Treatment for patients with autosomal dominant polycystic kidney disease in the chronic kidney disease without kidney replacement therapy in real-world clinical practice: a descriptive retrospective cohort study.

BACKGROUND: In real-world clinical practice, treatments selected for patients with autosomal dominant polycystic kidney disease (ADPKD) in the chronic kidney disease (CKD) without kidney replacement therapy (KRT) have not been reported. This study investigated the oral treatments used in these patients and the changes in their use in recent years. Additionally, we studied the factors affecting tolvaptan dose reduction or discontinuation. METHODS: This retrospective cohort study was conducted using the medical records of 160 hospitals in Japan. Patients with ADPKD or polycystic kidney disease registered on the database between January 2014 and December 2020 were selected. Changes in prescription proportions over time were assessed using the Cochran-Armitage test. We focused on patients prescribed with >15 mg of tolvaptan daily to identify the factors related to its dose reduction or discontinuation and used Multivariate Cox regression analysis to evaluate them. RESULTS: Tolvaptan use in patients with ADPKD in the CKD without KRT stage has increased. As of 2020, 25% of patients were treated with tolvaptan. Overall, 3639 patients with ADPKD were enrolled in the database, of whom 156 were treated with tolvaptan. Of these, 64 patients (41%) reduced or discontinued tolvaptan during the observation period. The presence of an estimated glomerular filtration rate <60 mL/min/1.73 m2 at the beginning of the treatment was associated with a higher risk of tolvaptan dose reduction or discontinuation. CONCLUSION: The proportion of patients with ADPKD treated with high-dose tolvaptan is increasing. However, patients with late-stage CKD tended to reduce or discontinue tolvaptan.

Effect of multidisciplinary care on diabetic kidney disease: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) is the most common disease among patients requiring dialysis for the first time in Japan. Multidisciplinary care (MDC) may prevent the progression of kidney failure. However, the effectiveness and timing of MDC to preserve kidney function in patients with DKD is unclear. Therefore, the aim of this study was to investigate whether MDC for patients with DKD affects the preservation of kidney function as well as the timing of MDC in clinical practice. METHODS: In this retrospective cohort study, we identified patients with type 2 diabetes mellitus and DKD from April 2012 to January 2020 using a nationwide Japanese healthcare record database. The fee code for medical guidance to prevent dialysis in patients with diabetes was used to distinguish between the MDC and non-MDC groups. The primary outcome was a 40% decline in the estimated glomerular filtration rate, and secondary outcomes were death, hospitalization, permanent dialysis, kidney failure with replacement therapy, and emergency temporary catheterization. Propensity score matching was performed, and Kaplan-Meier and multivariable Cox regression analyses were performed. RESULTS: Overall, 9,804 eligible patients met the inclusion criteria, of whom 5,614 were matched for the main analysis: 1,039 in the MDC group, and 4,575 in the non-MDC group. The primary outcome did not differ between the groups (hazard ratio: 1.18, [95% confidence interval: 0.99-1.41], P = 0.07). The groups also did not differ in terms of the secondary outcomes. Most patients with DKD received their first MDC guidance within 1 month of diagnosis, but most received guidance only once per year. CONCLUSIONS: Although we could not demonstrate the effectiveness of MDC on kidney function in patients with DKD, we clarified the characteristics of such patients assigned the fee code for medical guidance to prevent dialysis related to diabetes.

Metformin-associated lactic acidosis exacerbated by acute kidney injury in an overseas traveler.

We report the case of metformin-associated lactic acidosis (MALA) exacerbated by acute kidney injury (AKI) in a 65-year-old Asian American woman who was an overseas traveler. She had vomiting and diarrhea before arriving in Osaka, Japan, from the Philippines. She suffered from worsening respiratory distress, consciousness loss and anuria the day after coming to Japan. When she arrived at our emergency room via ambulance, she appeared to be in a state shock. Arterial blood gas analysis revealed severe lactic acidosis (pH 6.681, PO2 302 Torr under O2 supplementation, PCO2 15 Torr, HCO3-1.7 mmol/L, and lactate 17.00 mmol/L). She also had renal failure (BUN 108 mg/dL and serum creatinine 8.68 mg/dL) with hyperkalemia (6.1 mEq/L). We collected medical information from family members, and found her prescription medicines including metformin, diuretics and angiotensin-converting enzyme inhibitor (ACEI). We diagnosed her with MALA due to an unintended overdose of metformin resulting from acute kidney injury that can be induced by ACEI and diuretics in the volume-depleted condition. We immediately started hemodialysis therapy. Although she had a temporary cardiopulmonary arrest at the beginning of the treatment, her physical status was gradually improved and the severe acidemia resolved. On hospital day 4, she had urine and no longer needed hemodialysis therapy. On day 14, she was discharged and returned to the United States without noticeable sequelae. This is a case report of an overseas traveler who was successfully rescued through the collection of accurate medical information and understanding of the pathological condition.

Sequential occurrence of microscopic polyangiitis and anti-glomerular basement membrane disease in a patient with small cell lung cancer: a case report.

