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Background: Retinopathy and left ventricular hypertrophy (LVH) are representative markers of microvascular and cardiac dysfunction in patients with chronic kidney disease (CKD). However, their relationship and their combined effects on clinical outcomes are unknown., Methods: We included 401 patients with nondialysis-dependent CKD stage 3-5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. The presence of LVH was identified by echocardiography. The clinical significance of retinopathy and LVH was evaluated in terms of the rate of renal function decline and for any cardiovascular event (CVE)/death., Results: CKD patients with retinopathy had a higher prevalence of LVH than those without retinopathy (38.9% vs. 27.6%, P=0.017). The presence of retinopathy was independently associated with LVH (odds ratio 1.69, 95% confidence interval [CI] 1.02, 2.80). Compared with subjects without either retinopathy or LVH, the coexistence of retinopathy and LVH was independently associated with rapid renal function decline (β=-3.28; 95% CI -6.52, -0.04), whereas retinopathy or LVH alone were not. Patients with both retinopathy and LVH had a higher risk of CVE/death (adjusted hazard ratio 2.75; 95% CI 1.44, 5.26) than patients with either factor alone. A significant synergistic interaction was observed between retinopathy and LVH to predict CVE/death (P for interaction=0.049)., Conclusions: Retinopathy was independently associated with LVH. The coexistence of retinopathy and LVH was associated with higher risks of CKD progression and CVE/death than was either factor alone, and their combined effects synergized to predict the risk of CVE/death., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.) more...

Background: Impaired vitamin D metabolism may contribute to the development and progression of chronic kidney disease. The purpose of this study was to determine associations of circulating vitamin D with the degree of proteinuria and estimated glomerular filtration rate (eGFR) in patients with biopsy-proven glomerular diseases. Methods: Clinical and biochemical data including blood samples for 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels were collected from patients at the time of kidney biopsy. Results: Serum 25(OH)D levels were not different according to eGFR. However, renal function was significantly decreased with lower serum 1,25(OH) 2 D levels ( P < 0.001). The proportions of nephrotic-range proteinuria and renal dysfunction (eGFR ≤ 60 mL/min/1.73 m 2 ) progressively increased with declining 1,25(OH) 2 D but not 25(OH)D. Multivariable linear regression analysis showed that 25(OH)D was significantly correlated with serum albumin and total cholesterol (β = 0.224, P = 0.006; β = -0.263, P = 0.001) and 1,25(OH) 2 D was significantly correlated with eGFR, serum albumin and phosphorus (β = 0.202, P = 0.005; β = 0.304, P < 0.001; β = -0.161, P = 0.024). In adjusted multivariable linear regression, eGFR and 24hr proteinuria were independently correlated only with 1,25(OH) 2 D (β = 0.154, P = 0.018; β = -0.171, P = 0.012), but not 25(OH)D. The lower level of 1,25(OH) 2 D was associated with the frequent use of immunosuppressive agents ( P < 0.001). Conclusion: It is noteworthy in these results that circulating 1,25(OH) 2 D may be superior to 25(OH)D as a marker of severity of glomerular diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists. more...

Aims: Chronic kidney disease (CKD) and retinopathy share the common pathophysiology of microvascular dysfunction. It is unclear whether the clinical significance of diabetic retinopathy (DMR) and hypertensive retinopathy (HTNR) differs in CKD patients., Methods: We included 684 nondialysis-dependent CKD stage 3-5 patients with diabetes or hypertension: 501 patients with diabetes and 183 with hypertension. The clinical significance of DMR and HTNR was evaluated in terms of the rate of renal function decline and composite of any cardiovascular event or death., Results: DMR was observed in 261 (52.1%) CKD patients with diabetes, and HTNR in 44 (24.0%) CKD patients with hypertension. In the diabetes group, the renal function decline rate was significantly steeper in patients with than in those without DMR (-7.4 ± 9.8mL/min/1.73m(2)/yr vs. -2.4 ± 7.6mL/min/1.73m(2)/yr; P<0.001). In multivariate analysis, DMR were independently associated with a rapid decline in renal function (β=-2.44; P=0.20). However, HTNR did not affect the renal function decline in CKD patients. The composite event-free survival rate was lower in patients with diabetes and DMR than in those without DMR (P=0.043). Patients with diabetes and DMR were independently associated with a 2.13-fold increased risk for composite events (P=0.010). HTNR was not associated with higher risk for composite events in CKD patients., Conclusion: Coexistence of diabetes and DMR were independently associated with CKD progression and composite cardiovascular event/death, but the clinical significance of HTNR is less clear in CKD patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.) more...

Purpose: The immunochemical fecal occult blood test (iFOBT) is a useful method to screen for lower gastrointestinal (GI) bleeding-related lesions. However, few studies have investigated the diagnostic utility of iFOBT in chronic kidney disease (CKD)., Methods: We included 691 patients with nondialysis-dependent CKD stages 2-5 or those receiving dialysis. Bleeding-related lower GI lesions were identified by colonoscopy, and the diagnostic utility of iFOBT was evaluated., Results: Bleeding-related lower GI lesions were found in 9.2% of 491 patients with CKD stage 2, 17.8% of 107 patients with CKD stage 3/4, and 25.8% of 93 patients with CKD stage 5/dialysis (p < 0.001). Compared with CKD stage 2, CKD stage 5/dialysis was independently associated with a 2.80-fold risk for bleeding-related lesions (p = 0.019). The iFOBT was positive in 92 (13.3%) patients and the area under the receiver operating curve (AUC) for a bleeding-related lesion was 0.64 (p < 0.001). The sensitivity of iFOBT increased as the CKD stage worsened (20.0 vs 52.6 vs 58.3%; p = 0.002). However, the specificity to detect bleeding-related lesions decreased with the severity of CKD stage (94.6 vs. 78.4 vs. 76.8%; p < 0.001). The AUC of iFOBT to detect adenoma or carcinoma was 0.54 (p = 0.046), and a similar pattern of sensitivity and specificity was observed between different CKD stages., Conclusions: The prevalence of bleeding-related lower GI lesions and the sensitivity of iFOBT to detect these GI lesions increased in advanced CKD. However, iFOBT should be used cautiously in these patients because its specificity decreased. more...

