Bone marrow-derived mesenchymal stem cells attenuate tubulointerstitial injury through multiple mechanisms in UUO model.

Current evidence supports the use of bone marrow-derived mesenchymal stem cells (MSCs) for a diverse range of clinical applications, and many studies have shown that MSCs have renal-protective effects, but the mechanism is not well understood. Therefore, in this study, we aim to further identify whether MSCs can attenuate renal fibrosis by decreasing tubulointerstitial injury in a unilateral ureteral obstruction (UUO) model. In this study, we cultured MSCs and then transplanted them into a UUO model through the tail vein. Histology, cell proliferation, peritubular capillary (PTC) loss and myofibroblast markers were examined on days 3, 7 and 14 after surgery. We demonstrated that renal interstitial fibrosis in the MSC group was significantly attenuated compared with the UUO and DMEM groups. Moreover, MSC treatment inhibited the loss of PTCs and increased parenchymal cell proliferation. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by MSC infusion. Furthermore, MSCs attenuated tubulointerstitial infiltration of macrophages in UUO mice. Tubulointerstitial damage plays a very important role in the progression of chronic kidney disease (CKD). PTC loss, macrophage recruitment, and myofibroblast activation are directly correlated with the development of renal tubulointerstitial fibrosis. Our results suggest that MSC infusion in the UUO model is a promising therapeutic strategy for promoting kidney repair.

Characterization of soluble thrombomodulin levels in patients with stage 3-5 chronic kidney disease.

OBJECTIVE: This study aims to test the serum levels of soluble thrombomodulin (TM) in patients with chronic kidney disease (CKD)3-5 and to assess their connection with the different stages and severity of disease. METHODS: Sixty-seven patients with CKD are included, disease severity was evaluated accordingly to CKD staging and clinical data is collected. Nineteen healthy volunteers served as healthy controls. Serum soluble TM is analyzed by ELISA. RESULTS: The levels of soluble TM in all patients with CKD were significantly higher than those of healthy controls (p < 0.001). CKD5 patients showed higher serum levels of soluble TM, in comparison to CKD4 patients (p = 0.001), CKD3 patients (p < 0.001), and healthy controls (p < 0.001). The correlation analysis revealed significant correlation between serum soluble TM and disease severity (r = 0.714, p < 0.001). Serum soluble TM was found to be correlated with eGFR (r = -0.766; p < 0.001) and serum creatinine (r = 0.778, p < 0.001). CONCLUSION: Soluble TM concentrations significantly increase in the CKD patients and are associated with the severity of the disease. Soluble TM may play critical roles in the development of CKD, as a biomarker of endothelial cells damage, anticoagulation and anti-inflammation.

Epidemiology and risk factors for chronic kidney disease in patients with ischaemic stroke.

BACKGROUND: There is growing evidence for an association between chronic renal disease (CKD) and adverse cerebrovascular events because of the overlap of several risk factors. The purpose of this study is to examine the epidemiology of CKD and the characteristics of risk factors for CKD in the population with ischaemic stroke. METHODS: This retrospective study included 571 patients with ischaemic stroke. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation. Renal function was assessed according to the Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD classification. RESULTS: Study demonstrated that the major factors associated with CKD in the ischaemic stroke patients were age, diabetes mellitus, hypertension, systolic blood pressure, LDL cholesterol and serum uric acid. Diabetes mellitus (OR 4·146, 95% CI 1·047-16·418, P = 0·043), hypertension and diabetes mellitus (OR 3·574, 95% CI 1·248-10·234, P = 0·018), serum uric acid (OR 1·010, 95% CI 1·006-1·013, P < 0·001) and LDL cholesterol (OR 1·431, 95% CI 1·063-1·928, P = 0·018) were independent risk factors associated with CKD in the patients with ischaemic stroke. CONCLUSIONS: The patients with ischaemic stroke may be considered as a high-risk population for CKD and be aggressively managed for CKD prevention. The high prevalence of CKD in population with ischaemic stroke prompts the need for greater public awareness about risks of CKD.

