Serum 1,25-Dihydroxyvitamin D and the Development of Kidney Dysfunction in a Japanese Community

Izumaru, Kensuke; Ninomiya, Toshiharu; Nagata, Michio; Usui, Tomoko; Yoshida, Daigo; Yonemoto, Koji; Fukuhara, Mikio; Tsuruya, Kazuhiko; Kitazono, Takanari; Kiyohara, Yutaka

doi:10.1253/circj.cj-13-0422

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…Consistent with this paradigm, we note that other read-outs of known renal anabolic functions, i.e. hemoglobin (from erythropoietin) and 1,25-hydroxyvitamin D levels are associated with renal disease progression [24–27]. In addition to reporting on renal metabolic capacity, we do not rule out the possibility that select metabolite depletions could play a causal role in disease progression; for example, as the substrate for nitric oxide synthase, limited arginine bioavailability could have deleterious vascular effects pertinent to CKD progression.…”

Section: Discussionsupporting

confidence: 54%

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study

Rhee

Clish

Wenger³

et al. 2016

Am J Nephrol

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Background: Whereas several longitudinal metabolomics studies have been conducted in individuals with normal estimated glomerular filtration rate (eGFR) at baseline, disease progression among individuals with established chronic kidney disease (CKD) has not been rigorously examined. Methods: We performed a nested case-control study of rapid CKD progression in the Chronic Renal Insufficiency Cohort Study, profiling baseline plasma from 200 individuals each with eGFR slope <-3 ml/min/1.73 m²/year (cases) or between -1 and +1 ml/min/1.73 m²/year (controls), matched on baseline eGFR and proteinuria. To directly assess how the kidney modulates circulating metabolites, we profiled plasma from the aorta and renal vein of 25 hospital-based individuals. Results: At baseline, cases and controls had a mean eGFR of 41.7 ± 13.3 and 45.0 ± 14.5 ml/min/1.73 m², respectively. Ten plasma metabolites were nominally associated with CKD progression in logistic regression models adjusted for age, sex, race/ethnicity, hypertension, systolic and diastolic blood pressure, diabetes, eGFR and proteinuria; no metabolite achieved the Bonferroni-adjusted significance threshold (p < 0.0003). In a cross-sectional analysis, all 6 of the metabolites that were higher in cases than controls were significantly associated with eGFR at baseline. By contrast, threonine, methionine and arginine were lower in cases than in controls and had no association with baseline eGFR. Furthermore, in the hospital-based cohort that underwent renal arteriovenous sampling, these 3 metabolites were net released from the kidney. Combining these metabolites into a panel of markers further strengthened their association with CKD progression. Conclusion: Our results motivate interest in arginine, methionine and threonine as potential indicators of renal metabolic function and markers of renal prognosis.

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Section: Discussionsupporting

confidence: 54%

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study

Rhee

Clish

Wenger³

et al. 2016

Am J Nephrol

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“…16, 17 We performed a screening survey for the present study in 2002 and 2003. 18 Briefly, a total of 3,328 residents aged ≥40 years (77.6% of the total population in this age group) underwent examination. After excluding 30 subjects who did not consent to participate in the study, 86 for whom no urine or blood sample was obtained, 250 with an eGFR <60 ml/min/1.73 m 2 , and 538 with a urine albumin-creatinine ratio (U-ACR) ≥30 mg/g, the remaining 2,424 participants (1,042 men and 1,382 women) were enrolled in the baseline examination.…”

Section: Study Participantsmentioning

confidence: 99%

Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community　– The Hisayama Study –

