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Background Blood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD. Methods In this prospective study, we enrolled 459 patients with CKD (stages 3–5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18). Results During a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72–2.58), 1.87 (0.95–3.66), and 2.66 (1.23–5.76) ( P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69–1.87), 0.95 (0.58–1.55), and 1.26 (0.78–2.03), respectively ( P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome. Conclusions Higher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression. Electronic supplementary material The online version of this article (10.1186/s12882-019-1306-1) contains supplementary material, which is available to authorized users.

Background: Several studies have shown that the neutrophil/lymphocyte ratio (NLR) is a marker that reflects the state of systemic inflammation. A high NLR was reported to be associated with cardiovascular events and mortality. However, little is known about the association between NLR and kidney disease progression in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to determine whether NLR is associated with renal outcomes in CKD patients. Methods: This prospective observational study included 350 consecutive patients with stage 1–4 CKD treated between June 2009 and November 2016. Data were collected until June 2017. The endpoint was the composite of end-stage renal disease requiring dialysis or death. Subjects were divided into two groups according to high and low NLR levels. A Cox proportional hazards model was used to determine the risk factors for composite outcomes. Results: The composite endpoint was observed in 83 patients during the median follow-up period of 31.8 months: 29 in the low NLR group and 54 in the high NLR group. Multivariable analysis showed that the high NLR group had a significant increase in the hazard ratio (HR) for composite outcomes (HR 1.67, 95% confidence interval 1.02–2.77) compared with the low NLR group. Conclusion: The present study demonstrated that a high NLR was associated with poor renal outcomes, suggesting that NLR may be a useful marker for prognostic prediction in patients with CKD.

BackgroundElobixibat is an oral treatment candidate for chronic constipation with a novel mechanism of action via inhibition of the ileal bile acid transporter. We performed this randomized, double-blind, placebo-controlled, dose-finding phase IIb study in Japanese patients with chronic constipation to determine the optimal clinical dose of elobixibat.MethodsJapanese patients with chronic constipation were randomized to receive elobixibat (5, 10, or 15 mg) or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline in frequency of spontaneous bowel movements at Week 1 of treatment. Secondary endpoints and adverse events were also examined.ResultsAmong 226 patients who provided informed consent, 163 patients were randomized and included in the full analysis set. In the 10- and 15-mg groups, frequency of spontaneous bowel movements (±standard deviation) were significantly higher than baseline (5.7 ± 4.2 and 5.6 ± 3.5 times per week, respectively, compared with 2.6 ± 2.9 times per week in the placebo group [P = 0.0005, P = 0.0001, respectively]). Subgroup analysis indicated that elobixibat was equally effective in patients with or without constipation-predominant irritable bowel syndrome. Common adverse events included mild abdominal pain and diarrhea in the elobixibat groups; no serious or severe adverse events occurred. Elobixibat was well tolerated at once-daily oral doses up to 15 mg for 2 weeks.ConclusionsOur study results suggest that 10 mg of elobixibat is a clinically optimal dose for Japanese patients with chronic constipation.Clinical trial registration numberJapicCTI-142608.

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The purpose of this study was to evaluate the availability of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with hydroxyapatite (HA) and autogenous bone. Posterolateral intertransverse fusion between the fifth and sixth lumbar vertebrae was performed in 27 adult Japanese white rabbits. These 27 rabbits were classified into three groups: the autogenous bone group, the HA group, and the bone morphogenic protein (BMP) group. In the HA group, HA (0.5 g) mixed with iliac bone was grafted. In the BMP group, HA (0.5 g) soaked with rhBMP-2 (100 mg) and iliac bone was grafted. At 6 weeks after the procedure, bone union was evaluated. In the BMP group, all cases showed solid bone union, and fusion masses were stiffer than the masses obtained in the other group. Biomechanically and histologically, grafts of HA soaked with rhBMP-2 and iliac bone was clearly effective in obtaining a solid intertransverse arthrodesis.

✓ For lesions involving the anterior and/or middle column of the spine, an anterior approach is adequate for curetting the lesion and restoring spinal stability. Materials such as autogenous bone grafts, cages with bone chips, some artificial materials, or allografts are used as strut materials. Rib material is usually removed when the anterior approach is conducted for thoracic or thoracolumbar lesions. A rib itself is not rigid enough to support the load, and a bone union is not easily obtained. The purpose of this paper is to describe a method of grafting vascularized rib in folded form to fill the defects left after removal of a spinal lesion. The rib, with the artery and vein at two levels cranial to the involved vertebral body, was isolated from surrounding tissues such as the intercostal nerve, muscles, and pleura. After curetting the lesion, the rib was folded into three or four pieces to a length adequate to fill the defect and inserted as a pedicled vascularized graft. A total of 23 cases, including 14 men and nine women, underwent surgery in which this grafting technique was used. The pathological conditions requiring anterior decompression and fusion were spinal trauma in nine cases, spinal infection in six cases, osteoporotic fracture in seven cases, and spinal metastasis in one case. In all cases a solid bone union was obtained and all infections resolved. With vascularized rib graft folded into three to four pieces, solid bone union can be obtained without use of any other grafted materials even in cases of infection and osteoporosis.

Findings showed that posterior lumbar procedures, including retraction of paravertebral muscle, fenestration of the lamina, and retraction of the nerve root affect the posterior ramus. Excessive retraction of the nerve root has an especially disastrous effect on the posterior ramus. Such a violent maneuver within the spinal canal must be avoided.