Search Results (328)

Background: Although Duchenne muscular dystrophy (DMD) is primarily characterized as a skeletal muscle-wasting disorder, the resulting pathophysiological changes extend to multiple non-muscle tissues and organ systems. Among these, renal and urinary tract dysfunctions have been reported, albeit in relatively few studies, as potential complications in DMD patients, sometimes occurring from an early age. Importantly, as life expectancy improves, the incidence of renal impairment is also expected to increase. This narrative review summarizes the available evidence on kidney involvement in DMD and discusses the associated biomarkers of renal dysfunction within the context of multisystem disease progression. Methods: The review draws on data from both human and animal studies and analyzes published evidence to explore kidney involvement in DMD, with a focus on clinical manifestations, biomarkers of renal dysfunction, and potential pathogenic mechanisms. Results: Available data indicate a close association between cardiac and renal dysfunction, particularly in patients with advanced-stage DMD. The review explores potential underlying mechanisms of renal impairment, including intrinsic dystrophin deficiency in the kidney, secondary effects of cardiovascular complications, and the nephrotoxic impact of drug therapies, highlighting renal function as an active determinant of clinical risk. Conclusions: While cardiac function monitoring is already a cornerstone of multidisciplinary care for this multisystem disease, systematic assessment of renal function should also be implemented, with implications for clinical management and drug safety. Moreover, the risk of drug-induced nephrotoxicity warrants attention in both clinical management and the development of novel therapeutic strategies for DMD. Full article

Background/Objectives: Sarcopenia (Sp) and obesity (Ob) have significant negative effects on steatotic liver disease (SLD). Here, we examined the effects of sarcopenic Ob (SO) on liver fibrosis in patients with SLD. Methods: We included 811 patients who visited our outpatient clinic and underwent FibroScan (Echosens, France). Liver stiffness (LS) was assessed using body mass index (BMI) and grip strength (GS). We conducted a similar analysis by converting the difference in estimated glomerular filtration rate (dGFR) based on creatinine and cystatin C levels into GS. Results: The cutoff values for distinguishing metabolic dysfunction-associated steatotic liver disease (MASLD; 298 patients) with LS > 10 kPa (advanced fibrosis) were set separately for men and women using receiver operating characteristic analysis. BMI was set at >26 kg/m² in women and >27 kg/m² in men (modified Ob (mOb)), and GS was set at <16 kg in women and <31 kg in men (modified Sp (mSp)). The ratio of advanced fibrosis was higher in the group with both mSp and mOb (mSpOb) than in the group with mSp alone or mOb alone in MASLD or alcoholic liver disease (ALD, 97 patients). However, this association has not yet been observed in other diseases. The dGFR was used to set the cutoff value corresponding to advanced fibrosis. Sp-dGFR (SpdG) was >1.14 in women and >−0.76 in men in the MASLD group. mSpOb, SpdG and Ob are associated with advanced fibrosis in MASLD logistic regression analysis. Conclusions: SO, assessed using BMI and GS or dGFR, was associated with elevated LS in patients with SLD. Full article

Using colorimetric ELISA, this study aims to assess the impact of Gum Arabica (GA) consumption on functional molecular plasma biomarkers of chronic kidney disease (CKD) via a prospective cohort of GA-consumers (cases) vs. non-consumer (age- and CKD stage-matched) controls. Cohort’s hypertension (92.5%), dyslipidemia (64.8%), and diabetes mellitus (54.8%) were prevalent; the mean CKD duration was 6.94 years (SD 7.8) for both study groups. Comparable eGFR, sCr, ESR, CRP, HbA1c, FPG, UA, and fasting lipid parameters were in both study arms. In consumer cases, the mean duration of GA-consumption was 1.3 ± 1.1 (range 0.25–6) years with a mean dose of 1.7 ± 1.0 (range 0.5–6) spoons per day. Leucine-rich alpha 2-glycoprotein, plasminogen activator inhibitor 1, sirtuin 1, and SOST–sclerostin 1 were significantly (p value < 0.01) of lower concentrations, but lipocalin 2 and uromodulin were invariably (p value < 0.05) greater in the GA-consumer cases than those of controls. Strikingly, cystatin C, myeloperoxidase, orosomucoid 1, and symmetric dimethylarginine lacked any substantial variations in the GA-consumer cases vs. those in controls (p value > 0.05). Proportional correlations of CKD duration–PAI1 levels and sCr-lipocalin 2 levels but inverse correlations of orosomucoid 1-hypertension duration and SDMA-DBP were evident in cases. Full article

