Polyphyllin D induces necroptosis in neuroblastoma cells (IMR-32 and LA-N-2) in mice.

BACKGROUND: We previously reported that polyphyllin D, the main component of the traditional herbal medicinal Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aim of this investigation was to examine in vivo antitumor effects of polyphyllin D. METHODS: Subcutaneous tumors were established in immune-deficient BALB/c nude mice using human neuroblastoma cell lines IMR-32 and LA-N-2. To evaluate the polyphyllin D activity, we used a mouse model of IMR-32 or LA-N-2 cell lines and analyzed subcutaneous tumors. RESULTS: Subcutaneous tumor models were successfully established in mice using two human neuroblastoma cell lines. In the subcutaneous tumor model, porphyrin D was found to suppress tumor volume. We found that polyphyllin D suppressed the number of foci by Ki-67 staining (IMR-32 and LA-N-2; p < 0.01, 0.02, respectively). We found that polyphyllin D induces the RIPK3 expression, while polyphyllin D phosphorylates Ser358 in IMR-32 and Ser358 and Tyr376 in LA-N-2. CONCLUSION: We developed a mouse model of subcutaneous tumors of neuroblastoma and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma. Polyphyllin D can cause necroptosis depending on the cell type. The new drug can be expected by investigating a method to selectively induce cell death through the analysis of necroptosis.

Antitumor effect of polyphyllin D on liver metastases of neuroblastoma.

PURPOSE: We previously reported that polyphyllin D, a main component of the traditional Chinese medicinal herb Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aims of this investigation was to examine the presence or absence of in vivo anti-metastasis effects of polyphyllin D were to establish a liver metastasis model of neuroblastoma and to evaluate the anti-metastasis effects of polyphyllin D. METHODS: Subcutaneous and intraperitoneal tumors, and metastasis models were established in immune-deficient BALB/c nude and BALB/c Rag-2/Jak3 double-deficient (BRJ) mice using the human neuroblastoma cell lines IMR-32, LA-N-2, or NB-69. For evaluating polyphyllin D activity, we used a mouse model of liver metastasis with the IMR-32 cells line injected through the tail vein. We analyzed the livers number and area of liver tumors in of the phosphate buffer solution- and polyphyllin D-treated groups. RESULTS: Liver metastasis and intraperitoneal dissemination models were successfully established in immune-deficient BRJ mice using the three human neuroblastoma cell lines. In the liver metastasis, the model of IMR-32 cells, we found that polyphyllin D suppressed both the number and total area of metastatic foci the average number of metastatic foci, average focus areas, and number of cleaved caspase-3-positive cells were significantly lower in the polyphyllin D group (p = 0.016, 0.020, 0.043, respectively). CONCLUSIONS: We developed a mouse models of neuroblastoma metastasis and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.

Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation.

OBJECTIVES: To collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis. METHODS: Fifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians. RESULTS: The study population comprised 26 males and 24 females aged 0-61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment. CONCLUSIONS: In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.

Daily Meal Supplemented with Astaxanthin-Enriched Yolk Has Mitigative Effects against Hypertension in Spontaneously Hypertensive Rats.

The aim of this study was to investigate the effects of egg yolk powder enriched with astaxanthin (ASX-E) on blood pressure in spontaneously hypertensive rats (SHR) and to verify the benefits of ASX-E as a functional food. To investigate the antihypertensive effect, SHR were fed with an ASX-E mixed diet before hypertension development. Blood pressures were determined periodically during the study by the tail-cuff method. At the end of the study, animals were euthanized, and their thoracic aortas were collected to determine vascular conductance. The thoracic aorta tension was measured with a force displacement transducer. Concentration-dependent response relationships were determined by cumulative addition of 10-9-10-4 M Carbamoylcholine (Cch). Blood pressures of the SHR in the ASX-E mixed diet group were ASX-dose-dependently lower than that of those in the control group. In SHR fed with an ASX-E mixed diet, Cch induced vasorelaxation in the thoracic aorta with endothelium lining but not without endothelium. However, the antihypertensive effect of ASX-E was not observed on blood pressures in SHR that were fed with ASX-E only after the development of hypertension. Results suggest that ASX-E protects endothelial function and thereby prevents the development of hypertension. Hence, the results of our research indicate that daily consumption of ASX-E has a potential benefit on human health.

