Background Urinary tract infections (UTIs) are the most frequent infectious complication after kidney transplantation and are associated with rehospitalizations, impaired allograft function, and reduced graft and recipient survival. Their clinical relevance is amplified by chronic kidney disease (CKD)–related immune dysfunction and the rising burden of antimicrobial resistance Methods We provide a focused narrative review of classification, pathophysiology, risk factors, and evidence-based management and prevention strategies for UTIs in kidney transplant recipients, with emphasis on antimicrobial stewardship and non-antibiotic adjuncts Results Post-transplant UTI risk is highest in the early months and is driven by intensive immunosuppression, perioperative urological devices (bladder catheter, ureteral stents), delayed graft function/ischemia–reperfusion injury, and urodynamic abnormalities (post-void residual, vesicoureteral reflux). Female sex and pregnancy further increase susceptibility. Urine cultures must be interpreted in the context of time from transplantation and symptoms. Systematic treatment of asymptomatic bacteriuria is not beneficial and may increase antibiotic exposure and selection of multidrug-resistant organisms. Conversely, symptomatic, complicated, and recurrent UTIs warrant prompt empiric therapy followed by rapid de-escalation based on culture and susceptibility results. Preventive strategies targeting adhesion and colonization include adequate hydration, standardized cranberry preparations with therapeutically effective proanthocyanidin dosing, methenamine hippurate in selected patients, and topical vaginal estrogen in peri-/postmenopausal women; evidence for D-mannose and probiotics remains inconsistent. Emerging mechanistic insights highlight uromodulin as a key anti-adhesive and neutrophil (NET)-modulating defense factor, while SGLT2 inhibitors may modify tubular biomarkers; a UTI episode should not automatically prompt treatment discontinuation Conclusions UTI management after kidney transplantation should adopt an integrated, multimodal approach combining stewardship-driven antibiotic use with tailored non-antibiotic preventive interventions to reduce recurrences, curb resistance, and preserve long-term allograft longevity.

Proteinuria is a strong predictor of graft failure in kidney transplant recipients (KTRs). While non-steroidal mineralocorticoid receptor antagonists (NS-MRAs), particularly finerenone, have demonstrated renoprotective benefits in chronic kidney disease, KTRs were excluded from pivotal trials. Evidence on finerenone's safety and antiproteinuric effects in this population remains limited. This retrospective observational study evaluated 13 diabetic KTRs with persistent proteinuria despite optimized renin-angiotensin system blockade and sodium-glucose cotransporter 2 inhibitor therapy. Finerenone (10 mg/day) was added to standard care. Clinical and laboratory parameters, including estimated glomerular filtration rate (eGFR), serum electrolytes, total proteinuria, albuminuria, and their creatinine ratios, were assessed at baseline, 3 months, and 6 months. Safety outcomes focused on hyperkalemia and eGFR. Finerenone was discontinued in one patient due to hyperkalemia. In the remaining 12, 24-h proteinuria and urinary protein-to-creatinine ratio declined at 3 months and stabilized by 6 months. Conversely, no statistically significant changes were observed in albuminuria or the albumin-to-creatinine ratio. No clinically relevant changes occurred in eGFR, blood pressure, body weight, or serum electrolytes. This is the first study assessing finerenone in diabetic KTRs. Finerenone was well tolerated, was associated with an early reduction in proteinuria, and showed no adverse effects on graft function. These findings provide novel insights into the safety and potential role of finerenone in kidney transplant recipients.

Background: SGLT2 inhibitors (SGLT2is) lower glucose and have renoprotective effects, including reducing proteinuria. In kidney transplant recipients (KTRs), proteinuria impacts graft and patient survival. While SGLT2is benefits have been reported in diabetic KTRs, the data on non-diabetic KTRs are poor, and no data are available for albuminuria and non-albumin proteinuria. This study assessed the effects of dapagliflozin on urinary protein excretion in KTRs with and without diabetes. Methods: This analysis, from the Salerno CKD Cohort Study, included 66 KTRs (≥1 year post-transplant) with proteinuria despite renin-angiotensin system inhibitor therapy. The patients received dapagliflozin (10 mg/day) for six months, with assessments at the baseline (T0), three months (T1), and six months (T2); adverse events were monitored. The primary outcomes were changes in the urinary total, albumin, and non-albumin proteins. The secondary outcomes included weight, blood pressure, and eGFR. Results: At T1, the urinary total, albumin, and non-albumin proteins were significantly decreased, with a greater reduction in the non-albumin proteins vs. albumin (-27% vs. -9.4%, p = 0.001). No further changes occurred at T2. The patients' weight and blood pressure also declined, while their eGFR and glucose remained stable. The non-albumin protein reduction was correlated with weight loss and diastolic blood pressure changes. Two patients discontinued use due to adverse events (one with a urinary tract infection, one with hypotension). Conclusions: Dapagliflozin reduces proteinuria, particularly non-albumin proteins, in KTRs with and without diabetes, with a low incidence of adverse effects. Further studies are needed to confirm the long-term benefits, especially in non-diabetic recipients.

