Search Results (2,038)

Renal cell carcinoma (RCC) is frequently detected incidentally, and no widely adopted noninvasive biomarkers are available for RCC diagnosis or prognosis. In this regard, cell-free microRNAs (cfmiRs) have emerged as promising candidates due to their stability in biological fluids. In this narrative review, we summarize translational studies published from 2010 to 2025 that evaluated serum, plasma, or urinary cfmiRs for RCC diagnosis, prognosis, recurrence surveillance, or treatment-response monitoring. Forty-two studies met inclusion criteria, comprising 3454 patients with RCC and 2445 healthy donors. Twenty-nine studies assessed diagnostic performance, fewer evaluated prognostic applications, and none examined treatment-response monitoring. Multi-miRNA panels generally reported higher performance than single-miRNA assays. Serum was the most frequently studied biofluid in this review (n = 26), followed by urine (n = 12) and plasma (n = 4). Urinary biomarkers demonstrated high specificity and the practical advantage of noninvasive collection. Although limited in number, prognostic studies identified associations between cfmiRs and overall survival, recurrence-free survival, metastasis-free survival, and other clinically relevant outcomes. However, substantial heterogeneity in study design, assay methods, and reporting limited comparisons across studies. Current evidence supports continued evaluation of cfmiRs as adjunctive biomarkers alongside imaging or histopathology, but multicenter validation, standardized methods, and more robust evidence are required before clinical implementation. Full article

Background and Objectives: Pulsed field ablation (PFA) and cryoballoon ablation (CRYO) are established approaches for pulmonary vein isolation in atrial fibrillation (AF). Given emerging concerns regarding hemolysis following PFA, this pilot study aims to directly compare outcomes between these modalities. This study aims to evaluate differences in laboratory parameters potentially compatible with hemolysis and procedural safety between PFA and CRYO among AF patients. Materials and Methods: In this retrospective single-center analysis, 33 symptomatic AF patients underwent either PFA (n = 17) or CRYO (n = 16). Hemoglobin, hematocrit, platelet count, total bilirubin and renal function were measured at all three pre-specified time points: baseline, immediately after ablation and on day 1. Group × time interactions were tested with linear mixed-effects models, and changes are reported with 95% confidence intervals (CIs). Acute kidney injury (AKI) was defined by KDIGO serum creatinine criteria and assessed individually; sensitivity analyses were restricted to pulmonary-vein-isolation (PVI)-only procedures. Additionally, procedural metrics and complication frequencies were analyzed between groups. Results: The baseline demographics and clinical characteristics did not differ significantly between both groups. Both ablation techniques led to substantial reductions in hemoglobin following the procedure, with no between-group difference (day-1 change −1.84 vs. −1.57 g/dL; difference −0.27, 95% CI −1.01 to +0.47; group × time p = 0.192). Notably, total bilirubin increased to a greater extent with PFA (day-1 change +0.48 vs. +0.15 mg/dL; difference +0.33, 95% CI +0.06 to +0.59; group × time p = 0.003), with the largest separation immediately after ablation (1.43 ± 0.36 vs. 0.99 ± 0.35 mg/dL, p = 0.001). No patient in either group met KDIGO criteria for AKI of any stage; the largest post-procedural rise in creatinine was +0.10 mg/dL in both groups. Conclusions: Both PFA and CRYO caused acute declines in hemoglobin, and total bilirubin rose more after PFA, with no accompanying change in renal function. Further studies involving larger cohorts and direct hemolysis biomarkers are necessary to corroborate these findings. Full article

The recent introduction of “molecularly defined renal cell carcinomas” in the World Health Organization classification has significantly expanded the diagnostic spectrum of renal neoplasia, highlighting entities characterized by specific genetic alterations with potential clinical and therapeutic relevance. However, the recognition of these tumors in routine practice remains challenging due to overlapping morphological features and variable access to molecular testing. In this context, immunohistochemistry (IHC) has emerged as a practical and widely available tool that can act as a surrogate for underlying molecular alterations. Depending on the biological context, IHC may reflect genetic events either through protein overexpression, as in fusion-driven tumors, or through loss of expression associated with gene inactivation in metabolically or chromatin remodeling-deficient neoplasms. Accordingly, IHC plays a central role as a screening and triage method within the diagnostic workflow of these entities. Overall, IHC remains an indispensable component in the evaluation of molecularly defined renal cell carcinomas, but its optimal use requires integration with morphological assessment and, in most cases, confirmatory molecular testing. The aim of this review is to provide a comprehensive and evidence-based overview of the main immunohistochemical surrogates used in molecularly defined renal cell carcinomas, including TFE3-, TFEB-, and ALK-rearranged tumors, as well as SDH-, FH-, and SMARCB1-deficient neoplasms, highlighting their diagnostic applications, strengths, pitfalls, and role within an integrated diagnostic workflow. For each marker, the biological rationale, expected staining patterns, diagnostic applications, and major pitfalls are discussed, with particular emphasis on variability across studies and technical limitations. Full article

