Francesco Trepiccione

Background: Glucose exposure in peritoneal dialysis contributes to local peritoneal membrane injury and systemic metabolic complications. The osmo-metabolic approach seeks to reduce glucose burden by using alternative osmotic agents such as xylitol and L-carnitine. PolyCore is a novel glucose-free bimodal peritoneal dialysis solution combining icodextrin (4%), xylitol (1.5%), and L-carnitine (0.02%), designed to provide sustained ultrafiltration while improving biocompatibility. Methods: Human peritoneal mesothelial cells were exposed to PolyCore, icodextrin 7.5% solution, or a control medium. Cell viability, transepithelial electrical resistance, fibrosis-related gene expression, and α-SMA (alpha-smooth muscle actin) protein expression were assessed. In parallel, the EXCITE study was designed as a phase II, single-arm, prospective pilot trial evaluating PolyCore in 28 adults with end-stage kidney disease receiving incremental peritoneal dialysis. Results: PolyCore preserved mesothelial cell viability and barrier integrity, with transepithelial resistance values comparable to control and significantly higher than icodextrin 7.5%. Compared with icodextrin 7.5%, PolyCore showed a more favorable expression profile of mesothelial-to-mesenchymal transition markers, with lower α-SMA and vimentin and preserved E-cadherin. The EXCITE study will assess safety and preliminary efficacy, including dialysis adequacy, ultrafiltration, solute removal, metabolic parameters, and patient-reported outcomes. Conclusions: PolyCore showed favorable in vitro biocompatibility compared with standard icodextrin 7.5% and may represent a glucose-free bimodal strategy for peritoneal dialysis. EXCITE will provide first clinical assessment on the safety and preliminary efficacy of PolyCore.

Background: Commencing peritoneal dialysis (PD) with a lower dose (incremental PD) is a common strategy to improve patient acceptance and reduce treatment burden. However, specific dietary protein recommendations for incremental PD are lacking. Methods: An interim analysis of the I-COPE PD study cohort aimed to assess one-year changes in serum albumin, body mass index (BMI), and metabolic parameters in a cohort of patients on incremental PD. Following local protocols, patients were categorized into two groups according to protein diet prescription: protein diet (PrD) ≤ 0.6 and PrD > 0.6 g/kg/day. Longitudinal changes at baseline, 6 and 12 months were analyzed using mixed-effects models adjusted for age, sex, diabetes, residual kidney function and serum albumin at baseline. Results: We included 205 patients (mean age 63.3 ± 14.2 years; 66% male; 30% diabetes; 92.2% CAPD) and in 45.4% a PrD ≤ 0.6 g/kg/day was prescribed. Baseline demographic, clinical, lab and therapeutic characteristics were well-balanced between the two diet groups. After one year of follow-up, the prevalence of patients persisting in incremental PD was not different between the two dietary groups (59.1% in PrD ≤ 0.6 vs. 63.3% in PrD > 0.6, log-rank test = 0.759), and both groups showed a similar trend in serum albumin, characterized by an initial decline followed by stabilization (p = 0.647), with no significant differences in BMI (p = 0.461). Despite comparable dialysis adequacy, patients on PrD ≤ 0.6 exhibited significantly lower serum urea, phosphate, and potassium levels over time compared to the PrD > 0.6 group. Conclusions: In patients starting incremental PD, the prescription of a lower protein diet could be associated with better control of uremic toxins, while serum albumin levels over time remain comparable to those observed in patients under a higher-protein diet.

Lithium (Li) increases replication-dependent histone H4 in urine and in principal and intercalated cells, so histone H4 is a possible urinary marker for Li-induced cellular remodeling.

Introduction Cystinuria is a rare inherited disorder characterized by recurrent cystine stone formation. When lifestyle modification and urine alkalinization fail, cystine-binding medication such as tiopronin and D-penicillamine are indicated. Despite proven benefit, their accessibility across Europe appears limited. We hypothesized that access to this medication is restricted and varies substantially between European countries. Methods We surveyed physicians affiliated with the European Reference Network for Rare Kidney Diseases (ERKNet) regarding access barriers and prescribing practices. The online questionnaire was completed by 40 clinicians from 15 countries. Results Eighty-five percent of respondents had prescribed cystine-binding medication in the past two years, with tiopronin being the preferred agent. However, 30% reported having no access to tiopronin at all, and 83% of recent prescribers experienced accessibility problems, including high costs and unfilled prescriptions. Substantial differences were observed both between and within countries. Prescription rates correlated with physicians’ cystinuria caseload. Discussion Cystine-binding medication is poorly and inconsistently accessible across Europe. Coordinated efforts are urgently needed to stabilize supply and ensure equitable, affordable access.

Introduction: Bartter syndrome (BS) is a rare inherited salt-wasting disorder affecting the thick ascending limb of the loop of Henle. It is characterized by hypokalemic metabolic alkalosis, polyuria, and secondary normotensive hyperaldosteronism. A minority of patients may progress to end-stage kidney disease while maintaining polyuria and normokalemia. Peritoneal dialysis (PD) may represent a suitable option for these patients when kidney transplantation is not available. However, due to its rarity, there are no data on PD-related outcomes. Methods: Here, we report 2 cases of PD treatment in BS from two Italian referral centers. Results: In both cases, PD was discontinued early because of peritonitis. Conclusion: Although no causal relationship can be established, these observations highlight the need for heightened vigilance regarding infectious complications in this population.

