Aortic Arch Calcification and Bone-Associated Molecules in Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Aortic arch calcification (AoAC) is a fatal complication in dialysis. AoAC progression-related molecules in continuous ambulatory peritoneal dialysis (CAPD) remain unclear. METHODS: AoAC was estimated using plain chest radiography scoring (AoACS) in 30 CAPD patients (age 49.3 ± 13.4 years). AoAC progression was defined as increased AoACS on follow-up chest X-ray at the end of the study (progressors). Fibroblast growth factor-23 and osteoprotegerin (OPG) were measured. RESULTS: Median follow-up was 38.5 months. Progressors were older, had shorter PD vintage, higher body mass index, and higher serum OPG levels (255.6 ± 109.2 pg/mL) than nonprogressors (183.4 ± 68.2 pg/mL; p = 0.0400). Progressors also showed higher pulse pressure (62.4 ± 20.0 mm Hg) and pulse wave velocity (1,909.9 ± 310.6 cm/s) than nonprogressors (48.5 ± 13.6 mm Hg; p = 0.0030 and 1,390.1 ± 252.8 cm/s; p = 0.0005, respectively). CONCLUSION: AoAC progression was associated with increased aortic stiffness. OPG may be associated with AoAC progression in CAPD.

Effect of ischemic compression performed by family caregivers on myofascial pain syndrome and the care burden of the families of patients: a multicenter open-label randomized comparative study.

BACKGROUND: Ischemic compression is a manual therapy technique for myofascial pain. This study aimed to verify the effect of ischemic compression performed by family caregivers on myofascial pain syndrome (MPS) in patients and on the family's care burden. METHODS: This multicenter, open-label, randomized, comparative study included patients with myofascial pain and their family caregivers who were randomized into the following groups: ischemia compression (performed by a family caregiver), sham ischemia compression, or untreated control. The effectiveness and safety of ischemic compression and the burden on family caregivers were evaluated. The primary endpoint was the rate of 50% or more improvement in the patient's mean numerical rating scale pain score in the previous 24 hours, 14 days after starting the intervention. The secondary endpoint was the rate of change in the family caregivers' reaction assessments. RESULTS: A total of 75 patients and caregivers (70 patients with cancer and family caregivers) who received home medical care were enrolled at three facilities. The study completion rate was 94.7%, and there were no adverse events. The rate of 50% or more improvement in the numerical rating scale score was 64.0% in the ischemic compression group, 16.0% in the sham ischemic compression group, and 4.0% in the control group (P<0.001). Caregivers' self-esteem was significantly lower in the ischemic compression and sham ischemic compression groups than in the control group. However, there was no significant difference between the two groups (P=0.370). CONCLUSIONS: Ischemic compression for myofascial pain in patients performed by family caregivers can increase the analgesic effect in patients and self-esteem in family caregivers. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry (approval number: UMIN000036605).

Correlation of new bone metabolic markers with conventional biomarkers in hemodialysis patients.

BACKGROUND: New bone metabolic markers have become available clinically for evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim of this study was to correlate these new bone metabolic markers with conventional markers in regular hemodialysis (HD) patients. METHODS: One hundred forty three HD patients underwent cross-sectional assessment. Two bone formation markers, bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were selected for study. RESULTS: Both circulating OC and NTx levels showed positive correlations with serum intact parathyroid hormone (iPTH) levels. The levels of NTx and OC showed a strongly positive correlation, although they are known to be markers of different aspects of bone metabolism: bone formation and resorption. Patients with high iPTH (≥300pg/mL) had significantly higher levels of all the three bone markers compared with patients with low or normal iPTH . CONCLUSION: Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating bone turnover in HD patients and may eventually prove useful in the management of patients with CKD-MBD.

The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age.

