In Joo Kim

Cystatin C as an Early Biomarker of Nephropathy in Patients with Type 2 Diabetes

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.

Prevalence of erectile dysfunction in Korean men with Type 2 diabetes mellitus.

Aims  We investigated the prevalence and risk factors for developing erectile dysfunction (ED) in 1312 Korean men with diabetes in a multicentre study.

Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients

AIM The aim of this study was to evaluate the association of urinary tubular markers, interleukin-18 (IL-18) and angiotensinogen with albuminuria in early nephropathy of type 2 diabetics. METHODS Urine levels of tubular markers (kidney injury molecule [KIM]-1, neutrophil gelatinase-associated lipocalin [NGAL] and liver-type fatty acid-binding protein [L-FABP]), proinflammatory marker (IL-18), and a marker of intrarenal renin-angiotensin system (RAS) status (angiotensinogen) were determined in 118 patients with type 2 diabetes mellitus and 25 non-diabetic controls with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m(2). RESULTS Urinary levels of KIM-1, NGAL, IL-18 and angiotensinogen were significantly higher in macroalbuminuria group compared with control and normo- and microalbuminuria groups but not significantly different between control and normoalbuminuria group. Urinary tubular markers were positively correlated with urinary IL-18 and angiotensinogen, respectively. The urinary albuminuria was correlated with all investigated urinary markers in univariate analysis. After adjusting for several clinical parameters, urinary KIM-1, NGAL and angiotensinogen were significantly associated with albuminuria. CONCLUSIONS The results of this study suggest that urinary tubular markers may be independently associated with albuminuria in the early stage of nephropathy in type 2 diabetics (eGFR ≥ 60 mL/min/1.73 m(2)) and may reflect inflammatory processing and the activation of the intrarenal RAS.

Urinary Cystatin C and Tubular Proteinuria Predict Progression of Diabetic Nephropathy

OBJECTIVE The aim of this study was to evaluate the association of urinary cystatin C, a tubular damage marker, with the progression of type 2 diabetic nephropathy. RESERCH DESIGN AND METHODS The baseline values of serum and urinary cystatin C were measured as primary parameters and those of urinary nonalbumin protein (NAP) were measured as secondary parameters. In this prospective observational study, a total of 237 type 2 diabetic patients were followed up for 29 months (13–44 months). RESULTS Both the urinary cystatin C-to-creatinine ratio (CCR) and NAP-to-creatinine ratio (NAPCR) were significantly different according to the degree of albuminuria. Both markers had strongly positive correlations at baseline. After adjusting for several clinical factors, both urinary CCR and NAPCR had significant associations with the decline of the estimated glomerular filtration rate (eGFR) (r = 0.160, P = 0.021; r = 0.412, P < 0.001, respectively). Urinary CCR had positive correlations with the decline of eGFR in the subpopulation of patients with eGFR ≥60 mL/min/1.73 m2. In patients with eGFR ≥60 mL/min/1.73 m2 and normoalbuminuria, only urinary NAPCR showed a significant association with the decline of eGFR; urinary CCR did not. In multivariate regression analysis, the number of patients who progressed to chronic kidney disease stage 3 or greater was higher in those in the upper tertiles of both the urinary levels of cystatin C and NAP than in those in the lower tertiles. CONCLUSIONS The results of this study suggest that urinary cystatin C and NAP may be predictors of the progression of type 2 diabetic nephropathy.

Coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma: the influence of lymph node metastasis.

The aim of this study was to evaluate the influence of coexistent Hashimotos thyroiditis with papillary thyroid carcinoma on lymph node metastasis.

Clinical Implication of PET/MR Imaging in Preoperative Esophageal Cancer Staging: Comparison with PET/CT, Endoscopic Ultrasonography, and CT

This was a study to compare the diagnostic efficacies of endoscopic ultrasonography (EUS), CT, PET/MR imaging, and PET/CT for the preoperative local and regional staging of esophageal cancer, with postoperative pathologic stage used as the reference standard. Methods: During 1 y, 19 patients with resectable esophageal cancer were enrolled and underwent preoperative EUS, CT, PET/CT, and PET/MR imaging. A chest radiologist and nuclear medicine physician retrospectively reviewed the images and assigned tumor and lymph node stages according to the seventh version of the TNM system and the American Joint Committee on Cancer staging system. Four patients who were treated nonsurgically were excluded from data analysis. The efficacies of EUS, CT, PET/CT, and PET/MR imaging were compared. Results: Primary tumors were correctly staged in 13 (86.7%), 10 (66.7%), and 5 (33.3%) patients at EUS, PET/MR imaging, and CT, respectively (P value ranging from 0.021 to 0.375). The accuracy of determining T1 lesions was 86.7%, 80.0%, and 46.7% for EUS, PET/MR imaging, and CT, respectively. For distinguishing T3 lesions, the accuracy was 93.3% for EUS and 86.7% for both PET/MR imaging and CT. For lymph node staging, the accuracy was 83.3%, 75.0%, 66.7%, and 50.0% for PET/MR imaging, EUS, PET/CT, and CT, respectively. In addition, area-under-the-curve values were 0.800, 0.700, 0.629, and 0.543 for PET/MR imaging, EUS, PET/CT, and CT, respectively. Conclusion: PET/MR imaging demonstrated acceptable accuracy for T staging compared with EUS and, although not statistically significant, even higher accuracy than EUS and PET/CT for prediction of N staging. With adjustments in protocols, PET/MR imaging may provide an important role in preoperative esophageal cancer staging in the future.

Soluble α-klotho as a novel biomarker in the early stage of nephropathy in patients with type 2 diabetes.

