Anti-phospholipid antibodies nephropathy is associated with an increased risk of kidney failure: a systematic literature review and meta-analysis.

Background: Anti-phospholipid antibodies nephropathy (aPL-N) is a complex feature of anti-phospholipid syndrome due to microvascular lesions. Renal prognosis and predictors of outcome are not yet known. Methods: We performed a systematic review of the literature (February 2006-January 2024) using the PubMed, Scopus, Cochrane Library and EMBASE databases. Two reviewers independently conducted literature screening and data extraction in a blinded, standardized manner. A random effects model was used to pool odds ratios (ORs) [with 95% confidence interval (CI)] for the primary analysis, the risk of kidney failure. Subgroup analyses were performed for clinical and laboratory features that predicted renal outcomes. Heterogeneity was assessed by I2. Results: Six records involving 709 patients were included in the meta-analysis. Biopsy-proven aPL-N was found in 238/832 (28.6%) patients. Acute kidney injury (AKI) was present at diagnosis in 20/65 (30.8%), while 73/233 (31.3%) patients with aPL-N developed chronic kidney disease (CKD)/end-stage kidney disease (ESKD) at follow-up. aPL-N was associated with an increased risk of CKD/ESKD [OR 6.89 (95% CI 2.42-19.58)] and AKI [OR 2.97 (95% CI 1-4-6.29)]. Arterial hypertension and positivity for lupus anticoagulant, anti-cardiolipin antibodies and anti-ß2 glycoprotein I antibodies were associated with an increased risk of developing aPL-N [OR 3.7 (95% CI 1.9-7.23), OR 4.01 (95% CI 1.88-8.53), OR 2.35 (95% CI 1.31-4.21) and OR 19.2 (95% CI 2.91-125.75), respectively]. Conclusion: aPL-N is associated with poor renal outcomes. High blood pressure and aPL positivity have been identified as predictors of adverse renal outcomes. This up-to-date knowledge on renal outcomes and predictors of renal outcomes in aPL-N enables a personalized follow-up and therapeutic approach.

The Rationale for Combining Normothermic Liver Machine Perfusion with Continuous Renal Replacement Therapy to Maintain Physiological Perfusate during Ex Vivo Organ Perfusion.

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.

The Quality of Life in Elderly Patients in Comprehensive Conservative Management or Hemodialysis: A Case-Control Study in Analogous Basal Conditions.

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.

Glucose-Free Solutions Mediated Inhibition of Oxidative Stress and Oxidative Stress-Related Damages in Peritoneal Dialysis: A Promising Solution.

Oxidative stress (OxSt) and inflammation are common in end-stage renal disease and dialysis patients; they are known risk factors for cardiovascular disease and mortality. In peritoneal dialysis (PD), OxSt and inflammation are even further increased compared to the already increased oxidative stress of their pre-dialysis phase. This is due to the high glucose-based solutions currently used, whose continuous contact with the peritoneal membrane can induce significant long-term morphological and functional changes (mesothelial to mesenchymal transition, thickening, neo-angiogenesis and fibrosis) of the peritoneal membrane. Oxidative stress plays a very important role in these processes, which may compromise the peritoneal dialysis procedure. There is, therefore, the need for more biocompatible dialysis fluids with polymers other than glucose to prevent and treat OxSt and inflammation. The most known and used of such glucose-free and more biocompatible peritoneal dialysis solutions is icodextrin, which has shown a protective effect from oxidative stress. This has supported the consideration of the use of glucose-free-based peritoneal dialysis fluids in order to reduce oxidative stress and improve peritoneal membrane survival. Studies investigating peritoneal dialysis with the use of osmo-metabolic agents (L-carnitine, xylitol and their combination) in peritoneal fluids replacing glucose-based fluids are, in fact, ongoing. They represent a promising strategy to reduce OxSt, preserve the peritoneal membrane's integrity and improve patients' outcome.

The Role of Daily Dialysate Calcium Exposure in Phosphaturic Hormones in Dialysis Patients.

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions.

Long-term outcome of COVID-19 patients with acute kidney injury requiring kidney replacement therapy.

BACKGROUND: Limited data existed on the burden of coronavirus disease 2019 (COVID-19) renal complications and the outcomes of the most critical patients who required kidney replacement therapy (KRT) during intensive care unit (ICU) stay. We aimed to describe mortality and renal function at 90 days in patients admitted for COVID-19 and KRT. METHODS: A retrospective cohort study of critically ill patients admitted for COVID-19 and requiring KRT from March 2020 to January 2022 was conducted in an Italian ICU from a tertiary care hospital. Primary outcome was mortality at 90 days and secondary outcome was kidney function at 90 days. RESULTS: A cohort of 45 patients was analyzed. Mortality was 60% during ICU stay and increased from 64% at the time of hospital discharge to 71% at 90 days. Among 90-day survivors, 31% required dialysis, 38% recovered incompletely, and 31% completely recovered renal function. The probability of being alive and dialysis-free at 3 months was 22%. CONCLUSIONS: Critically ill patients with COVID-19 disease requiring KRT during ICU stay had elevated mortality rate at 90 days, with low probability of being alive and dialysis-free at 3 months. However, a non-negligible number of patients completely recovered renal function.

"Every Cloud Has a Silver Lining": How Three Rare Diseases Defend Themselves from COVID-19 and What We Have Learnt from It.

