The Italian Society of Nephrology has tasked its Working Group on Physical Exercise with developing a consensus statement document on physical activity and exercise in patients with chronic kidney disease (CKD). This paper consists of 16 points that were discussed, and approved using the mini-Delphi method by 15 members of the working group. Each statement is based on a comprehensive review of the literature, clinical experience, and expert opinions. Overall, the statements affirm that regular physical activity and exercise training offer numerous benefits to CKD patients, including improved physical function, enhanced cardiometabolic and neuromuscular function, cognitive benefits, and an overall improvement in quality of life. Furthermore, exercise may provide nephroprotection and reduce mortality. These advantages are observed across all CKD stages, whether on conservative therapy or kidney replacement therapy (hemodialysis or peritoneal dialysis), and in kidney transplant recipients. Moreover, when physical activity and exercise training are implemented with appropriate precautions, they are safe in CKD patients. Gradual physical activity and customized exercise programs should be tailored to the patient's exercise tolerance, potentially enhancing compliance. Clinicians are encouraged to use a series of questionnaires and tests to assess the patient's level of physical activity and performance. However, exercise and physical activity are poorly implemented in clinical practice due to many barriers related to patients and healthcare staff. Overcoming these barriers requires the proactive role of the nephrologists, who should actively incorporate exercise training and promote physical activity within routine care plans. Adopting a multidisciplinary team approach, which includes nephrologists, nurses, exercise professionals, and dietitians, is crucial for providing comprehensive rehabilitation for CKD patients. Integrating new technologies and remote check ups could further enhance the effectiveness of these interventions. Graphical abstract

Polycystic Kidney Diseases (PKDs) consist of a genetically and phenotypically heterogeneous group of inherited disorders characterized by numerous renal cysts. PKDs include autosomal dominant ADPKD, autosomal recessive ARPKD and atypical forms. Here, we analyzed 255 Italian patients using an NGS panel of 63 genes, plus Sanger sequencing of exon 1 of the PKD1 gene and MPLA (PKD1, PKD2 and PKHD1) analysis. Overall, 167 patients bore pathogenic/likely pathogenic variants in dominant genes, and 5 patients in recessive genes. Four patients were carriers of one pathogenic/likely pathogenic recessive variant. A total of 24 patients had a VUS variant in dominant genes, 8 patients in recessive genes and 15 patients were carriers of one VUS variant in recessive genes. Finally, in 32 patients we could not reveal any variant. Regarding the global diagnostic status, 69% of total patients bore pathogenic/likely pathogenic variants, 18.4% VUS variants and in 12.6% of patients we could not find any. PKD1 and PKD2 resulted to be the most mutated genes; additional genes were UMOD and GANAB. Among recessive genes, PKHD1 was the most mutated gene. An analysis of eGFR values showed that patients with truncating variants had a more severe phenotype. In conclusion, our study confirmed the high degree of genetic complexity at the basis of PKDs and highlighted the crucial role of molecular characterization in patients with suspicious clinical diagnosis. An accurate and early molecular diagnosis is essential to adopt the appropriate therapeutic protocol and represents a predictive factor for family members.

Chronic kidney disease (CKD) is a growing global health burden, strongly associated with cardiovascular disease, the leading cause of mortality in this population. Dyslipidemia is a key metabolic abnormality in CKD, but traditional lipid measures such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides often fail to capture the complexity of lipid disturbances in CKD and after kidney transplantation. Apolipoproteins have emerged as more reliable markers of cardiovascular and renal risk. Elevated apolipoprotein B (ApoB), reduced apolipoprotein A1 (ApoA1), and a higher ApoB/ApoA1 ratio are linked to CKD progression, cardiovascular events, and post-transplant complications, including post-transplant diabetes mellitus. Lipoprotein(a), a genetically determined atherogenic lipoprotein, accumulates in CKD due to impaired clearance and further increases cardiovascular risk. Other apolipoproteins, such as APOL1 and APOE, modulate CKD susceptibility through lipid-dependent and independent mechanisms. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of lipid metabolism, and PCSK9 inhibitors may represent a promising therapeutic option, though evidence in advanced CKD and transplant recipients is still limited, especially regarding their effects on apolipoproteins. This review summarizes current evidence on apolipoproteins and PCSK9 in CKD and transplantation, with attention to their potential as biomarkers and therapeutic targets.