Most published reports indicate that intensified hemodialysis results in better pregnancy outcomes. Here we studied clinical characteristics and the outcomes of 28 pregnant women receiving hemodialysis. We found an association between maternal blood data and birth weight, and gestational age and outcomes. There were 18 surviving infants who were followed up for one year. In the others there were 4 spontaneous abortions, 1 stillbirth, 3 neonatal deaths and 2 deaths after birth. Analysis of blood chemistry for 20 pregnancies from 12 weeks of gestation until delivery showed that the average hemoglobin level was significantly higher in the group that successfully delivered than in the unsuccessful group. There were significant negative relationships between the blood urea nitrogen (BUN) level and the birth weight or gestational age in the latter cohort. A birth weight equal to or greater than 1500 g or a gestational age equal to or exceeding 32 weeks corresponded to BUN levels of 48-49 mg/dl or less. Whether the low BUN is the direct cause of the improved outcome remains to be examined.

Carnitine Profile by Tandem Mass Spectrometry and Dialysis Patients.

BACKGROUND: Carnitine deficiency is a common condition in hemodialysis patients. Therefore, abnormalities in fatty acid metabolism and organic acid metabolism are also common in dialysis patients. Tandem mass spectrometry is a standard technique in pediatric and neonatal medicine. However, it could be a new powerful tool in other fields for estimating the state of intracellular fatty acid metabolism. SUMMARY: Tandem mass spectrometry has recently revealed the relationships between carnitine profile and dialysis patients' anemia, reduced physical function, and survival rate. Fatty acid and organic acid metabolism, which could previously only be evaluated qualitatively, can now be quantitatively assessed. Key Message: The applications of tandem mass spectrometry are expected to expand not only in the field of dialysis but also in clinical medicine in general.

Ferritin: Diversity and Management of Ferritin Measurement Methods.

BACKGROUND: Serum ferritin is one of the most important and widely used markers of iron metabolism, and is a recommended standard index of iron dynamics in guidelines for renal anemia in many countries. However, serum ferritin measurement has several disadvantages. For example, it is prone to being influenced by underlying disease, and there is considerable systematic bias among different methods of measurement. SUMMARY: Systematic bias affects not only the measurement results, but also the therapeutic strategy to be used in accordance with the relevant guidelines, and consequently the cost of medical treatment. Key Messages: Manufacturers should reduce variability in their serum ferritin assay kits. Researchers should take into account propagation of error in the analysis of measurement values, and clinicians should evaluate laboratory data with care.

Association between Increases in Normalized Protein Catabolic Rate and Increases in Creatinine Generation Rate in Dialysis Patients.

The older dialysis population is growing, and malnutrition and wasting syndrome are great concerns in this population. The management of these syndromes includes appropriate nutritional intake and physical activity. However, whether management in the form of an increase in protein intake has a beneficial effect on muscle mass has not been demonstrated. In this study, we investigated an association between changes of normalized protein catabolic rate (nPCR), as a proxy for protein intake and percent creatinine generation rate (%CGR), as a proxy for muscle mass in patients receiving hemodialysis. Multiple linear regression models were employed, and we included several sensitivity analyses. The results showed that increases in nPCR were associated with increases in %CGR. The association was stronger in patients with baseline %CGR levels below 100%. This was the first study to demonstrate that an increase in dietary protein intake might increase the muscle mass, but this study had certain limitations. Future interventional studies will be needed to investigate whether increases in protein intake have a beneficial effect on sarcopenia, protein-energy wasting, and frailty.

Achievement of the Japanese Society for Dialysis Therapy guideline targets for mineral metabolism measures: one Japanese university center result.

A consensus conference for the Guidelines for the Management of Secondary Hyperparathyroidism in Chronic Dialysis Patients was conducted in the general meeting of the Japanese Society for Dialysis Therapy (JSDT) in June 2006, and the guidelines were proposed in the Journal of JSDT in 4 months later. The aim of this study was performed on the status of observance with the data, based on 6 months later proposal of the guidelines. Only 48.9% stayed within the range specified by the calcium and phosphorus guideline. Moreover, only 12% of patients were able to remain within the ranges specified by all three guidelines (calcium, phosphorus, and PTH), 6 months later proposal of the guidelines. In our institution, compliance with the JSDT guidelines was inadequate. Major reasons were the special characteristics of the medical care system and patients in our institution as a university hospital. Further improvement in the contents and method of the use of the guidelines is necessary alongside observation of the present situation in Japan.

An overview of regular dialysis treatment in Japan (as of 31 December 2004).

A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not necessarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arterial blood HCO(3-). Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally maxacalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D preparation decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%.

