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.

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.

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 p22^phox 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). p22^phox 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.

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.

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.

Mycobacterium chimaera infections are becoming increasingly frequent in patients with a history of cardiac surgery. We herein report a case of a patient admitted to the Nephrology Unit of Padua University Hospital with deteriorating kidney function, pancytopenia, hypercalcemia, and respiratory symptoms that emerged seven years after they underwent heart surgery for prosthetic aortic valve replacement. A kidney biopsy revealed non-caseating necrotizing granulomatous interstitial nephritis, which was initially diagnosed as idiopathic granulomatous interstitial nephritis. The patient was treated with intravenous corticosteroids since no active infections, including mycobacterial infections, were detected. The negativity of the Mycobacterium molecular test following the kidney biopsy delayed the diagnosis of a Mycobacterium chimaera disseminated infection with endocarditis, myositis, cerebral, and kidney involvement, as blood cultures were available only after six weeks. The patient was started on antimicrobial therapy with azithromycin, moxifloxacin, rifampicin, and ethambutol while prednisone was tapered down, leading to an improvement in kidney function, blood count, and blood calcium level. Our case suggests that a Mycobacterium chimaera infection should be considered for patients with a history of cardiac surgery and granulomatous interstitial nephritis even in the absence of mycobacteria in a kidney biopsy.