Arctigenin induces apoptosis in human hepatoblastoma cells.

PURPOSE: Arctigenin has been shown to have anti-tumor effects in various types of cancers. This study was conducted to verify these effects in the human-derived hepatoblastoma cell line, HUH-6 clone 5 (hereinafter, HUH-6). METHODS: Arctigenin was added to cultured HUH-6 cells, and cellular activity was evaluated by MTS assay. To determine the relationship between reduced cellular activity and apoptosis, we measured the activities of caspase 3/7, 8, and 9 and conducted flow cytometry with Annexin V/PI staining. RESULTS: The MTS assay revealed that cellular activity decreased after arctigenin treatment in a concentration-dependent manner (IC50 = 4 µM). To investigate apoptosis induction, activity assays of caspase 3/7, 8, and 9 were performed. While caspase 3/7 and 8 exhibited high activity, caspase 9 showed no activity. Thus, apoptosis induction may have involved the action of tumor necrosis factor receptor 1 (TNFR1). Flow cytometry conducted with Annexin V/PI staining revealed the occurrence of early apoptosis. CONCLUSION: We found that arctigenin has anti-tumor effects in HUH-6 cells in a concentration-dependent manner. Arctigenin may have exerted its anti-tumor effect by inducing apoptosis via TNFR1, which recruits Complex IIa to activate caspase 8 and 3/7. These results may be useful for developing therapeutic agents for hepatoblastoma.

[LAPAROSCOPIC LYMPHADENECTOMY FOR POSTOPERATIVE LYMPH-NODE METASTASIS OF RENAL MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA: A CASE REPORT].

We describe renal mucinous tubular and spindle cell carcinoma (MTSCC) that metastasized to the lymph nodes seven years after radical nephrectomy. An 80-year-old man was admitted for treatment of a right renal tumor. A 6.5×6.0-cm tumor in the right kidney (cT1bN0M0) revealed by abdominal computed tomography was treated by laparoscopic radical nephrectomy. The pathological findings at that time suggested papillary renal cell carcinoma type 1. Imaging findings seven years later revealed enlarged pre-caval and right external iliac lymph nodes indicative of delayed metastasis, and these were treated by laparoscopic lymphadenectomy. The pathological findings and re-evaluation of the primary tumor suggested MTSCC. The patient remains free of metastasis at 24 months of follow-up. MTSCC has been a distinct entity in the World Health Organization classification of kidney tumors since 2004. Tumors consist of tubules and cords separated by pale mucinous material in some areas, whereas others have dense cellularity without significant mucin. They are usually of low malignant potential, and metastasis has rarely been reported. To our knowledge, this is the first report of MTSCC with retroperitoneal lymph node metastasis treated by lymphadenectomy.

Enantioselective synthesis of α-silylamines by Meerwein-Ponndorf-Verley-type reduction of α-silylimines by a chiral lithium amide.

Meerwein-Ponndorf-Verley-type reduction of N-tosylsilylimines with chiral lithium amide 2 affords α-silylamines in high enantioselectivity. Since the enantioselectivity observed was inconsistent with our previously proposed chairlike six-membered transition structure, we performed density functional theory (DFT) calculations on transition states leading to (S)- and (R)-7a and (S)- and (R)-7e using an N-phenylsulfonyl derivatives 12 and 13 as model systems. Results of the calculations showed that the structures are considerably deformed from the chairlike form with steric repulsions between the 1'-methylene group and the imine-carbon substituents playing an important role in the control of the enantioselectivity.

A simple and reliable multi-gene transformation method for switchgrass.

