BackgroundAcute tubulointerstitial nephritis (ATIN) has been increasingly recognized as an important manifestation of kidney injury associated with the use of immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4). While the exact pathophysiology remains unknown, corticosteroids are the mainstay of management.Case presentationWe describe a 67-year-old man with stage IV non-small-cell lung cancer who developed kidney injury during treatment with the anti-PD-1 antibody nivolumab. A kidney biopsy showed ATIN without granuloma formation. Considering their mechanism of action, immune checkpoint inhibitors can alter immunological tolerance to concomitant drugs that have been safely used for a long time. For more than 4 years before the initiation of nivolumab therapy, the patient had been receiving the proton pump inhibitor lansoprazole, known to cause drug-induced ATIN, without significant adverse events including kidney injury. He showed rapid improvement in kidney function in 3 days (creatinine decreased from 2.74 to 1.82 mg/dl) on discontinuation of lansoprazole. He then received 500 mg intravenous methylprednisolone for 3 days followed by 1 mg/kg/day oral prednisolone and his creatinine levels eventually stabilized around 1.7 mg/dl. Drug-induced lymphocyte stimulation test (DLST) for lansoprazole was positive.ConclusionsThe rapid improvement of kidney function after discontinuation and DLST positivity indicate that lansoprazole contributed to the development of ATIN during nivolumab therapy. Considering the time course, it is plausible that nivolumab altered the long-lasting immunological tolerance against lansoprazole in this patient. To the best of our knowledge, this is the first case report of DLST positivity for a drug that had been used safely before the initiation of an immune checkpoint inhibitor. Although corticosteroid therapy is recommended, the recognition and discontinuation of concomitant drugs, especially those known to induce ATIN, is necessary for the management of kidney injury associated with anti-PD-1 therapy.

Tight junctions are the main intercellular junctions of podocytes of the renal glomerulus under nephrotic conditions. Their requisite components, claudins, still remain to be identified. We have measured the mRNA levels of claudin subtypes by quantitative real-time PCR using isolated rat glomeruli. Claudin-5 was found to be expressed most abundantly in glomeruli. Mass spectrometric analysis of membrane preparation from isolated glomeruli also confirmed only claudin-5 expression without any detection of other claudin subtypes. In situ hybridization and immunolocalization studies revealed that claudin-5 was localized mainly in glomeruli where podocytes were the only cells expressing claudin-5. Claudin-5 protein was observed on the entire surface of podocytes including apical and basal domains of the plasma membrane in the normal condition and was inclined to be concentrated on tight junctions in puromycin aminonucleoside nephrosis. Total protein levels of claudin-5 in isolated glomeruli were not significantly upregulated in the nephrosis. These findings suggest that claudin-5 is a main claudin expressed in podocytes and that the formation of tight junctions in the nephrosis may be due to local recruitment of claudin-5 rather than due to total upregulation of the claudin protein levels.

AimWe evaluated several sarcopenia‐related hormones, cytokines and uremic toxins to identify the humoral factors associated with sarcopenia and frailty in Japanese hemodialysis patients.MethodsTwenty Japanese patients aged ≥65 years who underwent maintenance hemodialysis therapy at Uonuma Kikan Hospital for more than 6 months were included in this retrospective cross‐sectional study. Clinical data, including physical function and mental state, were obtained from the clinical records collected during the regular evaluation at the beginning of each hemodialysis therapy session, 3 days after the previous hemodialysis therapy. The diagnosis of sarcopenia and frailty was based on the Asian Working Group for Sarcopenia 2019 and the Japanese version of the Cardiovascular Health Study, respectively. The mental state of patients was evaluated using the Japanese version of the Patient Health Questionnaire 9 (J‐PHQ‐9).ResultsIn univariate analyses, plasma brain‐derived neurotrophic factor (BDNF) levels were significantly lower in patients with severe sarcopenia and frailty. The plasma BDNF concentration was correlated with muscle strength and physical performances, such as the 6‐m walk test, Short Physical Performance Battery and 5‐time chair stand test. BDNF was also correlated with body weight, hemodialysis vintage, and serum levels of total protein and indoxyl sulfate but not with body mass index, appendicular skeletal muscle mass, serum interleukin 6 levels, or J‐PHQ‐9 scores. The odds ratio per 100 pg/mL of BDNF for the prevalence of frailty was 0.353.ConclusionsBDNF is associated with decreased physical performance and the prevalence of severe sarcopenia and frailty in Japanese maintenance hemodialysis patients. Geriatr Gerontol Int 2021; 21: 27–33.

An 88-year-old woman presented with fever and acute posterior neck pain. A CT scan revealed calcification of the transverse ligament and crown-like calcification around the odontoid process. According to the clinical and radiological findings, she was diagnosed with crowned dens syndrome (CDS). Her symptoms drastically improved following treatment with oral nonsteroidal anti-inflammatory medication. An X-ray of her wrist, elbow, shoulder and knee joints showed asymptomatic calcium deposits, suggesting underlying crystalline deposition disease. CDS may occur as the initial presentation of crystalline deposition disease. The measurement of procalcitonin and an X-ray survey of the major joints may be helpful for the diagnosis of CDS.

Background and objectives: A new assessment system for bone histology, termed the turnover-mineralization-volume system, is advocated for patients with chronic kidney disease-related mineral and bone disorder. The system measures cancellous bone volume (BV/TV) as a third major evaluation axis; however, the physiologic significance of BV/TV remains unclear.Design, setting, participants, & measurements: Conventional bone histomorphometry was performed in 75 iliac bone samples obtained from dialysis patients. In 47 of the 75 samples, the remaining samples were subjected to direct microfocus x-ray computed tomographic observation. Quantitative morphologic examinations, including micro-bone mineral densitometry, and marrow space star volume, Euler number, and node-strut analyses, were performed in the virtual three-dimensional space reconstructed from the microfocus x-ray computed tomographic images.Results: The levels of BV/TV were comparable in each of the conventional bone histomorphometric criteria. No significant correlations were found between BV/TV and other parameters. Two-and three-dimensional BV/TVs were significantly correlated with cancellous bone mass but not with cortical bone thickness or cortical bone mass. Two-and three-dimensional BV/TVs were significantly correlated with trabecular bone connectivity as determined by marrow space star volume, Euler number, and node-strut analyses.Conclusions: In dialysis patients, BV/TV is not dependent on bone turnover or bone mineralization. BV/TV is unlikely to indicate the balance between bone formation and bone resorption. Instead, it reflects trabecular bone connectivity, and improved trabecular bone connectivity is physiologically beneficial in terms of bone quality. The turnover-mineralizationvolume system offers an advantage over the conventional system for the assessment of bone quality.