BACKGROUND: The association between a preceding malignancy and the onset of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in several studies. While the co-existence of ANCA and anti-glomerular basement membrane (GBM) antibodies in an individual patient is not a common occurrence, this double-positive disease currently has no optimal treatment method. Herein, we report a case of a double-positive disease involving the sequential development of acute kidney injury (AKI) and diffuse alveolar hemorrhage (DAH) in a patient with small cell lung cancer (SCLC). CASE PRESENTATION: A 75-year-old Japanese woman was diagnosed with small cell lung cancer (cT3N2M1b cStage IV) and received chemotherapy. After one cycle of chemotherapy, she experienced fever and malaise. Her serum creatinine level rapidly increased, and she tested positive for myeloperoxidase (MPO)-ANCA and anti-GBM antibody. She was diagnosed with AKI due to microscopic polyangiitis (MPA) based on renal biopsy. Corticosteroid therapy was initiated, which improved her renal dysfunction. Eight days after she was discharged from the hospital, she complained of dyspnea and bloody sputum, and her condition rapidly progressed to respiratory failure. Upon chest imaging, ground-glass opacities were seen in her bilateral lower lungs. Laboratory examinations after admission revealed a lower MPO-ANCA titer and an elevated anti-GBM antibody titer compared to her previous admission. We diagnosed her with DAH due to an anti-GBM disease. After corticosteroid pulse therapy, plasma exchange was performed five times; her oxygen saturation and chest radiologic findings improved gradually. Following five cycles of plasma exchange, her oxygen saturation recovered to 95% in room air. CONCLUSIONS: To our knowledge, this is the first reported case of vasculitis caused by MPA and anti-GBM disease leading to the development of AKI and DAH during treatment of SCLC. SCLC, MPA, and anti-GBM disease may occur sequentially. A double-positive disease might have a worse prognosis; therefore, intensive therapy is more likely to achieve a better outcome.

Chromosome analysis of blastocysts derived from single pronuclear zygotes by array CGH and clinical outcomes by the transfer of single pronuclear zygotes.

PURPOSE: This study aimed to explore the aneuploidy of blastocysts derived from single pronuclear (1PN) zygotes, almost 75% of which were regarded as diploid, using array CGH and examine the pregnancy outcomes. METHODS: Embryonic aneuploidy screening of sixteen embryos from 1PN zygotes and sixteen embryos from 2PN zygotes was performed using array CGH in study 1. In addition, the reproductive outcome of 1761 single blastocysts, after untested frozen-thawed blastocyst transfer in IVF/ICSI patients, was retrospectively analyzed and compared between the 1PN and 2PN groups in study 2. RESULTS: The aneuploidy rates were 30.8% (4/13) in 1PN IVF, 33.3% (1/3) in 1PN ICSI, 46.2% (6/13) in 2PN IVF, and 100% (3/3) in 2PN ICSI. The 1PN group achieved clinical pregnancy in 25.0% (7/28) of IVF and 30.0% (3/10) of ICSI, whereas these rates in the 2PN control group were 44.6% (557/1250) of IVF and 37.4% (177/473) of ICSI. No miscarriage occurred in the pregnancies from 1PN zygotes, whereas the rates of miscarriage in the 2PN control group were 22.6% (126/557) in IVF and 22.2% (39/176) in ICSI. The delivery rate was similar in all groups. Ten deliveries in the 1PN group showed no newborn malformation. CONCLUSION: Within the limits of the small sample size, our results suggest that the aneuploidy and delivery rates of the blastocysts derived from 1PN zygotes are the same as those derived from 2PN zygotes. Blastocysts derived from 1PN zygotes may be used clinically and could increase the chance of pregnancy.

[A CASE OF ANAPHYLAXIS CAUSED BY LANDLOCKED AYU FISH, KOAYU FISH, FROM LAKE BIWA].

A 28-year-old man was transferred to our emergency room for dyspnea and wheals on the entire body. He had eaten landlocked ayu fish (Plecoglossus altivelis) the so-called "koayu fish", from Lake Biwa, and had immediately experienced a stomachache. Wheals and dyspnea developed one hour later and were successfully treated with intravenous corticosteroids. The patient was examined for koayu fish and related allergens by skin prick and allergen-specific immunoglobulin E (IgE) (ImmunoCAP®) tests. Positive skin prick results were obtained for Lake Biwa koayu fish (raw and heated) as well as for standard skin test allergens (prepared by Torii pharmaceuticals) including shrimp, crab, and squid. Negative prick test results were observed for regular ayu fish and other fish such as horse mackerel, sardine, salmon, mackerel, codfish, and tuna. Allergen-specific IgE tests (ImmunoCAP ®) showed positivity for shrimp, crab, ticks, moths, and mosquitoes, while ImmunoCAP® tests were negative for the allergen components rGad c 1 (pollackparvalbumin) and rPen a 1 (shrimp tropomyosin). Moreover, enzyme-linked immunosorbent assay (ELISA) tests were negative for mackerel parvalbumin and collagen. We considered this case to be of anaphylaxis caused by koayu fish from Lake Biwa and speculated that a novel koayu-specific antigen might have been the cause of the condition.