The Effect of Vitamin K2 Supplementation on PIVKA-II Levels in Patients with Severe Motor and Intellectual Disabilities Undergoing Long-Term Tube Feeding.

Nutritional support is essential for patients with severe motor and intellectual disabilities (SMID) to ensure the smooth provision of medical care. These patients often require long-term tube feeding with enteral formulas, potentially leading to deficiencies in vitamins and trace elements. Additionally, frequent antibiotic use for infections often disrupts gut microbiota, inhibiting vitamin K2 production by intestinal bacteria. We assessed the serum protein induced by vitamin K absence or antagonists-II (PIVKA-II) and undercarboxylated osteocalcin (ucOC) levels to assess the vitamin K status in 20 patients with SMID (median age: 44.1 years, 11 men and 9 women) undergoing long-term tube feeding for durations ranging from 3 to 31 years. Thirteen (65%) and nine (45%) patients had elevated PIVKA-II (<40 mAU/mL) and serum ucOC levels (reference value < 4.50 ng/mL), respectively. Dietary vitamin K1 intake did not differ between patients with and without elevated PIVKA-II levels. Vitamin K2 supplementation for 3 months decreased serum PIVKA-II levels near those within the reference range. Approximately half of the patients with SMID on tube feeding had subclinical vitamin K deficiency. Further studies are needed to ascertain if long-term vitamin K2 supplementation effectively prevents vitamin K deficiency-induced hypercoagulation, osteoporosis, and vascular calcification in patients with SMID.

Recent Advances in the Nutritional Screening, Assessment, and Treatment of Japanese Patients on Hemodialysis.

Patients on hemodialysis (HD) have a higher rate of protein-energy wasting (PEW) due to lower dietary intake of energy and protein (particularly on dialysis days) and greater loss of many nutrients in the dialysate effluent than other patients. The most well-known method of nutritional screening is the subjective global assessment. Moreover, the Global Leadership Initiative on MalnutIrition has developed the first internationally standardized method for diagnosing malnutrition; however, its use in patients on HD has not been established. In contrast, the nutritional risk index for Japanese patients on HD has recently been developed as a screening tool for malnutrition in patients on HD, based on the modified PEW criteria. These tools are beneficial for screening nutritional disorders, enabling registered dietitians to assess patients' dietary intake on dialysis and non-dialysis days and provide advice on dietary intake, especially immediately after dialysis cessation. Oral supplementation with enteral nutrients containing whey protein may also be administered when needed. In patients that experience adverse effects from oral supplementation, intradialytic parenteral nutrition (IDPN) should be combined with moderate dietary intake because IDPN alone cannot provide sufficient nutrition.

Methods and Nutritional Interventions to Improve the Nutritional Status of Dialysis Patients in JAPAN-A Narrative Review.

Patients receiving dialysis therapy often have frailty, protein energy wasting, and sarcopenia. However, medical staff in Japan, except for registered dietitians, do not receive training in nutritional management at school or on the job. Moreover, registered dietitians work separately from patients and medical staff even inside a hospital, and there are many medical institutions that do not have registered dietitians. In such institutions, medical staff are required to manage patients' nutritional disorders without assistance from a specialist. Recent studies have shown that salt intake should not be restricted under conditions of low nutrition in frail subjects or those undergoing dialysis, and protein consumption should be targeted at 0.9 to 1.2 g/kg/day. The Japanese Society of Dialysis Therapy suggests that the Nutritional Risk Index-Japanese Hemodialysis (NRI-JH) is a useful tool to screen for older patients with malnutrition.

Chronotherapy with a Renin-angiotensin System Inhibitor Ameliorates Renal Damage by Suppressing Intrarenal Renin-angiotensin System Activation.

Objective The intrarenal renin-angiotensin system (RAS) is activated in chronic kidney disease (CKD) patients and is not suppressed at night in CKD patients showing nocturnal hypertension, contributing to renal damage. Furthermore, changes in RAS inhibitor administration from morning to evening, namely chronotherapy, ameliorates renal damage at night. We attempted to clarify whether or not chronotherapy ameliorates renal damage by suppressing the intrarenal RAS activity. Methods We recruited 34 CKD patients with RAS inhibitors in the morning. We conducted ambulatory blood pressure (BP) monitoring and urine collection and evaluated urinary albumin (Alb) and angiotensinogen (AGT), which are surrogate markers for intrarenal RAS activity during the day and at night, respectively. The same experiments were conducted after changing the administration time. The ratio of values associated with morning versus evening dosing was defined as the morning to evening (M/E) ratio. Results The M/E ratio of urinary Alb had a significant and positive relationship with that of urinary AGT during the day and at night in all CKD patients. However, no significant relationships were found between the M/E ratios of urinary Alb and AGT using multiple linear regression analyses. Conversely, there was a significant and positive relationship between the M/E ratios of urinary Alb and AGT at night but not during the day in CKD patients whose estimated glomerular filtration rate was <45 mL/min/1.73 m2 and whose night-to-day ratio of systolic BP was >0.90, even after adjustment. Conclusion This study indicated that chronotherapy with RAS inhibitors improved the renal damage via intrarenal RAS suppression, especially in CKD patients with an impaired renal function and nocturnal hypertension.