The process of SARS-CoV-2 infection, responsible for the COVID-19 pandemic, is carried out through different steps, with the interaction between ACE2 and Spike protein (S) being crucial. Besides of that, the acidic environment of endosomes seems to play a relevant role in the virus uptake into cells and its intracellular replication. Patients affected by two rare genetic tubulopathies, Gitelman's and Bartter's Syndromes, and a rare genetic metabolic disease, Fabry Disease, have shown intrinsic protection from SARS-CoV-2 infection and COVID-19 on account of specific intrinsic features that interfere with the virus uptake into cells and its intracellular replication, which will be reported and discussed in this paper, providing interesting insights for present and future research.

Stage 5 Chronic Kidney Disease: Epidemiological Analysis in a NorthEastern District of Italy Focusing on Access to Nephrological Care.

BACKGROUND: We conducted a retrospective epidemiological study about the prevalence of stage 5 chronic kidney disease (CKD) in a high-income district, comparing some demographic characteristics and outcomes of those patients who had nephrological consultations and those who had not. RESULTS: In a district of 400,000 adult subjects in 2020, 925 patients had an estimated glomerular filtration rate (eGFR) under 15 mL/min and CKD. In the same period, 747 (80.4%) patients were assessed by nephrologists, while 178 (19.6%) were not. Age (88 vs. 75, p < 0.0001), female gender (66.3% vs. 47%, p < 0.001), and eGFR (12 vs. 9 mL/min, p < 0.001) were significantly different in the patients assessed by a nephrologist as compared those who did not have nephrological care. Furthermore, unfollowed CKD patients had a significantly higher death rate, 83.1% versus 14.3% (p < 0.0001). CONCLUSIONS: About 20% of ESKD patients did not receive a nephrologist consultation. Older people and women were more likely not to be referred to nephrology clinics. Unfollowed patients with stage 5 CKD had a significantly higher death rate.

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

The Ultrasound Renal Stress Test for the Assessment of Functional Renal Reserve in Kidney Transplantation: A Pilot Study in Living Donors.

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.

Coronary sinus diameter to estimate congestion and predict survival.

Background: Congestion predicts a poor prognosis, but its assessment is challenging in clinical practice and requires a multiparametric approach. We investigated if the coronary sinus (CS) diameter can predict mortality in a human model of rapid fluid unloading. Methods: We measured by echocardiography the CS, and the inferior vena cava (IVC) for comparison, in 60 patients with end-stage chronic kidney disease (ESKD) immediately before and after hemodialysis (HD; age 76 [57-81] years, 40% female, left ventricular ejection fraction 57 [53-56]%). Patients were prospectively followed up for all-cause mortality. Results: HD-induced decongestion decreased the maximum diameters of both CS and IVC (p ≤ 0.001 for all). The maximum diameter of the CS (CSmax) was as accurate as the IVC maximum diameter and collapsibility for the identification of congestion, defined as pre-hemodialysis status (AUROC CSmax = 0.902 vs IVC = 0.895, p = n.s.). A CSmax diameter after hemodialysis > 9 mm predicted all-cause mortality at 12 months (Log-rank Chi square = 11.49, p < 0.001). Conclusions: A persistently dilated CS after hemodialysis is a marker of residual congestion and predicts death at one year in high-risk ESKD patients.

Varicella Zoster vaccination in hemodialysis patients: The state of the art.

Varicella Zoster Virus (VZV) infection is a common childhood exanthematous disease, which in adults and immunocompromised people may result in severe neurologic complications. Up to one-third of infected subjects may have VZV clinical reactivation particularly if immunocompromised. Patients affected by end-stage renal disease on hemodialysis present immunodepression that contributes to their higher incidence of VZV infections and reactivation. While antiviral treatment in these patients shows low efficacy, the prevention of VZV through vaccination avoids the primary infection and the risk of reactivation. Two VZV vaccines are currently available: the live attenuate Zoster Vaccine (LZV) and a Recombinant Zoster Vaccine (RZV), with the latter appearing to provide greater efficacy. Given the higher incidence of VZV infection and reactivation, the lesser response to antivirals and the lower impact of VZ vaccine in hemodialysis patients in terms of side effects, a higher diffusion of VZV vaccination should be promoted by nephrologists in these patients in particular in those with future transplant opportunities.

Safety of Citrate Anticoagulation in CKRT: Monocentric Experience of a Dynamic Protocol of Calcium Monitoring.

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.

Oxidants and Cardiorenal Vascular Remodeling-Insights from Rare Genetic Tubulopathies: Bartter's and Gitelman's Syndromes.

Two human genetic tubulopathies, Bartter's (BS) and Gitelman's (GS) syndromes, have normo/hypotension and absent cardiac remodeling despite their apparent angiotensin system (RAS) activation. This seeming contradiction has led to an extensive investigation of BSGS patients, the result of which is that BSGS represents a mirror image of hypertension. BSGS's unique set of properties has then permitted their use as a human model to probe and characterize RAS system pathways and oxidative stress in cardiovascular and renal remodeling and pathophysiology. This review details the results using GSBS patients that provide a deeper understanding of Ang II signaling and its associated oxidants/oxidative stress in humans. By providing a more complete and complex picture of cardiovascular and renal remodeling pathways and processes, studies of GSBS can inform the identification and selection of new targets and therapies to treat these and other oxidant-related disorders.

Biochemical Mechanisms beyond Glycosphingolipid Accumulation in Fabry Disease: Might They Provide Additional Therapeutic Treatments?

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Currently, enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease's progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. Several studies reported how secondary biochemical processes beyond Gb3 and lyso-Gb3 accumulation-such as oxidative stress, compromised energy metabolism, altered membrane lipid, disturbed cellular trafficking, and impaired autophagy-might exacerbate Fabry disease adverse outcomes. This review aims to summarize the current knowledge of these pathogenetic intracellular mechanisms in Fabry disease, which might suggest novel additional strategies for its treatment.