Key pathological features characterize minimal change disease-like IgA nephropathy.

AIMS: A subset of IgA nephropathy (IgAN) patients exhibiting minimal change disease (MCD) like features present with nephrotic-range proteinuria and warrants immunosuppressive therapy (IST). However, the diagnosis of MCD-like IgAN varied by reports. We aimed to identify the key pathological features of MCD-like IgAN. METHODS: In this cohort, 228 patients had biopsy-proven IgAN from 2009 to 2021, of which 44 without segmental sclerosis were enrolled. Patients were classified into segmental (< 50% glomerular capillary loop involvement) or global (> 50%) foot process effacement (FPE) groups. We further stratified them according to the usage of immunosuppressant therapy after biopsy. Clinical manifestations, treatment response, and renal outcome were compared. RESULTS: 26 cases (59.1%) were classified as segmental FPE group and 18 cases (40.9%) as global FPE group. The global FPE group had more severe proteinuria (11.48 [2.60, 15.29] vs. 0.97 [0.14, 1.67] g/g, p = 0.001) and had a higher proportion of complete remission (81.8% vs. 20%, p = 0.018). In the global FPE group, patients without IST experienced more rapid downward eGFR change than the IST-treated population (-0.38 [-1.24, 0.06] vs. 1.26 [-0.17, 3.20]mL/min/1.73 m2/month, p = 0.004). CONCLUSIONS: The absence of segmental sclerosis and the presence of global FPE are valuable pathological features that assist in identifying MCD-like IgAN.

Incidence of soft tissue sarcoma in Taiwan: A nationwide population-based study (2007-2013).

BACKGROUND: Asian studies on soft tissue sarcoma (STS) incidence, irrespective of the primary site, are scant. METHODS: STS data were acquired from the population-based 2007-2013 Taiwan Cancer Registry of the Health and Welfare Data Science Center, Taiwan. Histological subtype-, site-, sex-, and age-specific STS incidence rates were analyzed according to the 2013 classification of the World Health Organization. RESULTS: In total, 11,393 patients with an age-standardized incidence rate (ASIR) of 5.62 (95% confidence interval, 5.51-5.73) per 100,000 person-years were identified. Overall, a male predominance (sex-standardized incidence rate ratio, 1.2) was noted, and the rate increased with age, peaking at >75 years. Approximately 30% of STSs occurred in connective, subcutaneous, and other soft tissues and 70% in other sites. In addition to connective, subcutaneous, and other soft tissues, the three most common primary sites were the stomach (15.9%), skin (14.3%), and small intestines (10.5%). Gastrointestinal stromal tumor was the most common subtype (29.2%; ASIR, 1.55/100,000 person-years), followed by liposarcoma (11.5%; ASIR, 0.63/100,000 person-years) and leiomyosarcoma (9.7%; ASIR, 0.53/100,000 person-years). Compared with relevant data from Western countries, the incidence rate of angiosarcomas was higher than that in other regions, whereas the incidence rates of leiomyosarcoma and Kaposi sarcoma were lower than those in other regions. CONCLUSION: STS incidence varied by histological subtype, sex, age, and primary site in an Asian population. Our results suggested regional and racial discrepancies in the incidence rates of certain STS subtypes.

Transcatheter arterial embolization with trisacryl gelatin microspheres (Embosphere(®)) leads to life-threatening tumor lysis syndrome in a rectal carcinoid patient with hepatic metastases.

The incidence of gastrointestinal carcinoids appears to be increasing, and the rectum is the third most common location. Transcatheter arterial embolization (TAE) with trisacryl gelatin microspheres (Embosphere(®)) has been reported as an effective method for hepatic metastases of rectal carcinoids. Complications are uncommon and usually of minor consequence. We report an unusual case of a 34-year-old man with tumor lysis syndrome following TAE with Embosphere(®) in a patient with multiple hepatic metastases of a rectal carcinoid. Early detection and effective treatment are essential for this rare but potentially catastrophic complication.

Acute kidney injury network classification predicts in-hospital and long-term mortality in patients undergoing elective coronary artery bypass grafting surgery.

