Search Results (272)

Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article

Background: Rapid loss of residual kidney function (RKF) is associated with unfavorable outcomes. We conducted an RCT to compare the effects on RKF preservation of incremental HD between once-weekly HD (1-WHD) and twice-weekly HD (2-WHD). Methods: ESKD patients with an eGFR of 5–10 mL/min/1.73 m² and urine output of ≥800 mL/day were randomly assigned to receive either once-weekly HD (1-WHD) or twice-weekly HD (2-WHD) for 12 months. Patients in the 1-WHD group were prescribed once-weekly HD combined with low-protein diet (0.6 g/kg/day) supplemented with keto-analogues (KAs) 0.12 g/kg/day. In the 2-WHD group, patients received twice-weekly HD with a regular-protein diet. Primary outcomes were changes in RKF by renal clearance and urine volume. Nutritional status, muscle parameters, and quality of life (QoL) were also assessed. Results: A total of 30 incident HD patients were randomized. Baseline RKF, urine volume, and demographic were not different between groups. After 3 months, urine volume was significantly higher in the 1-WHD group than in the 2-WHD group (1921 ± 767 mL/day vs. 1305 ± 599 mL/day, p = 0.02), and these significant findings persisted throughout the entire study period. For RKF, 1-WHD also had a lesser decline in urinary urea (CUrea) and creatinine clearance (CCr) than 2-WHD, with statistically significant differences observed from months 6–12. By month 6, the 1-WHD group exhibited significantly higher CUrea and CCr compared to the 2-WHD group, with CUrea at 3.2 ± 2.3 vs. 1.7 ± 1.0 mL/min (p = 0.03) and CCr at 5.9 ± 3.6 vs. 3.8 ± 1.4 mL/min (p = 0.04), respectively. Serum albumin levels, skeletal muscle mass, anemia status, metabolic parameters, protein-bound uremic toxins, and QoL scores were comparable between the two groups. Conclusions: Incremental HD, starting with once-weekly HD combined with protein restriction supplemented with KAs, appears to better preserve RKF among incident HD patients compared to twice-weekly HD with a regular-protein diet. This HD regimen was also associated with safety in metabolic and nutritional profiles. Full article

Background: Blood pressure (BP) variability has been increasingly recognized as a predictor of cardiovascular and renal outcomes. However, the relevance of specific dynamic indices such as the maximum slope of systolic blood pressure (max SBP slope), derived through partial Fourier series modeling, in relation to early renal damage remains underexplored. Methods: A total of 389 patients with essential hypertension were enrolled and stratified according to the estimated glomerular filtration rate (eGFR) ≥ or <90 mL/min/1.73 m² and the presence of subclinical renal damage, defined by elevated urinary albumin excretion (AER) and/or reduced eGFR. All participants underwent clinical and biochemical evaluation, as well as 24-h ambulatory blood pressure monitoring (ABPM), including advanced hemodynamic analysis using Fourier-based modeling. Results: Patients with eGFR < 90 mL/min/1.73 m² were older and exhibited higher waist circumference, uricemia, albuminuria, and systolic BP values, including the elevated max SBP slope (12.8 vs. 10.8 mmHg/h, p = 0.028). Subclinical renal damage was associated with older age; male sex; smoking; and higher levels of uricemia, clinical, and ambulatory BP, and the max SBP slope (14.2 vs. 10.7 mmHg/h, p = 0.007). The max SBP slope positively correlated with AER (r = 0.215, p < 0.001) and inversely with eGFR (r = −0.153, p = 0.002). In multivariate linear regression, the max SBP slope remained independently associated with AER (β = 0.220, p < 0.001), along with mean 24-h SBP, male sex, and the day–night SBP percentage dip. Logistic regression confirmed these associations with subclinical renal damage (max SBP slope OR: 1.536; 95% CI: 1.241–2.004; p = 0.001). Conclusions: The max SBP slope, a dynamic index of BP derived via Fourier analysis, is independently associated with markers of subclinical renal damage in hypertensive patients. This suggests that incorporating such advanced metrics into ABPM evaluation may improve early risk stratification and help identify individuals at greater risk of renal impairment, even in the absence of overt kidney disease. Full article