Circulating monocyte-platelet aggregates with different monocyte subsets and their association with disease severity in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is usually considered an immune inflammatory disease. Interaction between platelets and monocytes is associated with immune inflammation. Cross-talk between platelets and monocytes is reflected by formation monocyte-platelet aggregates (MPAs). This study aims to test MPAs and MPAs with the different monocyte subsets to evaluate their association with disease severity in CKD. METHODS: Forty-four hospitalized patients with CKD and twenty healthy volunteers were enrolled. The proportion of MPAs and MPAs with the different monocyte subsets were tested by flow cytometry. RESULTS: The proportion of circulating MPAs in all patients with CKD were significantly higher than those of healthy controls (p<0.001). A higher proportion of MPAs with classical monocytes (CM) was found in CKD4-5 patients (p=0.007), while another higher proportion of MPAs with non-classical monocytes (NCM) was found CKD2-3 patients (p<0.001). The proportion of MPAs with intermediate monocytes (IM) in CKD 4-5 group was significantly higher in comparison to CKD2-3 group and healthy controls (p<0.001). Circulating MPAs were found to be correlated with serum creatinine (r=0.538, p<0.001) and eGFR (r=-0.864, p<0.001). The AUC for MPAs with IM was 0.942 (95% CI 0.890-0.994, p<0.001). CONCLUSIONS: Study results highlight the interplay between platelets and inflammatory monocytes in CKD. There are alterations in circulating MPAs and MPAs with the different monocyte subsets in CKD patients compared to controls which change with CKD severity. The MPAs may have an important role in the development of CKD or as a predictive marker for monitoring disease severity.

Characterization of interleukin-33 and soluble ST2 in serum and their association with disease severity in patients with chronic kidney disease.

INTRODUCTION: This study aims to test the serum levels of interleukin-33 (IL-33) and soluble ST2 (sST2) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity. METHODS: Sixty-nine patients with CKD were enrolled, disease severity was assessed, and clinical data were collected. Twelve healthy volunteers served as healthy individuals. Serum IL-33 and sST2 were tested by enzyme-linked immunosorbent assay. RESULTS: The patients were classified into five categories based on their estimated glomerular filtration rate (eGFR). No difference was found as to the serum concentration of IL-33 between CKD patients and healthy individuals (p = 0.656), while a higher serum level of sST2 was found in CKD patients (p = 0.003). The correlation analysis revealed a significant correlation between the serum level of sST2 and disease severity (r = 0.586; p < 0.001). A higher level of sST2 was found in CKD patients with elevated parathyroid hormone (p = 0.001). Serum sST2 correlated with parathyroid hormone (r = 0.412; p < 0.001), serum phosphorus (r = 0.545; p < 0.001), and serum calcium (r = -0.494; p < 0.001). CONCLUSION: An elevated concentration of serum sST2 is found in CKD patients and correlates with disease severity. Serum sST2 may be also associated with parathyroid hormone disorder of CKD. The sST2 may have an important role in the development of CKD or as a marker of disease severity.

Elevated Soluble Podoplanin Associates with Hypercoagulability in Patients with Nephrotic Syndrome.

Podoplanin (PDPN) promotes platelet aggregation and activation by interacting with C-type lectin-like receptor 2(CLEC-2) on platelets. The interaction between the upregulated PDPN and platelet CLEC-2 stimulates venous thrombosis. PDPN was identified as a risk factor for coagulation and thrombosis in inflammatory processes. Hypercoagulability is defined as the tendency to develop thrombosis according to fibrinogen and/or D dimer levels. Nephrotic syndrome is also considered to be a hypercoagulable state. The aim of this study is to investigate the association of soluble PDPN/CLEC-2 with hypercoagulability in nephrotic syndrome. Thirty-five patients with nephrotic syndrome and twenty-seven healthy volunteers were enrolled. PDPN, CLEC-2 and GPVI concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Patients with nephrotic syndrome showed higher serum levels of PDPN and GPVI in comparison to healthy controls (P < .001, P = .001). PDPN levels in patients with nephrotic syndrome were significantly correlated with GPVI (r = 0.311; P = .025), hypoalbuminemia (r = -0.735; P < .001), hypercholesterolemia (r = 0.665; P < .001), hypertriglyceridemia (r = 0.618; P < .001), fibrinogen (r = 0.606; P < .001) and D-dimer (r = 0.524; P < .001). Area under the curve (AUC) for the prediction of hypercoagulability in nephrotic syndrome using PDPN was 0.886 (95% CI 0.804-0.967, P < .001). Cut-off value for the risk probability was 5.88 ng/ml. The sensitivity of PDPN in predicting hypercoagulability was 0.806, and the specificity was 0.846. When serum PDPN was >5.88 ng/ml, the risk of hypercoagulability was significantly increased in nephrotic syndrome (OR = 22.79, 95% CI 5.92-87.69, P < .001). In conclusion, soluble PDPN levels were correlated with hypercoagulability in nephrotic syndrome. PDPN has the better predictive value of hypercoagulability in nephrotic syndrome as well as was a reliable indicator of hypercoagulable state.