Chronic kidney disease (CKD) is a progressive disease in which accurate estimation of glomerular filtration rate (GFR) is essential for staging and guiding therapy. Serum creatinine is widely used but influenced by non-renal factors, while cystatin C and β2-microglobulin (β2M) may provide complementary information related to filtration and tubular or inflammatory factors. This study compared the discriminatory performance of creatinine, cystatin C and β2M for separating CKD stage 3 from stage 4 within the 2021 CKD-EPI eGFR framework in 45 adults with CKD stages 3–4. CKD stage classification was defined using the 2021 CKD-EPI creatinine and creatinine–cystatin C equations (eGFRcr, eGFRcr–cys) with a threshold of 30 mL/min/1.73 m². Receiver operating characteristic (ROC) analysis evaluated each marker’s ability to distinguish moderate from severe CKD. Creatinine showed high diagnostic accuracy (AUC up to 0.98). Cystatin C achieved 100% specificity at the optimal cut-off for severe CKD and showed comparable diagnostic accuracy to creatinine under the eGFRcr–cys framework (AUC 0.978 vs. 0.957). β2M demonstrated AUCs up to 0.97, with sensitivity and specificity above 90%. These findings support a multi-marker evaluation within the 2021 CKD-EPI-based staging, rather than validation against measured GFR. Larger studies incorporating measured GFR and relevant clinical confounders are warranted. Full article

Background: Metabolic syndrome (MetS) comprises interrelated metabolic abnormalities that collectively confer increased risk of cardiovascular disease and hepatic morbidity. The MAF-5 score is a non-invasive prognostic marker of liver fibrosis and mortality, while Cystatin C (CysC) is a sensitive indicator of renal function that also reflects inflammation, atherosclerosis, and metabolic dysfunction. Although both MetS and CysC have been widely studied, their potential interplay via MAF-5 remains unclear. We aimed to investigate the relationship between MAF-5 scores and CysC levels in MetS patients for the first time. Materials and Methods: Adults (≥18 years) with MetS were included in this study. MAF-5 scores (based on waist circumference, BMI, diabetes status, AST, and platelet count) and CysC levels were recorded. The MAF-5–CysC relationship was assessed via Pearson correlation. Participants were grouped into MAF-5 quartiles, and continuous variables were compared using ANOVA with Bonferroni-corrected pairwise tests. Results: We included 347 MetS patients (54.8% female, median age 54 years). The median MAF-5 score was 1.25, and MAF-5 correlated positively with CysC (r = 0.357, p < 0.001). CysC levels differed significantly across MAF-5 quartiles (Q1 = 0.96, Q2 = 0.99, Q3 = 1.06, Q4 = 1.09; p < 0.001), with Q4 showing higher values than Q1 and Q2. Conclusions: A significant correlation was found between MAF-5 scores and CysC in patients with MetS. CysC levels differed significantly across MAF-5 quartiles, suggesting a potential link between systemic inflammation, liver fibrosis, and CysC. These results highlight shared inflammatory and fibrotic pathways, underlying metabolic dysfunction. Clinically, combined assessment of MAF-5 and CysC may improve risk stratification, identifying patients at higher risk for hepatic fibrosis and adverse outcomes. Full article