The complex nature of immune system behavior in both autoimmune diseases and transplant rejection can be understood through the lens of avalanche dynamics in critical-point systems. This paper introduces the concept of the “immunological avalanche” as a framework for understanding unpredictable patterns of immune activity in both contexts. Just as avalanches represent sudden releases of accumulated potential energy, immune responses exhibit periods of apparent stability followed by explosive flares triggered by seemingly minor stimuli. The model presented here draws parallels between immune system behavior and other complex systems such as earthquakes, forest fires, and neuronal activity, where localized events can propagate into large-scale disruptions. In autoimmune conditions like systemic lupus erythematosus (SLE), which affects multiple organ systems including the kidneys in approximately 50% of patients, these dynamics manifest as alternating periods of remission and flares. Similarly, in transplant recipients, the immune system exhibits metastable behavior under constant allograft stimulation. This critical-point dynamics framework is characterized by threshold-dependent activation, positive feedback loops, and dynamic non-linearity. In autoimmune diseases, triggers such as UV light exposure, infections, or stress can initiate cascading immune responses. In transplant patients, longitudinal analysis reveals how monitoring oscillatory patterns in blood parameters and biological age markers can predict rejection risk. In a preliminary study on kidney transplant, all measured variables showed temporal instability. Proteinuria exhibited precise log–log linearity in power law analysis, confirming near-critical-point system behavior. Two distinct dynamic patterns emerged: large oscillations in eGFR, proteinuria, or biological age predicted declining function, while small oscillations indicated stability. During avalanche events, biological age increased dramatically, with partial reversal leaving persistent elevation after acute episodes. Understanding these dynamics has important implications for therapeutic approaches in both contexts. Key findings suggest that monitoring parameter oscillations, rather than absolute values, better indicates system instability and potential avalanche events. Additionally, biological age calculations provide valuable prognostic information, while proteinuria measurements offer efficient sampling for system dynamics assessment. This conceptual model provides a unifying framework for understanding the pathogenesis of both autoimmune and transplant-related immune responses, potentially leading to new perspectives in disease management and rejection prediction.

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.

BACKGROUND:Chronic kidney disease (CKD) is often associated with infertility and adverse pregnancy outcomes. Kidney transplantation improves fertility and maternal-fetal health, while assisted reproductive technologies, including in vitro fertilization (IVF), offer additional opportunities. However, there are no documented cases of heterologous IVF in kidney transplant recipients in the literature. CASE PRESENTATION:We report the case of a 47-year-old female with autosomal dominant polycystic kidney disease (ADPKD) who underwent a kidney transplant in 2018. In 2022, she underwent heterologous IVF to prevent the transmission of ADPKD. Pregnancy was achieved after the third embryo transfer, with stable graft function and no major complications. A cesarean section at 37 weeks resulted in the birth of a healthy female newborn. One year postpartum, renal function remained stable. DISCUSSION AND CONCLUSION:Pregnancy in kidney transplant recipients is high-risk, requiring careful immunosuppressive management and multidisciplinary monitoring. This case highlights the feasibility of heterologous IVF in transplant recipients, expanding reproductive options for patients with hereditary kidney diseases.

