Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review.

BACKGROUND: Light chain cast nephropathy (LCCN) is the most common renal disease caused by multiple myeloma (MM). In addition to ordinary light chain protein casts, there are a few rare casts with unique shapes, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC). CASE PRESENTATIONS: Here, we report two patients. Patient 1 is a 72-year-old man who was clinically diagnosed with MM and acute kidney injury (AKI). Pathological examination of a renal biopsy revealed that there were many amyloid casts in the distal tubules that had a lightly-stained central area and a deeply-stained burr-like edge. The marginal zone of the cast was positive for Congo red staining and contained numerous amyloid fibers, as observed by electron microscopy. No systemic amyloidosis was found. The patient received 4 courses of bortezomib-based chemotherapy, and then, his MM achieved partial remission. Patient 2 is a 57-year-old man who was also clinically diagnosed with MM and AKI. Pathological examination of a renal biopsy showed that there were many crystalline casts in the distal tubules that were fully or partially composed of crystals with different shapes, including rhomboid, needle, triangle, rectangle and other geometric shapes. Congo red staining was negative. Crystals were also detected in the urine of this patient. After 9 courses of treatment with a bortezomib-based regimen, his MM obtained complete remission and his renal function returned to normal. CONCLUSIONS: LCAC and LCCC nephropathy caused by MM are two rare types of LCCN, and both have their own unique morphological manifestations. LCAC nephropathy may not be accompanied by systemic amyloidosis. The diagnosis of these two unique LCCNs must rely on renal biopsy pathology, and the discovery of urine crystals is of great significance for indicating LCCC nephropathy.

SMRT sequencing revealed to be an effective method for ADTKD-MUC1 diagnosis through follow-up analysis of a Chinese family.

We reported a large Chinese family diagnosed with autosomal dominant tubulointerstitial kidney disease caused by MUC1 mutation (ADTKD-MUC1). Cytosine duplication within a string of 7 cytosines in the variable-number tandem repeats (VNTR) region of the MUC1 gene was detected by long-read single-molecule real-time (SMRT) sequencing. MUC1 frameshift protein (MUC1fs) was found to be expressed in renal tubules and urinary exfoliated cells by pathological examination. The family, which consisted of 5 generations including 137 individuals, was followed for 5 years. Genetic testing was performed in thirty-four individuals, 17 of whom carried MUC1 mutations. The ADTKD-MUC1-affected individuals had an elevated incidence of hyperuricaemia without gout attack. Within five years, higher baseline levels of urinary α1-microglobulin were detected in affected individuals with rapidly progressing renal failure than in affected individuals with stable renal function, and the increases manifested even before increases in serum creatinine. This study demonstrates that SMRT sequencing is an effective method for the identification of MUC1 mutations. The pathological examination of MUC1fs expression in renal tissue and urinary exfoliated cells can contribute to early screening of family members suspected to be affected. It is suggested that affected individuals with elevated urinary α1-microglobulin levels should be closely monitored for renal function.

IgG4-related sialadenitis complicated with type III mixed cryoglobulinemia: A case report.

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases. PATIENT CONCERNS: A 55-year-old female was admitted because of dry mouth and teeth falling off. DIAGNOSES: The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4 plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine. INTERVENTIONS AND OUTCOMES: After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS. LESSONS: Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice.

OBJECTIVE: Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice. DATA SOURCES: All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019. STUDY SELECTION: This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia. RESULTS: Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances. CONCLUSIONS: Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

Derivation and validation of a prediction score for acute kidney injury secondary to acute myocardial infarction in Chinese patients.

