Publications by authors named "WenLv Lv"

13 Publications

  • Page 1 of 1

Prostaglandin E induced cardiac hypertrophy through EP2 receptor-dependent activation of β-catenin in 5/6 nephrectomy rats.

ESC Heart Fail 2021 Apr 6. Epub 2021 Apr 6.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.

Aims: Prostaglandin E (PGE2) is involved in the development of cardiac hypertrophy. However, whether PGE2 regulates the chronic kidney disease-associated cardiac hypertrophy and the tentative mechanism remains to be elucidated.

Methods And Results: We explored the effect of PGE2 receptor inhibitors on cardiac hypertrophy in vitro and in a 5/6 nephrectomy (5/6NT) rat model using quantitative reverse transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence staining assays. The result showed that EP2 and EP4 receptors were both up-regulated in the PGE2-treated cardiomyocyte cells. PGE2 treatment enhanced active β-catenin (non-phosphorylated) signalling through mediating EP2 and EP4 receptors. Interestingly, inhibition of EP2 receptor suppressed PGE2-induced cardiomyocyte hypertrophy and cardiac fibrosis-related proteins in vitro. In the 5/6NT rat model, the increased secretion PGE2 was identified in the 5/6NT rat model for 2 weeks (P = 0.0251). EP2 receptor inhibitor administration significantly improved the cardiac function and fibrosis in 5/6NT rats.

Conclusions: Our study demonstrated that inhibition of EP2 receptor could improve PGE2-induced cardiac hypertrophy in 5/6NT rats. The exploration of these mechanisms may contribute to the optimization of therapy in chronic kidney disease accompanied cardiac hypertrophy in clinic.
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http://dx.doi.org/10.1002/ehf2.13269DOI Listing
April 2021

The Effect of Postoperative Fluid Balance on the Occurrence and Progression of Acute Kidney Injury After Cardiac Surgery.

J Cardiothorac Vasc Anesth 2020 Oct 10. Epub 2020 Oct 10.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China; Shanghai Institute of Kidney Disease and Dialysis, Shanghai Laboratory of Kidney Disease and Dialysis, Shanghai Medical Center of Kidney Disease, Shanghai, People's Republic of China. Electronic address:

Objectives: In addition to the association between positive fluid balance (FB) and acute kidney injury (AKI) after cardiac surgery reported by former studies, this study examined the relationship between FB and progressive AKI.

Design: A retrospective, observational study.

Setting: University teaching, grade A tertiary hospital in Shanghai, China.

Participants: Adult patients after cardiac surgery from July-December 2016.

Interventions: Perioperative data relating to postoperative fluid intake and output were collected. AKI progression was defined as a worsening of AKI stage. FB was calculated as (fluid intake [L] - fluid output [L]/body weight [kg] × 100%).

Measurements And Main Results: The study comprised 1,522 patients. The incidences of AKI and progressive AKI were 33.1% (n = 504) and 18.1% (n = 91), respectively. There was an exponential increase between 24-hour FB and AKI occurrence, and an approximate "U"-shape association between 48-hour FB and AKI progression. Multivariate logistic regression showed that 24-hour FB ≥5% was an independent risk factor for AKI incidence (odds ratio [OR] 3.976; p < 0.001) and 48-hour FB <-5% or ≥3% was associated with an increase of AKI progression (FB <-5%, OR 7.078 [p = 0.031]; FB 3%-5%, OR 6.598 [p = 0.020]; FB ≥5%, OR 16.453 [p < 0.001]).

Conclusions: An exponential increase was found between 24-hour FB and AKI occurrence and a "U"-shape association between 48-hour FB and AKI progression. Both excessively negative and positive accumulative 48-hour FB increased the risk of AKI progression, suggesting cautious monitoring and application of fluid load in clinical practice.
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http://dx.doi.org/10.1053/j.jvca.2020.10.007DOI Listing
October 2020

Differences between exhausted CD8 T cells in hepatocellular carcinoma patients with and without uremia.

Can J Physiol Pharmacol 2021 Apr 15;99(4):395-401. Epub 2020 Aug 15.

Shanghai Institute of Kidney and Dialysis, Shanghai, China.

