Search Results (85)

Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article

Introduction: This study aims to investigate the clinical impact of Omicron Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection on the clinical presentation of Coronavirus Disease 2019 (COVID-19) in the very old (≥80 years old) population. Methods: All patients aged 80 years or older, hospitalized from March 2020 to June 2023 with a SARS-CoV-2 infection in one of the 17 COVID-19 units in eight cities of Campania, southern Italy, were enrolled in a multicenter, observational, retrospective study. Results: 341 patients ≥ 80 years of age were included: 80 of them in the Omicron and 261 in the non-Omicron period. Patients admitted during the Omicron period were older (p = 0.0001) and more comorbid, showing more frequently arterial hypertension (p = 0.018), cardiovascular disease (p = 0.0001), chronic kidney disease (CKD) (p = 0.002), chronic obstructive pulmonary disease (COPD) (p = 0.001), and active cancer (p = 0.0001). Severe and critical outcomes were observed more often in the non-Omicron variant (p = 0.0001). Patients in the Omicron group did not show a significantly prolonged hospitalization time (p = 0.063) or a higher likelihood of death during hospitalization (p = 0.097). Discussion: In our study, despite the greater frailty of patients hospitalized during the Omicron period, the disease appeared less severe compared to previous waves, suggesting that the lower severity of the disease could be attributed to virological rather than population characteristics. These findings underscore the importance of prevention strategies for older people, as the administration of vaccination and early antiviral therapies in at-risk subjects. Full article

Background: Immune checkpoint inhibitors (ICIs) have significantly modified the management of metastatic cancers; however, their nephrotoxic potential remains underappreciated. While acute kidney injury (AKI) is a known immune-related adverse event, the subacute spectrum of kidney injury—termed acute kidney disease (AKD)—has not been adequately explored in this setting. Methods: We conducted a retrospective cohort study in 226 adult patients with metastatic solid tumors who received ICIs between 2017 and 2023 at a single tertiary care center. AKD was defined according to the 2024 “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria. Multivariable logistic regression was used to identify predictors of AKD. Results: AKD occurred in 46 patients (20.4%) within 90 days of ICI initiation, with 16 (7.1%) experiencing persistent dysfunction beyond 30 days. Independent predictors of AKD included higher body surface area (OR 8.17, p = 0.03) and baseline use of nonsteroidal anti-inflammatory drugs (OR 29.74, p = 0.014). Baseline antibiotics showed a trend toward association (p = 0.054). Concurrent chemotherapy was associated with a trend toward protection. The predictive model showed good discrimination (AUC 0.778). No significant differences in other grade ≥2 immune-related adverse events were observed between the AKD and non-AKD groups. Conclusions: AKD is a frequent and underrecognized renal complication in patients receiving ICIs, with implications for both renal and oncological outcomes. Identifying high-risk patients and integrating longitudinal renal monitoring into immunotherapy care pathways may improve safety and treatment continuity. Full article

Patients with chronic kidney disease (CKD) face an increased risk of early vascular aging, progressive vascular calcification, and premature death. With increasing age, mitochondrial function and mitochondrial DNA copy number (mtDNA-cn) decline. This has been identified as an independent predictor of frailty and mortality in cardiovascular diseases (CVDs) and cancer. However, the relationship between mtDNA-cn and vascular calcification in the context of a uremic milieu remains ambiguous. We hypothesize that a lower mtDNA-cn is associated with medial calcification, as both are linked to impaired vascular health and accelerated aging. mtDNA-cn was analyzed in 211 CKD5 patients undergoing renal transplantation (RTx) and 196 healthy controls using quantitative PCR (qPCR) for three mtDNA genes (mtND1, mtND4, and mtCOX1) and single-locus nuclear gene hemoglobin beta (HbB). In 32 patients, mtDNA-cn was also quantified one year after RTx. The association between mtDNA-cn and vascular calcification scores, circulatory cell-free (ccf) mtDNA in plasma, and the surrogate marker of biological aging (skin autofluorescence) and CVD risk was assessed. mtDNA-cn was significantly lower in CKD5 patients than in controls and correlated with biological age, vascular calcification, and CVD risk. One year after RTx there was a significant recovery of mtDNA-cn in male patients compared to baseline levels. mtDNA-cn and ccf-mtDNA were inversely correlated. This prospective study provides novel insights into the link between low mtDNA-cn and vascular aging. It demonstrates that RTx restores mtDNA levels and may improve oxidative phosphorylation capacity in CKD. Further investigation is warranted to evaluate mtDNA as a biologically relevant biomarker and a potential therapeutic target for early vascular aging in the uremic environment. Full article