Background: The clinical significance of preexisting microcalcification in the iliac artery is undetermined in renal transplant recipients., Methods: We obtained iliac artery segments from 90 transplant recipients at the time of renal transplantation and performed von Kossa staining for microcalcification. The clinical significance of intimal microcalcification was evaluated with allograft survival rate, rate of graft function decline, and composite of any cardiovascular event or patient death. Expression of fetuin-A and C-reactive protein, key regulators of calcification, was also investigated in the iliac artery., Results: Intimal microcalcification was positive in 48 (53.3%) patients, and its intensity was correlated positively with intimal C-reactive protein intensity (P = 0.019). Allograft survival in patients positive for intimal microcalcification was lower than patients who were negative (P = 0.017). The patients with positivity for both intimal microcalcification and fetuin-A showed lower allograft survival rate than patients with intimal microcalcification positivity alone (P = 0.012). The rate of renal graft function decline was significantly steeper in patients positive for intimal microcalcification than in patients who were negative (P = 0.036). In multivariate analysis, positivity for both intimal microcalcification and fetuin-A was an independent predictor for renal graft function decline (β = -10.21; P = 0.011). The intimal microcalcification was not associated with composite-event free survival., Conclusion: Preexisting intimal microcalcification in the iliac artery predicts a lower allograft survival rate and rapid decline of allograft function. Positivity of fetuin-A with intimal microcalcification further reduces allograft survival rate and an independent predictor for renal graft function decline. more...

Background/aims: Atrial fibrillation (AF) often coexists with acute myocardial infarction (AMI), and chronic kidney disease (CKD) is a major risk for AMI. However, the combined impact of CKD and AF on the mortality and morbidity in AMI population has not been determined., Methods: Between January 2004 and December 2009, a total of 4,738 AMI patients were enrolled prospectively. Patients were divided into four groups according to the combined status of CKD and AF. The primary endpoint was a combination of 5-year major adverse cardiac and cerebrovascular events (MACCE)., Results: The prevalence of AF was significantly higher in CKD patients than in non-CKD patients (6.76 vs. 3.31%, p < 0.001). The highest cumulative event rate of MACCE and death was observed in patients with both CKD and AF (68.5 and 64.0%), respectively. In multivariable analyses, compared with patients with neither AF nor CKD, hazard ratios (HR) for composite of MACCE were 1.66 (95% CI, 1.14-2.41), 1.24 (95% CI, 1.06-1.46), and 2.10 (95% CI, 1.42-3.13) for patients with AF only, those with CKD only, and those with both CKD and AF, respectively (p for interaction = 0.935). Patients with both CKD and AF had a greatest risk for all-cause mortality (HR 2.54; 95% CI, 1.60-4.53), and the significant synergistic interaction was observed between CKD and AF (p for interaction = 0.015)., Conclusion: The combined effect of AF and CKD on the risk of MACCE after an AMI is stronger than any separate condition, and it confers a synergistic effect on the all-cause mortality risk., (© 2014 S. Karger AG, Basel.) more...

Background and Aim: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression., Methods: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated., Results: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p < 0.001) and level of proteinuria (β = -2.36, p = 0.015) were independently associated with the rate of renal function decline., Conclusions: Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline. more...

Objective: Anemia and iron deficiency are common complications in patients with chronic kidney disease (CKD). However, information about the diagnostic indicators of bleeding-related upper gastrointestinal (GI) tract lesions is sparse and few studies have investigated anemic upper GI tract lesions., Methods: We included 165 anemic patients with non-dialysis-dependent CKD stages 3 to 5 (44 patients at stage 3, 52 patients at stage 4, and 69 patients at stage 5). Transferrin saturation (TSAT), serum ferritin, mean corpuscular volume, and corrected reticulocyte count data were collected to evaluate their diagnostic use for bleeding-related upper GI tract lesions, which were identified by esophagogastroduodenoscopy., Results: Bleeding-related GI tract lesions were found in 57 patients (34.5%). The area under the receiver-operating characteristic curve used to predict bleeding-related lesions was 0.63 for TSAT (P = 0.007), and the best cutoff value was 19.7% (sensitivity, 0.53; specificity, 0.76). The combination of cutoffs TSAT less than 20% or serum ferritin less than 100 ng/mL produced a 17% increment in sensitivity compared with that of TSAT less than 20% alone. The corrected reticulocyte levels and mean corpuscular volume had no significant diagnostic use. In patients with CKD stage 5, the sensitivity of TSAT or its combination with serum ferritin less than 100 ng/mL was significantly lower than in patients with CKD stage 3 (all P < 0.05)., Conclusions: Transferrin saturation is a significant predictor of anemic lesions in the upper GI tract, and serum ferritin can increase the sensitivity of TSAT. However, these indicators should be used with caution in patients with CKD stage 5 because their sensitivity is poor in this context. more...