Pulmonary cryptococcosis mimicking lung cancer with multiple lung metastases.

The differential diagnosis of a lung mass with multiple pulmonary nodules includes metastases of lung cancer, mycobacterial infections, and pulmonary mycosis. Pulmonary cryptococcosis should be recognized, especially in immunocompromised patients.

Differences in characteristics and risk factors for acute kidney injury between elderly and very elderly patients: a retrospective review.

BACKGROUND: Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study aimed to clarify the characteristics and risk factors for AKI in this population. METHODS: This retrospective observational study was performed with the clinical data of all outpatients and inpatients aged ≥ 65 years at the time of enrolment at Kochi Medical School Hospital between 1 January 1981 and 31 December 2021. The primary cohort was divided into those aged 65-74 and ≥ 75 years. The primary outcome was the occurrence of AKI. RESULTS: Of 83,822 patients, 38,333 were included in the 65-74-year-old group, whereas 45,489 were included in the ≥ 75-year-old group. Prevalences of the first AKI event in the 65-74-year-old and ≥ 75-year-old groups were 11.9% and 12.4%, respectively. Overall, lower estimated glomerular filtration rate, lower albumin level, lower or higher level of serum uric acid, and histories of diabetes mellitus, chronic heart failure, ischaemic heart disease, non-ischaemic heart disease, cerebrovascular disease, cancer, and liver disease were independent risk factors for an AKI event. The risk factors for AKI unique to each cohort were using non-steroidal anti-inflammatory drugs (NSAIDs) and loop diuretics (L-DI), and histories of hypertension (HT) and vascular diseases (VD) in men aged 65-74 years; using NSAIDs, angiotensin-converting enzyme inhibitors (ACEIs), L-DI and other diuretics (O-DI), and histories of HT and VD in men aged ≥ 75 years; using NSAIDs and O-DI and not using angiotensin-receptor blockers (ARBs), and a history of HT in women aged 65-74 years; and use of L-DI and a history of VD in women aged ≥ 75 years. Presence of proteinuria was a risk factor for developing AKI. CONCLUSIONS: Many AKI risk factors reported thus far are associated with AKI development. However, there are differences in the effects of the renin-angiotensin system inhibitors, ACEIs, and ARBs (ARBs may be protective). Additionally, the U-shaped relationship between AKI onset and uric acid levels differs between sexes in the elderly population, similar to other age groups, but this sex difference disappears in the very elderly population. Pre-existing chronic kidney disease is a risk factor for the development of AKI.

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.

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.

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.

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.

Knockout of Zeb2 ameliorates progression of renal tubulointerstitial fibrosis in a mouse model of renal ischemia-reperfusion injury.

BACKGROUND: Zeb2, a zinc finger E-box-binding homeobox transcription factor, regulates transforming growth factor (TGF)-ß signaling pathway. However, its role in the pathogenesis of acute kidney injury (AKI) and AKI-to-chronic kidney disease (CKD) transition is unclear. METHODS: We evaluated Zeb2 function in a bilateral renal ischemia-reperfusion injury (IRI)-induced AKI model using proximal tubule-specific Zeb2 conditional knockout (Zeb2-cKO) and wild-type (WT) mice, and in renal biopsy samples. RESULTS: In Zeb2-cKO mice, the levels of plasma creatinine and blood urea nitrogen post-IRI were significantly lower than that in WT mice. Immunohistological analysis revealed mild tubular injury, reduced neutrophil infiltration, fewer fibrotic changes and reduced expression of fibrotic proteins [collagen type IV, α-smooth muscle actin (α-SMA), fibronectin and connective tissue growth factor (CTGF)], at 3-14 days post-IRI. Zeb2 expression was upregulated in proximal tubular cells post-IRI in WT mice. Zeb2 siRNA transfection reduced TGF-ß-stimulated mRNA and protein expression of collagen type IV, α-SMA, fibronectin and CTGF in cultured renal tubular cells. Patients with AKI-to-CKD transition exhibited high Zeb2 expression in renal tubules, as revealed by renal biopsy. Hypoxia and CoCl2-treatment upregulated Zeb2 promoter activity and mRNA and protein expression in cultured renal tubular epithelial cells, suggesting a regulatory role for hypoxia. CONCLUSIONS: Zeb2 was upregulated in renal tissues in both mice and humans with AKI. Zeb2 regulates fibrotic pathways in the pathogenesis of AKI and AKI-to-CKD transition. Therefore, inhibition of Zeb2 could be a potential therapeutic strategy for AKI.

Lupus-related protein-losing enteropathy associated with pseudo-pseudo Meigs' syndrome and successfully treated with hydroxychloroquine.

We herein report the first case of lupus-related protein-losing enteropathy associated with pseudo-pseudo Meigs' syndrome. Lupus-related protein-losing enteropathy and pseudo-pseudo Meigs' syndrome are extremely rare complications in patients with systemic lupus erythematosus, Both have a similar clinical course characterized by producing marked ascites, and respond to steroids in typical cases. However, in our case, steroid monotherapy was inadequate and the addition of hydroxychloroquine was effective for their treatment. Furthermore, no reports have previously confirmed elevated CA 125 levels with lupus-related protein-losing enteropathy or increased 99mTc-HSA activity with pseudo-pseudo Meigs' syndrome. In addition, we are the first to report an evaluation of the histopathology of lupus-related protein-losing enteropathy. Previously reported cases have been described as being caused by either pseudo-Meigs's syndrome or lupus-related protein-losing enteropathy as the cause of the rare pathology that causes marked pleural effusion and ascites in patients with systemic lupus erythematosus, but it has not been evaluated whether the other is co-occurring. Our case highlights that there is a potential case of overlapping lupus-related protein-losing enteropathy and pseudo-Pseudo-Meigs's syndrome. Furthermore, it is possible that patients with marked ascites with elevated CA 125 levels were mistakenly diagnosed with Meigs's syndrome or pseudo-Meigs's syndrome associated with malignant or benign ovarian tumors and underwent surgery. Clinicians should not forget SLE with pseudo-Pseudo-Meigs's syndrome as one of the differential diagnoses for marked ascites with elevated CA 125 levels.

Long-term continuous use of proton-pump inhibitors is associated with renal function decline in patients without acute kidney injury.

BACKGROUND: Proton-pump inhibitors (PPIs) are widely used to treat gastroesophageal reflex disease, peptic ulcer disease, and stress ulcer prophylaxis. This study estimated the progress rate of renal dysfunction in patients taking PPIs in clinical settings and compared the results with those of patients taking histamine-2 receptor antagonists (H2RAs). METHODS: We retrospectively reviewed patients' data collected from Kochi Medical School Hospital's information system between 2001 and 2019. Patients were classified into PPI and H2RA groups, and survival time was defined as the period between initial drug administration and a 30% decrease in estimated glomerular filtration rate (eGFR). RESULTS: On survival analysis, the PPI group was associated with higher event incidence rates compared to that in the H2RA group. The rate of underlying disease was significantly higher in the PPI group than in the H2RA group, with no significant differences in age and sex between the groups. Comparing the PPI group to the H2RA group, the use of aspirin, clopidogrel, statin, and angiotensin II receptor blocker was significantly higher, whereas the use of non-steroidal anti-inflammatory drugs and steroids was significantly less. Regarding survival rate and 30% decrease in eGFR, the PPI group had a significantly higher survival rate compared to that in the H2RA group at 730 days, but not earlier. PPI use, older age, and eGFR ≥ 90 mL/min/1.73 m2 exhibited high hazard ratios. CONCLUSIONS: PPI use was significantly associated with an increased risk of chronic kidney disease development compared to that with H2RA use.