Background/Objectives. Pentoxifylline (PTF) is an effective treatment to delay the progress of Diabetic Nephropathy; it also has beneficial effects on heart failure, two closely related clinical conditions. However, the simultaneous Nephroprotective and Cardioprotective effects of PTF have not been appropriately analyzed. The objective of this study was to analyze if both effects occur together in Diabetic patients. Material and Methods. A Randomized Controlled Trial was performed to compare Placebo (P-G) vs. PTF (400 mg/8 h) (PTF-G) in patients with CKD stages III–IV (KDIGO) due to Diabetic Nephropathy. Creatinine-Cystatin C-based Estimated Glomerular Filtration Rate (eGFRCysCCr) and Microalbuminuria were evaluated at baseline, six, and twelve months. Echocardiographic assessment of heart morphology and function was performed. Results. Ninety-three patients were available for the final analysis, 52 in the PTF group and 41 in the P group. There were no differences in clinical and biochemical parameters between groups at baseline. At 6 months, microalbuminuria changed 27.96 ± 43.06 in P-G and −30.27 ± 41.48 mg/24 h in PTF-G (p < 0.001), eGFRCysCCr changed −1.55 ± 7.10 in P-G and 1.40 ± 7.28 mL/min/1.73 m² in PTF-G (p = 0.083), and left ventricular mass index (LVMI) changed 10.86 ± 16.40 in P-G and −2.71 ± 19.52 g/m² in PTF-G (p = 0.001). At 12 months, microalbuminuria changed 24.10 ± 43.28 in P-G and −43.18 ± 52.13 mg/24 h in PTF-G (p < 0.001), eGFRCysCCr changed −6.55 ± 10.18 in P-G and 0.98 ± 8.17 mL/min/1.73 m² in PTF-G (p = 0.008), and LVMI changed 20.79 ± 20.06 in P-G and −0.82 ± 25.95 g/m² in PTF-G (p = 0.028). No significant adverse events occurred in any group. Conclusions. Pentoxifylline is a safe and effective treatment with combined Nephroprotective and Cardioprotective effects in advanced diabetic nephropathy. Full article

The estimated glomerular filtration rate (eGFR) is a cornerstone of kidney function assessment. Widely used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine (eGFR_cr), cystatin C (eGFR_cysC), or both (eGFR_cr-cysC) are influenced by non-glomerular filtration rate (GFR) factors, and their performance may vary across clinical contexts. We retrospectively analyzed 435 adult patients with simultaneous serum creatinine and cystatin C measurements. eGFR was calculated using CKD-EPI 2021 (creatinine), CKD-EPI 2012 (cystatin C), and CKD-EPI 2021 (combined) equations. Patients were classified into Kidney Disease: Improving Global Outcomes (KDIGO) GFR categories (G1–G5), and discrepancies between equations were identified. 44 patients (10.1%) showed discordant GFR categorization across all three equations and underwent detailed clinical assessment. 16 of the 44 discordant cases had clinically confirmed chronic kidney disease (CKD). The combined equation aligned with the clinical diagnosis in all CKD cases. eGFR_cr overestimated kidney function in 10/16 patients, while eGFR_cysC produced lower values in 8/16, consistent with early CKD but potentially influenced by inflammation or obesity. Reclassification occurred in 9/16 patients when switching from eGFR_cr to eGFR_cr-cysC, including four who shifted from G2 to G3a–G4. A significant difference was observed between eGFR_cr and eGFR_cr-cysC (p < 0.05). The combined CKD-EPI equation demonstrated the best clinical concordance, supporting its broader use when diagnostic accuracy is essential. Full article

Background/Objectives: Associations between renal function, as measured by the estimated glomerular filtration rate (eGFR) or its decline (dGFR), and clinical parameters in patients with rheumatoid arthritis (RA) were evaluated using a retrospective case–control series dataset. Methods: Patients with RA who followed up for one or more consecutive years were recruited for the study. For calculating the eGFR, cystatin C (CysC) was adopted. The moment when CysC was measured was set as the baseline. The association between the eGFR and baseline clinical parameters, including disease activity in RA as measured by the simplified disease activity index (SDAI), was statistically evaluated. The association between the mean annual decline in the eGFR from the baseline and clinical parameters was also statistically assessed. Results: A total of 513 patients were enrolled; with a mean age of 70.9; a mean follow-up length of 52.5 months; a mean BMI of 22.9; a 68.7 eGFR; and a mean annual dGFR of 2.74. Significant parameters that correlated with the eGFR were age; rheumatoid factor titer; C-reactive protein; the presence of hypertension; chronic heart failure; chronic obstructive pulmonary disease; type 2 diabetes mellitus; methotrexate administration; and polypharmacy at baseline. An annual dGFR was correlated with the follow-up length, and the mean SDAI score multiplied by the yearly length of the follow-up was significantly correlated. Conclusions: Many factors confound the determination of the eGFR in RA patients. The disease activity score and length of time are the key factors for declining eGFRs. Full article