Comparative efficacy of acyclovir and vidarabine on the replication of varicella-zoster virus.

Acyclovir and less frequently, vidarabine are (or have been) used in the treatment of varicella-zoster virus (VZV) infection and are administered either intravenously (vidarabine) or orally (acyclovir, up to five times per day). The pharmacological bases of the administration interval were modeled in vitro in this study. Incubation of VZV-infected cultures with acyclovir or vidarabine for 24, 48, 72 and 96h showed similar duration-dependent anti-viral activities as assessed by a plaque-reduction assay. Treatment with vidarabine for only 8h/day for 4 days (intermittent treatment) showed anti-VZV activity equivalent to that of continuous treatment for 4 days in terms of the inhibitory dose that reduced plaque formation by 50% (IC(50)). In contrast, intermittent treatment with acyclovir exhibited a 7.9 times higher IC(50) value than that of continuous treatment. The mode of inhibition of expression of most of viral protein was similar in both drugs, but the degree of inhibition was different for each protein. Thus, vidarabine with a limited period of treatment showed anti-VZV activity comparable to continuous treatment with acyclovir, indicating the longer duration of anti-viral activity of vidarabine.

Identification of ribonucleotide reductase mutation causing temperature-sensitivity of herpes simplex virus isolates from whitlow by deep sequencing.

Herpes simplex virus 2 caused a genital ulcer, and a secondary herpetic whitlow appeared during acyclovir therapy. The secondary and recurrent whitlow isolates were acyclovir-resistant and temperature-sensitive in contrast to a genital isolate. We identified the ribonucleotide reductase mutation responsible for temperature-sensitivity by deep-sequencing analysis.

Therapeutic basis of vidarabine on adenovirus-induced haemorrhagic cystitis.

When adenovirus causes haemorrhagic cystitis in immunocompromised patients, vidarabine is used for its treatment because therapeutic choice is limited. Although vidarabine has been reported to be effective for these patients, its therapeutic basis has not yet been established. Vidarabine dose-dependently inhibited viral replication as assessed by a yield reduction assay. Viral protein synthesis was dose-dependently inhibited by vidarabine but not at all by acyclovir, and the degree of inhibition by vidarabine was different for each of the viral proteins, ranging from 0-40% of the untreated control. These results indicated the specificity and mechanism of action of vidarabine against adenovirus. The concentration of vidarabine and its metabolite in the bladder is suggested to exhibit effective anti-adenoviral activity in suppressing the replication of adenovirus. Thus, our results support vidarabine therapy as a possible candidate for adenovirus-induced haemorrhagic cystitis in immunocompromised patients.

An evaluation of 1-84 PTH measurement in relation to bone alkaline phosphatase and bone Gla protein in hemodialysis patients.

BACKGROUND/AIM: It has been suggested that higher levels of parathyroid hormone (PTH) are required to maintain normal bone turnover in chronic hemodialysis (HD) patients. Serum PTH levels determined by intact PTH (i-PTH) assay may overestimate the actual activity of circulating PTH in HD patients. The aim of the present study was to assess the clinical usefulness of whole PTH assay on the evaluation of bone turnover in HD patients. MATERIALS AND METHODS: We performed measurement of parameters on bone turnover in 179 HD patients (116 men, 63 women; mean age 61.0 +/- 13.1 years). Serum whole PTH levels were determined as cyclase-activating PTH (CAP) by an immunoradiometric assay, and compared with those of i-PTH. Cyclase-inactivating PTH (CIP) was calculated as (i-PTH-CAP). The correlations between serum whole PTH levels and clinical parameters such as serum levels of Ca, P, bone alkaline phosphatase (BAP), bone Gla protein (BGP), total protein (TP), albumin (Alb), urea nitrogen (SUN), and creatinine (Cr) were analyzed using multivariate analysis. RESULTS: The mean values of i-PTH and CAP were 124.1 +/- 97.4 and 86.9 +/- 71.6 pg/ml, respectively, indicating that the serum CAP levels were about 70% of i-PTH levels. The serum CAP levels significantly correlated with that of i-PTH (r = 0.959, p < 0.001). Moreover, a significant positive correlation between serum CAP levels and metabolic bone markers such as BAP (r = 0.400, p < 0.01) and BGP (r = 0.481, p < 0.01) was observed. Stepwise multivariate analysis revealed that serum levels of CAP were significantly determined by serum levels of Ca, P, Alb, and oral dosage of vitamin D (F ratio = 18.81, adjusted r(2) = 0.302). CONCLUSIONS: These data suggest that the biological activity of circulating PTH in HD patients is lower than the levels estimated by conventional i-PTH assay.

