The Transfer of the Hepatocyte Growth Factor Gene by Macrophages Ameliorates the Progression of Peritoneal Fibrosis in Mice.

Growing evidence indicates that hepatocyte growth factor (HGF) possesses potent antifibrotic activity. Furthermore, macrophages migrate to inflamed sites and have been linked to the progression of fibrosis. In this study, we utilized macrophages as vehicles to express and deliver the HGF gene and investigated whether macrophages carrying the HGF expression vector (HGF-M) could suppress peritoneal fibrosis development in mice. We obtained macrophages from the peritoneal cavity of mice stimulated with 3% thioglycollate and used cationized gelatin microspheres (CGMs) to produce HGF expression vector-gelatin complexes. Macrophages phagocytosed these CGMs, and gene transfer into macrophages was confirmed in vitro. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) for three weeks; seven days after the first CG injection, HGF-M was administered intravenously. Transplantation of HGF-M significantly suppressed submesothelial thickening and reduced type III collagen expression. Moreover, in the HGF-M-treated group, the number of α-smooth muscle actin- and TGF-ß-positive cells were significantly lower in the peritoneum, and ultrafiltration was preserved. Our results indicated that the transplantation of HGF-M prevented the progression of peritoneal fibrosis and indicated that this novel gene therapy using macrophages may have potential for treating peritoneal fibrosis.

Hydroxychloroquine suppresses anti-GBM nephritis via inhibition of JNK/p38 MAPK signaling.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) nephritis, characterized by glomerular crescent formation, requires early treatment because of poor prognosis. Hydroxychloroquine (HCQ) is an antimalarial drug with known immunomodulatory, anti-inflammatory, and autophagy inhibitory effects; it is recognized in the treatment of autoimmune diseases such as systemic lupus erythematosus. However, its effect on anti-GBM nephritis remains unknown. In this study, we investigated the effect of HCQ on anti-GBM nephritis in rats. METHODS: Seven-weeks-old male WKY rats were administered anti-GBM serum to induce anti-GBM nephritis. Either HCQ or vehicle control was administered from day 0 to day 7 after the induction of nephritis. Renal function was assessed by measuring serum creatinine, proteinuria, and hematuria. Renal histological changes were assessed by PAS staining and Masson trichrome staining, and infiltration of macrophages was assessed by ED-1 staining. Mitogen-activated protein kinase (MAPK) was evaluated by western blotting, while chemokine and inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay using urine sample. RESULTS: HCQ treatment suppressed the decline in renal function. Histologically, extracapillary and intracapillary proliferations were observed from day 1, while fibrinoid necrosis and ED-1 positive cells were observed from day 3. Rats with anti-GBM nephritis showed high levels of monocyte chemotactic protein-1 and tumor necrosis factor-α. These changes were significantly suppressed following HCQ treatment. In addition, HCQ suppressed JNK/p38 MAPK phosphorylation. CONCLUSION: HCQ attenuates anti-GBM nephritis by exerting its anti-inflammatory effects via the inhibition of JNK/p38 MAPK activation, indicating its therapeutic potential against anti-GBM nephritis.

An inhibitor of Krüppel-like factor 5 suppresses peritoneal fibrosis in mice.

BACK GROUND: Krüppel-like transcription factor 5 (KLF5) is a transcription factor regulating cell proliferation, angiogenesis and differentiation. It has been recently reported that Am80, a synthetic retinoic acid receptor α-specific agonist, inhibits the expression of KLF5. In the present study, we have examined the expression of KLF5 in fibrotic peritoneum induced by chlorhexidine gluconate (CG) in mouse and evaluated that Am80, as an inhibitor of KLF5, can reduce peritoneal fibrosis. METHODS: Peritoneal fibrosis was induced by intraperitoneal injection of CG into peritoneal cavity of ICR mice. Am80 was administered orally for every day from the start of CG injection. Control mice received only a vehicle (0.5% carboxymethylcellulose solution). After 3 weeks of treatment, peritoneal equilibration test (PET) was performed and peritoneal tissues were examined by immunohistochemistry. RESULTS: The expression of KLF5 was less found in the peritoneal tissue of control mice, while KLF5 was expressed in the thickened submesothelial area of CG-injected mice receiving the vehicle. Am80 treatment reduced KLF5 expression and remarkably attenuated peritoneal thickening, accompanied with the reduction of type III collagen expression. The numbers of transforming growth factor ß-positive cells, α-smooth muscle actin-positive cells and infiltrating macrophages were significantly decreased in Am80-treated group. PET revealed the increased peritoneal permeability in CG mice, whereas Am80 administration significantly improved the peritoneal high permeability state. CONCLUSIONS: These results indicate the involvement of KLF5 in the progression of experimental peritoneal fibrosis and suggest that Am80 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of KLF5 expression.