The prognosis of sarcopenia is poor in cancer patients. Recently, urinary titin, a biomarker of muscle damage, has been suggested as a potential marker for sarcopenia. However, its utility in patients with unresectable digestive malignancies remains unclear. In addition, sex differences have been reported in the association between sarcopenia and urinary titin levels. This study aimed to evaluate urinary titin as a diagnostic marker for unresectable digestive malignancies, focusing on sex differences. This retrospective study enrolled 96 patients (58 males, 38 females; median age 70), and urinary titin was evaluated as a diagnostic biomarker in relation to clinical factors (e.g., age, Eastern Cooperative Oncology Group performance status [ECOG PS], albumin [Alb]) and muscle indicators (e.g., psoas muscle index [PMI], handgrip strength). In male patients, urinary titin levels were significantly higher in the sarcopenia subgroup (5.78 vs. 2.79 pmol/mgCr, p = 0.008), and multivariate analyses identified urinary titin as an independent predictor of sarcopenia (odds ratio 13.4, p = 0.028). The receiver operating characteristic (ROC) analysis demonstrated fair diagnostic performance (area under the curve [AUC] 0.729), with an optimal cutoff value of 3.676 pmol/mgCr. Urinary titin may serve as a useful non-invasive diagnostic biomarker for sarcopenia in patients with unresectable digestive malignancies, particularly in males. These findings suggest that sex-specific approaches are required for sarcopenia assessment with urinary titin. Full article

Hypertension and diabetes mellitus are key contributors to kidney damage, with the renal tubule playing a central role in the progression of kidney disease. MicroRNAs have important regulatory roles in renal injury and are among the most abundant cargos within extracellular vesicles (EVs), emerging as novel kidney disease biomarkers and therapeutic tools. Previously, we identified miR-200a-3p and its target SIRT1 as having a potential role in kidney injury. We aimed to evaluate miR-200a-3p levels in EVs from patient’s urine and delve into its function in causing tubular injury. We quantified miR-200a-3p urinary EV levels in hypertensive patients with and without diabetes (n = 69), 42 of which were with increased urinary albumin excretion (UAE). We analysed miR-200a-3p levels in EVs and cellular pellets, as well as their targets at mRNA and protein levels in renal tubule cells (RPTECs) subjected to high glucose and Angiotensin II treatments, and observed their influence on apoptosis, RPTEC markers and tubular injury markers. We conducted microRNA mimic and inhibitor transfections in treated RPTECs. Our findings revealed elevated miR-200a-3p levels in increased UAE patient urinary EVs, effectively discriminating UAE (AUC of 0.75, p = 0.003). In vitro, miR-200a-3p and renal injury markers increased, while RPTEC markers, SIRT1, and apoptosis decreased under treatments. Experiments using miR-200a-3p mimics and inhibitors revealed a significant impact on SIRT1 and decrease in tubular damage through miR-200a-3p inhibition. Increased levels of miR-200a-3p emerge as a potential disease marker, and its inhibition provides a therapeutic target aimed at reducing renal tubular damage linked to hypertension and diabetes. Full article

Background/Objectives: The role of glycogen metabolism in diabetic kidney disease (DKD) remains unclear. This study investigated the therapeutic potential of asiatic acid (AA) on glycogen metabolism in DKD and its underlying mechanisms. Methods: A DKD mouse model was established using a high-fat diet and streptozotocin, followed by AA treatment for 8 weeks. Network pharmacology and molecular docking identified STBD1 as a potential target of AA, and its overexpression in mice was performed. Results: AA reduced blood glucose levels and the urinary albumin-to-creatinine ratio (UACR) and downregulated TGFβ-1, KIM-1, and PDK4. Additionally, AA treatment reversed abnormal glycogen accumulation and restored STBD1 expression. Network pharmacology and molecular docking identified STBD1 as a potential target of AA, and its overexpression in mice demonstrated similar beneficial effects. Gene enrichment analysis revealed that STBD1 is involved in key metabolic pathways related to DKD. Conclusions: These findings suggest that AA alleviates renal damage in DKD, possibly through modulation of STBD1, highlighting its therapeutic potential and the critical role of STBD1 in renal glycophagy. Full article