Fabry disease (FD) is caused by mutations in the galactosidase alpha (GLA) gene which lead to the accumulation of globotriaosylceramide (Gb-3). Enzyme replacement therapy (ERT) and oral chaperone therapy are the current pharmacological treatments for this condition. However, in the literature, there is a growing emphasis on exploring non-pharmacological therapeutic strategies to improve the quality of life of patients with FD. In particular, the nutritional approach to FD has been marginally addressed in the scientific literature, although specific dietary interventions may be useful for the management of nephropathy and gastrointestinal complications, which are often present in patients with FD. Especially in cases of confirmed diagnosis of irritable bowel syndrome (IBS), a low-FODMAP diet can represent an effective approach to improving intestinal manifestations. Furthermore, it is known that some food components, such as polyphenols, may be able to modulate some pathogenetic mechanisms underlying the disease, such as inflammation and oxidative stress. Therefore, the use of healthy dietary patterns should be encouraged in this patient group. Sports practice can be useful for patients with multi-organ involvement, particularly in cardiovascular, renal, and neurological aspects. Therefore, the aim of this review is to summarize current knowledge on the role of nutrition and physical activity in FD patients.

Magnesium (Mg²⁺) is essential for cardiovascular and metabolic health, yet hypomagnesemia is common in kidney transplant recipients (KTRs) due to immunosuppressive therapy and renal dysfunction. Oral Mg²⁺ supplementation is often ineffective due to poor absorption and side effects. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to increase serum Mg²⁺ in chronic kidney disease, but their effects in KTRs, particularly patients without diabetes, remain unclear. This observational study assessed 63 KTRs treated with dapagliflozin, analyzing the serum Mg²⁺ levels at baseline and after 3 and 6 months. The hypomagnesemia prevalence, associations with oral supplementation, diabetes status, and diuretic use were evaluated. The results showed a significant Mg²⁺ increase with SGLT2i therapy, reducing hypomagnesemia regardless of the diabetes status. Oral supplementation did not correlate with improved Mg²⁺ levels, reinforcing its limited efficacy. Additional benefits included reductions in the body weight, blood pressure, and serum urate without compromising graft function. SGLT2i may offer a novel approach to managing hypomagnesemia in KTRs, potentially reducing the reliance on ineffective supplements while providing renal and cardiovascular benefits. Further research is needed to confirm these findings and elucidate the underlying mechanisms.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common monogenic disorder characterized by renal cysts and progressive renal failure. In kidney diseases, adipose tissue undergoes functional changes that have been associated with increased inflammation and insulin resistance mediated by release of adipokines. Adiponectin is involved in various cellular processes, such as energy and inflammatory and oxidative processes. However, it remains to be determined whether adiponectin is involved in the concomitant metabolic dysfunctions present in PKD. In this scenario, we aimed to analyze: (a) PPARγ, ADIPOQ, ADIPOR1 and ADIPOR2 gene variations in 92 ADPKD patients through PCR-Sanger sequencing; and (b) adiponectin levels and its oligomerization state by ELISA and Western Blot. Our results indicated that: (a) 14 patients carried the PPARγ SNP, 29 patients carried the ADIPOQ SNP rs1501299, and 25 patients carried the analyzed ADIPOR1 SNPs. Finally, 82 patients carried ADIPOR2 SNPs; and (b) Adiponectin is statistically lower in ADPKD patients compared to controls, and further statistically lower in ESRD than in non-ESRD patients. An inverse relationship between adiponectin and albumin and between adiponectin and creatinine and a direct relationship between adiponectin and eGFR were found. Interestingly, significantly lower levels of adiponectin were found in patients bearing the ADIPOQ rs1501299 SNP and associated with low levels of eGFR. In conclusion, adiponectin levels and the presence of ADIPOQ rs1501299 genotype are significantly associated with a worse ADPKD phenotype, indicating that both could potentially provide important insights into the disease. Further studies are warranted to understand the pathophysiological role of adiponectin in ADPKD patients.