Individualizing Therapy in Lupus Nephritis

An, Yu; Zhang, Haitao; Liu, Zhihong

doi:10.1016/j.ekir.2019.08.005

Cited by 10 publications

(8 citation statements)

References 54 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…About 60% of patients develop this condition, with approximately 20% progressing to end-stage kidney disease (ESRD) (1). Combination therapy with mycophenolate mofetil (MMF), calcineurin inhibitors (CNI) and steroids produces complementary effects and also minimizes toxicity (2). This therapy is recommended as the initial treatment for LN and produces better efficacy and more complete remission compared with intravenous cyclophosphamide (IVCY) and steroids (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis

Liang

Liu

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

ObjectivesCombination therapy with mycophenolate mofetil, tacrolimus and steroids are effective in achieving complete remission in lupus nephritis (LN). Combination therapy uniquely downregulated caspase-1 compared with monotherapies, which can cleave gasdermin D (GSDMD) and was recently identified as the pyroptosis executioner. We therefore investigated whether combination therapy enabled the suppression of caspase-1/GSDMD-mediated pyroptosis in LN.MethodsExpression and activation of GSDMD were detected in kidney specimens of the human and mouse with LN using immunohistochemical staining and immunoblotting. Primary podocytes isolated from MRL/lpr mice were incubated with LPS+ATP, and pretreated with monotherapy or combination therapy. Inhibition of caspase-1/GSDMD-induced pyroptosis by combination therapy were assessed in MRL/lpr mice and human specimens. Pyroptosis was examined using a FAM caspase-1 kit and flow cytometry. The correlation between pyroptosis in peripheral blood and the systemic lupus erythematosus disease activity index (SLEDAI) was analyzed.ResultsKidney tissue specimens from LN patients and mice exhibited greatly increased expression levels and cleavage of GSDMD. In cultured podocytes, combination treatment significantly suppressed the activation of NLRP3 and caspase-1 and reduced GSDMD N-terminal levels. Combination therapy repressed disease progression through inhibition of caspase-1/GSDMD-mediated pyroptosis in both humans and MRL/lpr mice. Caspase-1/PI positive cell numbers in peripheral blood were positively correlated with SLE-DAI. LN patients with complete remission and partial remission had remarkably reduced caspase-1/PI positive cell numbers compared to baseline. Ac-FLTD-CMK, a GSDMD-derived inhibitor, prevented the development of LN.ConclusionCombination therapy suppressed caspase-1/GSDMD-mediated pyroptosis in vitro and in vivo and reduced disease progression.

show abstract

Section: Introductionmentioning

confidence: 99%

Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis

Liang

Liu

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Only few treatments targeting general mechanisms of CKD progression have been proven to retard renal functional decline. However, an increasing understanding of the pathophysiology of certain forms of renal disease has increased our armamentarium for the specific treatment of some forms of CKD [3][4][5][6][7]. Hence, establishing a precise diagnosis is of great importance for disease-modifying treatments of renal diseases.…”

