Unveiling the Patterns of Water Diuresis in Profound Hyponatremia Management in Intensive Care Unit Settings.

BACKGROUND: Hyponatremia treatment guidelines recommend avoiding excessive increases in serum sodium concentration (s[Na]) to prevent osmotic demyelination syndrome. Although an unexpected rise in s[Na] has been attributed to water diuresis during the treatment of hyponatremia, clinical courses of water diuresis are unclear. We conducted this study to investigate the clinical characteristics of water diuresis during profound hyponatremia management. METHODS: In this retrospective observational study, we examined patients with profound hyponatremia (s[Na] ≤120 mEq/L) admitted to the intensive care unit of a Japanese hospital. The manifestation of water diuresis was defined as a urine volume ≥2 ml/kg/h and a urinary sodium plus potassium concentration (u[Na+K]) ≤50 mEq/L. We analyzed changes in urine volume and u[Na+K] over time for patients experiencing water diuresis. This analysis employed a mixed-effects model with spline terms for time, and the results are graphically presented. RESULTS: Among 47 eligible patients, 30 (64%) met the criteria for water diuresis. The etiologies of hyponatremia were drug-related hyponatremia (n=10; 33%), primary polydipsia (n=8; 27%), hypovolemic hyponatremia (n=7; 23%), syndrome of inappropriate secretion of antidiuresis (n=7; 23%), and acute heart failure (n=1; 3%). Among patients with water diuresis, 27 (90%) experienced the manifestation of water diuresis within 24 hours after the start of correction. The increased urine volume and decreased u[Na+K] levels began several hours before the peak manifestation of water diuresis. Within 6 hours after the manifestation of water diuresis, 29 patients (97%) received electrolyte-free infusions and 14 (47%) received desmopressin. One patient (3%) with water diuresis experienced overcorrection. CONCLUSIONS: Water diuresis is common during the treatment for profound hyponatremia and typically occurs within the first 24 hours, preceded by changes in urinary characteristics. Early detection and prompt response to water diuresis through urine monitoring during the early periods of hyponatremia treatment may be effective for managing water diuresis.

Recipients of public assistance with advanced chronic kidney disease: insights into receiving a presentation of kidney replacement therapy options and polypharmacy from Japanese investigators with innovative network about kidney disease study.

BACKGROUND: The characteristics of patients with advanced chronic kidney disease (CKD) who are recipients of public assistance in Japan, and the adequacy of their medical care have not been reported previously. METHODS: The records of patients with CKD stage G5 who visited nine facilities in Japan from April to June 2013 were retrospectively reviewed to compare the characteristics and care of recipients of public assistance with those of non-recipients. Receiving a presentation of kidney replacement therapy (KRT) options and polypharmacy were used as indicators of suboptimal medical care. RESULTS: Of the 592 patients included in this analysis (mean age, 69.6 years; male, 59.3%), 56 (9.5%) were recipients of public assistance and 536 (90.5%) were non-recipients of public assistance. The prevalence of diabetes mellitus, unmarried status, and living alone were higher in recipients of public assistance. In multivariable logistic regression analysis, compared with non-recipients of public assistance, recipients of public assistance were less likely to receive a presentation of KRT options (adjusted odds ratio [aOR], 0.31; 95% confidence interval [CI], 0.17-0.56), and were more likely to receive ≥ 10 (aOR, 1.92; 95% CI, 1.05-3.51), and ≥ 15 (aOR, 2.78; 95% CI, 1.23-6.26) types of medication. CONCLUSIONS: Patients with advanced CKD receiving public assistance were less likely to receive a presentation of KRT options and more likely to receive ≥ 10 and ≥ 15 types of medication, suggesting that recipients of public assistance are more likely to receive suboptimal medical care.

The Association between High-Dose Allopurinol and Erythropoietin Hyporesponsiveness in Advanced Chronic Kidney Disease: JOINT-KD Study.

INTRODUCTION: The aim of the study was to explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5. METHODS: We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (>50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs. RESULTS: A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR = 1.98, 95% confidence interval: 1.10-3.57). CONCLUSIONS: Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents.

Renal Immune-related Adverse Event of Pembrolizumab Masked by Pemetrexed.

A Japanese woman in her 60s developed a kidney injury 9 weeks after treatment with pemetrexed, carboplatin, and pembrolizumab for stage IV lung adenocarcinoma. A renal biopsy showed chronic tubulointerstitial damage with minimal focal interstitial inflammation, consistent with pemetrexed-induced nephropathy; thus, pemetrexed was withdrawn. However, the kidney injury continued to worsen. A repeated biopsy showed severe acute tubulointerstitial nephritis, suggestive of a pembrolizumab-induced immune-related adverse event (irAE). The worsening after pemetrexed discontinuation suggested that the irAE had already begun, as the first biopsy showed focal inflammation. This case suggests thatcombining immune checkpoints and chemotherapy requires considering concurrent drug-induced nephrotoxicity.