BACKGROUND: Acute kidney injury (AKI) is a major complication of acute myocardial infarction(AMI), which can significantly increase mortality. This study is to analyze the related risk factors and establish a prediction score of acute kidney injury in order to take early measurement for prevention. METHODS: The medical records of 6014 hospitalized patients with AMI in Beijing Anzhen Hospital from January 2010 to December 2016 were retrospectively analyzed. These patients were randomly assigned into two cohorts: one was for the derivation of prediction score (n = 4252) and another for validation (n = 1762). The criterion for AKI was defined as an increase in serum creatinine of ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h. On the basis of odds ratio obtained from multivariate logistic regression analysis, a prediction score of acute kidney injury after AMI was built up. RESULTS: In this prediction score, risk score 1 point included hypertension history, heart rate > 100 bpm on admission, peak serum troponin I ≥ 100 µg/L, and time from admission to coronary reperfusion > 120 min; risks score 2 points included Killip classification ≥ class 3 on admission; and maximum dosage of intravenous furosemide ≥ 60 mg/d; risks score 3 points only included shock during hospitalization. In addition, when baseline estimated glomerular filtration rate (eGFR) was less than 90 ml/min·1.73 m2, every 10 ml/min·1.73 m2 reduction of eGFR increased risk score 1 point. Youden index showed that the best cut-off value for prediction of AKI was 3 points with a sensitivity of 71.1% and specificity 74.2%. The datasets of derivation and validation both displayed adequate discrimination (an area under the ROC curve, 0.79 and 0.81, respectively) and satisfactory calibration (Hosmer-Lemeshow statistic test, P = 0.63 and P = 0.60, respectively). CONCLUSIONS: In conclusion, a prediction score for AKI secondary to AMI in Chinese patients was established, which may help to prevent AKI early.

Artificially Cultivated Ophiocordyceps sinensis Alleviates Diabetic Nephropathy and Its Podocyte Injury via Inhibiting P2X7R Expression and NLRP3 Inflammasome Activation.

BACKGROUND/AIMS: It is known that chronic low-grade inflammation contributes to the initiation and development of both diabetes and diabetic nephropathy (DN), so we designed this study to investigate the role of P2X7R and NLRP3 inflammasome in DN pathogenesis and the antagonistic effects of artificially cultivated Ophiocordyceps sinensis (ACOS). METHODS: A rat model of DN caused by high-fat-diet feeding and low-dose streptozotocin injection and a mouse podocyte injury model induced by high-glucose (HG) stimulation were established, and the intervention effects of ACOS on them were observed. The biological parameters of serum and urine and the pathological manifestations of kidney tissue were examined. The expression of mRNA and protein of P2X7R and NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and downstream effectors (IL-1ß and IL-18), as well as podocyte-associated molecules, was determined by real-time quantitative PCR and Western blot assay, respectively. RESULTS: The DN rats showed to have developed insulin resistance, elevated fasting blood glucose, increased urinary protein excretion, and serum creatinine level as well as corresponding glomerular pathological alterations including podocyte damages. ACOS significantly antagonized the above changes. The experiments in vivo and in vitro both displayed that the mRNA and protein expression of P2X7R, NLRP3, ASC, caspase1 (procaspase-1 mRNA in the gene level and active caspase-1 subunit P10 in the protein level), IL-1ß, and IL-18 was significantly upregulated and the mRNA and protein expression of podocyte-associated molecules was significantly changed (downregulation of nephrin, podocin, and WT-1 expression and upregulation of desmin expression) indicating podocyte injury in the kidney tissue of DN rats and in the HG-stressed mouse podocytes, respectively. ACOS also significantly antagonized all the above changes. CONCLUSION: Our research work suggests that P2X7R and NLRP3 inflammasome are involved in the pathogenesis of DN, and ACOS can effectively inhibit the high expression of P2X7R and the activation of NLRP3 inflammasome, which may contribute to the therapeutic effects of Ophiocordyceps sinensis.

Purinergic 2X7 Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome.

BACKGROUND: The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome. METHODS: A mouse model of ORG was established by high-fat diet feeding. The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079). The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3, ASC, and caspase-1, as well as the podocyte-associated molecules including nephrin, podocin, and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Western blot analysis, respectively. RESULTS: The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo, which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules. Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression of podocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro, and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079. CONCLUSIONS: P2X7R could trigger the activation of NLRP3 inflammasome, and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

Aldosterone is involved in the pathogenesis of obesity-related glomerulopathy through activation of Wnt/ß-catenin signaling in podocytes.