Anti-glomerular Basement Membrane Disease with Antiphospholipid Syndrome.

A 48-year-old woman presented with a fever, microscopic hematuria, proteinuria, and rapid deterioration of the renal function. Pulmonary alveolar hemorrhaging and a high level of anti-glomerular basement membrane (GBM) antibodies (700 IU/mL) were observed. Based on her medical history and positive findings of serum lupus anticoagulant, anti-phospholipid antibody syndrome (APS) was suspected. A renal biopsy revealed cellular crescentic glomerulonephritis with thrombosis, suggesting anti-GBM disease with catastrophic APS. The patient was treated with pulse steroid therapy, plasma exchange, hemodialysis, and intravenous cyclophosphamide pulse therapy. To our knowledge, this is the first report of a patient with anti-GBM disease and APS.

Detection of Rhizopus-specific antigen in human and murine serum and bronchoalveolar lavage.

Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1 ng/ml) than that in invasive pulmonary aspergillosis patients (0.53 ng/ml) and the negative control (0.49 ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis.

Hexapeptide derived from prothymosin alpha attenuates cisplatin-induced acute kidney injury.

BACKGROUND: Prothymosin alpha (ProTα) is a nuclear protein expressed in virtually all mammalian tissues. Previous studies have shown that ProTα exhibits protective effects against ischemia-induced cell death in various cell types. Recently, the 6-residue peptide P6Q (NEVDQE), the modified form of the active 6-residue core (51-56) in ProTα, has also been shown to have protective effects against retinal ischemia. However, it remains to be elucidated whether P6Q is effective against acute kidney injury (AKI). Therefore, we investigated the renoprotective effect of P6Q on cisplatin-induced AKI. METHODS: Cultured HK-2 cells were treated with cisplatin for 24 h and pretreatment with ProTα or P6Q was carried out 30 min before cisplatin treatment. Cell viability was evaluated using the MTT assay. In an in vivo study, 8-week-old male Wistar rats were divided into control, cisplatin treated, and cisplatin treated with P6Q injection groups. In the last of these, P6Q was injected intravenously before cisplatin treatment. Then, we evaluated the renoprotective effect of P6Q. RESULTS: In the study on cultured cells, pretreatment with ProTα or P6Q prevented cisplatin-induced cell death. In the in vivo study, pretreatment with P6Q significantly attenuated cisplatin-induced increase in serum creatinine and blood urea nitrogen levels, renal tubular cell injury, and apoptosis. Moreover, P6Q attenuated the mitochondrial apoptotic pathway and accelerated Akt phosphorylation after cisplatin-induced renal damage. CONCLUSION: Taken together, our findings indicate that P6Q can attenuate cisplatin-induced AKI and suppress the mitochondrial apoptotic pathway via Akt phosphorylation. These data suggest that P6Q has potential as a preventative drug for cisplatin-induced AKI.

Effect of statin on life prognosis in Japanese patients undergoing hemodialysis.

