Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

Hypopituitarism due to CNS Aspergillus Infection.

A 59-year-old man was admitted to our hospital with hyponatremia. An endocrine examination indicated panhypopituitarism, and magnetic resonance imaging revealed a mass-like lesion in the pituitary gland. Sinus endoscopy revealed a fungal mass in the sphenoid sinus, and the patient was diagnosed with hypopituitarism due to aspergillosis of the central nervous system (CNS). The patient's hyponatremia resolved with hydrocortisone replacement. Although the right internal carotid artery was eventually occluded, antifungal medications were administered for the aspergillosis, and the patient's general condition improved. The patient's CNS lesions have remained under control since discharge. This is the first case to suggest that ACTH secretion may be relatively preserved in Aspergillus-induced hypopituitarism.

Clinical significance of amphiregulin in patients with chronic kidney disease.

BACKGROUND: Amphiregulin (AREG) is a ligand of epidermal growth factor receptor (EGFR), which plays an important role in injury-induced kidney fibrosis. However, the clinical significance of serum soluble AREG in chronic kidney disease (CKD) is unclear. In this study, we elucidated the clinical significance of serum soluble AREG in CKD by analyzing the association of serum soluble AREG levels with renal function and other clinical parameters in patients with CKD. METHODS: In total, 418 Japanese patients with CKD were enrolled, and serum samples were collected for the determination of soluble AREG and creatinine (Cr) levels, and other clinical parameters. Additionally, these parameters were evaluated after 2 and 3 years. Moreover, immunohistochemical assay was performed ate AREG expression in the kidney tissues of patients with CKD. RESULTS: Soluble AREG levels were positively correlated with serum Cr (p < 0.0001). Notably, initial AREG levels were positively correlated with changes in renal function (ΔCr) after 2 (p < 0.0001) and 3 years (P = 0.048). Additionally, soluble AREG levels were significantly higher (p < 0.05) in patients with diabetic nephropathy or primary hypertension. Moreover, AREG was highly expressed in renal tubular cells in patients with advanced CKD, but only weakly expressed in patients with preserved renal function. CONCLUSION: Serum soluble AREG levels were significantly correlated with renal function, and changes in renal function after 2 and 3 years, indicating that serum soluble AREG levels might serve as a biomarker of renal function and renal prognosis in CKD.

Hypereosinophilic syndrome presenting as eosinophilic gastroenteritis exacerbated by clopidogrel bisulphate.

Clopidogrel is a widely prescribed prodrug with antithrombotic activity that functions by irreversibly inhibiting the P2Y12 receptors on platelets; nevertheless, drug-induced eosinophilia from this drug is rarely reported. An 81-year-old man was diagnosed with cerebral infarction 2 months earlier and was admitted to our hospital with rash, fever, wheezing, and stomach discomfort after being initiated with clopidogrel treatment. Based on his medical history, chest CT, and gastroscopy, we diagnosed him with clopidogrel-induced hypereosinophilic syndrome. After discontinuation of clopidogrel, the eosinophilia and symptoms improved. In cases of drug-induced eosinophilia, it is important to obtain a detailed medical history.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia.

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (ß coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

Incidence of acute kidney injury and decreased estimated glomerular filtration rate according to the site of cancer.

BACKGROUND: The epidemiology of renal impairment in patients with cancer remains unclear. We aimed to clarify associations between various cancer sites and renal impairment. METHODS: We reviewed data from 5674 patients aged ≥ 18 years receiving cancer treatment at a single hospital facility. The primary endpoints were the occurrence of acute kidney injury (AKI), a 30% decrease in the estimated glomerular filtration rate (eGFR), or death. Survival time was defined as the time from study enrolment to AKI occurrence. Kaplan-Meier and Cox proportional hazard analyses were performed. RESULTS: Hazard ratios (HRs) for AKI occurrence and a ≥ 30% decline in eGFR were significantly higher for kidney, urinary tract, pancreatic, liver, and gallbladder cancers than for colon cancer. Compared with colon cancer, digestive tract cancer showed a significantly higher HR for AKI occurrence alone. The HRs for a ≥ 30% decline in eGFR were significantly higher for patients aged 71‒77 years or ≥ 78 years than for those aged < 68 years, and for patients with eGFR ≥ 90 mL/min/1.73 m2 or 30-44 mL/min/1.73 m2 than for those with eGFR = 45‒59 mL/min/1.73 m2. CONCLUSIONS: Kidney, urinary, hepatobiliary, or pancreatic cancer are associated with a higher risk of AKI development and eGFR decrease than other cancers. Renal function changes should be more closely monitored in patients with these cancers.