The purpose of this study was to explore the differences between exhausted CD8 T cells in hepatocellular carcinoma (HCC) patients with and without uremia. We enrolled 45 uremic patients who were recently diagnosed with HCC into the HCC + uremia cohort and similar patients with HCC but without uremia into the HCC-only cohort. Lymphocytes were obtained from the two cohorts, and exhausted CD8 T cells, comprising PD-1CD8, TIM-3CD8, and LAG-3CD8 T cells, were sorted and expanded in vitro. After expansion, the proportions of PD-1CD8, TIM-3CD8, and LAG-3CD8 T cells were significantly higher in the HCC-only cohort than in the HCC + uremia cohort. CD8 T cells expressing PD-1, TIM-3, or LAG-3 showed increased tumor reactivity and release of interferon-γ in vitro; however, these cells demonstrated weaker anti-tumor activity in HCC + uremia patients than in HCC-only patients. Among the expanded lymphocytes, only the decreased proportion of PD-1CD8 T cells significantly correlated with the HCC + uremia cohort (odds ratio of 2.731,  = 0.009). We concluded that peripheral CD8 T cells expressing PD-1, TIM-3, or LAG-3 from the HCC + uremia cohort were dysfunctional in vitro. Among these populations, PD-1CD8 T cells were most evident in HCC patients with uremia.
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http://dx.doi.org/10.1139/cjpp-2019-0641DOI Listing
April 2021

The significance of serum levels of soluble interleukin-2 receptor in patients undergoing maintenance hemodialysis.

Ren Fail 2020 Nov;42(1):419-427

Shanghai Institute of Kidney and Dialysis, Shanghai, China.

Elevated serum levels of sIL-2R are commonly observed in patients undergoing maintenance hemodialysis (MHD). However, the clinical implications in these subjects are unclear. This study is aimed to assess the significance of elevated sIL-2R levels in MHD patients. A total of 382 MHD patients were followed-up from September 2016 to December 2019. Patients were divided into two groups: high sIL-2R, with sIL-2R levels ≥2-fold of the upper limit of normal (710 U/ml); and low sIL-2R, with sIL-2R levels < 2-fold the upper limit of normal. The relationships between sIL-2R levels and other clinical parameters, as well as patient prognosis were both assessed. The median concentration of sIL-2R was 1268 U/mL. A total of 372 (97.38%) patients exhibited sIL-2R levels higher than the upper limit of the normal range. Multiple linear regression analysis revealed that monocyte count (β = 0.1571,  = 0.01), and β-MG (β = 0.2635,  < 0.0001), hemoglobin (β = -0.1610,  = 0.001), SCr (β = -0.3471,  < 0.0001), and HDL-C (β = -0.1091,  = 0.029) levels were independent factors influencing serum concentrations of sIL-2R. High sIL-2R was significantly correlated with non-cardiovascular-related mortality (OR 2.97 [95% CI 1.59-5.56;  = 0.001), of which 39 (82.98%) were attributed to infection and/or cancer. Elevated sIL-2R is prevalent in MHD patients and related with several unfavorable parameters. sIL-2R appears to have no ability to predict cardiovascular mortality, which accounts for approximately one-half of all deaths. However, sIL-2R may be beneficial in predicting noncardiovascular mortality.
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http://dx.doi.org/10.1080/0886022X.2020.1761388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269077PMC
November 2020

Efficacy of Early Goal-Directed Renal Replacement Therapy for the Treatment of Acute Kidney Injury After Heart Transplantation: A Single-Center 10-Year Experience.

J Cardiothorac Vasc Anesth 2020 Jun 21;34(6):1534-1541. Epub 2019 Nov 21.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Institute of Kidney Disease and Dialysis, Shanghai Laboratory of Kidney Disease and Dialysis, Shanghai Medical Center of Kidney Disease, Shanghai, China. Electronic address:

Objective: Acute kidney injury (AKI) after heart transplantation is a common and serious complication. The present study aimed to evaluate the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of AKI after heart transplantation.

Design: Retrospective, observational study.

Setting: Grade A tertiary hospital that performs more than 4,000 cardiac surgery procedures per year.

Participants: Patients who underwent heart transplantation with postoperative AKI and received renal replacement therapy from January 2008 to June 2018.

Interventions: Patients were divided into a late GDRRT group (LGDRRT) (January 2008-September 2012) or an early GDRRT group (EGDRRT) (October 2012-June 2018).

