Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease

Background

Klotho is a single-pass transmembrane protein, which appears to be implicated in aging. The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD).

Methods

The levels of soluble Klotho in the serum and urine obtained from one hundred thirty-one CKD patients were determined by a sandwich enzyme-linked immunosorbent assay system.

Results

The amount of urinary excreted Klotho during the 24 hr period ranged from 1.6 to 5178 ng/day (median 427 ng/day; interquartile range [IR] 56.8-1293.1), and the serum Klotho concentration ranged from 163.9 to 2123.7 pg/ml (median 759.7 pg/ml; IR 579.5-1069.1). The estimated glomerular filtration rate (eGFR) was significantly correlated with the log-transformed values of the amount of 24 hr urinary excreted Klotho (r?=?0.407, p?<?0.01) and the serum Klotho levels (r?=?0.232, p?<?0.01). However, a stepwise multiple regression analysis identified eGFR to be a variable independently associated only with the log-transformed value of the amount of 24-hr urinary excreted Klotho but not with the log-transformed serum Klotho concentration. Despite the strong correlation between random urine protein-to-creatinine ratio and the 24 hr urinary protein excretion (r?=?0.834, p?<?0.01), a moderate linear association was observed between the log-transformed value of the amount of 24 hr urinary excreted Klotho and that of the urinary Klotho-to-creatinine ratio (Klotho/Cr) in random urine specimens (r?=?0.726, p?<?0.01).

Conclusions

The amount of urinary Klotho, rather than the serum Klotho levels, should be linked to the magnitude of the functioning nephrons in CKD patients. The use of random urine Klotho/Cr as a surrogate for the amount of 24-hr urinary excreted Klotho needs to be evaluated more carefully.

     

The effect of a prostaglandin E1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis

Background

Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D).

Methods

QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0–100).

Results

Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5–15, 15–30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group.

Conclusion

According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.     

Analysis of Mutations in the Urate Transporter 1 (URAT1) Gene of Japanese Patients with Hypouricemia in Northern Japan and Review of the Literature

Background. Renal hypouricemia is an autosomal recessive disorder resulting from inactivating mutations in the urate transporter 1 (URAT1) encoded by SLC22A12. To date, 10 mutations have been identified and W258X in the URAT1 gene is the predominant cause in middle to southwestern Japan. However, it is still unclear whether there is a regional specific distribution of mutations in northern Japan. In this study, we analyzed mutations in the URAT1 gene of five Japanese patients with renal hypouricemia in northern Japan. Methods. Peripheral blood mononuclear cells were isolated from patients with hypouricemia and healthy control subjects. A mutation analysis of the URAT1 gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. Results. We identified two mutations. These mutations [c.269G>A (R90H) and c.774G>A (W258X)] have been reported in Japanese patients. Two of five patients were homozygotes (W258X), two carried single heterozygous mutations (W258X), and the remaining one was a compound heterozygote (R90H and W258X). Conclusions. Our study suggests that there is no regional different distribution of the URAT1 genetic mutations in Japanese with renal hypouricemia.     

Uncemented third-generation ceramic-on-ceramic total hip arthroplasty using metal acetabular shell with direct taper locking liner

Background

The ceramic-on-ceramic (CoC)-bearing couple in total hip arthroplasty (THA) was developed to reduce the wear debris and osteolysis. Although the mechanical strength of third-generation ceramic has improved over previous generations, the risk of osteolysis and ceramic fracture is still an important concern.

Methods

We studied 124 uncemented THAs with third-generation CoC-bearing couple implanted between 2000 and 2004. The ceramic liner and head were secured with the direct taper locking mechanism. One hundred and eleven hips were followed-up for minimum of 8 years, with an average follow-up period of 10.1 years (range 8.0–12.8 years). Patients were evaluated with a particular emphasis on the prevalence of the osteolysis and the ceramic fracture.

Results

The survivorship with the end point as implant revision for any reason was 94.9 % (95 % confidence intervals 90.0–99.3 %) at 12.8 years. Revisions were performed because of one ceramic liner fracture, three dislocations, and two deep infections. No radiographic evidence of wear or osteolysis was observed. The preoperative Merle d’Aubigne and Postel hip score increased from 11.6 to 17.1.

Conclusions

Patients, who received third-generation CoC THA had no detectable wear and osteolysis. One ceramic fracture occurred, and the main reason for revision was dislocation.     