Dietary exposure to a high dose of cadmium (Cd) ≥ 100 µg/day for at least 50 years or a lifetime intake of Cd ≥ 1 g can cause severe damage to the kidneys and bones. Alarmingly, however, exposure to a dose of Cd between 10 and 15 µg/day and excretion of Cd at a rate below 0.5 µg/g creatinine have been associated with an increased risk of diseases with a high prevalence worldwide, such as chronic kidney disease (CKD), fragile bones, diabetes, and cancer. These findings have cast considerable doubt on a “tolerable” Cd exposure level of 58 µg/day for a 70 kg person, while questioning the threshold level for the Cd excretion rate of 5.24 µg/g creatinine. The present review addresses many unmet challenges in a threshold-based risk assessment for Cd. Special emphasis is given to the benchmark dose (BMD) methodology to estimate the Cd exposure limit that aligns with a no-observed-adverse-effect level (NOAEL). Cd exposure limits estimated from conventional dosing experiments and human data are highlighted. The results of the BMDL modeling of the relationship between Cd excretion and various indicators of its effects on kidneys are summarized. It is recommended that exposure guidelines for Cd should employ the most recent scientific research data, dose–response curves constructed from an unbiased exposure indicator, and clinically relevant adverse effects such as proteinuria, albuminuria, and a decrease in the estimated glomerular filtration rate (eGFR). These are signs of developing CKD and its progression to the end stage, when dialysis or a kidney transplant is required for survival. Full article

Cardiovascular–kidney–metabolic (CKM) syndrome represents a complex interplay between cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders, significantly impacting cancer patients. The presence of CKM syndrome in cancer patients not only worsens their prognosis but also increases the risk of major adverse cardiovascular events (MACE), reduces quality of life (QoL), and affects overall survival (OS). Furthermore, several anticancer therapies, including anthracyclines, tyrosine kinase inhibitors, immune checkpoint inhibitors, and hormonal treatments, can exacerbate CKM syndrome by inducing cardiotoxicity, nephrotoxicity, and metabolic dysregulation. This review explores the pathophysiology of CKM syndrome in cancer patients and highlights emerging therapeutic strategies to mitigate its impact. We discuss the role of novel pharmacological interventions, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and soluble guanylate cyclase (sGC) activators, as well as dietary and lifestyle interventions. Optimizing the management of CKM syndrome in cancer patients is crucial to improving OS, enhancing QoL, and reducing MACE. By integrating cardiometabolic therapies into oncologic care, we can create a more comprehensive treatment approach that reduces the burden of cardiovascular and renal complications in this vulnerable population. Further research is needed to establish personalized strategies for CKM syndrome prevention and treatment in cancer patients. Full article