Obesity-related glomerulopathy (ORG) is morphologically characterized by glomerulomegaly with or without observable focal segmental glomerulosclerosis under light microscope, with decreased podocyte density and number, and with increased foot­process width observed under electron microscope. The severity of podocyte injury is correlated with the degree of proteinuria and renal dysfunction. However, the pathogenesis of ORG is not well understood. The aim of the present study was to explore the possible pathogenic role of aldosterone (ALDO) in ORG. In the in vivo animal experiments, body weight, Lee's obesity index, abdominal fat index, urinary protein excretion, average glomerular diameter were significantly increased, the mRNA and protein expression of podocyte­associated molecules including nephrin, podocin, podoplanin and podocalyxin were significantly reduced, and the Wnt/ß­catenin signaling pathway was activated in ORG model mice compared with the Control mice, whereas the administration of spironolactone significantly ameliorated these effects. In the in vitro experiments on cultured podocytes, the mRNA and protein expression levels of the aforementioned podocyte­associated molecules were significantly downregulated and the Wnt/ß­catenin signaling pathway was activated following ALDO stimulation, whereas eplerenone significantly attenuated all the above effects. Dickkopf­related protein 1 (DKK1), an inhibitor of Wnt/ß­catenin signaling pathway, also reduced the effects of ALDO exposure on the expression of podocyte­associated molecules. The present study hypothesized that ALDO may be involved in the pathogenesis of ORG through the activation of Wnt/ß­catenin signaling pathway in podocytes.

Aristolochic Acid-Induced Autophagy Promotes Epithelial-to-Myofibroblast Transition in Human Renal Proximal Tubule Epithelial Cells.

Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial-to-myofibroblast transition (EMT). However, the relationship between AA-induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation. The enhancement of autophagy using autophagy inducers, rapamycin or serum-free medium, led to an aggravation of EMT and upregulated expression of fibronectin, a component of extracellular matrix, in AA-treated HKC cells. In contrast, the inhibition of autophagy by autophagy inhibitor, 3-methyladenine, or by knockdown of Beclin 1 led to an attenuation of EMT and downregulated expression of fibronectin in AA-treated HKC cells. Taken together, our study suggests that, after AA stimulation, two types of cell responses of HKC cells, autophagy and EMT, will successively appear, and autophagy can promote EMT of HKC.

Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy.

BACKGROUND AND OBJECTIVES: The research work in the past years showed that detection of phospholipase A2 receptor (PLA2R) antigen and its dominant IgG4 autoantibody in glomerular deposits of patients with membranous nephropathy (MN) was useful for the differentiation between primary MN (PMN) and secondary MN (SMN), but so far such research data from large Chinese patient series is little. Here, we are going to report a research work in a Chinese cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study enrolled 179 patients with PMN, 40 patients with membranous lupus nephritis (LN-MN), 26 patients with hepatitis B virus-associated MN (HBV-MN), 2 patients with malignancy-associated MN (M-MN) and one patient with IgG4-related MN (IgG4-MN). PLA2R and IgG subclasses in glomerular deposits of these patients were examined by immunofluorescence and/or immunohistochemical staining, and the potential value of the above examinations for differential diagnosis of PMN and SMN was evaluated. RESULTS: Glomerular PLA2R deposition was present in 92.2% patients with PMN and 7.7% patients with HBV-MN, but none of the patients with LN-MN. Predominant/codominant IgG4 deposition was found in 93.3% patients with PMN and 11.5% patients with HBV-MN, but none of the patients with LN-MN. The two M-MN patients both had glomerular PLA2R and predominant/codominant IgG4 deposition. The one IgG4-MN patient had deeply staining IgG4 but no PLA2R in glomeruli. CONCLUSIONS: The glomerular PLA2R and predominant/codominant IgG4 deposition is frequently observed in Chinese patients with PMN. Immunofluorescence and immunohistochemical staining of renal biopsy tissue for detection of glomerular PLA2R and IgG subclasses deposition can help to distinguish PMN from LN-MN and most of HBV-MN.