Whole‐exome sequencing of a unique brain malformation with periventricular heterotopia,cingulate polymicrogyria and midbrain tectal hyperplasia

We report a case of an infant with unique and unreported combinations of brain anomalies. The patient showed distinctive facial findings, severe delay in psychomotor development, cranial nerve palsy and seizures. Brain magnetic resonance imaging performed at 5 days of age revealed complex brain malformations, including heterotopia around the mesial wall of lateral ventricles, dysmorphic cingulate gyrus, and enlarged midbrain tectum. The patient unexpectedly died at 13 months of age. Postmortem pathological findings included a polymicrogyric cingulate cortex, periventricular nodular heterotopia, basal ganglia and thalamic anomalies, and dysmorphic midbrain tectum. Potential candidate genes showed no abnormalities by traditional PCR‐based sequencing. Whole‐exome sequencing confirmed the presence of novel gene variants for filamin B (FLNB), guanylate binding protein family member 6, and chromosome X open reading frame 59, which adapt to the autosomal recessive mode or X‐linked recessive mode. Although immunohistochemical analysis confirmed the expression of FLNB protein in the vessel walls and white matter in autopsied specimens, there may be functional relevance of the compound heterozygous FLNB variants during brain development.     

One-phase vs 2-phase treatment for developing Class III malocclusion: A comparison of identical twins

Despite the known influence of early treatment on the facial appearance of growing patients with skeletal Class III malocclusion, few comparative reports on the long-term effects of different treatment regimens (1-phase vs 2-phase treatment) have been published. Uncertainty remains regarding the effects of early intervention on jaw growth and its effectiveness and efficiency in the long term. In this case report, we compared the effects of early orthodontic intervention as the first phase of a 2-phase treatment vs 1-phase fixed appliance treatment in identical twins over a period of 11 years. Facial and dental changes were recorded, and cephalometric superimpositions were made at 4 time points. In spite of the different treatment approaches, both patients showed identical dentofacial characteristics in the retention phase. Through this case report, we intended to clarify the benefits of undergoing 1-phase treatment against 2-phase treatment protocols for treating growing skeletal Class III patients.     

Evaluation of a newly proposed renal risk score for Japanese patients with ANCA-associated glomerulonephritis

Clinical and Experimental Nephrology - We determined the usefulness and prognostic ability of the renal risk score (RRS), proposed in Europe, for Japanese patients with antineutrophil cytoplasmic...     

Prognostic Significance of Hiatal Hernia in Patients with Gastric Cancer Located within the Upper-Third of the Stomach

World Journal of Surgery - Gastric cancers located within the upper-third of the stomach (UGC), especially the esophagogastric junction GC (EGJGC), have distinct clinicopathological features due to...     

Screening and management for ischemic heart disease in patients undergoing emergency surgery for a type A acute aortic dissection

Purpose

We assessed the incidence of coronary artery disease (CAD) during hospitalization after emergency surgery for a type A acute aortic dissection.

Methods

A total of 123 patients underwent multi-slice computed tomography (MSCT) scans during an early stage after surgery. The patients were divided into two groups: group I consisted of 14 patients (11.4 %) who had coronary artery stenosis of more than 75 % on MSCT, and group II consisted of 109 patients (88.6 %) who had no coronary lesions.

Results

The prevalence of diabetes, dyslipidemia and a smoking history was significantly higher in group I. Although the serum low-density lipoprotein cholesterol levels were similar, the high-density lipoprotein cholesterol (HDL) level was significantly lower in group I (36.4 ± 7.9 mg/dl) than in group II (49.6 ± 13.5 mg/dl, P = 0.0005). The maximum carotid intima-media thickness (IMT) was significantly thicker in group I (1.17 ± 0.37 mm) compared to group II (0.96 ± 0.33 mm, P = 0.0297). The logistic regression analysis detected that a carotid IMT over 1.1 mm (odds ratio 4.35, P = 0.0371) and HDL less than 40 mg/dl (odds ratio 3.90, P = 0.0482) were predictors for CAD.

Conclusions

CAD screening should be recommended for patients with aortic dissection who have several atherosclerosis risk factors, even after emergency surgery.     

Stem cell factor‐activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration

Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with motor neuron death. Several experimental treatments, including cell therapy using hematopoietic or neuronal stem cells, have been tested in ALS animal models, but therapeutic benefits have been modest. Here we used a new therapeutic strategy, bone marrow transplantation (BMT) with stem cell factor (SCF)‐ or FMS‐like tyrosine kinase 3 (flt3)‐activated bone marrow (BM) cells for the treatment of hSOD1(G93A) transgenic mice. Motor function and survival showed greater improvement in the SCF group than in the group receiving BM cells that had not been activated (BMT alone group), although no improvement was shown in the flt3 group. In addition, larger numbers of BM‐derived cells that expressed the microglia marker Iba1 migrated to the spinal cords of recipient mice compared with the BMT‐alone group. Moreover, after SCF activation, but not flt3 activation or no activation, the migrating microglia expressed glutamate transporter‐1 (GLT‐1). In spinal cords in the SCF group, inflammatory cytokines tumor necrosis factor‐α and interleukin‐1β were suppressed and the neuroprotective molecule insulin‐like growth factor‐1 increased relative to nontreatment hSOD1(G93A) transgenic mice. Therefore, SCF activation changed the character of the migrating donor BM cells, which resulted in neuroprotective effects. These studies have identified SCF‐activated BM cells as a potential new therapeutic agent for the treatment of ALS. © 2014 Wiley Periodicals, Inc.