Simultaneous subacute interstitial nephritis and anticoagulant-related nephropathy related to novel oral anticoagulants use.

Introduction: Interstitial nephritis related to novel oral anticoagulants was only reported in sporadic case reports and none was accompanied by anticoagulants related nephropathy (ARN).Case Report: We presented here a case of biopsy-proven subacute interstitial nephritis (SubAIN) accompanied by ARN after oral dabigatran to alarm clinicians. This case manifested with gross hematuria, acute kidney injury, slightly prolonged thrombin time, moderate anemia, moderate proteinuria, a large quantity of intratubular hemoglobin casts confirmed by hemoglobin antibody immunohistochemical staining which presumed to occur around 1 week after dabigatran and subacute interstitial nephritis accompanied by focal proliferative glomerulonephritis. Serum creatinine level did not continue to elevate after discontinuation of the oral anticoagulant. With the subsequent supportive therapy, it decreased to some extent then reduced to normal with the help of prednisone (half of the full dose).Conclusions: When we came across a patient who manifested as hematuria or acute kidney injury with a history of anticoagulants usage, we should think of ARN and pay more attention on history collection. Secondly, subacute interstitial nephritis may coexist with ARN. Thirdly, hemoglobin immunohistochemical staining may be helpful to make it clear whether the intra-tubular protein casts came from red blood cells. In addition, for those patients who may have decreased kidney function, anticoagulants dose should be reduced to prevent the occurrence of ARN.

Correction to: The elevated levels of urinary angiotensinogen are correlated with the severity of idiopathic membranous nephropathy.

Following publication of the original article [1], it was reported that, due to a typesetting mistake, the three tables and two figures for this article were included as an Additional file instead of in the body of the article. The original publication of this article has been updated to correct this.

The elevated levels of urinary angiotensinogen are correlated with the severity of idiopathic membranous nephropathy.

BACKGROUND: Immunosuppressive treatment will predispose an idiopathic membranous nephropathy (iMN) patient to opportunistic infections. Disease severity is one of the main concerns for making the treatment decision. Urinary angiotensinogen (UAGT) level has been shown highly correlated with intrarenal renin-angiotensin system (RAS) activity and severity of chronic kidney diseases (CKD). We aimed to test the relationship between the UAGT level and the severity of iMN. METHODS: This cross-sectional study included a total of 48 biopsy-proven iMN patients, 46 minimal change disease (MCD) patients, and 44 healthy volunteers. The clinical and laboratory data and urine samples were collected from all subjects before the use of RAS inhibitors. We determined the UAGT levels with a method of enzyme-linked immunosorbent assay. RESULTS: The UAGT levels were not different between the iMN (277.05 ± 61.25, µg/g.Cr) and MCD patients (244.19 ± 40.24, µg/g.Cr), but both of them were significantly higher than those of healthy controls (6.85 ± 1.10, µg/g.Cr). UAGT levels were correlated negatively with serum albumin (r = - 0.393, p = 0.006) and estimated glomerular filtration rate (eGFR) (r = - 0.352, p = 0.014) and positively with 24-h proteinuria (r = 0.614, p < 0.001) in iMN patients but not in MCD patients. Multivariate linear regression analysis revealed that only proteinuria independently determinate the levels of UAGT (ß = 0.649, p < 0.001) in iMN patients. CONCLUSIONS: UAGT levels were correlated negatively with serum albumin and glomerular filtration rate and positively with proteinuria in iMN patients at the onset. This suggests that elevated levels of UAGT are associated with the severity of iMN. The UAGT level may be used as a cofactor for deciding immunosuppressive therapy in iMN patient.

C3a mediates epithelial-to-mesenchymal transition in proteinuric nephropathy.

Tubulointerstitial inflammation and progressive fibrosis are common pathways that lead to kidney failure in proteinuric nephropathies. Activation of the complement system has been implicated in the development of tubulointerstitial injury in clinical and animal studies, but the mechanism by which complement induces kidney injury is not fully understood. Here, we studied the effect of complement on the phenotype of tubular epithelial cells. Tubular epithelial cells exposed to serum proteins adopted phenotypic and functional characteristics of mesenchymal cells. Expression of E-cadherin protein decreased and expression of both alpha-smooth muscle actin protein and collagen I mRNA increased. Exposure of the cells to the complement anaphylotoxin C3a induced similar features. Treating with a C3a receptor (C3aR) antagonist prevented both C3a- and serum-induced epithelial-to-mesenchymal transition. In the adriamycin-induced proteinuria model, C3aR-deficient mice demonstrated less injury, preserved renal function, and improved survival compared with wild-type mice. Furthermore, the kidneys of C3aR-deficient mice had significantly less interstitial collagen I and alpha-smooth muscle actin. In summary, the complement anaphylotoxin C3a is an important mediator of glomerular and tubulointerstitial injury and can induce tubular epithelial-to-mesenchymal transition.

The history of hemodialysis in China.

The technique of hemodialysis was introduced into China more than 50 years ago; and both research and use of clinical hemodialysis began in mid-1960s to late-1960s. A brief review of the history of hemodialysis in China is presented here, including a brief description of pioneers and their contributions, local development and use of dialyzers, hemodialysis machines, and vascular access, and dialysis management and logistics.

Serum uric acid and endothelial dysfunction in continuous ambulatory peritoneal dialysis patients.

UNLABELLED: Endothelial dysfunction is an early predictor of cardiovascular events. Hyperuricemia has been shown to be associated with increased cardiovascular mortality. It remains unclear if serum uric acid (UA) is associated with endothelial dysfunction in peritoneal dialysis patients. METHODS: In this cross-sectional study, the relationship of UA and endothelial dysfunction was investigated in 189 stable peritoneal dialysis patients. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. RESULTS: UA levels did not differ between 93 male and 96 female patients (416.31 +/- 86.93 vs. 395.52 +/- 87.47 mumol/l, p > 0.05). Patients were grouped into three tertiles on the basis of their serum UA levels. Systolic blood pressure (p = 0.007), serum phosphate (p = 0.005), high-sensitive C-reactive protein (hs-CRP) (p < 0.001), and FMD (p = 0.016) were all different among UA tertiles. FMD was found to be related with UA (p = 0.002) and hs-CRP (p = 0.006) in a Pearson's correlation analysis. Multivariate regression analysis showed that only UA was an independent determinant of FMD (beta = -0.237, p = 0.036). CONCLUSION: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.

Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury.

Increased exposure of the tubular epithelium to filtered protein is a proposed mechanism of progressive renal failure associated with glomerular disease, but how this protein overload translates into tubular damage remains unclear. We have examined a model of adriamycin-induced proteinuria to determine the effect of locally synthesized C3, the central proinflammatory protein of the complement cascade. C3-/- kidney isografts placed in wild-type C3+/+ mice were protected from proteinuria-associated complement activation, tubular damage, and progressive renal failure despite the presence of abundant circulating C3. The quantity of urinary protein was unaffected by the absence of C3, and thus the influence of C3 was not explained by alteration in the filtered protein load. These results suggest that local synthesis of complement from renal epithelial cells is a critical mediator of tubular damage in proteinuria-associated renal disease. Our results concur with previous findings of increased synthesis of C3 in human tubular epithelium exposed to high concentrations of protein in vitro. Because progressive renal damage in humans associates with proteinuria regardless of cause, our findings have implications for the pathogenesis and treatment of renal failure from many common causes, immunological and nonimmunological.