The complex behavior of the immune system in kidney transplant patients is analogous to avalanche dynamics in critical-point systems, characterized by periods of stability punctuated by sudden immune activity flares. This study introduces the concept of “immunological avalanche” as a framework for understanding the unpredictable patterns of transplant rejection. Like complex systems such as earthquakes and neural networks, transplanted patients' immune systems comprise myriad interacting immune cells under constant allograft stimulation. These systems exhibit metastable behavior: long periods of apparent equilibrium punctuated by sudden, large-scale immune responses triggered by minimal perturbations. This critical-point dynamics helps explain the unpredictable patterns of transplant rejection, where minor immunological triggers can cascade into systemic responses. This study investigates how longitudinal analysis of blood parameters can reveal critical-point indicators for predicting transplant rejection risk in kidney recipients. We examine the oscillatory patterns of multiple blood markers, while simultaneously analyzing an estimate of DNA methylation patterns in peripheral cells to assess both chronological and biological age. By identifying “avalanche-like” dynamics in these parameters, we aim to develop an early warning system for predicting future rejection events. This approach combines traditional biomarker monitoring with epigenetic clock analysis to create a more comprehensive risk assessment model. We conducted a retrospective two-center study analyzing data from 10 transplanted patients (mean transplant vintage 8 years) over 7 years, with 30-day average sampling intervals. We monitored graft function parameters, hemochrome, and estimated epigenetic age using the Phenoage algorithm. Sample entropy quantified temporal series information content. All measured variables demonstrated temporal instability with varying magnitudes. Phenoage-estimated biological age showed both minor fluctuations and significant variations correlating with major creatinine level changes. Proteinuria exhibited precise log-log linearity in power law analysis, confirming near-critical-point system behavior. This fully demonstrates a near-critical-point system with rare large avalanche events. Two distinct dynamic patterns emerged: large oscillations in eGFR or proteinuria or biological age predicted declining graft function with major avalanche events, while small oscillations indicated system stability. During avalanche events, biological age increased dramatically (up to 20 years above chronological age), with partial reversal leaving a persistent 3-year elevation after each acute kidney injury episode. This study reveals three key findings: (1) monitoring creatinine and proteinuria level oscillations, rather than absolute values, better indicates system instability and potential avalanche events; (2) biological age calculations provide valuable prognostic information; (3) proteinuria measurements offer an efficient sampling parameter for system dynamics assessment. These insights suggest new approaches for monitoring transplant stability and predicting rejection episodes.

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.

Background: Kidney transplant (KTx) recipients exhibit impaired responses to SARS-CoV-2 vaccination. Correlates of vaccine-induced immunity and risk factors for breakthrough infection are not fully defined. This study evaluated the humoral response trajectories and determinants of breakthrough infection in KTx recipients. Methods: KTx recipients received two doses of the BNT162b2 mRNA vaccine three weeks apart and a booster after six months. Patients were categorized based on pre-vaccination status: previous COVID-19 disease (DIS), asymptomatic SARS-CoV-2 infection (INF), or infection-naïve (NEG). Serum anti-spike antibody titers were assessed at baseline, before the second dose, and at 1, 3, 6, 9, and 12 months. Linear mixed models and survival analyses were performed. Results: Of 326 enrolled patients, 189 with complete time-point data were included in the longitudinal analysis. Antibodies were detectable in 89% of DIS/INF at baseline and 91% before the second dose, but were negligible in NEG. In NEG, the seropositivity increased after vaccination and booster, reaching 78% at 12 months. Age (-5% per year, p < 0.001) and BMI (+10% per unit, p = 0.004) influenced titers; antimetabolites and steroids had strong negative effects (-70%, p = 0.005; -84%, p = 0.001). Breakthrough infections occurred in 104 (31.9%); 40% were asymptomatic, and 2 patients died. An mTOR inhibitor was associated with a reduced infection risk (OR 0.27 [CI: 0.09-0.70], p = 0.009). Higher antibody titers correlated with delayed infection (p = 0.063). Conclusions: In KTx patients, humoral response to SARS-CoV-2 vaccination is limited in infection-naïve patients but improved by booster dosing; the hybrid immunity is more effective. Immunosuppressive regimens influence the immune response, and mTOR inhibitors may protect against breakthrough infection.