Takae

Nagata

Hata

et al. 2016

Circ J

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Background: Growing evidence suggests that high serum uric acid (SUA) levels are causally related to increased risk of chronic kidney disease (CKD). However, few studies have investigated the influence of elevated SUA levels on the incidence of kidney dysfunction and albuminuria separately in community-based populations. Methods and Results:A total of 2,059 community-dwelling Japanese subjects aged ≥40 years without CKD were followed for 5 years. CKD was defined as kidney dysfunction (estimated glomerular filtration rate <60 ml/min/1.73 m 2 ) or albuminuria (urine albumin-creatinine ratio ≥30 mg/g). The odds ratio (OR) for the development of CKD was estimated according to quartiles of SUA (≤4.0, 4.1-4.9, 5.0-5.8, and ≥5.9 mg/dl). During the follow-up, 396 subjects developed CKD, of whom 125 had kidney dysfunction and 312 had albuminuria. The multivariable-adjusted risk of developing CKD increased with higher SUA levels (OR 1. Conclusions:Higher SUA levels were a significant risk factor for the development of both kidney dysfunction and albuminuria in a general Japanese population. (Circ J 2016; 80: 1857 -1862

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“…Vitamin D deficiency was associated with a higher annual incidence of albuminuria, decreased eGFR, and independently predicted 5-year incidence of albuminuria [6]. Vitamin D deficiency was also a significant risk factor for the development of CKD stage 3–5 [7, 8]. In addition, vitamin D deficiency is independently associated with a higher risk of 50% increase in baseline serum creatinine, ESRD, or death in patients with type II diabetic nephropathy (DN) [9].…”

Section: Introductionmentioning

confidence: 99%

A double-blind, randomized, placebo-controlled trial of combined calcitriol and ergocalciferol versus ergocalciferol alone in chronic kidney disease with proteinuria

et al. 2017

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BackgroundKDOQI guideline suggests that nutritional vitamin D should be supplemented in chronic kidney disease (CKD) patients who have vitamin D insufficiency/deficiency. However, there are scarce data regarding the additional benefit of active vitamin D supplement in CKD patients who were receiving nutritional vitamin D supplement. This study was conducted to explore the effect of adding active vitamin D to nutritional vitamin D supplement on proteinuria and kidney function in CKD with vitamin D insufficiency/deficiency.MethodsThis double-blind, randomized placebo-controlled trial was performed to answer the above question. Sixty-eight patients with CKD stage 3–4, urine protein to creatinine ratio (UPCR) > 1 g/g, and serum 25OH-D level < 30 ng/mL were enrolled. Patients were randomly assigned to receive 12-week treatment with oral ergocalciferol plus placebo (n = 36) or oral ergocalciferol plus calcitriol (n = 32).ResultsThe mean baseline values of UPCR of both groups were comparable (3.6 ± 3.8 g/g in combined group and 3.5 ± 3.0 g/g in ergocalciferol group). Following 12-week treatment, there were significant reductions in UPCR from baseline in both groups (2.3 ± 2.1 g/g in combined group and 2.4 ± 2.0 g/g in ergocalciferol group). The percentage reductions in UPCR of both groups were not significantly different. The mean eGFR and blood pressure did not differ between baseline and 12-week follow-up and between both groups. No severe hypercalcemia or serious side effects were noted in both groups.ConclusionsThe proteinuria lowering effect of ergocalciferol in CKD patients with vitamin D deficiency was demonstrated. Additional calcitriol supplement did not have more effects on proteinuria.Trial registration(Thai Clinical Trials Registry (TCTR) 20140929002). Date of registration: September 27, 2014.

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Serum 1,25-Dihydroxyvitamin D and the Development of Kidney Dysfunction in a Japanese Community

Cited by 8 publications

References 38 publications

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study

Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community　– The Hisayama Study –

A double-blind, randomized, placebo-controlled trial of combined calcitriol and ergocalciferol versus ergocalciferol alone in chronic kidney disease with proteinuria

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Serum 1,25-Dihydroxyvitamin D and the Development of Kidney Dysfunction in a Japanese Community

Cited by 8 publications

References 38 publications

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study

Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community – The Hisayama Study –

A double-blind, randomized, placebo-controlled trial of combined calcitriol and ergocalciferol versus ergocalciferol alone in chronic kidney disease with proteinuria

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Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community　– The Hisayama Study –