Hirsutella sinensis Attenuates Aristolochic Acid-Induced Renal Tubular Epithelial-Mesenchymal Transition by Inhibiting TGF-ß1 and Snail Expression.

OBJECTIVE: To investigate the inhibitory effect of Hirsutella sinensis (HS) on epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells induced by aristolochic acid (AA) and its possible mechanism. METHODS: 18 male Sprague-Dawley rats were randomly and equally divided into the following 3 groups: AA group, AA+HS group and control group. Urinary protein excretion and creatinine clearance (CCr) were measured. All rats were sacrificed at the end of 12th week. The pathological examination of renal tissue was performed and the mRNA and protein expression of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), cytokeratin-18 and Snail in renal cortex were determined by real time quantitative PCR and immunohistochemical staining respectively. In addition, human renal proximal tubule epithelial cells line (HKC) was divided into the following 4 groups: AA group, AA+HS group, HS control group and control group. The above mRNA and protein expression in HKC was determined by real time quantitative PCR and Western blot respectively. RESULTS: (1) CCr was significantly decreased, and the urinary protein excretion and relative area of renal interstitial fibrosis were significantly increased in the rats of AA and AA+HS group compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly lightened in the rats of AA+HS group compared to those in AA group (P<0.05). (2) The mRNA and protein expression of TGF-ß1, α-SMA and Snail was significantly up-regulated and the expression of cytokeratin-18 was significantly down-regulated in the rat renal cortex as well as in the cultured HKC cells in AA and AA+HS groups compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly alleviated in AA+HS group compared to those in AA group (P<0.05 or P<0.01). (3) Knockdown endogenous Snail expression by siRNA could ameliorate AA-induced EMT of HKC cells, while overexpression of Snail by plasmid transfection diminished the antagonistic effect of HS on AA-induced EMT. These results suggest Snail might be a potential target of HS effect. CONCLUSION: HS is able to antagonize, to some extent, tubular EMT and renal interstitial fibrosis caused by AA, which might be related to its inhibitory effects on the TGF-ß1 and Snail expression.

[Application of Immunohistochemistry and Immunofluorescence Staining in Detection of Phospholipase A2 Receptor on Paraffin Section of Renal Biopsy Tissue].

OBJECTIVE: To evaluate the application of immunohistochemistry and fluorescence staining method in the detection of phospholipase A2 receptor (PLA2R) on paraffin section of renal biopsy tissue,and to find an accurate and fast method for the detection of PLA2R in renal tissue. METHODS: The PLA2R of 193 cases were detected by immunohistochemical staining,and the antigen was repaired by the method of high pressure cooker (HPC) hot repair plus trypsin repair. The 193 samples including 139 cases of idiopathic membranous nephropathy (IMN), 15 cases of membranous lupus nephritis, 8 cases of hepatitis B virus associated membranous nephropathy, 18 cases of IgA nephropathy, and 13 cases of minimal change diseases. To compare the dyeing effects, 22 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 4 different. METHODS: of antigen repairing,which included HPC hot repair, HPC hot repair plus trypsin repair, water bath heat repair, and water bath heat repair plus trypsin repair. To compare the dyeing effects, 15 paraffin sections of renal biopsy tissue of IMN cases with positive PLA2R were stained by using 3 different. METHODS: of antigen repairing,which included water bath heat repair plus trypsin repair, protease K digestion repair, and pepsin digestion repair. RESULTS: In 193 cases, the positive rate of PLA2R in IMN cases was 90.6% (126/139), and the other 54 patients without IMN were negative. Twenty-two IMN patients were positive for PLA2R by using the HPC heat repair plus trypsin repaire or the water bath heat repair plus trypsin repair;while only a few cases of 22 IMN cases were positive by using the HPC hot repair alone or water bath heat repair alone. Fifteen IMN patients were positive for PLA2R by using water bath heat repair plus trypsin repair,protease K digestion repair,and pepsin digestion repair, but the distribution of positive deposits and the background were different. CONCLUSIONS: PLA2R immunohistochemical staining can effectively identify IMN and secondary MN. For immunohistochemical staining and immunofluorescence staining, the preferred method of antigen repair is water bath heat repair plus trypsin repair.