KEY MESSAGE: A simple and reliable Agrobacterium -mediated transformation method was developed for switchgrass. Using this method, many transgenic plants carrying multiple genes-of-interest could be produced without untransformed escape. Switchgrass (Panicum virgatum L.) is a promising biomass crop for bioenergy. To obtain transgenic switchgrass plants carrying a multi-gene trait in a simple manner, an Agrobacterium-mediated transformation method was established by constructing a Gateway-based binary vector, optimizing transformation conditions and developing a novel selection method. A MultiRound Gateway-compatible destination binary vector carrying the bar selectable marker gene, pHKGB110, was constructed to introduce multiple genes of interest in a single transformation. Two reporter gene expression cassettes, GUSPlus and gfp, were constructed independently on two entry vectors and then introduced into a single T-DNA region of pHKGB110 via sequential LR reactions. Agrobacterium tumefaciens EHA101 carrying the resultant binary vector pHKGB112 and caryopsis-derived compact embryogenic calli were used for transformation experiments. Prolonged cocultivation for 7 days followed by cultivation on media containing meropenem improved transformation efficiency without overgrowth of Agrobacterium, which was, however, not inhibited by cefotaxime or Timentin. In addition, untransformed escape shoots were completely eliminated during the rooting stage by direct dipping the putatively transformed shoots into the herbicide Basta solution for a few seconds, designated as the 'herbicide dipping method'. It was also demonstrated that more than 90 % of the bar-positive transformants carried both reporters delivered from pHKGB112. This simple and reliable transformation method, which incorporates a new selection technique and the use of a MultiRound Gateway-based binary vector, would be suitable for producing a large number of transgenic lines carrying multiple genes.

Thirty-year follow-up of a TMD case treated based on the neuromuscular concept.

AIM: Occlusal therapy is employed to alleviate the symptoms of a temporomandibular disorder (TMD) at times. However, the long-term effect of occlusal therapy in the masticatory system is not well understood. This case study aims to present a 30-year follow-up of a TMD case. METHODOLOGY: The patient developed TMD with intermittent closed lock of the left temporomandibular joint (TMJ). Chief complaints included trismus, pain, and noise of the left TMJ during function. The patient's occlusal disharmony was assessed with use of electronic instruments and corrected based on the neuromuscular concept. A minimum-invasive and reversible approach using adhesive occlusal restorations was used. RESULTS: The jaw movement and masticatory muscle activity assessed at the 7- and 23-year follow-ups revealed that the established occlusion was well adapted, and re-established the patient's functional occlusion system. The patient has been free from TMD symptoms with the corrected occlusion for 30 years. CONCLUSIONS: Occlusal reconstruction based on the neuromuscular concept can be stably integrated into the patient's functional occlusion system.

Efficient Deep-Blue Multiple-Resonance Emitters Based on Azepine-Decorated ν-DABNA for CIEy below 0.06.

Ultrapure deep-blue emitters are in high demand for organic light-emitting diodes (OLEDs). Although color coordinates serve as straightforward parameters for assessing color purity, precise control over the maximum wavelength and full-width at half-maximum is necessary to optimize OLED performance, including luminance efficiency and luminous efficacy. Multiple-resonance (MR) emitters are promising candidates for achieving ideal luminescence properties; consequently, a wide variety of MR frameworks have been developed. However, most of these emitters experience a wavelength displacement from the ideal color, which limits their practical applicability. Therefore, a molecular design that is compatible with MR emitters for modulating their energy levels and color output is particularly valuable. Here, it is demonstrated that the azepine donor unit induces an appropriate blue-shift in the emission maximum while maintaining efficient MR characteristics, including high photoluminescence quantum yield, narrow emission, and a fast reverse intersystem crossing rate. OLEDs using newly developed MR emitters based on the ν-DABNA framework simultaneously exhibit a high quantum efficiency of ≈30%, luminous efficacy of ≈20 lm W-1, exceptional color purity with Commission Internationale de l'Éclairage coordinates as low as (0.14, 0.06), and notably high operational stability. These results demonstrate unprecedentedly high levels compared with those observed in previously reported deep-blue emitters.

Highly efficient multi-resonance thermally activated delayed fluorescence material toward a BT.2020 deep-blue emitter.

An ultrapure deep-blue multi-resonance-induced thermally activated delayed fluorescence material (DOB2-DABNA-A) is designed and synthesized. Benefiting from a fully resonating extended helical π-conjugated system, this compound has a small ΔEST value of 3.6 meV and sufficient spin-orbit coupling to exhibit a high-rate constant for reverse intersystem crossing (kRISC = 1.1 × 106 s-1). Furthermore, an organic light-emitting diode employing DOB2-DABNA-A as an emitter is fabricated; it exhibits ultrapure deep-blue emission at 452 nm with a small full width at half maximum of 24 nm, corresponding to Commission Internationale de l'Éclairage (CIE) coordinates of (0.145, 0.049). The high kRISC value reduces the efficiency roll-off, resulting in a high external quantum efficiency (EQE) of 21.6% at 1000 cd m-2.

