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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Slow continuous ultrafiltration (SCUF) is an extracorporeal therapy able to reduce fluid overload in chronic or acute heart failure resistant to diuretics. An in-vitro study demonstrated the SCUF feasibility using a standard fluid infusion central venous catheter (CVC). We describe the clinical application of this SCUF in regional citrate anticoagulation (SCUF-RCA) in a patient admitted to the Intensive Care Unit for acute decompensate heart failure with severe systemic fluid overload resistant to diuretics. To avoid risks deriving from a new catheterization, we used a pre-existing multi-lumen CVC for drug administration to provide 10 h of SCUF-RCA with a blood flow of 35 mL/min and 100 mL/h of ultrafiltration with a final weight loss of 1 Kilogram without technical and clinical complications. The patient had a hemodynamics improvement with the diuresis recovery from the previous oliguria after the SCUF-RCA. This clinical case can open the use of the SCUF-RCA in the clinical practice to treat the fluid overload unresponsive to maximal diuretic therapy not exposing the patient to the risks and complications related to the use of SCUF with CVC for dialysis and systemic anticoagulation with heparin. Accordingly, this technique may be useful in the treatment of fluid overload in outpatients. [ABSTRACT FROM AUTHOR]

Beta-thalassemia syndromes are the most common inherited monogenic disorders worldwide. The most common pathophysiologic and clinical renal disease manifestations of in β-TM patients is the tubular dysfunctions related to iron overload, chronic anemia, and the need for chronic iron chelation therapy. The aim of this pilot study is to apply an innovative ultrasound and Doppler technique to assess the Renal Functional Reserve (RFR) in β-TM patients, and to evaluate its reliability in iron overload tubulopathy. Ultrasound assessment of intra-parenchymal renal resistive index variation (IRRIV) has recently been proposed as a safe and reproducible technique to identify RFR presence. We define the preserved RFR when the Delta Renal Resistive Index (RRI) is >0.05 (baseline RRI—minimum RRI value during stress) in the Renal Stress Test (RST). Nineteen β-TM patients were enrolled for this study. In our series, we found a strong negative correlation between mean ferritin values and Delta RRI (R = −0.51, p = 0.03). This pilot study suggested the RST as reliable tool for assessing the RFR by ultrasound. Specifically, RST could help in clinical practice suggesting the patient's management and iron chelation therapy. [ABSTRACT FROM AUTHOR]

In the last few decades, the aging of the general population has significantly increased the number of elderly patients with end-stage kidney disease (ESKD) who require renal replacement therapy. ESKD elders are often frail and highly comorbid with social issues and seem to not benefit from dialysis in terms of survival and quality of life. Conservative management (CM) could represent a valid treatment option, allowing them to live for months to years with a modest impact on their habits. Despite these possible advantages, CM remains underused due to the myth of dialysis as the only effective treatment option for all ESKD patients regardless of its impact on quality of life and survival. Both CM and dialysis remain valid alternatives in the management of ESKD. However, assessing comorbidities, disabilities, and social context should drive the choice of the best possible treatment for ESKD, while in elderly patients with short life expectancies, referring them to palliative care seems the most reasonable choice. [ABSTRACT FROM AUTHOR]

It is known, in fact, that SARS-CoV-2 causes ACE2 downregulation impairing the ACE2-mediated Ang II conversion into Ang 1-7 with the loss of its vasodilatory, anti-inflammatory, antioxidant, and anti-atherosclerotic proprieties and of their protective impact on COVID-19 morbidity and mortality [[5]]. In vivo human data that may address the beneficial role of RAS blockers in COVID-19 and its complications may be provided by patients with Gitelman's and Bartter's syndromes (GS/BS). Keywords: Bartter's syndrome; Angiotensin II; RAS blockers; COVID-19; Gitelman's syndrome EN Bartter's syndrome Angiotensin II RAS blockers COVID-19 Gitelman's syndrome 593 596 4 11/14/22 20221220 NES 221220 The renin-angiotensin system (RAS) during COVID-19 pandemic has captured the interest as the severe coronavirus 2 (SARS-CoV-2) causing COVID-19 uses angiotensin-converting enzyme type 2 (ACE2) as an entry point into the cell [[1]]. [Extracted from the article]

COVID-19 often leads to acute respiratory distress syndrome complicated by acute kidney injury (AKI). The indications for renal replacement therapy for these patients are those commonly accepted to treat AKI. We describe a continuous veno-venous haemodialysis (CVVHD) protocol for AKI, which aims to provide the best treatment according to the particular patient's and medical personnels' needs in biohazard settings with limited human and technological resources. We designed a CVVHD protocol with a high cut-off (HCO) filter in regional citrate anticoagulation (RCA). The HCO filter in diffusion determines the enhanced cytokines clearance with less filter clotting due to a lower filtration fraction. In our hospital, at the beginning of the pandemic outbreak, we treated seven COVID-19 patients with AKI stage 2 and 3 and recorded the circuit lifespan and the number of interventions on monitors. CVVHD in RCA appears to be safe, effective and easy to be performed in a biohazard scenario using lower blood flows and less bag changes with fluid savings, a biohazard reduction and sparing of resources. Although the data come from a very small cohort, our protocol seems related to a low mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) contributes to DNA stability, protein synthesis and cardiac excitability, while Mg deficiency leads to increased cardiovascular mortality, diabetes, hyperparathyroidism and risk of fractures. In kidney transplant patients, calcineurin inhibitors (CNIs) downregulating Mg channel TRPM6 in the distal collecting tubule induce early hypomagnesemia (HypoMg), which is associated with a faster decline in allograft function. A new formulation, sucrosomial Mg (SucrMg), for oral supplements encapsulates Mg oxide in a phospholipid membrane covered by a sucrester matrix, enhancing gastric and intestinal Mg absorption. This study has evaluated Mg bioavailability, effectiveness and tolerance of SucrMg compared to the conventional preparation of Mg pidolate (PidMg). The association of blood Mg with risk of post-transplant dysglycemia and hyperparathyroidism has also been investigated. Forty hypomagnesemic adult single, double or combined kidney–pancreas or kidney–liver transplant recipients within 2 years from transplantation were recruited. In total, 16 patients received PidMg and 27 received SucrMg. Blood Mg was measured at baseline (T0), after 15 days (T1) and after 6 months (T2) of treatment. PTH, fasting glucose and calcium were measured at baseline and after 6 months of treatment. The tolerance was evaluated at the ambulatory visits. SucrMg compared to PidMg was more efficient at increasing Mg bioavailability at T1: p < 0.0001 vs. p = 0.72 ns, respectively, with a ∆% increase of 12.4% vs. 5.4%, p = 0.04. Both preparations increased blood Mg at T2, p < 0.0001 and p = 0.002, respectively. SucrMg was better tolerated. No difference was observed for fasting plasma glucose, PTH and calcium. On one hand, our study is the first among transplant patients to evaluate the efficacy of SucrMg in the correction of HypoMg, which might justify the limited number of patients enrolled and the short observation time; on the other hand, our results could serve as a useful working hypothesis for further studies with a larger number of transplant patients and an extended study duration to confirm the benefits observed with SucrMg. [ABSTRACT FROM AUTHOR]