Denileukin diftitox-induced systemic capillary leak syndrome with acute kidney injury.

Systemic capillary leak syndrome is a rare and life-threatening disorder, characterized by recurrent episodes of unexplained hypotension, hemoconcentration, and hypoalbuminemia. This condition is caused by leakage of plasma and proteins into the extravascular space and can be classified as either idiopathic or secondary. Secondary systemic capillary leak syndrome can result from cancer, infections, medications, or surgery. Systemic capillary leak syndrome frequently develops as a side effect of denileukin diftitox treatment of refractory cutaneous T-cell lymphoma. However, the pathophysiology of this disease is not well understood. Herein, we report a case of denileukin diftitox-induced systemic capillary leak syndrome.

Overlap of Thrombotic Microangiopathy and Mesangial Proliferative Glomerulonephritis Caused by Combination Therapy with Atezolizumab and Bevacizumab.

Vascular endothelial growth factor inhibitors and checkpoint inhibitors are effective treatments for solid tumors. These new classes of anti-cancer agents frequently cause kidney-related side effects. Although their anti-cancer effects may be enhanced when used in combination, the severity of their kidney-related side effects is unknown. We herein report the first case of thrombotic microangiopathy and mesangial proliferative glomerulonephritis caused by combined treatment with atezolizumab and bevacizumab in a 74-year-old man with hepatocellular carcinoma. The combination therapy was discontinued and replaced with intravenous methylprednisolone followed by oral prednisolone. Subsequently, the urinary protein excretion levels declined.

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.

Adult-onset Langerhans cell histiocytosis changing CNS lesion from pituitary to suprasellar extension.

Summary: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of abnormal Langerhans cells in various tissues and organs, including bone, skin, the lungs, and the pituitary gland. Hypothalamic-pituitary lesions in LCH often cause central diabetes insipidus (CDI), but the natural course of LCH in the CNS remains to be elucidated. In this study, we report an interesting case of altered LCH lesions in the CNS from the pituitary to the hypothalamus in a 45-year-old woman. She developed symptoms of polyuria and was diagnosed with CDI with lymphocytic hypophysitis due to an enlarged pituitary gland with stalk thickening shown on MRI. Short-term glucocorticoid therapy cured pituitary enlargement, but serum prolactin levels gradually increased. Six years later, the immunohistological findings of a skin biopsy revealed positive for leukocyte common antigen, S-100, and CD1a expression, indicating a diagnosis of LCH. MRI revealed a new lesion in the hypothalamus without pituitary involvement, likely due to LCH. Chemotherapy improved LCH lesions both in the skin and hypothalamus, but therapy was stopped on the patient's request. Although adult-onset LCH is rare, it should be considered as a differential diagnosis in cases of CDI as the primary disease. The clinical course in the present case indicated that LCH lesion was altered from pituitary to suprasellar extension; where such changes were observed, the possibility of LCH should be considered. Learning points: Diagnosing the primary disease of CDI is challenging; therefore, careful observation is necessary in pathologically unknown cases. Enhanced MRI should be performed in cases with suspected hypothalamic lesions, such as elevated serum prolactin. Although adult-onset LCH is rare, it should be considered a differential diagnosis in cases of CDI as the primary disease. The direction of changing CNS lesion from pituitary to suprasellar extension might be a unique MRI finding in LCH.