The effect of statin on hemodialysis patients is controversial. Although previous large-scale studies did not clarify its effect in this population, recent studies suggest that statins could be useful in reducing the risk of cardiovascular events and all-cause mortality in specific groups of patients undergoing hemodialysis. The aforementioned large-scale studies included a small percentage of Asians, and few studies have investigated the effects of statins in Asians undergoing hemodialysis. Thus, we investigated the benefits of statins in patients undergoing maintenance hemodialysis at a single center in Japan. We obtained demographic, clinical, and hemodialysis data of all patients who underwent maintenance hemodialysis at the Nagasaki Renal Center between July 2011 and June 2012. Patients were followed-up until June 2018. We studied 339 patients, of which 51 (15.0%) were prescribed pitavastatin. The mean observation period was 4.1±2.3 years, 43% were women, and the median hemodialysis vintage at baseline was 4.7 years. During the follow-up, 198 patients (58%) died, of which 22 (43%) were prescribed pitavastatin and 176 (61%) were not prescribed any statins. After propensity score matching based on age, sex, dialysis vintage, dialysis time, diabetes mellitus, ischemic heart disease, dry weight, left ventricular ejection fraction, and serum albumin, an intergroup comparison between those who received statins and those who did not (44 patients in each group) showed significant differences in survival rate based on the log-rank test (P<0.05). Although the causes of death did not differ significantly between groups, deaths due to cardiovascular events, infections, and cancer were fewer in the group prescribed statins. Our results suggest that statins may reduce mortality in Japanese patients undergoing maintenance hemodialysis. Although potential residual confounders exist, statins may have an influence on the reduction in the incidence of cardiovascular events, infections, and cancer. Nevertheless, further studies are required to prove this hypothesis.

Pathological Characteristics of Periodontal Disease in Patients with Chronic Kidney Disease and Kidney Transplantation.

Chronic kidney disease (CKD) is recognized as an irreversible reduction of functional nephrons and leads to an increased risk of various pathological conditions, including cardiovascular disease and neurological disorders, such as coronary artery calcification, hypertension, and stroke. In addition, CKD patients have impaired immunity against bacteria and viruses. Conversely, kidney transplantation (KT) is performed for patients with end-stage renal disease as a renal replacement therapy. Although kidney function is almost normalized by KT, immunosuppressive therapy is essential to maintain kidney allograft function and to prevent rejection. However, these patients are more susceptible to infection due to the immunosuppressive therapy required to maintain kidney allograft function. Thus, both CKD and KT present disadvantages in terms of suppression of immune function. Periodontal disease is defined as a chronic infection and inflammation of oral and periodontal tissues. Periodontal disease is characterized by the destruction of connective tissues of the periodontium and alveolar bone, which may lead to not only local symptoms but also systemic diseases, such as cardiovascular diseases, diabetes, liver disease, chronic obstructive pulmonary disease, and several types of cancer. In addition, the prevalence and severity of periodontal disease are significantly associated with mortality. Many researchers pay special attention to the pathological roles and clinical impact of periodontal disease in patients with CKD or KT. In this review, we provide information regarding important modulators of periodontal disease to better understand the relationship between periodontal disease and CKD and/or KT. Furthermore; we evaluate the impact of periodontal disease on various pathological conditions in patients with CKD and KT. Moreover, pathogens of periodontal disease common to CKD and KT are also discussed. Finally, we examine the importance of periodontal care in these patients. Thus, this review provides a comprehensive overview of the pathological roles and clinical significance of periodontal disease in patients with CKD and KT.

Evaluation of Candida peritonitis with underlying peritoneal fibrosis and efficacy of micafungin in murine models of intra-abdominal candidiasis.

Candida peritonitis is a crucial disease, however the optimal antifungal therapy regimen has not been clearly defined. Peritoneal fibrosis (PF) can be caused by abdominal surgery, intra-abdominal infection, and malignant diseases, and is also widely recognized as a crucial complication of long-term peritoneal dialysis. However, the influence of PF on Candida peritonitis prognosis remains unknown. Here, we evaluated the severity of Candida peritonitis within the context of PF and the efficacy of micafungin using mice. A PF mouse model was generated by intraperitoneally administering chlorhexidine gluconate. Candida peritonitis, induced by intraperitoneal inoculation of Candida albicans, was treated with a 7-day consecutive subcutaneous administration of micafungin. Candida infection caused a higher mortality rate in the PF mice compared with the control mice on day 7. Proliferative Candida invasion into the peritoneum and intra-abdominal organs was confirmed pathologically only in the PF mice. However, all mice in both groups treated with micafungin survived until day 20. Micafungin treatment tends to suppress inflammatory cytokines in the plasma 12 h after infection in both groups. Our results suggest that PF enhances early mortality in Candida peritonitis. Prompt initiation and sufficient doses of micafungin had good efficacy for Candida peritonitis, irrespective of the underlying PF.