Results: The LGDRRT group comprised 30 patients, and the EGDRRT group comprised 46 patients. Duration between surgery to renal replacement therapy (RRT) initiation in the EGDRRT group was significantly shorter than in the LGDRRT group (1 [1-3] d v 2 [2-3] d; p = 0.020). The in-hospital mortality in the EGDRRT group was significantly lower than that of the LGDRRT group (39.1% v 63.3%; p = 0.039). After multivariate adjustment for confounding factors, the hazard ratio for death in the LGDRRT group relative to the EGDRRT group was 2.028 (95% confidence interval 1.072-3.655; p = 0.048). Length of intensive care unit and hospital stays in the EGDRRT group was significantly shorter than that of the LGDRRT group (26 ± 18 d v 38 ± 20 d; p = 0.008 and 38 ± 33 d v 64 ± 45 d; p = 0.005, respectively). The complete renal recovery rate was much greater in the EGDRRT group than that of the LGDRRT group (50.0% v 20.0%; p < 0.001). Serum creatinine at discharge was significantly less in the EGDRRT group than that of the LGDRRT group (134.8 ± 97.3 μmol/L v 220.7 ± 113.6 μmol/L; p < 0.001). Cost of RRT in the EGDRRT group was significantly less than that of the LGDRRT group (0.54 ± 0.10 v. 0.63 ± 0.11 ten thousand USD; p < 0.001).

Conclusions: For heart transplantation recipients with AKI, EGDRRT can reduce the in-hospital mortality and the length of intensive care unit and hospital stays, improve the complete renal recovery rate, and reduce the cost of RRT.
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http://dx.doi.org/10.1053/j.jvca.2019.11.022DOI Listing
June 2020

Incidence, Risk, and Prognosis of Cancer in Patients on Chronic Hemodialysis.

Blood Purif 2020 17;49(3):310-321. Epub 2019 Dec 17.

Shanghai Institute of Kidney and Dialysis, Shanghai, China.

Background: Information concerning the cancer issue in Chinese patients on hemodialysis (HD) was lacking. Thus, we examined data from our dialysis registry to investigate the incidence of cancer, identify the possible factors, and explore outcomes after cancer diagnosis in patients on chronic HD.

Methods: A retrospective cohort study of 639 new-onset end-stage renal disease patients who started HD therapy during the period from July 1999 to December 2017 was retrieved from the database in our dialysis center. All eligible patients were followed up until renal transplantation, death, or end of study (March 31, 2019). The definition of a newly diagnosed cancer was that diagnosed 6 months after HD therapy initiation.

Results: Within a median follow-up period of 5.61 years, 58 patients (9.08%) have been diagnosed with cancer with the incidence of 1,494 per 105 person-years. The mean duration from HD initiation to cancer diagnosis was 5.22 ± 3.55 years. Digestive cancer (32.76%) was the most common followed by urologic cancer (18.97%) and lung cancer (15.52%). Advanced age at starting HD therapy (hazard ratio [HR] 1.04) and erythropoietin dosage ≥20,000 U/week (HR 1.95) were independent predictors for cancer occurrence. Of the 256 deaths during the follow-up period, 29 cases (11.33%) were attributed to cancer, with the mortality rate of 717 per 105 person-years. The 1-, 5-, and 10-year cumulative survival rates after cancer diagnosis were 58.73, 34.64, and 20.41%, respectively. A total of 32 patients (55.17%) did not receive any anti-cancer therapy, and the mortality in those patients was significantly increased as compared to patients who received anti-cancer therapy.

Conclusion: Cancer is common in HD patients due to the improved survival, and it has a negative effect on patient prognosis. Many patients have failed to receive optimal anti-cancer therapy, which calls for effective communication and cooperation among patients, dialysis unit, and oncology teams.
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http://dx.doi.org/10.1159/000504243DOI Listing
December 2019

Preoperative hidden renal dysfunction add an age dependent risk of progressive chronic kidney disease after cardiac surgery.

J Cardiothorac Surg 2019 Aug 22;14(1):151. Epub 2019 Aug 22.

Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.

Background: To study different value of estimated glomerular filtration rate with normal serum creatinine whether is a risk factor for hidden renal function of cardiac surgery outcomes.

Methods: A total of 1744 cardiac surgery patients with serum creatinine ≤1.2 mg/dL (female)/1.5 mg/dL (male) were divided into 3 groups: estimated glomerular filtration rate ≥ 90 mL/min/1.73 m (no renal dysfunction, n = 829), 60 ≤ estimated glomerular filtration rate < 90 mL/min/1.73 m (hidden renal dysfunction, n = 857), estimated glomerular filtration rate < 60 mL/min/1.73 m (known renal dysfunction, n = 58) and followed up for 3 years. Multivariate regression analyses for risk factors of postoperative acute kidney injury.