Evaluation of Ki-67 as prognostic factor for pediatric neuroblastoma and the possibility of molecular-targeted drugs with VEGF and PDGFR.

BACKGROUND: Neuroblastoma (NB) is a pediatric malignant solid tumor characterized as refractory cancer with poor prognosis. The Mitosis-Karyorrhexis Index (MKI) is a prognostic factor but is prone to observer bias. The usefulness of MKI with Ki-67, as a marker of malignancy, was investigated. The efficacy of molecular-targeted therapeutic agents with fewer side effects in tumors has been studied. Molecular-targeted therapy targets include vascular endothelial growth factor (VEGF), involved in tumor angiogenesis; c-Kit, receptor of Kit/stem cells involved in tumor growth, vasculature, and lymphangiogenesis; platelet-derived growth factor receptor (PDGFR); and B-Raf proto-oncogene, serine/threonine kinase (BRAF), involved in the RAS protein-mediated mitogen-activated protein kinase pathway. Therefore, expression profiles of these factors and growth inhibitory effects of molecular-targeted drugs against NB were investigated. METHODS: Ten frozen NB tissue samples collected from January 1993 to December 2017 were evaluated immunohistochemically for Ki-67 and VEGF. c-Kit, PDGFR, and BRAF expression levels were evaluated using enzyme-linked immunosorbent assays; relationships between these factors and clinicopathological parameters of NB were analyzed. RESULTS: Eight patients with NB showed no amplification of MYCN (MYCN proto-oncogene, bHLH transcription factor). There were two cases of ganglioneuroblastoma (GNB). More NB cells were positive for Ki-67 than for GNB cells. VEGF expression was observed in all NB specimens and was stronger in stage IIB and higher. No BRAF or c-Kit activity was observed; PDGFR activity was greater in NB than in GNB (P=0.02). CONCLUSIONS: Thus, Ki-67 may help evaluate NB malignancy. As the first therapy for NB prevents amplification of MYCN, agents targeting PDGFR as well as VGFG can inhibit NB cell proliferation.

Localization of estrogen receptor in the central lymphoid organs of chickens during the late stage of embryogenesis.

Immunological function in chicks is greatly affected by estrogen treatment during embryogenesis, but the mechanism of the estrogen effect is not fully understood. To elucidate the effect of estrogen on immune function, we observed estrogen receptor expression in the thymus and bursa of chick embryos by immunohistochemistry. We compared the distribution of estrogen receptor-positive cells with that of keratin-positive epithelial cells. Intense expression of estrogen receptors was detected in thymic and bursal lymphocytes. In peripheral lymphocytes, ER mRNA was detected by RT-PCR analysis. The results of fluorescence-activated cell sorting analysis indicated that the estrogen receptor was expressed in the cytoplasm of the lymphocytes. Furthermore, intense expression of the estrogen receptor was also confirmed in thymic Hassall's corpuscles, bursal follicle-associated epithelial cells, and the bursal interfollicular epithelium. Our results indicate that estrogen affects the differentiation of thymic and bursal lymphocytes, suggesting that the underlying role for estrogen in immune function.

Long-term results of splenomegaly after surgery for biliary atresia in the native liver.

BACKGROUND: Biliary atresia (BA) is a rare disorder characterized by obstructive jaundice in infants, shortly after birth. Postoperatively, some patients exhibit portal hypertension and progressive liver fibrosis. Splenomegaly is a symptom of portal hypertension. We aimed to investigate splenomegaly as a marker for complications of portal hypertension and the relationship between splenomegaly and liver fibrosis in the long-term native liver (NL). METHODS: Between 1977 and 2018, 71 patients underwent hepaticojejunostomy. We included 54 patients (34 NL group, 20 liver transplant (LT) group) who fulfilled the eligibility criteria. Spleen volume (SV), total bile acids, hyaluronic acid, type IV collagen, and aspartate aminotransferase-to-platelet ratio index (APRi) were measured. Data were analyzed using Student's t-test, regression analysis, and receiver operating characteristic (ROC) curve analysis (P < 0.05). RESULTS: Total bile acids, hyaluronic acid, type IV collagen, and APRi increased in NL patients with a large SV at >25 years. SV and type IV collagen were correlated with NL for >25 years (r = 0.79 [P = 0.006], y = 1.1 - [0.03 × type IV collagen] [P = 0.008]). In the ROC curve analysis, the cutoff value for type IV collagen was 165 ng/mL (P = 0.07). CONCLUSIONS: We suggest that SV as a prognostic index for End-Stage Liver Disease may be useful in biliary atresia. Long-term follow-up is necessary because the clinical course may be favorable in childhood but worsen during adulthood.