OBJECTIVE: Acute kidney injury (AKI) is a highly prevalent complication after cardiac surgery. It is associated with substantial morbidity and mortality. However, the definition of AKI has not been well established until the Acute Kidney Injury Network group outlined an easily used consentaneous staging system. The study aims to evaluate the association between this determination and in-hospital as well as long-term mortality in patients receiving elective coronary artery bypass grafting (CABG) surgery. METHODS: Patients undergoing elective CABG surgery from January 2003 to December 2007 in a tertiary medical center were studied. The Acute Kidney Injury Network classification was applied for the diagnosis of perioperative AKI. Medical history and intra-operative variables were collected retrospectively. Multivariate analysis was used to identify the independent risk factors of in-hospital and long-term mortality. Long-term survival rates were calculated using the Kaplan-Meier method. RESULTS: This study included 964 patients. The incidence of AKI following elective CABG was 19.8%. Only 7% of the study population developed AKI requiring renal replacement therapy after surgery. The overall in-hospital mortality rate was 5.1%. Significant independent risk factors for in-hospital mortality include increasing age, higher serum uric acid, postoperative requirement of intra-aortic balloon pumping (IABP) and extracorporeal membrane oxygenation (ECMO), perioperative AKI, and chronic dialysis (all p<0.05). Significant independent risk factors for long-term mortality include increasing age, lower serum albumin, higher serum uric acid, postoperative requirement of IABP and ECMO, perioperative AKI, and chronic dialysis (all p < 0.005). CONCLUSIONS: Acute Kidney Injury Network classification is a powerful tool to evaluate the prognostic impact of AKI on both in-hospital and long-term mortality among patients undergoing elective CABG surgery.

The dysregulated glomerular cell growth in Denys-Drash syndrome.

While diffuse mesangial sclerosis is traditionally described as being the glomerulopathy of Denys-Drash syndrome (DDS), the podocyte proliferative lesions may be overlooked in these DDS cases. In the present study, an evolving process is extrapolated from a selected case of DDS that demonstrated glomerulopathy with conspicuous podocyte proliferation. The observation that podocytes express proliferation markers (Ki67, proliferating-cell nuclear antigen and topoisomerase IIalpha) in non-proliferative, mature-looking glomeruli suggests an initial pathogenic act to activate or to keep podocytes from quiescence. The subsequent proliferation of podocytes is in keeping with downregulation of WT1 and cyclin kinase inhibitors of p16 and p21. The emergence of cytokeratin-positive cells in glomeruli that show typical mesangial sclerosis implies elimination of podocytes and replacement with tubular and/or parietal epithelial cells. The final scene of evolving glomerulopathy displays apoptosis and expression of Fas-L and Bax in sclerotic mesangial lesions, which eventually end up with global sclerosis. This novel concept of DDS glomerulopathy implies complex molecular mechanisms involved in glomerular injury.

Lipoprotein glomerulopathy associated with psoriasis vulgaris: report of 2 cases with apolipoprotein E3/3.

Lipoprotein glomerulopathy (LPG) is a rare disease, characterized by a special histology, including dilated glomerular capillaries filled with pale-stained and meshlike lipoprotein thrombi. It always presents with proteinuria or nephrotic syndrome. Although hyperlipidemia is not always seen, most patients have type III hyperlipoproteinemia with apolipoprotein (apo) E2/3 phenotyping. Although the clinical feature of LPG is rarely described, LPG associated with other glomerulopathy, including IgA nephropathy, membranous nephropathy, and lupus nephritis, has been documented. Until now, there have been no reports of psoriasis vulgaris associated with LPG. The authors present 2 cases of LPG with apo E3/3 genotyping associated with psoriasis vulgaris. The first patient was a 65-year-old woman who presented with nephrotic syndrome with daily urinary protein loss of 9.05 g and itchy erythematous scaly plaques on her trunk and lower limbs for 1 year. The renal biopsy results showed LPG, and the skin biopsy results showed psoriasis. The second patient was a 50-year-old man with history of psoriasis over his trunk and 4 limbs for 30 years. He also presented with nephrotic syndrome with daily urinary protein loss of 7.55 g. The renal biopsy results also showed LPG. The genotype of apo E showed E3/3, and lipoprotein electrophoresis showed a type III hyperlipoproteinemia-like pattern in both cases. The authors suggest that presence of apo E3/3 genotype cannot rule out the diagnosis of type III hyperlipoproteinemia and LPG. Besides, LPG should be included in the differential diagnosis of psoriatic patients with nephrotic syndrome, especially in Asian patients who show poor response to traditional therapy. Renal biopsy should be performed to make the definitive diagnosis.

TNF-alpha renders human peritoneal mesothelial cells sensitive to anti-Fas antibody-induced apoptosis.