Chronic kidney disease (CKD) is a global health issue with a rising prevalence, affecting 697.5 million people worldwide. It imposes a substantial burden, contributing to 35.8 million disability-adjusted life years (DALYs) and 1.2 million deaths in 2017. The mortality rate for CKD has increased by 41.5% between 1990 and 2017, positioning it as a significant cause of global mortality. CKD is associated with diverse health complications, impacting cardiovascular, neurological, nutritional, and endocrine aspects. One prominent complication is CKD–mineral and bone disorder (MBD), a complex condition involving dysregulation of bone turnover, mineralization, and strength, accompanied by soft tissue and vascular calcification. Alterations in mineral metabolism, including calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and Klotho, play pivotal roles in CKD-MBD. These disturbances, observed early in CKD, contribute to the progression of bone disorders and renal osteodystrophy (ROD). Vascular calcification (VC) is a key component of CKD-MBD, accelerated by CKD. The pathophysiology involves complex processes in vascular smooth muscle cells and the formation of calciprotein particles (CPP). VC is closely linked to cardiovascular events and mortality, emphasizing its prognostic significance. Various serum markers and imaging techniques, including lateral plain X-ray, Kauppila Score, Adragao Score, and pulse wave velocity, aid in VC detection. Additionally, pQCT provides valuable information on arterial calcifications, offering an advantage over traditional scoring systems. CKD poses a substantial global health burden, and its complications, including CKD-MBD and VC, significantly contribute to morbidity and mortality. Understanding the intricate relationships between mineral metabolism, bone disorders, and vascular calcification is crucial for effective diagnosis and therapeutic interventions.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factors, such as hypertension, diabetes, obesity, and smoking, among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D’s multifaceted and expanding actions concerning its involvement in CKD and CVD.

Kidney transplant recipients (KTRs) rely on immunosuppressants like mycophenolate to prevent organ rejection. However, mycophenolate often causes intestinal symptoms and inflammation in various organs, including the skin and the colon. While KTRs have an increased risk for skin cancer, the risk of colorectal cancer is not increased. Elucidating the histological alterations in the colon of KTRs and comparing these changes with known skin alterations would help understand how immunosuppressants influence cancer development and progression. Whole slide images from gut biopsies (Non-transplanted subjects n = 35, KTRs n = 49) were analyzed using the ImageJ and R programming environment. A total of 22,035 epithelial cells, 38,870 interstitial cells, 3465 epithelial cell mitoses, and 7477 endothelial cells, each characterized by multiple microscopy parameters, from a total of 1788 glands were analyzed. The large database was subsequently analyzed to verify the changes of inflammatory milieu in KTRs and in cancer. KTRs without colon-cancer showed a significantly higher density of interstitial cells in the colon compared to non-transplanted patients. Moreover, the increase in interstitial cell number was accompanied by subtle modifications in the architecture of the colon glands, without altering the epithelial cell density. We could not identify significant structural modifications in cancer samples between KTRs and non-transplanted patients. Our findings demonstrate an increased number of resident interstitial cells in the colon of KTRs, as in other patients treated with mycophenolate. These changes are associated with subtle alterations in the architecture of colon glands.

Pain is an unpleasant sensory and emotional experience. Adequate pain control is often challenging, particularly in patients with chronic pain. Despite advances in pain management, drug addiction, overtreatment, or substance use disorders are not rare. Hence the need for further studies in the field. The substantial progress made over the last decade has revealed genes, signalling pathways, molecules, and neuronal networks in pain control thus opening new clinical perspectives in pain management. In this respect, data on the epigenetic modulation of opioid and cannabinoid receptors, key actors in the modulation of pain, offered new perspectives to preserve the activity of opioid and endocannabinoid systems to increase the analgesic efficacy of opioid- and cannabinoid-based drugs. Similarly, upcoming data on cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant Cannabis sativa, suggests analgesic, anti-inflammatory, antioxidant, anticonvulsivant and ansiolitic effects and supports its potential application in clinical contexts such as cancer, neurodegeneration, and autoimmune diseases but also in health and fitness with potential use in athletes. Hence, in this review article, we summarize the emerging epigenetic modifications of opioid and cannabinoid receptors and focus on CBD as an emerging non-psychoactive cannabinoid in pain management in clinical practice, health, and fitness.