An overview of regular dialysis treatment in Japan (as of 31 December 2001).

Questionnaire forms for an annual survey conducted at the end of 2001 were sent out to 3520 institutions, and 3485 replies were received (response rate, 99.00%). According to the survey, the dialysis population of Japan at year end was 219 183 patients, up 6.3% (13 049) over the year before. This equals 1721.9 dialysis patients per million population. The gross mortality rate was 9.3% for the year extending from the end of 2000 to the end of 2001. The mean age of patients beginning dialysis was 64.2 years (+/- 13.7 SD). The mean age of the overall dialysis population in the study year was 61.6 years (+/- 13.1 SD), which was also a higher age than the year before. Among dialysis patients, the primary disease was diabetic nephropathy in 38.1% of patients, slightly down from 39.1% the previous year. Chronic glomerulonephritis was the primary disease in 32.4% of cases, a decrease from 34.7% the previous year. This survey included for the first time the items of the lowest blood pressure during hemodialysis session, vasopressor therapy before dialysis and vasopressor therapy during dialysis session. An analysis of the relationship between the type of vascular access used at the initiation of dialysis and the survival prognosis revealed a significantly higher risk of death in patients undergoing dialysis with synthetic arterio-venous (AV) fistula, AV shunt, or catheter implantation into a central vein than in those receiving dialysis treatments with a native fistula. There was a significantly lower risk of death in the patient group in whom the vascular access was created at 3-6 months before initiation of dialysis than in those in whom such access was created at the time of initiation or within 3 months before the initiation of dialysis. An analysis of the risk factors affecting survival prognosis in maintenance hemodialysis patients showed that risk factors for death are post-dialysis systolic blood pressure over 180 mm Hg and lower than 120 mm Hg, blood pressure elevating progressively from the start to the end of dialysis, serum high density lipoprotein cholesterol concentration of less than 30 mg/dL, and a higher ultrafiltration rate. In comparisons of the death risk between the patient group with a history of intervention for ischemic heart disease and the patient group with a history of myocardial infarction or heart failure but without such intervention, among diabetes patients, those who underwent percutaneous transluminal coronary angioplasty had a significantly lower risk of death than those in whom no intervention was made.

[Cause of death in dialysis patient--according to the survey of the Japanese Society for Dialysis Therapy].

Major causes of death in dialysis patients are heart failure, infection, cerebro-vascular accident, malignancy, myocardial infarction, and cardiovascular disturbance; they are 43.7% of all causes of death. Hyperphosphatemia and increased calcium-phosphorus product aggravate ectopic calcification, and raise mortality rate. According to statistical data from the Japanese Society for Dialysis Therapy, calcium and phosphate levels recently decreased, because of progress of therapeutic agents and increase in aged people. But extreme decreases of them are also the risk factors of mortality, so appropriate control into the recommended range is necessary.

[The medical treatment strategy of secondary hyperparathyroidism use of vitamin D in Europe and America].

The medical treatment strategies of vitamin D appeared in the guideline of K/DOQI (Kidney Disease Outcomes Quality Initiative) in the U.S. and Clinical algorithms on renal osteodystrophy in Europe. The target intact PTH value is 150-300 pg/mL (16.5-33.0 pmol/L) in U.S. and 9-18 pmol/L (82-164 pg/mL ) in Europe. It was set up more highly in U.S. than in Europe. A European and American medical treatment strategies are not so different from that of Japan in the routes and metabolites of vitamin Ds.

Effects of the ankle-brachial blood pressure index and skin perfusion pressure on mortality in hemodialysis patients.

