Hyperuricemia has been increasingly recognized as a modifiable contributor to chronic kidney disease (CKD) progression. Although the traditional classification of hyperuricemia distinguished between renal underexcretion and renal overload types, recent studies suggest that hyperuricemia in patients with CKD can result from heterogeneous excretory defects, including glomerular under-filtration and tubular over-reabsorption. These distinct phenotypes may drive divergent renal injury mechanisms. Experimental and clinical data reveal that monosodium urate crystals and soluble uric acid independently induce renal damage through oxidative stress, inflammasome activation, and endothelial dysfunction. Furthermore, clinical investigations showed inconsistent associations between serum uric acid levels and renal outcomes, suggesting that serum levels alone may not fully reflect urate-related renal risk. This has prompted increasing interest in uricosuric agents, particularly the selective urate reabsorption inhibitors (SURIs), which target tubular urate handling. Urate transporter 1 inhibitors have shown promise in enhancing urinary uric acid excretion and potentially preserving kidney function, especially in patients with CKD. In this review, we summarize the current evidence linking the emerging pathophysiological classification of hyperuricemia, mechanisms or urate-induced kidney injury, and therapeutic interventions. These insights may inform individualized approaches to urate-lowering therapy in CKD and support future research into phenotype-guided treatment strategies.

Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (BACH1), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway.

Background/Objectives: Muscle quality reflects functional characteristics beyond muscle mass and may offer prognostic insights in patients with chronic kidney disease (CKD). This study investigated whether muscle quality predicts sarcopenia and renal outcomes in non-dialysis CKD patients. Methods: We prospectively recruited 93 patients with CKD (stage G1–5). Muscle quality was evaluated using phase angle (PhA) derived from bioelectrical impedance analysis. Sarcopenia was diagnosed based on criteria from the Asian Working Group for Sarcopenia. The primary renal outcome was defined as a > 30% decline in eGFR or the initiation of dialysis. Logistic regression identified factors associated with sarcopenia. Kaplan–Meier and Cox regression analyses were used to assess predictors of renal outcomes. Results: Lower PhA (odds ratio [OR] 0.044, p = 0.002) and BMI (OR 0.648, p = 0.015) were independently associated with sarcopenia. Sex-specific PhA cutoffs of 4.50° for men and 4.00° for women yielded high diagnostic accuracy for sarcopenia (AUC: 0.878 and 0.969, respectively). Over a median observation period of 574 days, patients with lower PhA values showed a significantly higher risk of poor renal outcomes, independent of confounding factors (hazard ratio [HR] 4.540, p = 0.011), even after adjustment for age, sex, BMI, systolic blood pressure, diastolic blood pressure, eGFR, and albumin. However, muscle mass was not significantly associated with renal prognosis. Conclusions: PhA is a non-invasive marker that may reflect muscle quality and is associated with sarcopenia and renal outcomes in CKD. It may help inform risk stratification in clinical practice.

Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and iron metabolism. Methods: We retrospectively analyzed laboratory data related to erythropoiesis from 105 patients with CKD before and after treatment with HIF-PHI or ESA. The dialysis initiation and mortality rates were also assessed over a median follow-up of 614 days. Results: HIF-PHI and ESA significantly increased the hemoglobin levels within 6 months of treatment (9.5 ± 1.0 to 10.7 ± 1.1, p < 0.01, and 9.9 ± 1.5 to 10.7 ± 1.2 g/dL, p < 0.01, respectively). The HIF-PHI group demonstrated a significant decrease in red cell distribution width (14.5 ± 1.9% to 13.8 ± 1.4%, p < 0.01), suggesting improved erythropoiesis, and exhibited a lower cumulative incidence of outcomes. The aged-adjusted multivariate analysis confirmed the independent association between HIF-PHI treatment and reduced risk of cumulative outcome (p = 0.042). Conclusions: HIF-PHIs can serve as an alternative to ESA for managing renal anemia in CKD, improving both hematological parameters and long-term outcomes.

Background/Objectives: Distinguishing glomerulonephritis (GN) from diabetic kidney disease (DKD) and nephrosclerosis (NS) is clinically important. Urinary uromodulin (uUMOD), a biomarker of renal tubular integrity, may help discriminate among these chronic kidney disease (CKD) etiologies. We evaluated the diagnostic utility of uUMOD for differentiating GN from DKD and NS. Methods: This retrospective single-center study included 90 patients with biopsy-proven GN (n = 30), DKD (n = 25), or NS (n = 35). First-morning spot urine samples obtained before biopsy were analyzed for uUMOD concentration and normalized to urinary creatinine levels (uUMOD/Cr). Results: The uUMOD/Cr ratio was significantly higher in GN (21.2 mg/gCr [10.3–31.3]) than in DKD (5.5 [3.6–12.3], p < 0.001) or NS (10.7 [6.4–19.9], p = 0.021). In multivariate analyses adjusted for age, sex, estimated glomerular filtration rate, interstitial fibrosis, and urinary protein, the uUMOD/Cr ratio was independently associated with GN (p = 0.003) and this correlation remained statistically significant after additional adjustment for diabetes mellitus. Receiver operating characteristic curve analysis showed an area under the curve value of 0.833 for GN versus DKD, 0.714 for GN versus NS, and 0.764 for GN versus DKD and NS combined. A cutoff value of 16.5 mg/gCr yielded 72.8% sensitivity and 70.0% specificity for identifying GN. Conclusions: uUMOD secretion is preserved in GN compared to DKD or NS and shows moderate diagnostic utility for differentiating between these biopsy-proven CKD etiologies. uUMOD may serve as a simple, noninvasive biomarker when biopsy is difficult or clinical findings are inconclusive.

Background/Objectives: Accurate assessment of the glomerular filtration rate (GFR) is essential for managing chronic kidney disease (CKD). Although creatinine-based estimated GFR (eGFRcr) may be affected by reduced muscle mass, the contribution of muscle characteristics beyond muscle mass remains unclear. This study investigated whether phase angle (PhA), a bioelectrical impedance analysis-derived indicator associated with muscle quality, provides complementary information beyond appendicular skeletal muscle mass (ASM) regarding discordance between eGFRcr and a creatinine clearance (CCr)-based reference estimate. Methods: We enrolled 86 adults with CKD not receiving maintenance dialysis. CCr was calculated from 24 h urine collections, indexed to a standard body surface area (BSA) of 1.73 m², and multiplied by 0.715. KOI was calculated as eGFRcr divided by (BSA-indexed CCr × 0.715). A KOI > 1.2 was used as an exploratory threshold for clinically significant discordance. Results: KOI > 1.2 was observed in 24.4% of patients. KOI was negatively correlated with ASM (r = −0.301, p = 0.005) and PhA (r = −0.451, p < 0.001). Adding PhA to a multivariable linear regression model including ASM improved model performance (adjusted R², 0.060–0.200). Multivariable logistic regression, including ASM and PhA as explanatory variables, showed that only PhA remained independently associated with KOI > 1.2 (odds ratio, 0.258; 95% CI, 0.113–0.585; p = 0.001). Conclusions: PhA may provide complementary information beyond skeletal muscle mass for identifying patients with greater discordance between eGFRcr and corrected, BSA-indexed CCr. Further studies using measured GFR are needed to validate these findings.