BACKGROUND: Fas-mediated apoptosis is important in the regulation of immune response. Human peritoneal mesothelial cells (HPMCs) are able to regulate peritoneal inflammation, but the role of Fas in HPMCs is not clear. This study addresses the mechanisms of Fas-mediated apoptosis in HPMCs. METHODS: Tumour necrosis factor-alpha (TNF-alpha) primed HPMCs were stimulated with agonistic anti-Fas antibody. The expression of Fas was evaluated by real-time reverse transcription polymerase chain reaction (TaqMan quantitative polymerase chain reaction) and flow cytometry. Apoptosis was assessed by nuclear morphology, TUNEL assay, fractional DNA content and cytokeratin 18 cleavage. Caspase activation and bcl-2 expression were analysed by western blotting. The phagocytosis of apoptotic HPMCs was demonstrated by immunofluorescence and transmission electron microscopy. RESULTS: Cultured HPMCs constitutively expressed Fas, and the Fas expression was upregulated by TNF-alpha. TNF-alpha primed HPMCs underwent apoptosis after anti-Fas antibody treatment, and the apoptotic HPMCs could be phagocytosed by macrophages. TNF-alpha was able to downregulate bcl-2 expression. Activation of caspase-3 and caspase-8 was noted during the apoptotic process. The inhibitors of either caspase-3 or caspase-8 could prevent the Fas-induced apoptosis in HPMCs. We also detected increased HPMC apoptosis in dialysate effluent during the recovery phase of peritonitis in peritoneal dialysis patients. CONCLUSIONS: TNF-alpha directs HPMCs to commit apoptosis via the Fas/Fas ligand pathway through a modulation of Fas and bcl-2. Our study shows that HPMCs undergo apoptosis during peritonitis and suggests that the apoptosis of HPMCs may be related to the resolution of peritoneal inflammation.

Myofibroblastic conversion of mesothelial cells.

BACKGROUND: The continuous chemical, physical, and inflammatory insults of prolonged continuous ambulatory peritoneal dialysis (CAPD) incite mesothelial cell responses, which may result in peritoneal fibrosis. The transforming growth factor-beta (TGF-beta), especially the isoform TGF-beta 1, has long been known to play crucial role in the fibrogenic process. Although several studies have implicated TGF-beta in peritoneal fibrosis, the underlying mechanism has not been completely elucidated. METHODS: To test the effects of exogenous TGF-beta 1 on mesothelial cells, we assessed cytoarchitectural changes of human peritoneal mesothelial cells (HPMC) in in vitro culture by light, immunofluorescent, electron and immunoelectron microscopy, and differential gene expression analysis using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and cDNA expression array assays. RESULTS: The TGF-beta 1-induced myofibroblastic conversion was a transdifferentiation process resulting in characteristic myofibroblastic phenotype that included prominent rough endoplasmic reticuli (rER) with dilated cisternas, conspicuous smooth muscle actin (SMA) myofilaments, frequent intercellular intermediate and gap junctions, and active deposition of extracellular matrix (ECM) and formation of fibronexus. The gene expression array analysis revealed complex modulation of gene expression involving cytoskeletal organization, cell adhesion, ECM production, cell proliferation, innate immunity, cytokine/growth factor signaling, cytoprotection, stress response, and many other essential metabolic processes in mesothelial cells. CONCLUSION: This report describes myofibroblastic conversion of mesothelial cells, a previously undefined, yet frequently speculated, cell adaptive or pathogenic process. Our study helps to elucidate the complex molecular and cellular events involved in myofibroblastic conversion of mesothelial cells. We propose that differentiated epithelial cells of mesothelium convert or transdifferentiate into myofibroblasts, which implies the recruitment of fibrogenic cells from mesothelium during serosal inflammation and wound healing.

The association of non-small-cell lung cancer, focal segmental glomerulosclerosis, and platelet dysfunction.

Neoplasm-related nephrotic syndrome exhibiting focal segmental glomerulosclerosis (FSGS) has been reported mainly in patients with hematologic malignancies. The association of FSGS with carcinoma is very rare and nephrotic syndrome caused by FSGS has not yet been reported in patients with lung cancer. We report a case of nephrotic syndrome caused by FSGS in a 61-year-old man with advanced non-small-cell lung cancer. In addition, platelet dysfunction evidenced by prolonged bleeding time was noted. The renal problem and prolonged bleeding time resolved dramatically during radiotherapy for lung cancer. We speculate that both FSGS and prolonged bleeding time are paraneoplastic syndromes associated with lung cancer, although the underlying mechanisms of both conditions remain to be elucidated.