Background/Objectives: Methylglyoxal-derived hydroimidazolone-1 (MG-H1), an advanced glycation end product, has implications in the pathogenesis of diabetic kidney disease (DKD). Although liquid chromatography–mass spectrometry is the current gold standard for quantifying MG-H1, its overall complexity limits its utility. We developed an ELISA to measure MG-H1 using a specific monoclonal antibody. Methods: Competitive ELISA was used to quantify total, high-molecular-weight (HMW), and low-molecular-weight (LMW) MG-H1 in serum. The assay’s specificity was validated against structurally related compounds. Spike-and-recovery experiments were conducted to assess accuracy and precision. Serum samples from healthy controls, diabetic patients without kidney disease, and patients with DKD were analyzed (n = 10, 23, and 19, respectively). MG-H1’s correlation with renal biomarkers and diagnostic performance was assessed using receiver operating characteristic analyses. Results: The ELISA exhibited preferential reactivity toward MG-H1 compared with structurally related compounds. Spike-and-recovery experiments resulted in recovery rates ranging 108–119%. MG-H1 levels were increased in patients with DKD, although the magnitude of the changes varied among the MG-H1 forms. All MG-H1 forms correlated positively with serum creatinine and blood urea nitrogen, and negatively with estimated glomerular filtration rate. No significant correlations were observed with glycoalbumin, and only a modest association was observed between LMW MG-H1 and HbA1c. Exploratory ROC analyses suggested that all MG-H1 forms could discriminate DKD from DM, with total and HMW MG-H1 showing performance comparable to that of conventional renal function markers. Conclusions: This competitive ELISA enables high-throughput quantification of MG-H1 in serum and demonstrates analytical feasibility; further multicenter validation is required before clinical implementation. Full article

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. Given the significant adverse effects and inconsistent long-term efficacy of conventional immunosuppressive strategies, there is an unmet need for safer adjunctive therapies. Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed as potential candidates to address this therapeutic gap. Purpose: This narrative review summarizes the proposed mechanisms of action of omega-3 PUFAs in IgAN and critically evaluates the current clinical evidence regarding their therapeutic potential and limitations. Mechanisms: Emerging experimental data suggest that omega-3 PUFAs may modulate inflammatory and fibrotic pathways relevant to kidney injury. Proposed mechanisms include modulation of eicosanoid metabolism, attenuation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and generation of specialized pro-resolving mediators. In experimental studies, omega-3 PUFAs may also suppress nuclear factor kappa B (NF-κB)-driven transcription and attenuate mesangial cell proliferation, IgA immune-complex deposition, and transforming growth factor beta 1 (TGF-β1)/Smad3-mediated fibrotic signaling. Clinical Evidence: Conclusions: Omega-3 PUFAs have biological plausibility as adjunctive therapy in IgAN, but their clinical benefit remains uncertain. Available randomized trials and meta-analyses suggest possible modest effects on proteinuria in some settings, whereas evidence for preservation of kidney function or prevention of kidney failure is inconsistent and of low certainty. Future well-designed trials incorporating guideline-directed background therapy and biomarker-guided patient selection are essential to determine optimal dosing, formulation, biological exposure, and whether any patient subgroups derive clinically meaningful benefit. Full article