Membranous Nephropathy with Crescent after Hematopoietic Cell Transplantation.

A 44-year-old man who received allogenic hematopoietic stem cell transplantation after being diagnosed with acute myeloid leukemia developed nephrosis when the dose of tacrolimus was tapered. A renal biopsy showed the granular deposition of immunoglobulin G in the glomerular basement membrane and subepithelial electron-dense deposits, crescent formation, C4d-positive staining of the peritubular capillary, and subendothelial swelling, suggesting that the main pathological diagnosis was membranous nephropathy and that chronic graft-versus-host disease played a role in the etiology of nephrosis. We herein report a case of membranous nephropathy with various pathological findings. C4d deposition suggests complement activation and the involvement of humoral factors.

A case of mild phenotype Alport syndrome caused by COL4A3 mutations.

In a case of 41-year-old man with mild nephropathy, Alport syndrome (AS) was diagnosed from the renal biopsy. However, the α5 chain of type IV collagen expressed in the glomerular basement membrane, which was the atypical staining pattern of AS. Genetic testing suggested autosomal recessive AS from heterozygous mutations at two positions in the type IV collagen α3 chain. These two gene mutations represented a new pattern of mutation and was suggested the association with an atypical α5 chain expression and mild phenotype.

A Comparative Study of the Hemoglobin-Maintaining Effects Between Epoetin-ß Pegol and Darbepoetin-α in Patients with Chronic Kidney Disease During 3 Months Before Dialysis Initiation.

BACKGROUND AND OBJECTIVE: We compared the hemoglobin-maintaining effects between continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) in patients with chronic kidney disease (CKD) during the 3 months before dialysis initiation. METHODS: This study was conducted with 37 CERA-administered patients and 26 DA-administered patients who had initiated dialysis at a participating facility between January 2012 and December 2014. We investigated clinical laboratory data 3 months before and at dialysis initiation, and compared these data between the CERA and DA groups. RESULTS: No significant differences in hemoglobin level or reticulocyte count were found between the two groups 3 months before dialysis initiation. However, at dialysis initiation, the hemoglobin level (CERA 9.82 ± 1.52 vs. DA 8.79 ± 1.07 g/dL; P = 0.003) and the reticulocyte count (CERA 5.21 ± 2.95 vs. DA 3.15 ± 1.62 × 104/µL; P = 0.004) were significantly higher in the CERA group than in the DA group. Moreover, the extent of changes in the erythropoietin resistance index during the 3 months before dialysis initiation was significantly increased in the DA group compared with the CERA group. CONCLUSIONS: Our results suggest that CERA may be more effective than DA in maintaining hemoglobin levels in patients with CKD during 3 months before dialysis initiation.

Serum Endocan as a Predictive Marker for Decreased Urine Volume in Peritoneal Dialysis Patients.

BACKGROUND Endocan is expressed in vascular endothelial cells, and its expression is enhanced following endothelial injury via inflammatory cytokines. Subsequently, endocan is secreted into the circulation. Thus, serum endocan levels are considered a marker of endothelial injury. However, to the best of our knowledge, no data on the serum endocan levels in peritoneal dialysis (PD) patients are available. MATERIAL AND METHODS This study included 21 PD patients who underwent peritoneal equilibration test (PET) more than once between 2011 and 2015. Serum samples were collected from each patient, and the 24-h urine volume was measured at the time of PET. Serum endocan levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of the first PET, and their relationship with clinical data or the extent of urine volume decline (mL/year) was analyzed retrospectively. RESULTS Serum endocan levels were positively correlated with proteinuria level, serum creatinine level, serum tumor necrosis factor (TNF)-α level, ß2-microglobulin level, and PD drainage volume, but not with urine volume at baseline. The extent of decline in urine volume was significantly associated with serum endocan level, proteinuria level, serum creatinine level, and serum TNF-α level at baseline in a simple linear regression analysis. Moreover, multiple linear regression analysis showed that the serum endocan level and proteinuria level at baseline were independent predictors for the extent of decline in urine volume. CONCLUSIONS The results of this study indicate that serum endocan level and proteinuria level may be useful predictive markers for decreased urine volume in PD patients.