Predictive correction of serum sodium concentration with formulas derived from the Edelman equation in patients with severe hyponatremia.

Severe hyponatremia can cause life-threatening cerebral edema. Treatment comprises rapid elevation of serum sodium concentration; however, overcorrection can result in osmotic demyelination. This study investigated potential factors, including predictive correction based on the Edelman equation, associated with appropriate correction in 221 patients with a serum sodium concentration ≤ 120 mEq/L who were admitted to a hospital in Nagoya, Japan. Appropriate correction was defined as an elevation in serum sodium concentration in the range of 4-10 mEq/L in the first 24 h and within 18 mEq/L in the first 48 h after the start of the correction. Appropriate corrections were made in 132 (59.7%) of the 221 patients. Multivariate analysis revealed that predictive correction with an infusate and fluid loss formula derived from the Edelman equation was associated with appropriate correction of serum sodium concentration (adjusted odds ratio, 7.84; 95% confidence interval, 2.97-20.64). Relative without its use, the predictive equation results in a lower proportion of undercorrection (14.3% vs. 48.0%, respectively) and overcorrection (1.0% vs. 12.2%, respectively). These results suggest that predictive correction of serum sodium concentrations using the formula derived from the Edelman equation can play an essential role in the appropriate management of patients with severe hyponatremia.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Herpes zoster meningitis in a rheumatoid arthritis patient treated with tofacitinib.

A man in his 70s with rheumatoid arthritis presented with seizures and coma and was transferred to our emergency department. Two months prior to admission, he started to take tofacitinib 10 mg/day. On admission, we noted a rash with a blister on the forehead, and herpes zoster was diagnosed. Cerebrospinal fluid examination suggested meningitis. An MRI of the brain showed no abnormality. Based on these findings, he was suspected with herpes zoster meningitis. We discontinued tofacitinib and treated the patient with intravenous acyclovir for 2 weeks. He regained complete consciousness, but right forehead skin lesion, severe vision loss in the right eye and right facial nerve paralysis remained as sequelae. Six weeks after admission, we restarted tofacitinib with oral valaciclovir as antiviral prophylaxis. Two years after admission, we administered Shingrix, an adjuvant recombinant vaccine for herpes zoster, and discontinued oral valaciclovir.

Importance of ultrasound examination: A case of peritoneal catheter tunnel infection.

Some peritoneal dialysis catheter infections cannot be detected via a physical examination. Ultrasound of the PD catheter tunnel should be performed in cases of suspected infection or clinical abnormality at the catheter tunnel site.

Pericostal tuberculosis in a patient with systemic sclerosis:The relationship of two rare diseases.

Regardless of immunosuppressant use, physicians should be aware of pulmonary and extra-pulmonary tuberculosis in patients with autoimmune disease including systemic sclerosis, especially if they follow unusual clinical courses.

Application of MALDI-TOF MS to assess clinical characteristics, risk factors, and outcomes associated with anaerobic bloodstream infection: a retrospective observational study.

BACKGROUND: Correctly identifying anaerobic bloodstream infections (BSIs) is difficult. However, a new technique, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), enables more accurate identification and appropriate treatment. Anaerobic BSIs identified by MALDI-TOF MS were retrospectively analyzed to determine the clinical and microbiological features and patient outcomes based on the anaerobic genera or group. METHODS: Medical records of patients with anaerobic BSIs were used to conduct a single-center retrospective cohort study from January 2016 to December 2020 in Nagoya, Japan. Multivariate logistic regression analysis was performed to determine the independent risk factors for in-hospital mortality. RESULTS: Of the 215 patients with anaerobic BSIs, 31 had multiple anaerobic organisms in the blood culture, including 264 total episodes of anaerobic BSIs. Bacteroides spp. were isolated the most (n = 74), followed by gram-positive non-spore-forming bacilli (n = 57), Clostridium spp. (n = 52), gram-positive anaerobic cocci (GPAC) (n = 27), and gram-negative cocci (n = 7). The median patient age was 76 years; 56.7% were male. The most common focal infection site was intra-abdominal (36.7%). The in-hospital mortality caused by anaerobic BSIs was 21.3%, and was highest with Clostridium spp. (36.5%) and lowest with GPAC (3.7%). Age, solid tumors, and Clostridium spp. were independent risk factors for in-hospital mortality. CONCLUSIONS: We identified current anaerobic BSI trends using MALDI-TOF MS and reported that mortality in patients with anaerobic BSIs patients was highest with Clostridium spp. infections.

Combined light chain crystalline tubulopathy, podocytopathy, and histiocytosis associated with Bence-Jones κ protein diagnosed via immuno-electron microscopy.