Background: The objective of the present study was to evaluate the impact of dialysis on patients with upper tract urothelial carcinoma (UTUC) who are undergoing surgical intervention, as well as to identify predictive factors linked to contralateral recurrence. Methods: A retrospective review was conducted on patients who underwent radical nephroureterectomy (RNU) for non-metastatic UTUC at our institution from 2000 to 2013. The contralateral recurrence rate was calculated using the Kaplan–Meier method, and multivariate logistic regression analysis was employed to examine the relationship between clinicopathological characteristics and contralateral recurrence. Results: A total of 593 patients were included in this analysis, of which 31 (5.8%) experienced metachronous recurrence on the contralateral side. Kaplan–Meier analysis indicated a statistically significant reduction in the contralateral recurrence-free survival rate among female patients (p = 0.040), those with a prior history of bladder cancer (p < 0.001), individuals presenting with multiple tumors (p = 0.011), patients with advanced chronic kidney disease (CKD) (p < 0.001), and those requiring postoperative dialysis (p < 0.001). In contrast, preoperative hemodialysis status did not show a significant correlation with contralateral recurrence (p = 0.08). The multivariate analysis identified a history of bladder cancer (hazard ratio (HR), 3.19; 95% confidence interval (CI), 1.2–8.4; p = 0.018), the necessity for new hemodialysis postoperatively (HR, 5.34; 95% CI, 1.3-25.6; p = 0.034), and advanced CKD (HR, 2.52; 95% CI, 1.4–4.9; p = 0.021) as independent risk factors associated with an increased rate of contralateral recurrence. Conclusions: In conclusion, advanced CKD, a history of bladder cancer, and the initiation of new dialysis following surgery were identified as independent prognostic indicators for contralateral recurrence in patients with initial unilateral UTUC undergoing RNU. It is recommended that patients exhibiting these three adverse characteristics undergo rigorous monitoring of the contralateral upper urinary tract throughout the follow-up period. Full article

The El Valle Volcanic Complex, located in the province of Cocle, Panama, presents geological characteristics that could be linked to public health problems. This study focuses on the municipalities of San Juan de Dios, Pajonal, and Caballero, where water is consumed directly from springs (groundwater outcrops). The region has a high incidence of non-traditional chronic kidney disease (nt-CKD) that may be associated with the natural presence of potentially toxic elements (PTEs) in the water. This study aimed to analyze the concentration of PTEs in groundwater and assess the carcinogenic (CR) and non-carcinogenic (HQ) risk to human health from the direct ingestion of water. Sediments, rocks, and water samples were collected. Major ions and PTEs (As, Al, Ba, Co, Cu, Fe, Mn, Sr, Sb, Pb, V, and Zn) were measured, and the mineralogical composition of the rocks was analyzed. The results showed that Fe was the only PTE that exceeded the recommended concentration for drinking water, according to Panama regulations, and Pb according to USEPA. In Caballero and Pajonal, the acceptable threshold for CR and HQ was exceeded, a higher percentage than in San Juan de Dios. The PTEs that contribute most to the risk are Co, Cu, Pb, and As. This study suggests that the region’s historical volcanic activity, involving the release of minerals rich in these PTEs, along with the interaction between groundwater and volcanic rocks, may be contributing to the presence of PTEs in the water. This geological phenomenon could be what has led to prolonged exposure to these elements, which correlates with the high prevalence of chronic kidney disease in the area. This is a novel study, the first conducted in Panama, as it seeks to uncover the relationship between the geology of the site, the presence of PTEs in the groundwater of springs for human consumption, and the implication of health risks, with the aim of generating new information for decision makers for the generation of public policies on health issues such as nt-CKD and cancer in the region. Full article

Epidemiological studies suggest an increased risk of colorectal cancer (CRC) aggravation in patients with chronic kidney disease (CKD). Our previous study demonstrated that indoxyl sulfate, a uremic toxin whose concentration increases with CKD progression, exacerbates CRC through activation of the AhR and Akt pathways. Consequently, indoxyl sulfate has been proposed to be a significant link between CKD progression and CRC aggravation. The present study aimed to investigate the roles of c-Myc and β-Catenin, which are hypothesized to be downstream factors of indoxyl sulfate-induced AhR and Akt activation, in CRC cell proliferation and EGF sensitivity in HCT-116 CRC cells. Indoxyl sulfate significantly induced CRC cell proliferation at concentrations exceeding 62.5 µM, a process suppressed by the c-Myc inhibitor 10058-F4. Indoxyl sulfate activated the Akt/β-Catenin/c-Myc pathway as evidenced by the Akt inhibitor MK2206, which decreased both β-Catenin and c-Myc protein levels, and the β-Catenin inhibitor XAV-939, which reduced c-Myc protein levels. The AhR antagonist CH223191 also inhibited c-Myc upregulation, indicating involvement of the AhR/c-Myc pathway. MK2206 partially attenuated the indoxyl sulfate-induced AhR transcriptional activity, suggesting that Akt activation influences the AhR/c-Myc pathway. MK2206, CH223191, and 10058-F4 suppressed the increase in EGFR protein levels induced by indoxyl sulfate, indicating that the Akt/β-Catenin/c-Myc and AhR/c-Myc pathways enhance the sensitivity of HCT-116 CRC cells to EGF. These findings indicate that the elevation of indoxyl sulfate levels in the blood, due to CKD progression, could worsen CRC by promoting the proliferation of CRC cells and enhancing EGF signaling. Therefore, indoxyl sulfate could potentially serve as a therapeutic target for CRC aggravation in patients with CKD. Full article