In Myanmar, Russell’s viper (Daboia siamensis) bite is a significant public health problem. In this study, we expend upon our previous RNA-sequencing approach to characterize candidate toxin genes encoding D. siamensis toxins. The mRNA was extracted from Myanmar Russell’s viper venom glands. The RNAseq was performed using Illumina next-generation sequencing. Subsequently, candidate toxin transcripts were recognized by the Venomix pipeline. This study focused on 29 unique cDNA sequences representing eight newly identified venom gene families with low-to-moderate expression levels. These transcripts represented 0.088% of the total number of transcripts in the dataset. The translated protein sequences were analyzed for their conserved motifs and domains to predict their functions. They were neprilysins (bioactive peptide inactivators), cystatins (protease inhibitors with anti-metastatic activities), waprin and vipericidin (antimicrobial peptides), veficolin (platelet and complement activation), vespryns and three-finger toxins (elapid toxin homologs causing neurotoxic activity and tissue damage), and endothelial lipases (unknown function). Their functional activities should be further investigated for potential therapeutic applications, for example, in cancer or antibiotic-resistant infections. Full article

Background: Frailty is a major barrier to healthy ageing, yet early identification strategies remain limited. The serum creatinine-to-cystatin C ratio (sarcopenia index, SI) has emerged as a cost-effective biomarker of muscle mass and function, while physical activity (PA) is a key protective factor. However, their combined role in predicting frailty is unclear. This study aimed to investigate the independent and joint associations of SI and PA with incident frailty in middle-aged and older adults. Methods: We analyzed 5307 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018). SI was calculated from serum creatinine and cystatin C levels, and PA was assessed using standardized questionnaires. Frailty was defined using a 32-item Frailty Index (FI ≥ 0.25). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SI and PA with incident frailty, adjusting for sociodemographic and health-related factors. Effect modification by PA was formally tested. Results: Over the follow-up period, 1483 participants developed frailty (27.9%). Higher SI was inversely associated with frailty in a dose–response manner: compared with the lowest quartile, HRs (95% CIs) were 0.84 (0.73–0.97) for Q2, 0.83 (0.72–0.96) for Q3, and 0.69 (0.59–0.82) for Q4 (p-trend < 0.001). Each 10-unit increase in SI corresponded to a 6% lower frailty risk (HR = 0.94, 95% CI: 0.91–0.97). PA significantly modified this relationship (interaction p < 0.05), with the strongest protective effect of SI observed among individuals with low PA, and attenuation at higher PA levels. Conclusions: SI is independently associated with a lower risk of incident frailty, particularly among less physically active individuals. These findings support the potential use of SI as a feasible biomarker for early frailty risk stratification and highlight the importance of integrating biomarker-based screening with lifestyle interventions to prevent frailty. Full article

Human immunodeficiency virus (HIV) infection remains a major health burden in Sub-Saharan Africa, despite the widespread use of antiretroviral therapy (ART). Oxidative stress contributes to HIV-related comorbidities, including renal dysfunction. However, the role of oxidative stress in kidney impairment among people living with HIV (PLWH) is not fully understood. This cross-sectional study included PLWH on ART (n = 80), PLWH without ART (n = 27), and people not living with HIV (PNLWH) (n = 44). Oxidative stress was measured by serum malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (TAC), while renal function was assessed using cystatin C-based estimated glomerular filtration rate (eGFR_cystC). Participants on ART were older (median 43 years) and had higher CD4+ T-cell counts compared to those not on ART. PLWH on ART showed significantly elevated MDA levels compared to PLWH without ART (p < 0.001) and PNLWH (p = 0.001). There was no difference in superoxide dismutase (SOD) and TAC levels among the groups (p = 0.177 and 0.888, respectively). Among PLWH, MDA was higher in those with reduced renal function (eGFR_cystC < 90) versus normal function (p < 0.05). In PLWH on ART, SOD activity was significantly lower in mild renal impairment (eGFR_cystC 60–89) compared to normal function (p = 0.017), but no difference was observed in the TAC levels (p = 0.883). In PLWH on ART, regression analyses indicated no independent association between MDA and renal function decline, while higher SOD activity independently predicted better renal function (adjusted β = 2.26, p = 0.042). Oxidative damage accompanied by the inability of the body’s primary antioxidant defenses may be present at the early onset of renal function decline in PLWH. Superoxide dismutase, as an antioxidant defence enzyme, may be a key contributor to renal health in PLWH on ART. Future studies with larger cohorts and longitudinal designs are needed to clarify these relationships emanating from this pilot study. Full article

