Yuichi Sakamaki

Expression of SM22α (Transgelin) in Glomerular and Interstitial Renal Injury

Background/Aims: SM22α, transgelin, is abundantly expressed in smooth muscle tissues and our previous work demonstrated that it is a novel marker of injured glomerular epithelial cells in rat antiglomerular basement membrane nephritis. In this study, we investigated SM22α expression in models of glomerular and interstitial renal injury. Methods: The 5/6 nephrectomy (Nx) model, ischemia-reperfusion (I/R) model and puromycin aminonucleoside (PAN) nephrosis of rats were studied. Immunohistochemical analyses and immunoelectron microscopic studies of SM22α expression were performed. Results: In the 5/6 Nx model, SM22α was first expressed in peritubular interstitial cells and was also expressed in injured glomerular epithelial cells at 8 weeks. In the I/R model, SM22α expression was induced in peritubular interstitial cells as early as 12 h after I/R with expression sustained at 7 days. However, SM22α was not detected in any glomerular cells or tubular epithelial cells. In PAN nephrosis, SM22α was only expressed in glomerular epithelial cells after 1 week, but expression was transient. Conclusion: SM22α was expressed in glomerular epithelial cells and interstitial cells in renal injury. SM22α is differentially upregulated in various models of renal injury and merits further study.

Injured kidney cells express SM22α (transgelin): Unique features distinct from α‐smooth muscle actin (αSMA)

Aim:  SM22α (transgelin) has been focused upon as a player in the process of phenotypic changes of types of cells. The SM22α expression in the rat anti‐glomerular basement membrane (GBM) nephritis model and differences from an established phenotypic marker for the myofibroblast, α‐smooth muscle actin (αSMA), were investigated.

Quantitative Histological Analysis of SM22α (Transgelin) in an Adriamycin-Induced Focal Segmental Glomerulosclerosis Model

Background/Aims: SM22α, transgelin, has been revealed to be specifically expressed in glomerular epithelial cells and interstitial cells, according to the nature of the renal injury. In this study, quantitative analyses of SM22α positivity were performed to investigate the pathological significance of its expression. Methods: Kidney samples of adriamycin nephropathy underwent immunohistochemistry with a newly established anti-SM22α monoclonal antibody. The SM22α positivity was quantified by an image analyzer. The correlation of the histological values with biochemical data was investigated statistically. Microstructural localization of SM22α was studied by immunoelectron microscopy. Results: SM22α was expressed along the dense basal microfilaments of degenerating podocytes, and diffusely in interstitial cells. Both the extent and intensity of SM22α expression in glomerular and tubulointerstitial area were correlated with the deterioration of renal function and the severity of proteinuria. Stepwise multiple linear regression analysis revealed that the extent of its positivity in glomerular or tubulointerstitial area was the determinant of the amount of proteinuria or the deterioration of creatinine clearance (Ccr), respectively. Inversely, the deterioration of Ccr was the most important predictor of SM22α expression. Conclusion: SM22α expression in podocytes and interstitial cells represented the severity of proteinuria and the deterioration of renal function. SM22α expression in renal tissues might be a hallmark of kidney diseases.

Clinical practice guideline for drug-induced kidney injury in Japan 2016: digest version

The definition of DKI is a new onset of kidney injury or the worsening of an existing kidney injury due to drug administration. DKI can be classified based on the mechanism of pathogenesis, as well as on the damaged segment of the kidney. The classification based on the mechanism of pathogenesis is as follows: (1) toxic kidney injury (direct toxicity); (2) acute interstitial nephritis (AIN) due to allergic mechanism (hypersensitivity and direct toxicity); (3) indirect toxicity, such as electrolyte abnormalities and decrease of renal blood flow; and (4) obstruction of urinary tract. The classification based on the damaged segment of kidney is as follows: (1) glomerular injury; (2) tubular injury; (3) interstitial injury; and (4) vascular injury. The criteria for diagnosis are as follows: (1) new onset of kidney injury after the start of the administration of the candidate agent and (2) improvement or stoppage of the progression of the kidney injury after the cessation of the candidate agent, and all other causes can be ruled out. The cornerstone of treatment is the identification and cessation of the candidate agent as soon as possible.

Is IgA Nephropathy (IgAN) a Familial or Sporadic Disease

There have been several lines of evidences for familial aggregation of IgA nephropathy (IgAN), as well as mesangial deposition of IgA, suggesting that the susceptibility to this disease is genetically controlled. In our institute, family histories of hematuria, end-stage kidney disease, and glomerulonephritis are observed in about 10 % of cases with IgAN, even in those without any significant hereditary nephritis or kidney diseases. Recent large-scale genome-wide association studies (GWAS) of sporadic IgAN have identified multiple susceptibility loci, providing an insight into the genetic architecture of this disease, although each of their individual impact to the development of the disease is still not enough. It has been recognized that most of these loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. Further elucidation of the role of genetic variants underlying IgAN, and hologenetic views of gene variants and environmental factors, would be necessary to understand the precise pathogenic mechanism of IgAN in more detail.

Fabry disease associated with chronic meningitis and cerebral infarction

A 48‐year‐old man receiving enzyme replacement therapy for Fabry disease was admitted to Niigata Prefectural Shibata Hospital, Shibata, Japan, for a fever, headache, dysarthria and right hemiparesis. Aseptic meningitis and lacunar infarction were diagnosed, and symptomatic therapy and antiplatelet therapy improved the symptoms. As he had had a sub‐ever and headache once a month for 1 year, and developed a fever and headache again 2 months after discharge from our hospital, chronic meningitis was diagnosed. Prednisolone was introduced, and there was no relapse of meningitis thereafter. It is hypothesized that glycosphingolipids accumulated at the leptomeninges could induce aseptic meningitis and result in a shift to chronic meningitis. Chronic meningitis is implicated as the cause of a chronic headache in Fabry disease, and steroids could be a potential effective therapy.

A case of antiglomerular basement membrane glomerulonephritis complicated by membranous nephropathy

Abstract The sequential or simultaneous presentation of anti-glomerular basement membrane (anti-GBM) glomerulonephritis with membranous nephropathy (MN) has been infrequently reported. Although the mechanism underlying MN superimposed on anti-GBM glomerulonephritis is unknown, the two entities are believed to be interrelated. We report the case of a 75-year-old woman diagnosed with rapidly progressive glomerulonephritis. Renal biopsy revealed crescentic glomerulonephritis with linear and granular staining of immunofluorescent IgG1 and IgG4 granular staining on the capillary loops. Electron microscopy revealed extensive subepithelial deposits. These findings suggested simultaneous development of anti-GBM glomerulonephritis and MN in this case. Serum phospholipase A2 receptor (PLA2R) antibody was negative. The patient was treated with prednisolone and plasma exchange, resulting in resolution of renal insufficiency and a decrease in urinary protein. The rapid decrease in urinary protein and absence of PLA2R antibody suggest that the mechanism of MN associated with anti-GBM glomerulonephritis differs from that of primary MN.