Eradication therapy for Helicobacter pylori infection improves nutrition status in Japanese hemodialysis patients: a pilot study.

Plasma ghrelin level is influenced by Helicobacter pylori (H. pylori) status and the severity of gastric mucosal atrophy, and the ghrelin level is associated with nutrition status in hemodialysis patients. Here, we investigated the efficacy of H. pylori eradication therapy in improving nutrition status in relation to the ghrelin level in H. pylori-positive hemodialysis patients. Of H. pylori-positive patients receiving hemodialysis at 8 dialysis center, 21 patients underwent gastroduodenoscopy for evaluation of the severity of gastric atrophy, and nutrition markers and plasma ghrelin levels before and 1 year after H. pylori eradication therapy were evaluated. Serum cholinesterase level was significantly increased after H. pylori eradication compared with the level before eradication (303.2 ± 76.0 vs 287.3 ± 68.1 IU/L, p = 0.029). In particular, cholesterol (before, 196.6 ± 23.2 mg/dl; after, 206.1 ± 25.9 mg/dl, p = 0.042) and cholinesterase levels (before, 296.9 ± 70.8 IU/L; after, 316.4 ± 73.8 IU/L, p = 0.049) increased more strongly in patients with mild-moderate atrophy than those with severe atrophy, irrespective of improvement of plasma acyl-ghrelin and desacyl-ghrelin levels after eradication therapy. In conclusion, H. pylori eradication may improve nutrition status by increasing serum cholinesterase and cholesterol levels in hemodialysis patients, especially those with mild and moderate gastric mucosal atrophy.

Melatonin ameliorates intrarenal renin-angiotensin system in a 5/6 nephrectomy rat model.

BACKGROUND: Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. It has been reported that reactive oxygen species (ROS) are important components of intrarenal RAS activation. Melatonin is recognized as a powerful antioxidant, and we recently reported that impaired nighttime melatonin secretion correlates negatively with urinary angiotensinogen excretion, the surrogate marker of intrarenal RAS activity in patients with CKD. However, whether melatonin supplementation ameliorates the augmentation of intrarenal RAS in CKD has remained unknown. We aimed to clarify whether exogenous melatonin ameliorates intrarenal RAS activation via the reduction of ROS production. METHODS: 5/6 Nephrectomized (Nx) rats were used as a chronic progressive CKD model and compared with sham-operated control rats. The Nx rats were divided into untreated Nx rats and melatonin-treated Nx rats. The levels of intrarenal RAS, ROS components, and renal injury were evaluated after 4 weeks of treatment. RESULTS: Compared with the control rats, the untreated Nx rats exhibited significant increases in intrarenal angiotensinogen, angiotensin II (AngII) type 1 receptors, and AngII, accompanied by elevated blood pressure, higher oxidative stress (8-hydroxy-2'-deoxyguanosine), lower antioxidant (superoxide dismutase) activity, and increased markers of interstitial fibrosis (α-smooth muscle actin, Snail, and type I collagen) in the remnant kidneys. Treatment with melatonin significantly reversed these abnormalities. CONCLUSION: Antioxidant treatment with melatonin was shown to ameliorate intrarenal RAS activation and renal injury in a 5/6 Nx rat model.

Effects of change in the formulation of lanthanum carbonate on laboratory parameters.

Lanthanum carbonate (LC) is available in the two formulations of chewable tablets and granules. In this study, we changed the formulation of LC from chewable tablet to granules, and compared the laboratory parameters for 3 months before and after changing formulation in 58 hemodialysis (HD) patients. We also surveyed patients about their preferences for the two formulations. The mean serum phosphorus (P) levels decreased significantly (P < 0.01) from 6.7 mg/dL to 6.4 mg/dL after the change. The levels for serum albumin and geriatric nutritional risk index increased significantly (P < 0.01). Serum calcium levels also increased significantly (P < 0.01), while serum intact parathyroid hormone levels decreased significantly (P < 0.01). In the survey, approximately half of the patients responded that the granules were easier to take than the chewable tablets. These findings suggest that changing the formulation of LC to granules may reduce serum P levels of the HD patients in clinical practices.

Association of increased indoleamine 2, 3-dioxygenase with impaired natural killer cell activity in hemodialysis patients.