Background: Lower physical activity, lower alcohol intake, higher protein intake, higher sodium intake, and lower potassium intake related to greater kidney function decline over time, according to previous studies. The present study aimed to analyze the cumulative effects of these factors. Methods: This prospective, observational, population-based cohort study included 3039 adult examinees of the Gubbio study who participated in the baseline exam and 15-year follow-up exam. Kidney function was evaluated as estimated glomerular filtration rate (eGFR). Habitual physical activity in leisure time and habitual alcohol intake were assessed by questionnaires; dietary intakes of protein, sodium, and potassium were assessed by urinary markers. Based on previous reports, each one of the five modifiable factors was scored 0 for the tertile associated with smaller eGFR decline (low risk), 2 for the tertile associated with greater eGFR decline (high risk), and 1 for the intermediate tertile (intermediate risk). A cumulative score was calculated as the sum of the factor-specific scores and used as the main independent variable. Results: The cumulative score ranged from 0 to 10, that is, from low risk for all factors to high risk for all factors (skewness = 0.032, mean ± SD = 5 ± 2). To avoid the bias of low-n analyses, score 0 was re-coded as 1 and score 10 was recoded as 9; after re-coding, the cumulative score ranged from 1 to 9 (skewness = 0.016, mean ± SD = 5 ± 2). The cumulative score related to annualized eGFR change in multi-variable linear regression (slope = −0.027, 95%CI = −0.039/−0.014, p < 0.001); findings were consistent in apparently healthy examinees and other subgroups. De novo incidence of eGFR < 60 mL/min × 1.73 m2 was higher along the cumulative score (p < 0.001). Compared to score 1 (n examinees = 35, adjusted incidence = 2.0%), incidence of low kidney function was 4.5 times higher in score 5 (n examinees = 624, adjusted incidence = 8.9%) and 6.5 times higher in score 9 (n examinees = 86, adjusted incidence = 12.9%). The cumulative score related to incidence of low kidney function in multi-variable logistic regression (odds ratio = 1.19, 95%CI = 1.08/1.32, p < 0.001). Conclusions: The combination of five modifiable factors predicted large differences in long-term incidence of low kidney function.

Data are conflicting about the effects of alcohol intake on kidney function. This population-based study investigated associations of alcohol intake with kidney function and mortality. The study cohort included adult participants in Exam-1, Exam-2 (6-year follow-up), and Exam-3 (20-year follow-up) of the Gubbio study. Kidney function was evaluated as estimated glomerular filtration rate (eGFR, CKD-Epi equation, mL/min × 1.73 m2). Daily habitual alcohol intake was assessed by questionnaires. Wine intake accounted for >94% of total alcohol intake at all exams. Alcohol intake significantly tracked over time (R > 0.66, p < 0.001). Alcohol intake distribution was skewed at all exams (skewness > 2) and was divided into four strata for analyses (g/day = 0, 1–24, 25–48, and >48). Strata of alcohol intake differed substantially for lab markers of alcohol intake (p < 0.001). In multivariable regression, strata of alcohol intake related cross-sectionally to eGFR at all exams (Exam-1: B = 1.70, p < 0.001; Exam-2: B = 1.03, p < 0.001; Exam-3: B = 0.55, p = 0.010) and related longitudinally to less negative eGFR change from Exam-1 to Exam-2 (B = 0.133, p = 0.002) and from Exam-2 to Exam-3 (B = 0.065, p = 0.004). In multivariable Cox models, compared to no intake, intakes > 24 g/day were not associated with different mortality while an intake of 1–24 g/day was associated with lower mortality in the whole cohort (HR = 0.77, p = 0.003) and in the subgroup with eGFR < 60 mL/min × 1.73 m2 (HR = 0.69, p = 0.033). These data indicate a positive independent association of alcohol intake with kidney function not due to a mortality-related selection.

Prolonged mastication may induce an asymmetric modification of the local perfusion of the trigeminal principal nucleus. The aim of the present study was to evaluate the possible influence of vitamin C (vit. C) on such effect. Four groups of healthy volunteers underwent arterial spin labeling magnetic resonance imaging (ASL-MRI) to evaluate the local perfusion of the trigeminal nuclei after a vit. C-enriched lunch or a control lunch. Two ASL-MRI scans were acquired, respectively, before and after a 1 h-long masticating exercise or a 1 h long resting period. The results showed (i) an increased global perfusion of the brain in the vit. C-enriched lunch groups, (ii) an increased local perfusion of the right principal trigeminal nucleus (Vp) due to mastication, and (iii) a reduction of the rightward asymmetry of the Vp perfusion, due to mastication, after the vit C-enriched meal compared to the control meal. These results confirmed a long-lasting effect of prolonged mastication on Vp perfusion and also suggest a possible effect of vit. C on cerebral vascular tone regulation. Moreover, the data strongly draw attention on the side-to-side relation in Vp perfusion as a possible physiological parameter to be considered to understand the origin of pathological conditions like migraine.