Background/Objectives: Previous studies have shown an association between kidney function and age-related macular degeneration (AMD). This study aims to assess whether the kidney function-related parameters of serum cystatin C and creatinine levels are associated with increased risk of AMD and its subtypes. Methods: Genetic instruments for variants associated with serum cystatin C and creatinine levels as exposure at genome-wide significance (p < 5.0 × 10⁻⁸) were obtained from the UK Biobank. Genetic data for AMD and its subtypes were obtained from the FinnGen project. A two-sample Mendelian randomization analysis was performed to evaluate the causal effects of serum cystatin C and creatinine levels on AMD and its subtypes. Results: Using an inverse-variance weighted approach, higher cystatin C levels are associated with an increased risk of AMD [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.04 to 1.22, p = 0.004 for overall AMD; OR = 1.14, 95% CI: 1.04 to 1.25, p = 0.007 for dry AMD; OR = 1.14, 95% CI: 1.03 to 1.26, p = 0.011 for wet AMD]. However, serum creatinine levels did not significantly impact the risk of AMD or its subtypes. Conclusions: This study provides genetic evidence that higher cystatin C levels may be a causal risk factor for AMD and its subtypes, whereas serum creatinine was not. This result implies the need to investigate the effect of cystatin C on AMD potentially independent of kidney function. Full article

Background/Objectives: Acute kidney injury (AKI) is a common complication in hospitalized patients and carries a substantial risk of chronic kidney disease (CKD), dialysis dependence, and mortality. Although novel biomarkers such as NGAL, KIM-1, and cystatin C have shown promise, their high cost and limited availability restrict their use in routine practice, particularly in developing countries where CKD incidence is rising. The trajectory of serum creatinine decline after its peak may provide a simple, low-cost, and universally available prognostic marker for renal recovery. Methods: This retrospective cohort study included 817 adult patients diagnosed with AKI between January 2015 and December 2024. The creatinine decline rate was calculated as the difference between peak and discharge creatinine divided by hospital stay (mg/dL/day). Patients were stratified into rapid or slow decline groups according to the median value (0.19 mg/dL/day). Post-discharge outcomes, including CKD development, readmission, dialysis requirement, and mortality, were evaluated at 3, 6, and 12 months. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff for predicting renal recovery. Results: Patients in the rapid decline group (n = 409) were younger and had fewer comorbidities and shorter hospital stays than those in the slow decline group (n = 408). The ROC analysis yielded an AUC of 0.78 (95% CI 0.73–0.82, p < 0.001) with an optimal cutoff of 0.18 mg/dL/day (sensitivity 76%, specificity 71%). At 12 months, CKD (18.6% vs. 34.3%), dialysis requirement (3.4% vs. 8.8%), readmission (29.8% vs. 41.2%), and mortality (9.3% vs. 14.2%) were all significantly higher in the slow decline group (all p < 0.05). In multivariable analysis, faster creatinine decline independently predicted renal recovery (OR = 1.36 per 0.1 mg/dL/day, 95% CI 1.22–1.53, p < 0.001), along with younger age, higher serum albumin, and shorter hospital stay. In the longitudinal GEE model, both time (p = 0.004) and group effects (p < 0.001) remained significant, with an interaction effect (p = 0.018) indicating greater eGFR improvement over time among patients with rapid creatinine decline. Conclusions: The rate of creatinine decline is an independent predictor of long-term renal recovery following AKI. This simple and inexpensive parameter may complement novel biomarkers and serve as a practical risk-stratification tool in diverse clinical settings, especially where resources are limited. Prospective multicenter studies integrating albuminuria and emerging biomarkers are warranted to validate and expand these findings. Full article

