC1-depleted cells. Therefore, the proapoptotic function of NF-kappaB during cell death by FC1-depletion in kidney cells is evident.

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Cyst growth and expansion in autosomal dominant polycystic kidney disease (ADPKD) has been attributed to numerous factors, including ATP, cAMP and adenosine signalling. Although the role of ATP and cAMP has been widely investigated in PKD1-deficient cells, no information is currently available on adenosine-mediated signalling. Here we investigate for the first time the impact of abnormalities of polycystin-1 (PC1) on the expression and functional activity of adenosine receptors, members of the G-protein-coupled receptor superfamily. Pharmacological, molecular and biochemical findings show that a siRNA-dependent PC1-depletion in HEK293 cells and a PKD1-nonsense mutation in cyst-derived cell lines result in increased expression of the A(3) adenosine receptor via an NFkB-dependent mechanism. Interestingly, A(3) adenosine receptor levels result higher in ADPKD than in normal renal tissues. Furthermore, the stimulation of this receptor subtype with the selective agonist Cl-IB-MECA causes a reduction in both cytosolic cAMP and cell proliferation in both PC1-deficient HEK293 cells and cystic cells. This reduction is associated with increased expression of p21(waf) and reduced activation not only of ERK1/2, but also of S6 kinase, the main target of mTOR signalling. In the light of these findings, the ability of Cl-IB-MECA to reduce disease progression in ADPKD should be further investigated. Moreover, our results suggest that NFkB, which is markedly activated in PC1-deficient and cystic cells, plays an important role in modulating A(3)AR expression in cystic cells.

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