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and is associated with increased cardiovascular (CV) morbidity and mortality. Galectin-3 is a marker of fibrosis and adverse CV outcomes in chronic kidney disease (CKD), while mid-regional pro-atrial natriuretic peptide (MR-proANP) and heart-type fatty acid-binding protein (H-FABP) reflect myocardial wall stress and subclinical myocardial injury. Data on the combined behavior of these biomarkers in IgAN are limited. We investigated their association with renal function and cardiovascular parameters in IgAN. Methods: In this cross-sectional study, 90 patients with biopsy-proven IgAN were examined, but 76 patients’ data were evaluated. Serum galectin-3, MR-proANP, and H-FABP concentrations were measured by ELISA. Renal function was assessed using estimated glomerular filtration rate (eGFR, CKD-EPI). All patients underwent transthoracic echocardiography and arterial stiffness assessment, including pulse wave velocity of the aorta (PWVao) and central systolic blood pressure (SBPao). Results: Patients with reduced renal function (eGFR <60 mL/min/1.73 m²) had significantly higher galectin-3 (p = 0.011), MR-proANP (p < 0.001), and H-FABP (p < 0.001) concentrations. Biomarker levels increased progressively with declining eGFR. Galectin-3 concentrations were higher in patients with increased left ventricular mass index (p = 0.015). All three biomarkers were elevated in patients with higher central aortic systolic pressure. MR-proANP and H-FABP increased with worsening albuminuria, whereas galectin-3 did not. In multivariate analyses, eGFR was the only independent predictor of all three biomarkers. Conclusions: In IgAN, galectin-3, MR-proANP, and H-FABP concentrations are closely linked to renal function and markers of cardiovascular remodeling. These findings suggest that galectin-3, MR-proANP, and H-FABP provide complementary information regarding the complex interaction between renal dysfunction and cardiovascular remodeling in IgA nephropathy. Prospective multicenter studies are warranted to determine their incremental prognostic value and potential clinical utility for cardiovascular risk stratification. Full article

Background: Although advances in critical care have improved short-term outcomes, sepsis survivors continue to face substantial chronic morbidity and impaired long-term survival. Conventional threshold-based tools such as the Sequential Organ Failure Assessment (SOFA) and Modified Early Warning Score (MEWS) show moderate and variable discrimination across cohorts. Reported areas under the receiver operating characteristic curve (AUROCs) must therefore be interpreted in relation to the population, prediction horizon, and outcome used in each study rather than as direct head-to-head comparisons. Objectives: This review evaluates how artificial intelligence (AI) could be linked with dynamic plasma metabolites, particularly citrulline and β-hydroxybutyrate (3-HB), to support biologically informed sepsis phenotyping, while critically examining mechanistic evidence, clinical limitations, and translational readiness. Data Synthesis: Machine-learning and natural language processing architectures have shown promising discrimination in many early-detection studies, with pooled AUROCs near 0.87 and reported prediction windows extending to 48 h. However, performance estimates vary with cohort composition, outcome definition, and validation design, and they should not be ranked against unrelated biomarker studies. Human sepsis studies generally associate low or persistently low citrulline with impaired intestinal function and organ injury, but no sepsis-specific decision cutoff has been externally validated. For 3-HB, an AUROC of 0.8429 for septic liver injury was derived from a cohort of 57 patients and has not been shown to add value beyond routine liver tests or illness-severity measures. Murine experiments provide mechanistic hypotheses for ketone-mediated organ protection, but model-specific and sometimes opposing nutritional effects limit direct translation. These metabolites are therefore best considered candidate longitudinal features for multimodal phenotyping rather than stand-alone clinical triggers. Conclusions: Biologically informed algorithmic surveillance is a promising direction, but clinical implementation requires prospective serial sampling, explicit adjustment for renal, hepatic and nutritional confounders, head-to-head comparison with routine markers, and external validation of calibration and clinical utility. Until these requirements are met, citrulline and 3-HB should support research phenotyping rather than direct treatment selection. Full article

Hemodialysis (HD) is the most widely used renal replacement therapy for patients with end-stage renal disease (ESRD) and is frequently accompanied by long-term complications that impair quality of life, including metabolic and inflammatory disturbances. Growing evidence suggests that these complications may be linked to alterations in the gut microbiota; however, microbial composition and interaction patterns in HD patients remain incompletely characterized. In this exploratory, cross-sectional study, high throughput 16S rRNA gene sequencing was used to profile the fecal microbiota of patients undergoing hemodialysis and of healthy controls. The objective was to characterize associations between hemodialysis and gut microbial composition, ecological network organization, and predicted functional potential. Comparative analyses revealed significant differences in bacterial community structure and microbial networks in the HD cohort. Both gender and dialysis vintage were associated with variation in specific taxa, including increased detection of the Synergistetes phylum, particularly among male patients and those undergoing long-term HD. Associations were also observed between clinical and demographic factors and the relative abundance of several short-chain fatty acid-associated taxa, including members of the Lachnospiraceae and Ruminococcaceae families and the genus Bifidobacterium. Predicted functional potential (PICRUSt2) indicated distinct microbial metabolic profiles in HD patients compared with controls, particularly in pathways related to carbohydrate, nucleotide, and amino acid metabolism, with additional variation according to dialysis vintage. Overall, these findings provide an exploratory characterization of structural, compositional, and predicted functional alterations of the gut microbiota associated with hemodialysis. Although the modest cohort size precludes definitive conclusions, the results support the rationale for larger, longitudinal studies investigating microbiota-derived biomarkers and host–microbiome interactions in ESRD. Full article