Objective Although α-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble α-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary α-klotho levels are associated with albuminuria in kidney disease in diabetes. Research Design and Methods A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentrations of α-klotho were analyzed by enzyme-linked immunosorbent assay. Results Plasma α-klotho (572.4 pg/mL [95% CI, 541.9–604.6 pg/mL] vs. 476.9 pg/mL [95% CI, 416.9–545.5 pg/mL]) and urinary α-klotho levels (59.8 pg/mg creatinine [95% CI, 43.6–82.0 pg/mg creatinine] vs. 21.0 pg/mg creatinine [95% CI, 9.7–45.6 pg/mg creatinine]) were significantly higher in diabetic patients than non-diabetic controls. Among diabetic patients, plasma α-klotho concentration was inversely associated with albuminuria stages (normoalbuminuria, 612.6 pg/mL [95% CI, 568.9–659.6 pg/mL], microalbuminuria, 551.8 pg/mL [95% CI, 500.5–608.3 pg/mL], and macroalbuminuria, 505.7 pg/mL [95% CI, 439.7–581.7 pg/mL] (p for trend  = 0.0081), while urinary α-klotho levels were remained constantly high with increasing urinary albumin excretion. Conclusions Soluble α-klotho levels in plasma and urine may be novel and useful early markers of diabetic renal injury.

Clinical implication of plasma and urine YKL-40, as a proinflammatory biomarker, on early stage of nephropathy in type 2 diabetic patients

OBJECTIVE Chronic inflammation has emerged as being a key pathophysiology in the early stages of diabetic nephropathy. YKL-40 has been established as an inflammatory marker in chronic inflammation. The aim of this study was to evaluate the association of plasma and urine YKL-40 with albuminuria in the early stage of type 2 diabetic nephropathy. DESIGN AND METHODS A total of 75 type 2 diabetic patients and 22 nondiabetic controls with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m(2) were enrolled. Plasma and urine concentrations of YKL-40 were analyzed by ELISA kit. RESULTS The plasma levels of YKL-40 were significantly higher in the normoalbuminuric group with diabetes than in the control group, and increased with increasing severity of albuminuria among diabetes. However, urine YKL-40 was only increased in macroalbuminuric state. Plasma YKL-40 was positively correlated with urine YKL-40 (r=0.291, P=0.011). Urinary albumin significantly correlated with both plasma and urine YKL-40 in a univariate analysis. After adjusting for several confounding factors, plasma YKL-40 was significantly correlated with albuminuria (r=0.359; P=0.001), whereas urine YKL-40 did not show significant correlation with albuminuria (r=0.128, P=0.241). CONCLUSIONS Although urine YKL-40 has a limited role, plasma YKL-40, as an proinflammatory marker, was an independent factor associated with albuminuria in early stage of nephropathy in type 2 diabetes and might have an useful role as a noninvasive marker for the early diabetic nephropathy detection.

High-normal serum uric acid predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus and preserved kidney function

AIMS We evaluated whether high-normal serum uric acid (SUA) levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus and preserved kidney function at baseline. METHODS This was a retrospective observational longitudinal study of patients presenting at the Department of Endocrinology and Metabolism, Pusan National University Hospital. A total of 512 patients with type 2 diabetes mellitus and preserved kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2)) and normouricemia were included. The main outcome was development of CKD of stage 3 or greater. The patients were divided into four groups according to quartiles of SUA levels. RESULTS During the follow-up period, 62 (12.1%) patients had progressed to CKD 3 or greater. The group with the highest-normal range of SUA (Q4) showed a higher cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q4 vs. Q3; P = 0.037, Q4 vs. Q2; P<0.001, Q4 vs. Q1; P<0.001). In a univariate analysis, Q4 was significantly associated with the development of CKD 3 or greater (log-rank statistic, 31.93; P<0.001). In a multivariate analysis, Q4 (hazard ratio, 2.97; 95% confidence interval, 1.15-7.71; P = 0.025) showed a significant association with CKD 3 or greater. CONCLUSIONS High-normal SUA may predict the occurrence of CKD stage 3 or greater in patients with type 2 diabetes mellitus and preserved kidney function.

Predictive value of metabolic tumor volume measured by 18F-FDG PET for regional lymph node status in patients with esophageal cancer.

Objective: The aim of the current study was to investigate the predictive value of metabolic tumor volume (MTV) measured by 18F-FDG PET/CT for regional lymph node (rLN) metastasis in patients with esophageal cancer. Methods: A retrospective review identified 54 patients with surgically resected esophageal cancer who received 18F-FDG PET/CT at diagnosis of cancer. The 18F-FDG PET/CT findings for all primary cancer and rLN involvement were compared with the pathologic diagnosis within 5 weeks after surgical resection. The pathologic diagnoses of rLN state were confirmed by surgical resection. Univariate and multivariate analyses were used to analyze the associations among the pathologic rLN status and age, sex, T stage, location, differentiation, maximum standardized uptake value (SUVmax), MTV2.5, and MTV3. Results: The rLN(+) group showed statistically significant higher value of SUVmax than the rLN(−) group (P = 0.0011). The rLN(+) group showed statistically significant higher value of MTV2.5 (P = 0.0004) and MTV3 (P = 0.0005) than the rLN(−) group. In receiver operating characteristic analysis, the SUVmax, MTV2.5, and MTV3 did not show the statistical differences for the prediction of pathologic rLN involvement in esophageal cancer. In univariate analysis, T stage, SUVmax, MTV2.5, and MTV3 were factors significantly associated with pathologic rLN involvement. However, in multivariate analysis, the MTV2.5 and MTV3 were factors significantly associated with pathologic rLN involvement in esophageal cancer. Conclusion: Based on the presented results, the MTV measured by 18F- FDG PET/CT is a useful method for the prediction of pathologic rLN status in esophageal cancer patients. Further studies are needed to confirm these results and improve statistical accuracy.