Acute kidney injury (AKI) occurs commonly in hospitalized patients, especially patients in intensive care units (ICUs). Medications are among the major causative factors of AKI. This narrative review addressed and updated different aspects of anti-infective-associated AKI, including amphotericin B, cidofovir, foscarnet, polymyxins, vancomycin, and aminoglycosides. There is no standard definition or operational criteria to describe anti-infective-associated AKI. Characteristically, it usually occurs during the first two weeks of treatment and is typically dose dependent. Functional resolution occurs, but kidney injury can affect renal functional reserve and increase susceptibility to future AKI events. A variety of pathophysiological mechanisms impacting glomerular, tubular, and interstitial components of the kidney are usually responsible for the development of AKI from anti-infective medications. Oxidative stress and inflammation play a pivotal role in the pathogenesis of antibiotic-related AKI. Numerous patient-related, medication-related, and co-administered-related scenarios have been demonstrated as risk factors for anti-infective-induced AKI. Apart from traditional indexes of kidney function (serum creatinine and urine output), novel biomarkers of kidney function (e.g., serum cystatin C) and damage (e.g., urinary kidney-injury molecule-1 and neutrophil gelatinase-associated lipocalin) have been noticed in recent clinical studies with promising findings. The efficiency of preventive strategies against anti-infective-associated AKI in most cases appears to be variable, relative, and modest. Close and regular monitoring of kidney function parameters is crucial during treatment with nephrotoxic antibiotics. Currently, there is no definitive treatment modalities for the management of AKI with anti-infectives. Therefore, supportive care is the mainstay of treatment. Full article

In the context of multi-organ involvement in sepsis, cardiac toxicity is manifested as sepsis-induced cardiomyopathy (SICM). To date, no unified SICM definition exists, though a left ventricular ejection fraction ≤ 50% and/or an absolute drop ≥ 10% from baseline are the most widely accepted components. Several molecular pathways have been associated with SICM, including (i) pro-inflammatory mediator-induced cardiac depression; (ii) sarcolemmal membrane dysfunction; (iii) autonomic nervous system (ANS) imbalance; (iv) blunted cardiovascular response to catecholamines; (v) dysfunctional intracellular calcium handling; (vi) mitochondrial dysfunction; (vii) metabolic reprogramming; and (viii) disturbed endothelial and microcirculatory function. Atrial and ventricular arrhythmias—particularly atrial fibrillation—commonly complicate disease management and are associated with adverse outcomes. Key mechanisms outlining sepsis-induced arrhythmogenesis are (i) inflammation; (ii) electrolyte imbalances; (iii) myocardial ischemia; (iv) QT prolongation/dispersion; (v) adrenergic overactivation; (vi) calcium mishandling; and (vii) fever-induced arrhythmogenesis in Brugada. Established therapeutic approaches include prompt treatment with antibiotics, hemodynamic optimization, and/or selective use of beta-blockers. Furthermore, several molecules are currently being investigated targeting numerous pathways activated in sepsis. Vitamin C, ginsenoside Rc, Schistosoma Japonicum cystatin, and gasmerdin-D inhibitor Y2 exert anti-inflammatory actions, while melatonin and α-ketoglutarate regulate mitochondrial homeostasis. Triiodothyronine targets microcirculatory optimization and regulates protective pathways against stress-related cell death. Engineered exosomes may facilitate targeted drug delivery, inflammatory response modulation, and activation of pathways related to cell survival, while sodium octanoate exhibits anti-inflammatory actions coupled with improved energy metabolism. Finally, gene-regulating therapies aiming at inflammatory response optimization have also been proposed and are currently under development. Future research should aim to standardize the SICM definition, translate emerging therapeutics into clinical practice, identify novel molecular targets, and implement personalized treatment strategies for SICM. Full article