Background/Objectives:This study aimed to evaluate whether early renal perfusion scintigraphy is associated with sepsis severity and short-term mortality in an experimental polymicrobial sepsis model. Methods: A total of 90 female Wistar albino rats were divided into Control, mild sepsis, and severe sepsis groups using a cecal ligation and puncture (CLP) model. Renal perfusion was evaluated 5 h after sepsis induction using technetium-99m-labeled erythrocyte scintigraphy, expressed as the kidney-to-aorta (R/A) activity ratio. Survival was monitored for 5 days. Histopathological and biochemical analyses were also performed. Results: The kidney-to-aorta (R/A) activity ratio decreased progressively with increasing sepsis severity (all p < 0.001). Kaplan–Meier analysis demonstrated significantly reduced survival in septic animals (log-rank p < 0.001). The R/A ratio showed high discrimination for 5-day mortality (AUC = 0.944, 95% CI 0.902–0.986; p < 0.001). Univariable Cox proportional hazards analysis demonstrated that a lower R/A ratio was significantly associated with an increased hazard of death (HR = 0.005, 95% CI 0.001–0.036; p < 0.001). Histopathological injury scores and biochemical markers (TNF-α, VEGF, STAT3, NGAL, BUN, creatinine, and MDA) increased significantly with sepsis severity. Conclusions: Early Tc-99m-labeled erythrocyte renal perfusion scintigraphy was associated with sepsis severity and short-term mortality in experimental polymicrobial sepsis. These findings support further investigation of this imaging approach as an experimental marker of sepsis severity and outcome; however, external validation is required before clinical translation. Full article

Background: Mature microRNAs (miRNAs) have been implicated in inflammation and fibrosis and are associated with the pathogenesis of renal dysfunction. miRNAs are single-stranded RNAs approximately 22 nucleotides in length that can posttranscriptionally modify mRNA by base-pairing with its complementary sequences leading to the silencing of mRNA. Methods: We assessed circulating levels of miRNAs in the blood of dogs that were clinically diagnosed as having chronic kidney disease (CKD) post-mortem, after the dogs had lived their full lives. Gene expression was measured using a Canine miRNA PCR array from blood samples that were collected at the natural end-of-life necropsy from dogs with CKD (2–17 yr) and control dogs (5–13.5 yr). Results: End-of-life pathology reports indicated interstitial inflammation, fibrosis, and thickening of the Bowman’s capsule. Histopathological analysis of H&E-stained renal sections taken from end-of-life samples showed a significantly higher number of healthy glomeruli as assessed morphologically in controls compared with CKD. There was a significant decline in the levels of miRNAs cfa-let-7a, cfa-let-7c, cfa-let-7f, and cfa-let-7g in dogs with CKD compared with controls. In addition, there was also a ≥1.5-fold reduction in levels of cfa-miR-93, cfa-miR-122, cfa-miR-200a, and cfa-miR-204 in CKD compared with controls (all ns). These microRNAs may have potential anti-fibrogenesis effect and are also down-regulated in rodent models and in in vitro mechanistic models of renal fibrosis, leading to increased fibrosis. There was also a down-regulation of cfa-miR-16 (−2.76 fold, ns), which is consistent with its reported role in attenuating kidney injury independent of fibrosis. Conclusions: Down-regulation of these miRNAs may be indicative of a reduction in their role in attenuating renal function, leading to impaired kidney function and possibly fibrogenesis. Importantly, the circulating miRNAs may serve as non-invasive biomarkers for impaired renal function in CKD. Nutritional interventions that upregulate selected miRNAs may serve as important targets for slowing the progression of CKD. Full article