Indoleamine 2, 3-dioxygenase (IDO) suppresses adaptive immune response. However, there was no study to examine whether IDO activity is associated with immune parameters in dialysis patients. In this study, we estimated serum IDO activity by the kynurenine/tryptophan ratio (KTR), and compared KTR with natural killer (NK) cell activity, soluble interleukin-2 receptor (sIL-2R) and serum levels of trace elements such as selenium (Se) and zinc (Zn) that affect T-cell function in 28 hemodialysis (HD) patients (age: 72 ± 13 years old, time on HD: 79 ± 89 months). NK cell activity was decreased in 35.7% of the patients. KTR values were almost 10-times higher in HD patients (380.81 ± 385.46 mM/M) than those in the referred controls (32.9 ± 9.10 mM/M). KTR was lower in patients with impaired NK cell activity than those without (279 ± 111 vs. 565 ± 603 mM/M, P = 0.07). There was no relationship between KTR and sIL-2R and Zn, while KTR was significantly and negatively correlated with serum Se levels that can impair cellular immunity (r = -0.41, P < 0.05). Our findings suggest that increased IDO activity with Se deficiency may be associated with impaired NK cell function in HD patients.

Isolated adrenocorticotropic hormone deficiency presenting with hypercalcemia in a patient on long-term hemodialysis.

The authors report on a 44-year-old female hemodialysis (HD) patient who presented with hypercalcemia secondary to isolated adrenocorticotropic hormone (ACTH) deficiency. She had been suffering from nausea and abdominal pain caused by recurrent esophageal ulcer. Blood calcium (Ca) adjusted for serum albumin concentration was increased to 14.9 mg/dL (3.72 mmol/L) concurrently with fever and hypotension. Serum intact parathyroid hormone (PTH)-related peptide was not elevated, but serum intact PTH and 1,25-(OH)2 vitamin D3 were decreased to 31 pg/mL (ng/L) and 8.1 pg/mL (2.6 pmol/L), respectively. Endocrinologic examination found that plasma ACTH was reduced below 5.0 pg/mL (0.22 pmol/L). A single ACTH stimulation normally increased blood cortisol, whereas a single corticotropin-releasing hormone injection failed to increase plasma ACTH and cortisol. Pituitary magnetic resonance imaging disclosed no enlargement of pituitary gland. Circulating bone formation and absorption markers were not elevated. Blood Ca was normalized shortly after pamidronate disodium administration without glucocorticoid supplementation. This case suggested that secondary adrenal insufficiency caused by isolated ACTH deficiency could be an occult cause of severe hypercalcemia in HD subjects.

Elevation of blood thioredoxin in hemodialysis patients with hepatitis C virus infection.

BACKGROUND: Thioredoxin (TRX) is a stress-inducible thiol-containing protein, which has been shown to be an indicator of oxidative stress in a variety of diseases. The association between oxidative stress and hepatitis C virus (HCV) infection, however, remains unknown in hemodialysis patients. METHODS: We measured serum TRX levels in 85 hemodialysis patients positive for anti-HCV antibodies (age, 60 +/- 1 years old; hemodialysis duration, 17 +/- 1 years; M/F = 57/28) by enzyme-linked immunosorbent assay (ELISA), and examined whether blood TRX may be associated with HCV-related hepatic injury. RESULTS: Serum TRX was significantly higher in hemodialysis patients with HCV infection (112.3 +/- 3.7 ng/mL, N = 85) than in those without HCV infection (69.7 +/- 3.3 ng/mL, N = 59) (age, 69 +/- 2 years old; hemodialysis duration, 6 +/- 1 years; M/F = 32/27, P < 0.01) or normal subjects (28.0 +/- 5.4 ng/mL, N = 9). TRX was significantly correlated with time on hemodialysis (r = 0.27, P = 0.01) in HCV-positive patients, while it was associated with the patient's age in HCV-negative patients (r = 0.42, P < 0.01). Blood TRX was significantly correlated with asparate aminotransferase in patients with HCV infection (r = 0.34, P < 0.01) and without HCV infection (r = 0.46, P < 0.01). However, serum TRX was not associated with blood alanine aminotransferase, a relatively specific marker of hepatic cellular damage, in HCV-infected hemodialysis patients. A significant relationship was found between serum ferritin and TRX (r = 0.25, P = 0.02) and malondialdehyde (MDA) values (r = 0.25, P = 002) in HCV-positive patients. Serum TRX was also higher in the patients receiving weekly iron supplement with HCV infection (135.3 +/- 10.2 ng/mL vs. 110.2 +/- 3.9 ng/mL, P = 0.06) and without HCV infection (91.8 +/- 12.1 ng/mL vs. 65.2 +/- 2.7 ng/mL, P < 0.01). CONCLUSION: There was a greater increase in serum TRX in hemodialysis patients with HCV viremia than without HCV viremia. However, there may not be an association between serum TRX and HCV-related hepatic injury. TRX increased with serum ferritin in HCV-infected patients and further increased by iron infusion. These findings indicate that HCV infection and iron loading may aggravate oxidative stress in dialysis patients.