Results: The proportion of preoperative hidden renal dysfunction was 67.1% among patients ≥  65 years old and 44.1% among patients < 65 years old. Multivariate Cox regression analyses showed that for patients < 65 years, known renal dysfunction was a risk factor for postoperative acute kidney injury (P <  0.01) and progressive chronic kidney disease (P = 0.018), while hidden renal dysfunction was a risk factor for progressive chronic kidney disease (P = 0.024). For patients ≥  65 years, only known renal dysfunction was a risk factors for 3-year mortality (P = 0.022) and progressive chronic kidney disease (P <  0.01).

Conclusion: Hidden renal dysfunction was common in patients with normal serum creatinine for cardiac surgery, with a prevalence of 49.1%. For patients < 65 years old, hidden renal dysfunction was an independent risk factor for progressive chronic kidney disease.
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http://dx.doi.org/10.1186/s13019-019-0977-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704689PMC
August 2019

Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis.

Int J Clin Oncol 2019 Sep 10;24(9):1151-1160. Epub 2019 Jun 10.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Background: Patients on chronic hemodialysis (HD) have an increased incidence of malignancy due to decreased immunity. Soluble interleukin-2 receptor (sIL-2R), as an immunomodulator, seemed to have an effect in the process of malignancy. In this study, we aimed to evaluate the clinical significance of increased sIL-2R in the course of malignancy among HD patients.

Methods: Patients who undergoing chronic hemodialysis were followed for 24 months. Risk factors for malignancy events and malignancy-related mortality during the 2-year follow-up period were investigated among various clinicopathological variables.

Results: Of the 363 patients included in this research, 47 patients (12.95%) had a prior history of treated malignancy. During the 2-year follow-up period, malignancy events were detected in 15 (4.12%) patients. Sixty-seven patients died during the study period, of which nine patients (13.43%) were died of malignancy. Malignancy events reduced 2-year mortality significantly (log-rank = 23.02, P < 0.0001). Both high sIL-2R levels ( ≥ 2-fold upper limit of the normal value) (OR 6.6, P = 0.006) and a prior history of treated malignancy (OR 4.12, P = 0.018)were identified by multivariate logistic analysis as independent determinants for malignancy events. However, only the levels of sIL-2R (used as a continuous variable) had the significantly predictive effect on malignancy events and malignancy-related mortality in the following 2 years.

Conclusions: Elevated sIL-2R levels was commonly seen in serum of HD patients. And this elevated level increased the risk of malignancy. Aside from its role as a biomarker, sIL-2R may also exert biological effects in the course of malignancy.
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http://dx.doi.org/10.1007/s10147-019-01455-5DOI Listing
September 2019

Decreased percentage of peripheral naïve T cells is independently associated with ischemic stroke in patients on hemodialysis.

Int Urol Nephrol 2017 Nov 15;49(11):2051-2060. Epub 2017 Sep 15.

Division of Nephrology, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, 200032, China.

Purpose: Cerebrovascular complications, including ischemic stroke, account for poor outcomes in patients on hemodialysis. T cell responses may be involved in the pathogenesis of ischemic stroke. We aimed to evaluate the role of naïve T cells in development of ischemic stroke in patients on hemodialysis.

Methods: In this cross-sectional study, 156 patients on hemodialysis in our blood purification center were included. These patients were divided into the ischemic stroke (IS) group (61 cases) and non-ischemic stroke (non-IS) group (95 cases) according to a new diagnosis after initiation of hemodialysis. After being lysed with red blood cell lysis solution, peripheral blood was tested by flow cytometry to detect the expression of CD45RO and CCR7 in CD4 T and CD8 T cells. Correlation analysis and logistic regression analysis were conducted to identify potential independent risk factors for ischemic stroke.

Results: The percentage of peripheral naïve T cells was lower in the IS group [median (interquartile range (IQR)) 13.9% (8.6-22.9%)] compared with the non-IS group [median (IQR) 22.7% (15.9-32.2%), P < 0.001]. Spearman correlation analysis showed that naïve T cells were negatively associated with ischemic stroke (r = -0.308, P < 0.001). Multivariate logistic regression analysis showed that CD4 naïve T cells had an independent negative association with ischemic stroke in patients on hemodialysis (odds ratio 0.933, 95% CI 0.883, 0.986; P = 0.013).

Conclusion: A decrease in percentage of peripheral CD4 naïve T cells is a risk factor for ischemic stroke in patients on hemodialysis.
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http://dx.doi.org/10.1007/s11255-017-1691-yDOI Listing
November 2017

Indoxyl sulfate, a valuable biomarker in chronic kidney disease and dialysis.

Hemodial Int 2017 04 12;21(2):161-167. Epub 2016 Sep 12.

Shanghai Institute of Kidney and Dialysis, Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China.