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the population worldwide, accounting for more than 843 million (M) individuals. The prevalence of CKD (844 M patients) is higher than that of diabetes mellitus (422 M patients), cancer (42 M patients), and HIV (37 M patients), but people are often less aware of it. Global expert groups predict reductions in the nephrology workforce in the next decade, with a declining interest in nephrology careers. Over time, KDIGO guidelines have also focused on topics related to the prevention or management of CKD patients in real-life settings. On these premises, a new educational program with international experts in the field of nephrology took place from November 2022 until March 2023 in Milan, Italy. This multinational masterclass provided an educational platform providing unbiased education on diagnosis and treatment by sharing the most recent research data on CKD and comorbidities, therefore creating a snowball effect to increase the implementation of best practices worldwide, using examples from ‘real-life’ patient outcomes. This paper provides an overview of the International Nephrology Masterclass (INM) concept, summarizing the key lectures and discussions, and giving an outline of future key developments. Full article

Background: Patients with gout have several coexisting conditions that impact mortality. We analyzed the differences in clinical manifestations among Korean patients with gout and compared the causes of death based on sex using data from the Korean National Health Insurance Service-National Sample Cohort database. Methods: We included adults with gout receiving urate-lowering therapy (ULT) from 2002 until 2019. The clinical features and causes of death were compared between male and female patients. Multivariate Cox regression was performed to identify the risk factors contributing to all-cause mortality. Results: The results showed that female patients were older at the start of ULT and had more comorbidities. The most common cause of death among all patients with gout was chronic kidney disease (CKD). When observed separately by sex, lung cancer is the leading cause in males, versus CKD in females. Multivariate Cox analysis showed that old age at ULT start, low body mass index (BMI), current smoking, diabetes, CKD, cerebrovascular disease, malignancy, and low hemoglobin were significant risk factors for all-cause mortality in males; however, old age at ULT start, low BMI, CKD, malignancy, and low hemoglobin were significant risk factors in females. Conclusions: The clinical features and cause of death were different between male and female patients with gout, suggesting that treatment strategies for gout should be established differently depending on sex. Full article

Background: The malnutrition–inflammation score (MIS) is a practical and accessible tool for evaluating protein energy wasting (PEW) in patients on dialysis. However, the severity of PEW at each stage of chronic kidney disease (CKD), especially with late dialysis initiation, is unclear. Methods: We evaluated the MIS of 3659 patients with CKD stages 1–5 and the changes in their MIS results at baseline and at the time before dialysis initiation. Patients were defined to have PEW if they had a subjective global assessment (SGA) rating of C or lower. Results: The MIS increased substantially over a follow-up period of 6.12 years for 1124 patients just starting dialysis, with 49.3% having an MIS of 8. The pre-dialysis MIS was associated with baseline MIS, age, cardiovascular disease, and cancer. The prevalence of PEW based on an SGA rating of C or lower increased from 10.5% at baseline to 61.2% immediately before dialysis. The prevalence of PEW based on an MIS of ≥8 increased from 28.5% at baseline to 49.3% immediately before dialysis. In CKD stage 5 patients, 29.4% had PEW based on an MIS of 8 or less, and 11.6% had an SGA rating of C. The MIS was revealed to be associated with renal function, nutritional markers, and cardiometabolic disease (diabetes or cardiovascular disease). Conclusions: In conclusion, the MIS increased as CKD progressed to stages 4 and 5, as well as just prior to dialysis. Our study identified patients who required PEW assessment on the basis of their MIS results. Full article