The gut microbiota has emerged as a critical modulator in metabolic diseases, with substantial evidence supporting its role in attenuating diabetes-related nephropathy. Recent investigations demonstrate that strategic manipulation of intestinal microflora offers novel therapeutic avenues for safeguarding renal function against diabetic complications. This investigation sought to determine the nephroprotective potential of Lactobacillus rhamnosus GG (LGG) administration in diabetic nephropathy models. Six experimental cohorts were evaluated: control, probiotic-supplemented control, diabetic, diabetic receiving probiotic therapy, diabetic with antibiotics, and diabetic treated with both antibiotics and probiotics. Diabetic conditions were established via intraperitoneal administration of streptozotocin (50 mg/kg) following overnight fasting, according to validated protocols for experimental diabetes induction. Probiotic therapy (3 × 10⁹ CFU/kg, bi-daily) began one month before diabetes induction and continued throughout the study duration. Glycemic indices were monitored at bi-weekly intervals, inflammatory biomarkers, renal function indices, and urinary albumin excretion. The metabolic profile was evaluated through the determination of HOMA-IR and the computation of metabolic syndrome scores. Microbiome characterization employed 16S rRNA gene sequencing alongside metagenomic shotgun sequencing for comprehensive microbial community mapping. L. rhamnosus GG supplementation substantially augmented microbiome richness and evenness metrics. Principal component analysis revealed distinct clustering of microbial populations between treatment groups. The Prevotella/Bacteroides ratio, an emerging marker of metabolic dysfunction, normalized following probiotic intervention in diabetic subjects. Results: L. rhamnosus GG administration markedly attenuated diabetic progression, achieving glycated hemoglobin reduction of 32% compared to untreated controls. Pro-inflammatory cytokine levels (IL-6, TNF-α) decreased significantly, while anti-inflammatory mediators (IL-10, TGF-β) exhibited enhanced expression. The renal morphometric analysis demonstrated preservation of glomerular architecture and reduced interstitial fibrosis. Additionally, transmission electron microscopy confirmed the maintenance of podocyte foot process integrity in probiotic-treated groups. Conclusions: The administration of Lactobacillus rhamnosus GG demonstrated profound renoprotective efficacy through multifaceted mechanisms, including microbiome reconstitution, metabolic amelioration, and inflammation modulation. Therapeutic effects suggest the potential of a combined probiotic and pharmacological approach to attenuate diabetic-induced renal pathology with enhanced efficacy. Full article

Microalbuminemia, characterized by a urinary albumin concentration between 20 and 200 mg/L, is a critical marker in assessing the risk of chronic kidney disease (CKD), diabetic nephropathy, and various other chronic conditions. Previously, we developed and validated the MyACR point-of-care (PoC) device, which facilitates the monitoring of CKD progression through real-time data transmission, thus enhancing patient management. This device utilizes a spectrophotometric dye-binding assay to measure albumin and creatinine concentrations in urine samples, providing an albumin-to-creatinine ratio (ACR) result. In the present study, we introduced a refined version of the PoC device, MyμAlbumin, designed to offer a simple, accurate, specific, sensitive, and rapid method for detecting microalbumin in urine as an early indicator of CKD and related diseases. The measurement is based on a specific immunoturbidimetric assay in a microcuvette, using a total solution volume of 125 µL (n = 5 for each validation test). The MyμAlbumin device demonstrated excellent performance, achieving high accuracy (%DMV ≤ 4.67) and precision (%CV < 5) and a strong correlation (R² > 0.995) with laboratory spectrophotometry (dye-binding assay) and reference hospital-based immunoturbidimetric assay. Its high sensitivity (LOQ = 5 mg/L) positions MyμAlbumin as a highly viable and cost-effective tool for clinical use. Additionally, the device supports real-time, seamless data transmission, making it ideal for integration into remote healthcare settings. Full article

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. Full article

Albuminuria is a sensitive biomarker of kidney dysfunction, and the albumin/creatinine ratio (ACR) is an essential measure for monitoring diabetic kidney disease (DKD). Abnormal levels can indicate a propensity for progressive renal failure and other complications such as cardiovascular diseases. This study employed UV/Visible spectroscopy to analyze aqueous urine samples spiked with bovine serum albumin (BSA) and creatinine at clinically relevant concentrations (0–30 mg/L for albumin and 600–1800 mg/L for creatinine) using a multivariate method. UV/Visible spectra of co-spiked samples recorded in triplicate revealed distinct bands at 229 nm and 249 nm, corresponding to BSA and creatinine, respectively, alongside other amino acid bands. Partial Least Squares Regression (PLS-R) analysis for BSA yielded a Root Mean Square Error of Calibration (RMSEC) and Cross-Validation (RMSECV) values of 66.93 and 73.92 mg/L, respectively. For creatinine, RMSEC and RMSECV values were 244.32 and 275.65 mg/L, respectively. Prediction models for both BSA and creatinine compared to ELISA demonstrated a robust performance with R²_PRED values of 0.96 and 0.95, respectively, indicating strong model reliability. The Limit of Detection (LOD) for co-spiked samples was 19.82 mg/L for BSA and 58.43 mg/L for creatinine. The significance of the achieved Limit of Detection (LOD) lies in its ability to measure concentrations well below the normal physiological ranges of 0–30 mg/L for albumin and 600–1800 mg/L for creatinine. These results demonstrate the proof of concept of applying an UV/Visible-spectroscopy-based method as a rapid, cost-effective point-of-care (PoC) tool for ACR measurements, offering promising applications in the early diagnosis, monitoring, and prognosis of diabetic kidney disease and associated cardiovascular complications. The next stage will involve a pilot trial to evaluate the technology’s potential using clinical patients. Full article