Improvements in Pneumatosis Cystoides Intestinalis and Hepatic Portal Venous Gas with Conservative Therapy in a Patient on Maintenance Dialysis.

A 77-year-old man on maintenance dialysis developed hypotension, nausea and abdominal pain one hour after beginning to undergo hemodialysis. Abdominal computed tomography (CT) showed gas shadows in the intrahepatic portal vein and the small intestinal wall, but no signs indicating intestinal necrosis. Three days later, the gas shadows on abdominal CT disappeared by conservative therapy. In cases with both pneumatosis cystoides intestinalis and hepatic portal venous gas, intestinal necrosis should therefore be suspected and surgical therapy should also be considered, particularly in hemodialysis patients with a risk of intestinal ischemia. However, conservative therapy may be an option in cases with no intestinal necrosis.

Curcumin ameliorates nephrosclerosis via suppression of histone acetylation independent of hypertension.

BACKGROUND: Although histone acetylation, an epigenetic modification, has been reported to be related to the progression of various diseases, its involvement in nephrosclerosis is unclear. METHODS: Dahl salt-sensitive rats were used as a model of nephrosclerosis in this study. The rats were divided into three groups: (i) normal-salt diet group, (ii) high-salt diet group (HS), and (iii) HS administered daily with curcumin, a histone acetyltransferase inhibitor (HS+C). At 6 weeks after the treatment, the kidneys were dissected. Morphologic changes were assessed by Masson's trichrome staining. The number of macrophages, fibroblasts and the cells expressing acetylated histone H3 at Lys 9 (H3K9) were assessed by immunohistochemistry. RESULTS: Although both HS and HS+C rats revealed a marked increase in systolic blood pressure, serum creatinine was increased only in HS rats at 6 weeks. In the HS rats, nephrosclerosis was induced, accompanying a significant accumulation of macrophages and fibroblasts. The inflammation and fibrosis was markedly suppressed in the HS+C group. The level of histone acetylation at Lys 9 was enhanced in the HS rats, whereas curcumin administration suppressed the histone acetylation. Moreover, in the HS rats, interleukin-6 gene expression was associated with acetylated H3K9, as revealed by chromatin immunoprecipitation assay. CONCLUSIONS: Our results suggested that curcumin ameliorates nephrosclerosis via suppression of histone acetylation, independently of hypertension.

Chondroitin sulfate prevents peritoneal fibrosis in mice by suppressing NF-κB activation.

Long-term peritoneal dialysis causes peritoneal fibrosis, and previous reports suggest that inflammation plays a critical role in peritoneal fibrosis. Chondroitin sulfate (CS) suppresses the inflammatory response by preventing activation of nuclear factor (NF)-κB. We examined the effect of CS on the peritoneal fibrosis induced by chlorhexidine gluconate (CG) in mice. CS or water was administered daily. We divided mice into four groups: administered vehicle and water (control); administered vehicle and CS (CS); administered CG and water (CG); and administered CG and CS (CG+CS). Morphologic changes were assessed by Masson's trichrome staining. Inflammation- and fibrosis-associated factors were assessed by immunohistochemistry. Activation of NF-κB was examined by southwestern histochemistry. CS administration suppressed the progression of submesothelial thickening. The numbers of inflammation- and fibrosis-associated factors -positive cells were significantly decreased in the CG+CS group, compared to the CG group. Based on SWH, the CG+CS group contained significantly fewer NF-κB-activated cells than the CG group. Our results indicate that CS suppresses peritoneal fibrosis via suppression of NF-κB activation. These results suggest that CS has therapeutic potential for peritoneal fibrosis.