Background/Objectives: Autoimmune nodopathies are a distinct subgroup of immune-mediated peripheral neuropathies caused by antibodies targeting nodal and paranodal proteins, including contactin-1 (CNTN1). These disorders are frequently misclassified as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), despite fundamental differences in pathophysiology, clinical course, and treatment response. Growing evidence indicates that systemic manifestations, such as proteinuria, may represent relevant diagnostic red flags. We report a case of anti-CNTN1 autoimmune nodopathy with renal involvement and long-term follow-up after rituximab therapy. Methods: We describe the longitudinal clinical, electrophysiological, laboratory, and therapeutic features of a patient presenting with an acute/subacute sensory ataxic neuropathy evolving into a chronic immune-mediated disorder. Serial nerve conduction studies were performed during multiple hospital admissions and follow-up visits. Autoantibody testing for nodal/paranodal antigens was undertaken, and systemic biomarkers were monitored over time. Results: The patient initially exhibited a robust response to intravenous immunoglobulin (IVIg), consistent with an acute inflammatory neuropathy. Subsequent relapse was characterized by cranial nerve involvement, worsening sensory ataxia, peripheral edema, albuminocytologic dissociation on cerebrospinal fluid analysis, proteinuria, and an inverted albumin/gamma globulin ratio, redirecting the diagnostic hypothesis toward CIDP. The detection of anti-CNTN1 antibodies ultimately established the diagnosis of autoimmune nodopathy. Owing to poor durability of IVIg, rituximab was initiated, resulting in sustained clinical improvement and near-complete recovery of motor and sensory nerve conduction parameters at one-year follow-up (November 2025). Conclusions: This case emphasizes the diagnostic relevance of extraneurological biomarkers, including proteinuria and peripheral edema, in autoimmune nodopathies and supports early nodal/paranodal antibody testing in atypical demyelinating neuropathies. Prompt B-cell-directed therapy may enable functional recovery of nodal integrity and improve long-term outcomes. Further studies are needed to clarify potential immunological triggers, including anti-IL-23 therapies, in the pathogenesis of anti-CNTN1 autoimmune nodopathy. Full article

The renin–angiotensin–aldosterone system (RAAS) is a fundamental regulator of blood pressure, electrolyte balance, fluid homeostasis, and tissue remodeling. The discovery of the prorenin receptor (PRR), the protein encoded by the ATP6AP2 gene, has substantially expanded the classical RAAS paradigm by demonstrating that prorenin possesses biological activity beyond its proteolytic conversion to renin. Binding of renin or prorenin to PRR enhances local angiotensin II (Ang II) generation while simultaneously initiating Ang II-independent intracellular signaling pathways, including ERK1/2, mitogen-activated protein kinases, PI3K/Akt, transforming growth factor-β, and nuclear factor-κB, thereby promoting inflammation, oxidative stress, fibrosis, cellular proliferation, and extracellular matrix accumulation. Beyond its receptor function, PRR serves as an essential accessory component of the vacuolar H+-ATPase (V-ATPase) complex, regulating vesicular acidification, lysosomal function, autophagy, protein trafficking, cellular metabolism, and Wnt/β-catenin signaling. These diverse functions explain its indispensable role in embryonic development, cell differentiation, and tissue homeostasis, as evidenced by the embryonic lethality associated with ATP6AP2 gene deficiency. PRR is predominantly localized to intracellular organelles, including the endoplasmic reticulum, Golgi apparatus, endosomes, lysosomes, and autophagic vesicles, although membrane-bound and soluble forms also contribute to physiological and pathological processes. Increasing evidence implies dysregulated PRR signaling in the development and progression of hypertension, cardiovascular disease, chronic kidney disease, diabetes, obesity, and other metabolic disorders. This review summarizes current advances in PRR and soluble PRR biology, discusses unresolved mechanistic and translational questions, and evaluates the potential of PRR as a biomarker and therapeutic target for cardiovascular, renal, and metabolic diseases. Full article

Individuals with overweight and obesity consistently demonstrate lower circulating concentrations of serum 25-hydroxyvitamin D (25OHD), the primary biomarker of vitamin D status. Additionally, they exhibit an attenuated response to conventional vitamin D supplementation and may require doses approximately 2–3 times higher than those recommended for individuals with normal body weight to achieve equivalent serum 25OHD concentrations. However, accumulating evidence from randomized controlled trials raises concerns regarding the safety of high-dose vitamin D supplementation, with some studies reporting increased risks of falls and fractures, as well as potential adverse effects on bone mineral density and cognitive outcomes. Magnesium is an essential cofactor in vitamin D metabolism, participating in enzymatic processes required for the hepatic and renal hydroxylation of vitamin D into its active forms. Inadequate Magnesium status may therefore influence vitamin D status and response to vitamin D treatment. Previous randomized clinical trials suggest that Magnesium supplementation, administered either alone or in combination with moderate doses of vitamin D, can effectively increase serum 25OHD concentrations, particularly among individuals with overweight or obesity. Collectively, these findings suggest that optimizing Magnesium status may improve the response to vitamin D supplementation and potentially reduce the need for high-dose vitamin D therapy in obese individuals. Physicians treating overweight or obese patients for vitamin D deficiency should consider co-supplementation with Magnesium and/or encourage intake of Magnesium-rich foods to improve vitamin D status and supplementation outcomes in this population. Full article