Background/Objectives: While sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated additional non-glycemic benefits for renal protection in individuals with type 2 diabetes, less evidence is available for those with type 1 diabetes (T1D). To determine whether the adjunctive use of the SGLT2 inhibitor ipragliflozin confers kidney protection in individuals with T1D, we retrospectively analyzed data from a real-world cohort examined at 25 centers in Japan. Methods: We enrolled 359 subjects aged 20–74 years with T1D (IPRA group: 159 ipragliflozin users; control [CTRL] group: 200 non-users). The primary outcome was changes in the estimated glomerular filtration rate (eGFR) from baseline to 24 months after the initiation of ipragliflozin. The secondary outcomes were all other changes, including the urinary albumin–creatinine ratio (UACR) and urinary protein–creatinine ratio (UPCR). Results: The IPRA group’s eGFR decline slopes were 0.79 mL/min/1.73 m²/year milder than the CTRL group’s after propensity score matching, but this difference was not significant. The subjects complicated by chronic kidney disease (CKD) defined as UACR ≥ 30 mg/g and/or UPCR ≥ 0.5 g/g and/or eGFR < 60 mL/min/1.73 m² showed changes in UPCR (g/g) from baseline to 24 months that were significantly lower in the IPRA group (−0.27 ± 1.63) versus the CTRL group (0.18 ± 0.36) (p = 0.016). No significant increase in adverse events (including severe hypoglycemia and hospitalization due to ketosis/ketoacidosis or cardiovascular diseases) was observed in the IPRA group. Conclusions: Adjunctive treatment with ipragliflozin exerted potential renal benefits by decreasing proteinuria in T1D subjects with CKD. Further investigations are required to determine whether its additional benefits exceed the increased risk of ketoacidosis. Full article

Background/Objectives: Low vitamin D status seems to be associated with increased cardiometabolic risk, and was found to attenuate cardiometabolic benefits of statins in men. The aim of the current study was to investigate whether a different vitamin D status determines the pleiotropic effects of statins in women. Methods: This pilot, single-center, prospective, matched-cohort study included 78 women with hypercholesterolemia requiring statin therapy, assigned into one of three age-, plasma lipid-, and body mass index-matched groups: women with vitamin D deficiency (group I), women with vitamin D insufficiency (group II), and women with normal vitamin D homeostasis (group III). Throughout the study (16 weeks), all patients were treated with atorvastatin. The outcome of interest included plasma lipids, glucose homeostasis markers (fasting glucose, HOMA-IR and glycated hemoglobin), plasma levels of 25-hydroxyvitamin D, creatine kinase, uric acid, high-sensitivity C-reactive protein, homocysteine, fibrinogen, urinary albumin-to-creatinine ratio (UACR), and computed values of a 10-year risk of atherosclerotic events. Results: Compared to the control group (group III), group I was characterized by higher values of HOMA-IR, glycated hemoglobin, uric acid, hsCRP, homocysteine, fibrinogen, a UACR, and a 10-year risk of atherosclerotic events, whereas group II had higher values of hsCRP, homocysteine and a UACR. Atorvastatin reduced plasma levels of total and LDL cholesterol and a 10-year risk of atherosclerotic events in all study groups, but this effect was weakest in group I and strongest in group III. In group III, the drug decreased uric acid, hsCRP, homocysteine, fibrinogen, and the UACR. In the remaining groups, its effect was limited to a small decrease in only hsCRP (group I) or in hsCRP and homocysteine (group II). In group I, atorvastatin treatment was associated with an increase in HOMA-IR, glycated hemoglobin, and creatine kinase. Conclusions: Low vitamin D status may exert an unfavorable effect on the lipid-dependent and lipid-independent effects of atorvastatin in middle-aged or elderly women. Full article