The Protective Effects of Curcumin on Obesity-Related Glomerulopathy Are Associated with Inhibition of Wnt/ß-Catenin Signaling Activation in Podocytes.

The present study investigated the effects of curcumin, one of the most important active ingredients of turmeric, on podocyte injury in vitro and obesity-related glomerulopathy (ORG) in vivo. Cellular experiments in vitro showed that curcumin significantly antagonized leptin-induced downregulation of the mRNA and protein expression of podocyte-associated molecules including nephrin, podocin, podoplanin, and podocalyxin. Animal experiments in vivo showed that curcumin significantly reduced the body weight, Lee's index, abdominal fat index, urinary protein excretion, and average glomerular diameter and significantly upregulated the mRNA and protein expressions of the above podocyte-associated molecules in ORG mice. Furthermore, the experiments in vitro and in vivo both displayed that curcumin could downregulate the mRNA and protein expressions of Wnt1, Wnt2b, Wnt6, and ß-catenin and upregulate the phosphorylation level of ß-catenin protein in podocytes and renal tissue. In conclusion, curcumin is able to alleviate the harmful reaction of leptin on podocytes and reduce the severity of ORG. The above protective effects are associated with the inhibition of Wnt/ß-catenin signaling activation in podocytes.

Clinical prediction scores for type 1 cardiorenal syndrome derived and validated in chinese cohorts.

Type 1 cardiorenal syndrome is one of the major diseases threatening human life in China. The incidence of acute kidney injury (AKI) associated with acute heart failure (AHF), acute myocardial infarction (AMI), cardiac surgery, and coronary angiography has been reported to be 32.2, 14.7, 40.2, and 4.5%, respectively. In the past 2 years, we derived and validated 4 risk scores for the prediction of AKI associated with the above acute heart diseases as well as for examination and treatment in Chinese cohorts. A univariable comparison and a subsequent multivariate logistic regression analysis of the potential predictive variables of AKI in the derivation set were conducted and used to establish the prediction scores, which were then verified in the validation set. The area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness-of-fit statistic test were performed to assess the discrimination and calibration of the prediction scores, respectively. These 4 prediction scores all showed adequate discrimination (area under the ROC curve, ≥0.70) and good calibration (p > 0.05). Both Forman's risk score (for AKI associated with AHF) and Mehran's risk score (for AKI associated with coronary angiography) are widely applied around the world. The external validation of these 2 risk scores was performed in our patients, but their discriminative power was quite low (area under the ROC curve, 0.65 and 0.57, respectively). Therefore, these prediction scores derived from Chinese cohorts might be more accurate than those derived from different races when they are applied in Chinese patients.

Inhibition of local aldosterone by eplerenone reduces renal structural damage in a novel model of chronic cyclosporine A nephrotoxicity.

BACKGROUND AND OBJECTIVE: The fact that mineralocorticoid receptor antagonists reduce structural and functional alterations induced by cyclosporine A (CsA) indicates that aldosterone plays a key role in chronic CsA nephrotoxicity. We and other researchers have reported local renal aldosterone synthesis. To investigate local renal aldosterone's role in chronic CsA nephrotoxicity, we evaluated the effect of eplerenone (Epl) on renal structural damage and renal dysfunction in adrenalectomized (ADX) rats, and assessed whether the therapeutic benefit was associated with reduction of transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), plasminogen activator inhibitor type 1 (PAI-1) and collagen I (COL-I) expression. METHODS: Male Sprague-Dawley rats fed a normal-sodium diet were divided in four groups: sham-ADX, ADX, CsA, or Epl. Rats in the ADX, CsA and Epl groups were adrenalectomized first. Aldosterone, sodium and potassium levels in serum and urine were measured on the second day. Two weeks later, vehicle (sham-ADX and ADX group), CsA (25mg/kg/d), or CsA and Epl (100 mg/ kg/d) combination was administrated, respectively. After six weeks, urinary protein, creatinine clearance (Ccr), tubulointerstitial fibrosis (TIF), aldosterone level in kidney, and renal aldosterone synthase CYP11B2, COL-I, TGF-ß1, CTGF and PAI-1 gene expression levels were determined. RESULTS: On the second day after surgery, adrenalectomized rats showed undetectable aldosterone with natriuresis, hyponatremia, decreased urinary potassium excretion and hyperpotassemia. CsA reduced Ccr, induced urinary proteins and up-regulated COL-I, TGF-ß1, CTGF and PAI-1 gene expression with a significant development of TIF. Eplerenone administration prevented TIF and COL-I, TGF-ß1 and PAI-1 up-regulation but did not improve renal function. CONCLUSION: Our results suggest local renal aldosterone is an important mediator of renal injury induced by CsA.