Background: Gitelman's and Bartter's syndromes (GS/BS) are rare genetic tubulopathies characterized by electrolyte imbalance and activation of the renin-angiotensin-aldosterone system (RAAS). These syndromes have intriguing biochemical and hormonal abnormalities that lead them to be protected from hypertension and cardiovascular and renal remodeling. Summary: In this review, we explore the biochemical/molecular mechanisms induced by the activation of the RAAS and its counterregulatory arm which is particularly activated in GS/BS patients, in the context of blood pressure regulation. In addition, we report our findings in the context of the COVID-19 pandemic where we observed GS/BS subjects being protected from infection. Key Messages: The intracellular pathways induced by Ang II, starting from induction of oxidative stress and vasoconstriction, are crucial for the progression toward cardiovascular-renal remodeling and might be useful targets in order to reduce/halt the progression of Ang II/oxidative stress-induced cardiovascular-renal morbidity in several diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: In chronic kidney disease (CKD) patients blood pressure variability (BPV) is associated with poor outcome. Sleep disturbances alter BP profiles in hypertensives but their influence on BPV in CKD patients is unknown. We screened a cohort of CKD/ESRD patients to investigate whether sleep quality impacts on BPV. Methods: Consecutive CKD patients' sleep quality was assessed using validated questionnaires (Epworth Sleepiness Scale-ESS); International Restless legs scale-IRLS; Functional Outcomes of Sleep Questionnaire-FOSQ: Insomnia Severity Index-ISI; STOP-Bang). All patients underwent ambulatory blood pressure measurement. Results: 104 out of 143 enrolled patients (78.32% stage-3 CKD; 10.49% Stage-4; 11.19% Stage-5; 6.99% ESRD-under dialysis) completed all the questionnaires. 95.8% were hypertensives, 70% were non-dippers and 27.8% had resistant hypertension. STOPBang> 4 proved sleep disorders in 84.84% of patients. Patients with IRLS>10 had greater diastolic nocturnal standard deviation (DNSD) and a trend (p=0.05) for systolic nocturnal SD (SNSD). Patients with ISI>14 had greater SNSD and in 28.8% FOSQ showed severely impaired sleep quality. Their systolic nocturnal BPV was significantly greater. ISI was independently associated with SNSD. FOSQ and diastolic nocturnal BPV were negatively correlated at the bivariate analysis and FOSQ independently predicts systolic nocturnal BPV at multivariate regression analysis. Conclusions: In CKD patients impaired sleep quality increases BPV, might contribute to their disease progression and worsen prognosis. Searching for sleep problems in CKD patients could help planning their treatment of sleep problems contributing to CV risk reduction. Our data provide the rationale working hypothesis for the need of studies with larger number of patients aimed to demonstrate improved outcome of CKD progression and CV risk with the treatment also of sleep disorders. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22phox protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., p = 0.015, vs. 0.53 ± 0.11 d.u., p < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., p = 0.013 and vs. 0.47 ± 0.13 d.u., p < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, p = 0.012, vs. 1.97 ± 1.22 ng/mL, p = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment. [ABSTRACT FROM AUTHOR]

Dent’s disease (DD) involves nephrocalcinosis, urolithiasis, hypercalciuria, LMW proteinuria, and renal failure in various combinations. Males are affected. It is caused by mutations in the chloride channel CLCN5 gene. It has been suggested that DD is underdiagnosed, occurring in less overt forms, apparently without family history. A possible approach to this problem is to search for CLCN5 mutations in patients who may have a high prevalence of mutations: end-stage renal disease (ESRD) patients with previous calcium, struvite, or radio-opaque (CSR) stones. We looked for CLCN5 mutations in 25 males with ESRD–CSR stones selected from all of the patients (1,901 individuals, of which 1,179 were males) of 15 dialysis units in the Veneto region. One DD patient had a new DD mutation (1070 G>T) in exon 7. The new polymorphism IVS11–67 C>T was detected in intron 11 in one patient and one control. We also found 28 females with ESRD and stone history, and seven more males with ESRD and non-CSR stones. The prevalence of stone formers among dialysis patients in our region was 3.2%, much lower than the prevalence observed in older studies. Struvite stones continue to play a major role in causing stone-associated ESRD . [ABSTRACT FROM AUTHOR]