Comprehensive assessment of cardiovascular-kidney-metabolic (CKM) syndrome: Novel tools for assessment of cardiovascular risk and kidney outcomes in long-term kidney transplant patients.

BACKGROUND: Cardiovascular (CV)-kidney-metabolic (CKM) syndrome, a newly defined entity, offers a framework for assessing CV risk. Emerging evidence suggests that histone deacetylase sirtuin-1 (SIRT1) and adipokine chemerin hold promise as CKM markers. This study aimed to explore the relationship between CKM stage, clinical parameters, and both novel and established markers of CV and renal risk. METHODS: A cohort of 102 patients with long-term, stable kidney transplant (KTx) (>24 months) and median (interquartile range) follow-up of 83 (42-85) months was recruited alongside 32 healthy controls. Patients were classified into modified CKM stages following the American Heart Association guidance. Serum high-sensitivity interleukin-6 (hsIL-6), chemerin, and SIRT1 were measured using commercial immunoassay kits. The incidence of CV events (CVE), CV mortality, and permanent transfer to dialysis therapy were primary endpoints. RESULTS: CKM stage was associated with higher risk of CVE/CV death (HR 95% CI, 3.79 [1.16-12.42]; P = 0.03) and allograft loss (HR 95% CI, 2.05 [1.17-3.57]; P = 0.01). Elevated sirtuin-1 was associated with significantly lower risk of CV event/death (HR 95% CI, 0.11 [0.11-0.89]; P = 0.04), whereas high chemerin status was tied to dialysis risk (HR 95% CI, 5.77 [1.96-17.00]; P = 0.001) alone. In contrast to sirtuin-1, hsIL-6 and chemerin showed incremental changes across more advanced CKM stages, though statistically significant for hsIL-6 alone. In age-adjusted models for CV disease, independent associations with diabetes and total cholesterol were noted. CONCLUSIONS: Classifying patients based on modified CKM stages offers valuable prognostic insights for stable KTx recipients, particularly when assessing reno-cardiovascular risk. The investigated serum markers may serve as supplemental tools for refining risk stratification.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients.

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate-eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin-NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = -0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = -0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = -0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = -0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.