Identification of ABCG2 as an Exporter of Uremic Toxin Indoxyl Sulfate in Mice and as a Crucial Factor Influencing CKD Progression.

Chronic kidney disease (CKD) patients accumulate uremic toxins in the body, potentially require dialysis, and can eventually develop cardiovascular disease. CKD incidence has increased worldwide, and preventing CKD progression is one of the most important goals in clinical treatment. In this study, we conducted a series of in vitro and in vivo experiments and employed a metabolomics approach to investigate CKD. Our results demonstrated that ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a major transporter of the uremic toxin indoxyl sulfate. ABCG2 regulates the pathophysiological excretion of indoxyl sulfate and strongly affects CKD survival rates. Our study is the first to report ABCG2 as a physiological exporter of indoxyl sulfate and identify ABCG2 as a crucial factor influencing CKD progression, consistent with the observed association between ABCG2 function and age of dialysis onset in humans. The above findings provided valuable knowledge on the complex regulatory mechanisms that regulate the transport of uremic toxins in our body and serve as a basis for preventive and individualized treatment of CKD.

Efficacy of benzbromarone in hyperuricemic patients associated with chronic kidney disease.

We have retrospectively evaluated the uric acid control status and renal function changes over a period of up to 7 years in 35 patients with renal impairment who had stage 3 or higher chronic kidney disease (CKD; stage 3 in 32 patients, stage 4 in 2 patients, and stage 5 in 1 patient) associated with hyperuricemia and were receiving monotherapy with benzbromarone as an antihyperuricemic drug. Serum uric acid levels significantly decreased from 8.5 ± 0.9 to 6.1 ± 0.8 mg/dL at 6 months and were subsequently controlled at less than 7.0 mg/dL in most patients. Most patients received benzbromarone at a dose of 25-50 mg/day, whereas 150-200 mg/day was used in some patients with stage 4 or 5 CKD. No significant changes in estimated glomerular filtration rate (eGFR) from the baseline value of 46.2 ± 11.5 mL/minute/1.73 m(2) were found after benzbromarone therapy. Although the renal function impairment did not improve by reducing the serum uric acid levels with benzbromarone, the renal function did not deteriorate further on the therapy. These results suggest that benzbromarone is applicable to the management of hyperuricemia associated with renal impairment.

Long-term follow-up of 5 patients with intracranial germinoma initially treated by chemotherapy alone.

BACKGROUND: High rates of overall- and event-free survival have been reported in patients with intracranial germinoma treated by radiotherapy. We report the long-term results after treatment initially with chemotherapy, but without radiation. PATIENTS AND METHOD: Five patients with an intracranial germinoma were treated with 2 cycles of etoposide and cisplatin, without radiotherapy. All achieved complete remission; 3 suffered recurrence within 2 years and were again treated with 2 cycles of etoposide and cisplatin followed by radiotherapy. RESULTS: At long-term follow-up, each of the 5 patients was in complete remission without further recurrence. Each patient with a neurohypophyseal germinoma who presented with endocrinopathy had initially recovered endocrinological function. CONCLUSION: In a patient with a germinoma chemotherapy, and restriction of radiation to those with recurrence may allow restoration of hypophyseal function damaged by the intracranial germinoma without compromising long term survivial.

Cryoprotective activities of group 3 late embryogenesis abundant proteins from Chlorella vulgaris C-27.

The nucleotide sequence of hiC12, isolated as a cDNA clone of hardening-induced Chlorella (hiC) genes, was identified. The clone encodes a late embryogenesis abundant (LEA) protein having six repeats of a 11-mer amino acid motif, although in a slightly imperfect form. To overexpress the hiC61) and hiC12 genes, their coding regions were PCR amplified and subcloned into a pGEX-1lambdaT vector. The HIC6 and HIC12 proteins were expressed as GST fusion proteins in E. coli, then purified. The two HIC proteins were found to be effective in protecting a freeze-labile enzyme, LDH, against freeze-inactivation. On a molar concentration basis, they were about 3.1 x 10(6) times more effective in protecting LDH than sucrose and as effective as BSA. Cryoprotection tests with five kinds of chain-shortened polypeptides, synthesized based on the 11-mer amino acid motif of the HIC6 protein showed that the cryoprotective activity decreased with a decrease in the repeating units of the 11-mer motif. In fact, cryoprotective activities of three kinds of single 11-mer amino acids were very low even at high concentrations. All the results suggested that the sufficiently repeated 11-mer motif is required for the cryoprotective activities of Chlorella LEA proteins.