Cisplatin (CisPt) is a widely used chemotherapeutic agent. However, its nephrotoxic effects pose significant risks, particularly for the development of acute kidney injury (AKI) and potential progression to chronic kidney disease (CKD). The present study investigates the impact of non-lethal exposure of CisPt to immortalized human renal epithelial precursor TERT cells (HRTPT cells) that co-express PROM1 and CD24, markers characteristic of renal progenitor cells. Over eight serial passages, HRTPT cells were exposed to 1.5 µM CisPt, leading to an initial growth arrest, followed by a gradual recovery of proliferative capacity. Despite maintaining intracellular platinum (Pt) levels, the cells exhibited normal morphology by passage eight (P8), with elevated expression of renal stress and damage markers. However, the ability to form domes was not restored. RNA-seq analysis revealed 516 differentially expressed genes between CisPt-exposed and control cells, with significant correlations to cell cycle and adaptive processes, as determined by the Reactome, DAVID, and Panther analysis programs. The progenitor cells treated with CisPt displayed no identity, or close identity, with cells of the normal human nephron. Additionally, several upregulated genes in P8 cells were linked to cancer cell lines, suggesting a complex interaction between CisPt exposure and cellular repair mechanisms. In conclusion, our study demonstrates that renal progenitor cells can recover from CisPt exposure and regain proliferative potential in the continued presence of both extracellular CisPt and intracellular Pt. Full article

Cisplatin, widely used in chemotherapy, acts through mechanisms such as oxidative stress to damage the DNA and cause the apoptosis of cancer cells. Although effective, cisplatin treatment is associated with considerable side effects including chronic kidney disease (CKD). Studies on brown-strain Flammulina velutipes Singer (FVB) have shown its significant antioxidant and immunomodulatory effects. High-performance liquid chromatography (HPLC) confirmed that the FVB extract contained gallic acid and quercetin. This study investigated whether FVB extract can improve and protect against cisplatin-induced CKD in mice. C57BL/6 mice were used as an animal model, and CKD was induced through intraperitoneal cisplatin injection. FVB was orally administered to the mice for 14 consecutive days. N-acetylcysteine (NAC) was administered in the positive control group. Organ pathology and serum biochemical analyses were conducted after the mice were sacrificed. Significant dose-dependent differences were discovered in body mass, kidney mass, histopathology, renal function, inflammatory factors, and antioxidant functions among the different groups. FVB extract reduced the severity of cisplatin-induced CKD in pathways related to inflammation, autophagy, apoptosis, fibrosis, oxidative stress, and organic ion transport proteins; FVB extract, thus, displays protective physiological activity in kidney cells. Additionally, orally administered high doses of the FVB extract resulted in significantly superior renal function, inflammatory factors, antioxidative activity, and fibrotic pathways. This study establishes a strategy for future clinical adjunctive therapy using edible-mushroom-derived FVB extract to protect kidney function. Full article

Background and Hypothesis: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are significant risks for kidney cancer (KC) patients undergoing partial (PN) or radical nephrectomy (RN) and for living kidney donors (LKD). This study compares AKI and CKD incidence in these groups with a pre-operative glomerular filtration rate (GFR) over 60 mL/min/1.73 m². Methods: This study included 465 KC patients with cT1-2N0M0 kidney mass and 256 LKD who underwent nephrectomy at four Italian institutions from 2014 to 2021. Data on demographics, comorbidities, and therapies were analyzed. Serum creatinine and estimated GFR (eGFR) were measured before and after surgery. Outcomes were AKI (per KDIGO guidelines) and CKD stage progression. Analyses included descriptive statistics, ANOVA, logistic regression, and Kaplan–Meier survival. Results: Among 721 patients, significant age and gender differences were noted. Hypertension (41%) and diabetes (7.1%) were prevalent in RN and PN groups. Post-surgery AKI was more common in donors (84%), while CKD stage progression varied by surgery type (CKD stage G3 after 60 months: RN 48.91%, PN 18.22%, LKD 26.56%). Age, pre-surgery CKD, and surgery type predicted CKD progression. Limitations include retrospective design and bias. Conclusions: Both LKD and KC patients face similar AKI and CKD risks. Surgery type significantly influences AKI and CKD incidence, highlighting the importance of approach. Full article