We herein report a case of a combined crystalline light chain tubulopathy, podocytopathy, histiocytosis, and cast nephropathy in a patient with monoclonal gammopathy of renal significance (MGRS). A 66-year-old female with impaired renal function was referred to our department. Despite intravenous fluid resuscitation, the kidney function worsened progressively; thus, a kidney biopsy was performed. The kidney biopsy revealed light chain proximal tubulopathy (LCPT) with crystals, light chain crystal podocytopathy (LCCP), crystal-storing histiocytosis (CSH), and light chain cast nephropathy (LCCN). Of note, LCCP and CSH were diagnosed via electron microscopy. Serum and urine immunoelectrophoresis (IEP) revealed the presence of monoclonal Bence-Jones protein and free κ light chains. Bone marrow aspiration showed < 10% plasma cell proliferation. Thus, we had encountered a rare case in which a variety of kidney lesions were combined with MGRS. Most of the LCPT, LCCP, and CSH cases show monoclonal IgG κ, while our case showed Bence-Jones protein κ.

Glucocorticoid treatment is associated with ICU-acquired hypernatremia: a nested case-control study.

BACKGROUND: Hypernatremia is a major electrolyte disorder associated with death among critically ill patients. Glucocorticoid therapy may cause hypernatremia in refractory septic shock patients, but the association between glucocorticoid and intensive care unit (ICU)-acquired hypernatremia (IAH) remains unclear. The aim of this study was to clarify whether glucocorticoid administration was associated with IAH. METHODS: This was a nested case-control study using data from an established cohort including 121 IAH cases identified from 1756 patients who were admitted to ICU in a tertiary care facility in Japan. We included patients who were admitted with a normal range of serum sodium concentrations (130-149 mEq/L) from January 1, 2013 to December 31, 2015 and remained in ICU for ≥ 2 days. Hypernatremia was defined as serum sodium concentration ≥ 150 mEq/L. Each case was matched to one control. RESULTS: Multivariable conditional logistic regression revealed high-dose glucocorticoid {odds ratio (OR), 4.15 [95% confidence interval (CI) 1.29-13.4]}, acute kidney injury (AKI) [OR, 2.72 (95% CI 1.31-5.62)], and osmotic diuretics [OR, 3.44 (95% CI 1.41-8.39)] to be significantly associated with IAH. The contents and amounts of fluid infusion were not significantly associated with IAH. There were also significant duration-response effects between duration of glucocorticoid use and IAH; however, pulse glucocorticoid administration was not associated with IAH. CONCLUSION: In this nested case-control study, we demonstrated a significant association between IAH and high-dose glucocorticoid with significant duration-response effects. Serum sodium concentrations should be monitored carefully in critically ill patients administered prolonged high-dose glucocorticoid.

Clinical characteristics of bloodstream infection by Parvimonas micra: retrospective case series and literature review.

BACKGROUND: Gram-positive anaerobic (GPA) bacteria inhabit different parts of the human body as commensals but can also cause bacteremia. In this retrospective observational study, we analyzed GPA bacteremia pathogens before (2013-2015) and after (2016-2018) the introduction of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). METHOD: We conducted a retrospective observational study by searching the microbiology database to identify all positive GPA blood cultures of patients with GPA bacteremia diagnosed using the new technique, MALDI-TOF MS, between January 1, 2016 and December 31, 2018; and using a conventional phenotypic method between January 1, 2013 and December 31, 2015 at a single tertiary center in Japan. Parvimonas micra (P. micra) (17.5%) was the second most frequently identified GPA (MALDI-TOF MS); we then retrospectively reviewed electronic medical records for 25 P. micra bacteremia cases at our hospital. We also conducted a literature review of published cases in PubMed from January 1, 1980, until December 31, 2019; 27 cases were retrieved. RESULTS: Most cases of P. micra bacteremia were identified after 2015, both, at our institute and from the literature review. They were of mostly elderly patients and had comorbid conditions (malignancies and diabetes). In our cases, laryngeal pharynx (7/25, 28%) and gastrointestinal tract (GIT; 6/25, 24%) were identified as the most likely sources of bacteremia; however, the infection source was not identified in 9 cases (36%). P. micra bacteremia were frequently associated with spondylodiscitis (29.6%), oropharyngeal infection (25.9%), intra-abdominal abscess (14.8%), infective endocarditis (11.1%), septic pulmonary emboli (11.1%), and GIT infection (11.1%) in the literature review. Almost all cases were treated successfully with antibiotics and by abscess drainage. The 30-day mortalities were 4 and 3.7% for our cases and the literature cases, respectively. CONCLUSIONS: Infection sites of P. micra are predominantly associated with GIT, oropharyngeal, vertebral spine, intra-abdominal region, pulmonary, and heart valves. Patients with P. micra bacteremia could have good prognosis following appropriate treatment.