Section: Introductionmentioning

confidence: 99%

Safety of Kidney Biopsy when Performed as an Outpatient Procedure

Bonani

Seeger

Weber

et al. 2021

Kidney Blood Press Res

View full text Add to dashboard Cite

Introduction: Kidney biopsy remains the gold standard for the diagnosis of most renal diseases. A major obstacle to performing a biopsy is safety concerns. However, many safety measures are not evidence based and therefore vary widely between centers. We sought to determine the rate and timing of kidney biopsy complications in our center, to compare the complication rate between native and transplant kidney biopsies, to evaluate the feasibility of performing kidney biopsies as an outpatient procedure and the value of a postbiopsy ultrasound before discharge, and to identify risk factors for complications. Methods: We performed a single-center, retrospective, observational study at the Division of Nephrology of the University Hospital Zurich including all patients who underwent renal biopsy between January 2005 and December 2017. Major bleeding (primary outcome) and any other bleeding or nonbleeding complications (secondary outcomes) were compared between native and transplant kidney biopsies and between inpatient and outpatient procedures and correlated with clinical factors possibly affecting bleeding risk. Results: Overall, 2,239 biopsies were performed in 1,468 patients, 732 as inpatient and 1,507 as outpatient procedures. Major bleeding was observed in 28 (3.8%) inpatient and in 15 (1.0%) outpatient procedures, totaling to 43 (1.9%) of all biopsies. Major bleeding requiring intervention amounted to 1.0% (0.5% of outpatient procedures). Rate of major bleeding was similar between native and transplant kidneys. 13/15 (87%) bleeding episodes in planned outpatient procedures were detected during the 4-h surveillance period. Risk factors for bleeding were aspirin use, low eGFR, anemia, cirrhosis, and amyloidosis. Routine postbiopsy ultrasound did not change management. Conclusions: Kidney biopsy is an overall safe procedure and can be performed as an outpatient procedure in most patients with an observation period as short as 4 h. The value of routine postbiopsy ultrasound is questionable.

show abstract

“…In the treatment of SLE, the relationship between SLE activity and immunosuppression should be evaluated, and the side effects of glucocorticoids and other immunosuppressants should be closely monitored [ 24 ]. In this study, the non-PICS group had higher SLE activity and severe kidney injury, but the human and kidney survival rates were better than those of the PICS group, suggesting that whether to conduct high-dose glucocorticoids and adjust the type of immunosuppressant should not only consider the current degree of SLE activity.…”

Section: Discussionmentioning

confidence: 99%

Persistent inflammation–immunosuppression–catabolism syndrome in patients with systemic lupus erythematosus

Wei-xin

Wang

et al. 2023

Int Urol Nephrol

View full text Add to dashboard Cite

Objective To evaluate the clinical characteristics and prognosis of systemic lupus erythematosus (SLE) with persistent inflammation–immunosuppression–catabolism syndrome (PICS). Methods We retrospectively analyzed patients with SLE who were admitted to the renal intensive care unit (ICU) for over 14 days at Jinling Hospital from July 2010 to July 2018. According to the diagnostic criteria of PICS, we divided the SLE patients into a PICS group and a non-PICS group. We performed a multivariate Cox regression analysis on the risk factors for death in these two groups by comparing the clinical features and prognosis. Results A total of 96 SLE patients met the inclusion and exclusion criteria of this study, including 61 patients in the PICS group and 35 patients in the non-PICS group. The PICS group patients required a longer length of stay in ICU with higher inflammatory indicators (such as C-reactive protein, procalcitonin and interleukin-6) and lower immune levels (such as total, CD3 + , CD4 + , CD8 + and CD20 + lymphocytes) compared to the non-PICS group patients ( P < 0.01). Hemoglobin, platelets, serum creatinine, serum blood urea nitrogen and SLE Disease Activity Index (SLE-DAI) score in the PICS group were lower than those in the non-PICS group ( P < 0.05), suggesting severe hematological injury in the PICS group and relatively severe renal damage in the non-PICS group. The rates of PICS combined with sepsis, acute respiratory distress syndrome, mechanical ventilation, gram-positive bacteria, gram-negative bacteria, fungi and double infections were higher than those in the non-PICS group ( P < 0.05). The 3-year survival rate was 50.82% in the PICS group and 85.71% in the non-PICS group. The 3-year renal survival rate was 32.79% in the PICS group and 51.43% in the non-PICS group. Multivariate Cox regression found that the total lymphocyte count during ICU admission was an independent risk factor for death in SLE patients with PICS. Conclusion Patients with SLE complicated with PICS had longer ICU stays, a lower level of SLE activity, a higher risk of secondary infection and a significantly lower survival rate than non-PICS patients.

show abstract

Individualizing Therapy in Lupus Nephritis

Cited by 10 publications

References 54 publications

Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis

Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis

Safety of Kidney Biopsy when Performed as an Outpatient Procedure

Persistent inflammation–immunosuppression–catabolism syndrome in patients with systemic lupus erythematosus

Contact Info

Product

Resources

About