[Expression and significance of CD80/CD86 in renal tissue of lupus nephritis].

OBJECTIVE: To measure the expression of CD80 and CD86 in renal tissue of lupus nephritis (LN) and explore its mechanism in the development of LN. METHODS: Forty-nine patients with active LN and 9 patients with minor glomerular abnormalities tissues as controls were studied. The expression of CD80 and CD86 in renal tissues was detected by immunohistochemical methods. RESULTS: CD86 was expressed extensively in glomerulus, periglomerular area, tubular epithelial cells and peritubular interstitium, while CD80 was expressed only in tubular epithelial cells and peritubular interstitium. Moreover, the percentage of CD80+ and CD86+ cells in tubular epithelial cells and peritubular interstitium showed a tendency to increase with tubulointerstitial damage. The expression of CD80 and CD86 in renal tissue correlated with the systemic lupus erythematosus (SLE) disease activity index score, the degree of proteinuria, creatinine clearance and anti-dsDNA antibody. CONCLUSIONS: This study shows that increased CD80 and CD86 expression with the progression of tubulointerstitial lesion might play an important role in the development of lupus nephropathy, and the tubulointerstitial expression of CD80 and CD86 could potentially serve as a surrogate marker of SLE disease activity. The co-stimulatory molecules CD80 and CD86 might play an important role in the pathogenesis of LN.

Assessment of Renal Function and Risk Factors for Chronic Kidney Disease in Patients With Peripheral Arterial Disease.

Chronic kidney disease (CKD) and peripheral arterial disease (PAD) share common risk factors. We assessed renal function and the prevalence of CKD in patients with PAD and investigated the characteristics of the risk factors for CKD in this population. Renal function of 421 patients with PAD was evaluated. Among the participants, 194 (46.1%) patients had decreased estimated glomerular filtration rate (eGFR). The prevalence of CKD was much higher among patients with PAD. Hypertension (odds ratios [ORs] 2.156, 95% confidence interval [CI] 1.413-3.289, P < .001), serum uric acid (OR 3.794, 95% CI 2.220-6.450, P < .001), and dyslipidemia (OR 1.755, 95% CI 1.123-2.745, P = .014) were significantly associated with CKD and the independent risk factors for CKD in patients with PAD. CKD is common and has a high prevalence in a population with PAD. Patients with PAD may be considered as a high-risk population for CKD. Recognition and modification of risk factors for CKD might beneficially decrease CKD incidence and improve prognosis in patients with PAD.

Prevalence and risk factors for chronic kidney disease in patients with coronary artery disease.

OBJECTIVES: Chronic renal disease (CKD) is recognized as a worldwide public health problem. Traditional risk factors for CKD are also present in coronary artery disease (CAD). The purpose of this study is to examine the prevalence and characteristics of risk factors for CKD in the population with CAD. METHODS: Renal function was evaluated in 527 patients with CAD in order to assess characteristics of the incidence, risk factors for CKD in the population with CAD. In the present study in order to concentrate on evaluation for eGFR of the patients with CAD proteinuria is not included in the definition of CKD. RESULTS: Univariate analysis demonstrated that the major risk factors associated with CKD in the patients with CAD were age (P ≤ 0.001), smoking (P = 0.016), diabetes mellitus (P = 0.021), hypertension (P ≤ 0.001), and systolic blood pressure (P = 0.004). The percentages of patients with both hypertension and diabetes mellitus were significantly greater in the CKD3-4 group (P < 0.001). The results of multivariable analysis showed that hypertension (OR 1.925, 95% CI 1.196-3.098, P = 0.007), diabetes mellitus (OR 1.744, 95% CI 1.044-2.914, P = 0.034) and serum uric acid (OR 1.008, 95% CI 1.006-1.010, P ≤ 0.001) were independent risk factors for reduced eGFR. CONCLUSIONS: CKD is common and has a high prevalence in the population with CAD. Several risk factors are known to simultaneously affect heart and kidney. The patients with CAD may be considered as a high-risk population for CKD.