Chronic kidney disease (CKD) is an increasingly recognized disease with high global incidence and mortality. Yet, the existing diagnostic tools are not sufficient enough to predict prognosis of CKD and CKD comorbidities. Indoxyl sulfate, a typical uremic toxin, is of great importance in the development of CKD with its nephrotoxicity, cardiovascular toxicity, and bone toxicity. Some reports suggest that indoxyl sulfate directly associate with renal function loss and mortality in CKD patients. This review discusses the diagnostic value of indoxyl sulfate from its biological characteristics, pathophysiological effects, related therapies, and its diagnostic value in clinical studies.
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http://dx.doi.org/10.1111/hdi.12483DOI Listing
April 2017

The Prognostic Value of Red Blood Cell Distribution Width in Patients on Maintenance Hemodialysis.

Blood Purif 2016 6;42(4):314-321. Epub 2016 Oct 6.

Blood Purification Center, Zhongshan Hospital of Fudan University, Shanghai, PR China.

Aims: To examine the association between red blood cell distribution width (RDW) and mortality in hemodialysis (HD) patients.

Methods: Three hundred fifty six patients on HD for >3 months were enrolled and followed for 2 years. Patients were divided into 2 groups according to the median RDW value. Patient survival and risk factors for mortality were investigated.

Results: The 2-year survival rate was significantly lower in the high-RDW group (>14.9%; log-rank = 10.00, p = 0.0016). RDW (hazard ratio (HR) 1.34, 95% CI 1.04-1.71, p = 0.021), hemoglobin (HR 0.98, 95% CI 0.96-1.00, p = 0.023) and albumin (HR 0.90, 95% CI 0.82-0.99, p = 0.026) were independent predictors of mortality. Receiver operating characteristic curves of RDW to predict 2-year mortality had an area under the curve of 0.6487 (95% CI 0.5714-0.7260).

Conclusions: Abnormal RDW was common in HD patients and significantly related with poor outcomes in these patients.
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http://dx.doi.org/10.1159/000449421DOI Listing
December 2016

Clinical status of Sagliker syndrome: a case report and literature review.

Ren Fail 2014 Jun 27;36(5):800-3. Epub 2014 Feb 27.

Blood Purification Center, Zhongshan Hospital of Fudan University , Shanghai , P.R. China and.

In a 53-year-old woman, Sagliker syndrome developed during 22 years of treatment with intermittent hemodialysis as a result of severe secondary hyperparathyroidism (SHPT) complicating end-stage renal disease. She failed medical managements and lost her renal graft just after the kidney transplantation due to acute rejection. Although surgical parathyroidectomy was effective, the parathyroid hormone level became extremely high again due to recurrent hyperparathyroidism. It is possible that such patient could survive long-term with dialysis, but prevention of severe SHPT is the most important.
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http://dx.doi.org/10.3109/0886022X.2014.890110DOI Listing
June 2014

24-h residual urine volume at hemodialysis initiation: a possible predictor for acute ischemic stroke incurrence in hemodialysis patients.

Clin Neurol Neurosurg 2013 May 13;115(5):557-61. Epub 2012 Jul 13.

Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Background: Residual renal function (RRF) recently has been confirmed to be a significant predictor of morbidity and mortality in hemodialysis (HD) patients. As RRF is not exactly the same with 24-h residual urine volume, the aim of our study is to evaluate the association of residual urine volume with acute ischemic stroke (AIS) among HD patients.

Methods: 282 patients starting chronic HD in our center during January 2005 and December 2008 were enrolled. The clinical data at HD initiation and the occurrence of AIS since starting HD were recorded and obtained from our database. According to the prevalence of AIS, we divided 282 patients into the AIS group (n=69) and non-AIS (n=213) group.

Results: A total of 69 (24.5%) patients suffered from AIS since HD initiation. Patients with AIS were much older, with more diabetes, had higher levels of hemoglobin, while lower levels of residual urine volume and serum uric acid. In multivariate logistic regression analysis, old age (OR, 1.036; 95% CI, 1.009-1.063; P=0.008), diabetes (OR, 2.385; 95% CI, 1.074-5.294; P=0.033) and 24-h residual urine volume<1290 ml at HD initiation (OR, 2.446; 95% CI, 1.219-4.907; P=0.012) was significant predictors for future AIS occurrence during HD.

Conclusion: This study indicates that residual urine volume levels at HD initiation are inversely associated with AIS risk in future in chronic HD patients. Besides, aging and diabetes should also be noticed for prevention of AIS.
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http://dx.doi.org/10.1016/j.clineuro.2012.06.028DOI Listing
May 2013