OBJECTIVE: Clinically, the ankle-brachial blood pressure index (ABI) and skin perfusion pressure (SPP) are used to screen for subclinical peripheral artery disease. However, the association between the SPP and mortality in hemodialysis patients has not been previously reported. We investigated these factors and compared the ABI and SPP in patients receiving hemodialysis. METHODS: A total of 102 patients receiving maintenance hemodialysis were enrolled in this study. The ABI was determined using an ABI-form (Colin, Japan). The SPP was measured using a SensiLase(TM) PAD3000 (Kaneka, Osaka, Japan). RESULTS: The mean follow-up period was 3.2 ± 1.4 years. A multivariate Cox analysis identified a low ABI (p=0.019) and a low SPP (p=0.047) as being independent predictors of mortality. A receiver operating characteristic (ROC) analysis of the ABI revealed a cutoff point of 1.1 and an area under the curve (AUC) of 0.79, with a sensitivity of 90% and a specificity of 62%. A ROC analysis of the SPP revealed a cutoff point of 54.0 mmHg and an AUC of 0.71, with a sensitivity of 55% and a specificity of 84%. CONCLUSION: Both low ABI and SPP values were found to be independent risk factors for mortality among hemodialysis patients. The cutoff point for ABI as a predictor of mortality was 1.1, while that for SPP was 54.0 mmHg.

Flowcytometric analysis of lymphocytapheresis in a patient with recurrent FSGS after renal transplant.

Frequently, focal segmental glomerulosclerosis (FSGS) recurs after renal transplantation, resulting in poor graft survival. Pathological mechanisms of the recurrence are still unknown, but both B and T cell disorders are suspected based on much evidence. This supports theoretical benefits using plasma exchange (PE) and lymphocytapheresis (LCAP). A renal transplant was performed for a 35-year-old woman, who suffered steroid-resistant FSGS and developed to chronic kidney disease stage 5D at 31 years old. We treated the patient with recurrent FSGS by LACP and examined whether peripheral neutrophils were dynamically changed after the therapy. Further, we performed flowcytometric analysis to examine lymphocyte fractions before and after LCAP. The decrease of helper (CD4 positive) and memory (CD4 and CD45RO positive) T cells was prominent after LCAP. Although B cells were at the nadir because of rituximab treatment, LCAP also decreased peripheral B cells. These suggest that LCAP has the potential to suppress the activities of recurrent FSGS after renal transplant.

Successful cinacalcet treatment of refractory secondary hyperparathyroidism due to multiple lung parathyroid adenomas.

We describe a 56-year-old woman who presented with end-stage renal disease due to pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However, intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she underwent a second PTx. However, therapy failed to significantly decrease iPTH levels. A third PTx was performed, but no pathological parathyroid tissue was found. Computed tomography scan indicated the presence of multiple ectopic lung nodules and 26 nodules were surgically removed from the left lung. Despite surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually disappeared. Bone mineral density (BMD) was improved by administration of cinacalcet. In conclusion, cinacalcet was effective in this patient with refractory and inoperable sHPT. In addition, it improves their BMD and relieves bone pain.

Psoas abscess in hemodialysis patients.

BACKGROUND: The insidious onset and occult characteristic of psoas abscess can cause diagnostic delays, resulting in high mortality and morbidity rates. Here, we investigated the characteristics of psoas abscess in hemodialysis patients. METHODS: This study was carried out in eight patients with psoas abscess who were admitted in our hospital. The clinical data were retrospectively collected. RESULTS: The frequency of polycystic kidney disease as the primary cause of end-stage kidney disease was significantly higher in the hemodialysis patients with psoas abscess (25.0%) than in prevalent Japanese hemodialysis patients (3.4%, P = 0.028). All patients had a preceding infection (discitis in two, blood access-related infections in two, colitis in two, infection of a hematoma in the kidney in one, and endocarditis in one). Seven patients survived, while the remaining one patient died. CONCLUSION: Psoas abscess could be a complication of discitis, blood access infection and colitis in hemodialysis patients. The frequency of polycystic kidney disease as the primary cause of ESKD was significantly higher in the hemodialysis patients with psoas abscess than in prevalent Japanese hemodialysis patients. We should consider psoas abscess as a possibility in hemodialysis patients with infection of unknown cause, especially in patients with polycystic kidney disease.