Metagenomic mining and structure-function studies of a hyper-thermostable cellobiohydrolase from hot spring sediment.

Enzymatic breakdown is an attractive cellulose utilisation method with a low environmental load. Its high temperature operation could promote saccharification and lower contamination risk. Here we report a hyper-thermostable cellobiohydrolase (CBH), named HmCel6A and its variant HmCel6A-3SNP that were isolated metagenomically from hot spring sediments and expressed in Escherichia coli. They are classified into glycoside hydrolases family 6 (GH6). HmCel6A-3SNP had three amino acid replacements to HmCel6A (P88S/L230F/F414S) and the optimum temperature at 95 °C, while HmCel6A did it at 75 °C. Crystal structure showed conserved features among GH6, a (ß/α)8-barrel core and catalytic residues, and resembles TfCel6B, a bacterial CBH II of Thermobifida fusca, that had optimum temperature at 60 °C. From structure-function studies, we discuss unique structural features that allow the enzyme to reach its high thermostability level, such as abundance of hydrophobic and charge-charge interactions, characteristic metal bindings and disulphide bonds. Moreover, structure and surface plasmon resonance analysis with oligosaccharides suggested that the contribution of an additional tryptophan located at the tunnel entrance could aid in substrate recognition and thermostability. These results may help to design efficient enzymes and saccharification methods for cellulose working at high temperatures.

A new murine ileostomy model: recycling stool prevents intestinal atrophy in the distal side of ileostomy.

OBJECTIVES: Proximal stoma creation in neonates results in growth failure and distal intestinal atrophy. "Recycling stool" consists of stool injection from the proximal limb to the distal limb of a stoma. Because this method may prevent distal bowel atrophy and increase body weight, we investigated the effects of recycling stool upon distal intestinal mucosa by generating an ileostomy model in rats. METHODS: An ileostomy was created 5 cm proximal to the cecum in male Wistar/ST rats. Discharged stool or saline was injected into the distal limb, twice per day for 7 days. The intestinal adaptation was assessed by measuring the villus height and counting goblet cell number. Proliferation and apoptosis were analyzed by Ki67 and TUNEL immunostaining. RESULTS: The ratios of the height of the distal villi (D) to the that of proximal villi (P) were 0.97 (median [range] of D and P length: 421 [240-729] µm and 436 [294-638] µm, P<0.05) in the stool-injected group and 0.81 in the saline-injected group (442 [315-641] µm and 548 [236-776] µm, P<0.05). Compared with the saline-injected group, the stool-injected group showed elevated numbers of goblet cells (3.6 [2.0-7.6] vs. 4.9 [2.4-7.5] cells/100-µm villus length) and Ki67-positive cells (26.8% [13.8%-35.4%] vs. 40.1% [31.2%-45.7%]), along with a reduced number of apoptotic cells (5.0 [2.0-14.0] vs. 4.0 [1.0-9.0] cells/100-µm villus length). CONCLUSIONS: Recycling stool prevented distal intestinal atrophy; this experimental design may facilitate further studies concerning alternative methods to prevent intestinal atrophy and growth failure.

All-optical wavelength-routing switch with monolithically integrated filter-free tunable wavelength converters and an AWG.

We present a compact 4x8 wavelength-routing switch that monolithically integrates fast tunable wavelength converters (TWCs) and an arrayed-waveguide grating (AWG) for optical packet switching. The TWC consists of a double-ring-resonator-coupled tunable laser which allows rapid and stable switching, and an optical gate based on a parallel amplifier structure which prevents an input optical signal from being routed through the AWG (filter-free operation). A deep-ridge waveguide technology, employed for the AWG and ring resonators, facilitates the fabrication of the switch and makes the device compact. The filter-free TWCs achieve low crosstalk of the input optical signal of less than -22 dB. The wavelength routing operation of a non-return-to-zero (NRZ) signal at 10 Gbit/s is achieved with a switching time of less than 5 ns.