The prevalence of heart failure (HF) and of chronic kidney disease (CKD) is continuously rising. Both diseases require significant management efforts, and more importantly, HF is often associated with CKD, aggravating the clinical scenario and leading to “cardiorenal syndrome” (CRS). Although clinical studies suggest a bidirectional interaction between HF and CKD, the pathophysiological understanding of CRS remains incomplete. Several mechanisms are involved in CRS, including changes in systemic and renal hemodynamics, endothelial dysfunction, inflammation, and activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. However, the precise mechanisms are still unclear, partly because of the incomplete characterization of experimental models recapitulating CRS. In this review, we analyze recent studies using different animal models of CRS, such as primary HF, primary CKD, and the “double-hit” models that have been proposed to investigate the pathophysiology of this condition. In HF models, data on renal pathology showed renal fibrosis, inflammation, and decreased glomerular filtration rate (GFR), whereas kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were used as markers of early kidney damage. In CKD models, data on heart pathology indicated changes in hemodynamics, increased systolic blood pressure, and the presence of fibrosis. These models provide new insights into the pathophysiological development of CRS, particularly the “double-hit” models, which may offer more information about the cross talk between the heart and kidneys. This review emphasizes the complexity of CRS and highlights the need for further research to clarify the underlying interactions and mechanisms.

Introduction: CFHR5 nephropathy is considered a subtype of C3 glomerulopathy. It was originally described in Greek Cypriot families and it is characterized by the time with the development of microscopic hematuria and proteinuria associated with a fast progression toward ESKD, especially in men. These symptoms present an autosomal dominant inheritance pattern and are associated with the exon 2 to 3 duplication of the CFHR5 gene. Case Presentation: Here, we describe a novel clinical phenotype associated with a variant of the CFHR5. The affected subjects present the clinical features of autosomal dominant tubulo-interstitial kidney disease. They present with CKD of unknown origin with no hematuria nor proteinuria. Like the classical CFHR5 nephropathy, males have a worse prognosis than females, with a fast progression toward ESKD in the second-third decade of life. Kidney pathology shows severe tubular atrophy and interstitial fibrosis and infiltrate. Arteries involvement is characterized by thickening of the intima layer, while no major alterations are described at the glomerular level. Electron microscopy confirms no interstitial or glomerular filtration barrier alterations. Conclusion: The exact mechanism behind this phenomenon remains unclear; we hope that our case will encourage further investigation.

Key Points: Lack of transient receptor potential cation channel (TRPML-1) causes tubulopathy. Only adults affected of mucolipidosis type IV present kidney damage signs, including lower eGFR and higher levels of BUN/creatine in blood and proteinuria. TRPML-1 deficiency links lysosomal and autophagic dysfunction with inflammation in mucolipidosis type IV kidney disease. Background: Loss-of-function mutations in the lysosomal channel transient receptor potential cation channel (TRPML-1) cause mucolipidosis type IV (MLIV), a rare lysosomal storage disease characterized by neurological defects, progressive vision loss, and achlorhydria. Recent reports have highlighted kidney disease and kidney failure in patients with MLIV during the second to third decade of life; however, the molecular mechanisms driving kidney dysfunction remain poorly understood. Methods: A cross-sectional review of medical records from 21 patients with MLIV (ages 3–43 years) was conducted to assess kidney function impairment. In addition, we examined the kidney phenotype of MLIV mice at various ages, along with human kidney cells silenced for TRPML-1 and primary tubular cells from wild-type and MLIV mice. Immunohistology and cell biology approaches were used to phenotype nephron structure, the endolysosomal compartment, and inflammation. Kidney function was assessed through proteomic analysis of mouse urine and in vivo kidney filtration measurements. Results: Of the 21 patients with MLIV, only adults were diagnosed with stage 2–3 CKD. Laboratory abnormalities included lower eGFR and higher levels BUN/creatine in blood and proteinuria. In MLIV mice, we observed significant alterations in endolysosomal morphology, function, and impaired autophagy in proximal and distal tubules. This led to the accumulation of megalin (LRP2) in the subapical region of proximal tubular cells, indicating a block in apical receptor–mediated endocytosis. In vivo and in vitro experiments confirmed reduced fluid-phase endocytosis and impaired uptake of ligands, including β-lactoglobulin, transferrin, and albumin in MLIV proximal tubular cells. Urine analysis revealed tubular proteinuria and enzymuria in mice with MLIV. In addition, early-stage disease was marked by increased inflammatory markers, fibrosis, and activation of the proinflammatory transcription factor NF-κB, coinciding with endolysosomal defects. Importantly, adeno-associated viral–mediated TRPML-1 gene delivery reversed key pathological phenotypes in MLIV mice, underscoring TRPML-1's critical role in kidney function. Conclusions: Our findings link TRPML-1 dysfunction to the development of kidney disease in MLIV.