Gout is a crystal-induced inflammatory arthritis driven by hyperuricemia and monosodium urate (MSU) crystal deposition, yet urate burden alone does not explain why only a subset of hyperuricemic individuals develops clinical disease, why acute flares are usually self-limited, or why gout clusters with renal and cardiometabolic comorbidity. This structured narrative review uses a gout-specific redox-switch framework, defined as a context-dependent shift in uric acid biology according to concentration, compartment, crystallization state, xanthine oxidoreductase (XOR) activity, inflammatory priming, and disease stage rather than as a binary molecular event. We integrate evidence on XOR-derived reactive oxygen species (ROS), mitochondrial stress, NLRP3 inflammasome signaling, neutrophil oxidative responses, neutrophil extracellular traps (NETs), lipid peroxidation, and potential ferroptosis-related mechanisms. Evidence is classified into five categories: established, mechanistically supported, human-associative, conceptual, and emerging/unvalidated. The available human data support lipid-peroxidation and ferroptosis-associated molecular signatures, but do not yet establish ferroptotic cell death as a driver of gout. Therapeutic implications are therefore framed conservatively: urate-lowering therapy remains foundational, whereas redox-directed approaches require pathway specificity, disease-stage definition, and biomarker validation. The redox-switch concept is proposed as an organizing framework for mechanistic and translational research, not as a validated clinical algorithm. Full article

Background: Cisplatin is a widely used chemotherapeutic agent whose clinical application is often limited by severe hepatorenal toxicity associated with oxidative stress and cellular injury. Nicotinamide riboside (NR), a natural precursor of nicotinamide adenine dinucleotide (NAD+), has emerged as a promising cytoprotective compound with antioxidant and metabolic regulatory properties. This study investigated the protective effects of NR against cisplatin-induced hepatorenal toxicity and explored its potential mechanisms of action. Methods: Thirty-six adult male Wistar rats were randomly assigned to four groups (n = 6): control, cisplatin (7 mg/kg, i.p.), nicotinamide riboside (50 mg/kg/day, orally), and cisplatin plus NR. Renal and hepatic function biomarkers, lipid profile parameters, oxidative stress markers, and antioxidant status were evaluated. Relative mRNA expression of Nrf2 and NQO1 was determined using RT-qPCR. Histopathological examinations of liver and kidney tissues were also performed. Results: Cisplatin administration induced marked hepatorenal injury, evidenced by significant elevations in serum KIM-1 (395.27 vs. 116.04 ng/mL), urea (71.16 vs. 21.33 mg/dL), creatinine (3.49 vs. 0.26 mg/dL), AST (325.83 vs. 95.16 U/L), and ALT (102.83 vs. 45.50 U/L), accompanied by dyslipidemia, oxidative stress, and severe histopathological alterations. NR treatment significantly attenuated these changes, reducing KIM-1, urea, creatinine, AST, and ALT by 55.5%, 47.8%, 48.1%, 55.4%, and 33.5%, respectively, compared with the cisplatin group. NR also improved antioxidant status by increasing GSH and SOD levels while reducing MDA and NO concentrations. Hepatic NAD⁺ levels and the NAD⁺/NADH ratio were significantly decreased by cisplatin and significantly restored by NR treatment. In addition, NR significantly upregulated the relative mRNA expression of Nrf2 and NQO1 and markedly preserved hepatic and renal histological architecture. Pharmacological inhibition of Nrf2 with ML385 significantly attenuated these protective effects of NR across biochemical, lipid, and oxidative stress parameters, confirming that they are, at least in part, Nrf2-dependent. Conclusions: Nicotinamide riboside exerts protective effects against cisplatin-induced hepatorenal toxicity that are mechanistically linked to activation of the Nrf2/NQO1 antioxidant pathway and restoration of hepatic NAD⁺ homeostasis. This finding supports the potential of NR as an adjunctive strategy for mitigating cisplatin-associated hepatorenal injury and warrants further preclinical and clinical investigation. Full article