Derivation and validation of a risk score for contrast-induced nephropathy after cardiac catheterization in Chinese patients.

BACKGROUND: To derive and validate a risk score for prediction of contrast-induced nephropathy (CIN) in the Chinese patients undergoing cardiac catheterization. METHODS: The hospital medical records of 3945 patients undergoing coronary angiography or percutaneous coronary intervention were reviewed. Patients were randomly assigned into two cohorts: one was for derivation of risk score (n = 2764) and another for validation (n = 1181). The CIN was defined as an increase of serum creatinine level ≥44.2 µmol/L or ≥25 % and beyond its upper limit of normal value within 72 h following the procedure. On the basis of the odds ratio obtained from multivariate logistic regression, risk score of CIN was built up. The discrimination of the risk score was assessed using the area under the receiver operating characteristic curve and the calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: The incidences of CIN in the derivation and validation cohorts were 4.6 and 4.2 %, respectively. Independent predictors included age >60 years, hypertension, acute myocardial infarction, heart failure, use of intra-aortic balloon pump, decreased glomerular filtration rate and contrast volume >100 mL. The incidence of CIN was increased with increment of risk score. Both the derivation and validation cohorts showed adequate discrimination (an area under the ROC curve, 0.76 and 0.71, respectively) and good calibration (Hosmer-Lemeshow statistic test, P = 0.50 and P = 0.54, respectively). CONCLUSION: A simple risk score for prediction of CIN development after cardiac catheterization in Chinese patients was built up by this study. Use of this risk score may help clinicians to perform early preventative strategies to minimize the risk of CIN.

Relation between the interval from coronary angiography to selective off-pump coronary artery bypass grafting and postoperative acute kidney injury.

The aim of this study was to investigate whether there are effects of intervals between elective off-pump coronary artery bypass grafting (OPCABG) and coronary angiography (CAG) on postoperative acute kidney injury (AKI). The clinical data of patients undergoing OPCABG and CAG from June 2010 to December 2011 in Beijing Anzhen Hospital were retrospectively analyzed. All the patients were divided into AKI and non-AKI groups. Univariate analysis was performed to find possible factors associated with AKI. Multivariate logistic regression analysis was used to identify whether the short interval was one of the independent risk factors of AKI after adjusting for potential confounding variables. Of 1,513 patients, 529 patients (34.9%) developed AKI. The mortality rate in AKI group (4.9%) was >5× higher than that in non-AKI group (0.9%). The incidence of AKI was highest (56.1%) in patients in whom OPCABG was performed ≤24 hours after CAG. Multivariate logistic regression analysis showed that the interval of ≤24 hours between OPCABG and CAG did increase the risk of AKI (odds ratio 2.15, 95% confidence interval 1.10 to 4.20) after adjusting for the following confounding variables: diabetes mellitus, New York Heart Association heart function class III and IV, lower estimated glomerular filtration rate, numbers of coronary artery bypass grafts ≥3, intraoperative or postoperative intra-aortic balloon pump, intraoperative and postoperative red blood cells transfusion of >3 units, postoperative hypotension, dosage of furosemide of >100 mg/day. In conclusion, it was one of the independent risk factors of postoperative AKI that the OPCABG was performed ≤24 hours after CAG.