Objectives: This study investigated the effects and mechanisms of electrolyzed alkaline water (EAW), a type of drinking water, on hyperuricemia (HUA) in mice. Methods: A hyperuricemia model was established by intraperitoneal injection of potassium oxonate and free access to a high-purine diet. EAW was provided ad libitum for 21 days. Results: The results showed that EAW had little impact on the levels of blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, albumin, or xanthine oxidase in mice (p > 0.05). Interestingly, EAW ingestion induced significant reductions in uric acid and creatinine levels (p < 0.05), along with increased urinary uric acid excretion (p < 0.05) and less renal pathological changes in mice. Additionally, EAW upregulated GLUT9 gene expression (p > 0.05) and downregulated URAT1 protein expression. Conclusions: In conclusion, this study demonstrates that EAW promotes uric acid excretion by downregulating URAT1 and GLUT9 protein expression, resulting in a significant reduction in uric acid levels. Full article

Background and Objectives: Immunosuppressed patients are at higher risk of delayed diagnosis and atypical presentations in the emergency department (ED), requiring prompt management. This study compares febrile (≥37.5 °C) and afebrile (<37.5 °C) immunosuppressed patients admitted to the ED regarding clinical and laboratory parameters, including blood and urine tests, vital signs, final diagnoses, outcomes, and mortality. Materials and Methods: Eighty immunosuppressed patients aged 18–82 were prospectively evaluated from May 2019 to May 2020. Data on blood and urine tests, final diagnoses, outcomes, and mortality were recorded using a standardized form. Results: Among the 80 patients, 44 (55%) were female and 36 (45%) were male, with a mean age of 58.5 ± 14.72 years. The febrile patients showed higher admission levels of lactate dehydrogenase (LDH), interleukin-6 (IL-6), procalcitonin (PCT), and longer hospital stays than the afebrile patients. Mortality correlated with low albumin, oxygen saturation, platelet count, and total protein levels and elevated PCT and lipase levels. ICU admissions were linked to low albumin, total protein, and systolic blood pressure levels and elevated LDH, blood urea nitrogen, neutrophil count, and PCT levels. The fever status (febrile versus afebrile) had no significant relationship with the immunosuppression type, complaints, diagnoses, outcomes, or mortality. Final diagnoses varied by immunosuppression type: cholangitis in liver transplant recipients, respiratory infections in cancer patients, and urinary tract infections in kidney transplant recipients. Conclusions: Immunosuppressed patients can present with severe conditions, even without fever. Based on our findings, our study emphasizes that measuring PCT in immunosuppressed patients presenting to the emergency department with various complaints but without fever may help reduce the risk of delayed diagnosis. Full article

Background/Objectives: Critically ill patients can often present acid–base alterations. The aim of this study was to evaluate the prevalence and the time-course of acid–base alterations on intensive care unit (ICU) admission and on day one by the traditional standard base excess (SBE)-based and the Stewart methods in mechanically ventilated patients. Methods: A prospective observational study enrolling mechanically ventilated patients in the ICU was conducted. Arterial blood gas analysis, blood and urine samples were obtained on ICU admission and on day one. Plasmatic and urinary acid–base variables were compared among acidemic, alkalemic and patients with normal pH. The agreement between the SBE-based and Stewart methods was assessed at ICU admission and on day one. Results: One hundred and seventy-two patients were enrolled. On ICU admission, 55 (32%), 29 (17%) and 88 (51%) patients had acidemia, alkalemia and a normal pH, respectively. On day one, 12 (7%), 48 (28%) and 112 (65%) patients had acidemia, alkalemia and a normal pH with lower values of paCO2 and albumin. According to the SBE and Stewart approaches, the occurrence of metabolic acidosis was similar (24% vs. 35%), as well as the rate of metabolic alkalosis (16% vs. 23%) on ICU admission; on day one, the occurrence of metabolic acidosis was different (12% vs. 35%), as well as the rate of metabolic alkalosis (35% vs. 14%). The agreement between methods was estimated to be low both on ICU admission and on day one. Conclusions: Up to 50 % of mechanically ventilated patients presented acid–base derangements, mainly due to acidemia on ICU admission and to alkalemia after 24 h, secondary to alterations in carbon dioxide and plasma albumin. The agreement between the traditional and Stewart approaches was poor. The Stewart approach could be more accurate in detecting the acid–base disturbances in critically ill patients characterized by changes of mechanical ventilation and fluid administration. Full article