Oral administration of the probiotic bacterium Lactobacillus acidophilus strain L-55 modulates the immunological parameters of the laying hen inoculated with a Newcastle disease virus-based live attenuated vaccine.

Probiotic supplements containing living bacteria have attracted interest as a potential source of health benefits for humans and livestock. The aim of this study was to determine whether administration of Lactobacillus acidophilus strain L-55 (LaL-55) enhances the immune response among chicks exposed to a Newcastle disease virus (NDV)-based live attenuated vaccine. Oral administration of LaL-55 augmented the elevation in the total numbers of leukocytes and lymphocytes following inoculation with the NDV-based live attenuated vaccine. Monocyte counts increased after LaL-55 administration independent of inoculation with the NDV vaccine. Among chicks that were administered LaL-55, there was a dose-dependent increase in the NK cell activity measured by a 51Cr release assay at 2 weeks after the secondary NDV vaccine inoculation. Two weeks after the secondary inoculation with the NDV vaccine, interferon (IFN)-γ-mRNA expression was significantly elevated in mononuclear splenocytes from chicks that were administered LaL-55. Meanwhile, LaL-55 administration did not change the mRNA levels of IFN-α, IFN-ß, and interleukin-1ß. These results may suggest that coadministration of LaL-55 with an NDV vaccine augments the immune response against the virus. Therefore, LaL-55 may help protect against viral diseases in poultry.

Differential localizations of the myo-inositol transporters HMIT and SMIT1 in the cochlear stria vascularis.

The cochlear stria vascularis produces endolymph and thereby plays an active role in inner ear homeostasis. We recently reported that the H+/myo-inositol cotransporter (HMIT) gene is expressed in the stria vascularis. Here, we examined the protein localization of HMIT and Na+/myo-inositol cotransporter 1 (SMIT1) in the stria vascularis by immunohistochemistry. HMIT and SMIT1 were detected in the lateral wall of the cochlear duct. HMIT was widely detected throughout the stria vascularis, while SMIT1 was enriched in the strial basal cells. To examine the localization of HMIT in the stria vascularis in more detail, dissociated strial cells were immunostained, which resulted in the detection of HMIT immunoreactivity in marginal cells. These results indicate that HMIT is expressed in marginal cells and basal cells of the stria vascularis, while SMIT1 expression is enriched in basal cells. We speculate that HMIT and SMIT1 may play important roles in the homeostasis of cochlear fluids, for example by participating in pH regulation and osmoregulation.

Tailored Predictive Formulas for Glomerular Filtration Rate for Early Detection of Deteriorating Renal Function After Pediatric Living-Donor Liver Transplant.

OBJECTIVES: In pediatric patients, renal dysfunction after living-donor liver transplant is a major issue that is difficult to evaluate. Recently, predictive equations for Japanese children have been introduced. MATERIALS AND METHODS: We conducted a retrospective study by prospectively collecting data on 26 patients under 16 years old who underwent living-donor liver transplant between June 2004 and March 2015. Serum creatinine and cystatin C levels were measured. Paired t tests and Bland-Altman plots were used to compare the following formulas for estimated glomerular filtration rate: the Schwartz formula and 3 formulas that were matched with Japanese children (polynomial, simple, and cystatin C formulas). RESULTS: Average estimated glomerular filtrations rates (in mL/min/1.73 m2) were 143.46, 122.90, 121.58, and 123.31 using the Schwartz, polynomial, simple, and cystatin C formulas, respectively. The estimated glomerular filtrations rate for biliary atresia was 141.53 ± 31.37 versus 109.95 ± 19.52 for other diseases, with significant differences only noted with the cystatin C formula. The formulas tailored for Japanese children showed significantly lower estimated glomerular filtrations rates than those obtained using the Schwartz formula (P < .01). CONCLUSIONS: The use of formulas for measuring estimated glomerular filtrations rates that are based on race may allow early detection of deteriorating renal function.