The kampo medicine Daikenchuto inhibits peritoneal fibrosis in mice.

Long-term peritoneal dialysis therapy causes inflammation and histological changes in the peritoneal membrane. Inflammation generally activates fibroblasts and results in fibroblast-myofibroblast differentiation. Heat-shock protein 47 (HSP 47), a collagen-specific molecular chaperone, is localized in myofibroblasts and is involved in the progression of peritoneal fibrosis. Daikenchuto (DKT), a Kampo medicine, is used to prevent postoperative colon adhesion. It inhibits inflammation and HSP 47 expression in the gastrointestinal tract. We examined the effect of DKT on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in mice injected with 0.1% CG dissolved in 15% ethanol. DKT was dissolved in the drinking water. Histological changes were assessed using Masson trichrome staining. Cells expressing α-smooth muscle actin (α-SMA), HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 were examined immunohistochemically. Compared with the control group, the peritoneal tissues of the CG group were markedly thickened, and the number of cells expressing α-SMA, HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 was significantly increased. However, these changes were inhibited in the DKT-treated group. These results indicate that DKT can prevent peritoneal fibrosis by inhibiting inflammation and HSP 47 expression.

A case of membranoproliferative glomerulonephritis and AA amyloidosis complicated with pulmonary nontuberculous mycobacterial infection.

A 75-year-old man was diagnosed with pulmonary nontuberculous mycobacterial (NTM) infection in February 2005 and was treated with rifampicin, ethambutol, and clarithromycin. However, the infection was resistant to treatment, and his chest radiograph showed an abnormality that gradually seemed to aggravate. The patient's sputum was positive for Mycobacteria. Moreover, the patient had dyspnea and an underlying chronic inflammation in the lungs. He visited our hospital because of dyspnea and leg edema in June 2011. Laboratory evaluation on admission revealed proteinuria (6 g/day) and decreased serum total protein (5.8 g/dL) and albumin (1.6 g/dL) levels, indicating nephrotic syndrome. Percutaneous renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) in the acute stage and AA amyloidosis of mild degree. AA amyloidosis was also diagnosed histologically on gastric and colonic biopsy, in addition to renal biopsy. His renal function decreased gradually, and therefore, he underwent hemodialysis therapy in January 2012. However, his gastrointestinal-related symptoms persisted, and his appetite diminished, because of which he had become severely malnourished; he died 8 months later. This is a rare case of a patient with two different renal lesions (MPGN and AA amyloidosis) complicated with NTM. Our case suggests that MPGN and amyloidosis should be considered in elderly patients with nephrotic syndrome onset and chronic inflammation.

Three cases of concurrent infection with Mycobacterium tuberculosis and Cryptococcus neoformans.

Impaired cellular-mediated immunity is a known risk factor for both tuberculosis and cryptococcosis. However, pulmonary cryptococcosis associated with pulmonary tuberculosis is rare. We herein describe three cases of concurrent infection with Mycobacterium tuberculosis and Cryptococcus neoformans. All patients had underlying diseases; all three had uncontrolled diabetes mellitus, and other underlying diseases were liver cirrhosis, malignancy, and rheumatoid arthritis requiring long-term steroid use. We also review other relevant reports.

Concurrent subcutaneous candidal abscesses and pulmonary cryptococcosis in a patient with diabetes mellitus and a history of corticosteroid therapy.

A 50-year-old man with a history of long-term corticosteroid treatment following adrenalectomy for Cushing's syndrome and uncontrolled diabetes mellitus was admitted for an examination of an abnormal thoracic shadow. Cryptococcal serum antigens were positive, and the histopathology of a lung biopsy showed encapsulated yeast resembling Cryptococcus neoformans. On admission, the serum ß-D-glucan level was approximately twice the cutoff value, several nodules were observed on both legs and magnetic resonance imaging revealed subcutaneous abscesses. Candida albicans was identified from needle aspirates, and the patient was successfully treated with fluconazole and flucytosine. We herein report the first case of concurrent C. albicans skin abscesses and pulmonary cryptococcosis.