In the United States, approximately 35% of adults with Systemic Lupus Erythematosus (SLE) have clinical evidence of nephritis at the time of diagnosis; with an estimated total of 50–60% developing nephritis during the first 10 years of disease [1–4]. The prevalence of nephritis is significantly higher in African Americans and Hispanics than in Caucasians, and is higher in men than in women. Renal damage is more likely to develop in non-Caucasian groups [2–4]. Overall survival in patients with SLE is approximately 95% at 5 years after diagnosis and 92% at 10 years [5, 6]. The presence of lupus nephritis significantly reduces survival, to approximately 88% at 10 years, with even lower survival in African Americans [5, 6].

The American College of Rheumatology (ACR) last published guidelines for management of systemic lupus erythematosus (SLE) in 1999 [7]. That publication was designed primarily for education of primary care physicians and recommended therapeutic and management approaches for many manifestations of SLE. Recommendations for management of lupus nephritis (LN) consisted of pulse glucocorticoids followed by high dose daily glucocorticoids in addition to an immunosuppressive medication, with cyclophosphamide viewed as the most effective immunosuppressive medication for diffuse proliferative glomerulonephritis. Mycophenolate mofetil was not yet in use for lupus nephritis and was not mentioned. Since that time, many clinical trials of glucocorticoids-plus-immunosuppressive interventions have been published, some of which are high quality prospective trials, and some not only prospective but also randomized. Thus, the ACR determined that a new set of management recommendations was in order. A combination of extensive literature review and the opinions of highly qualified experts, including rheumatologists, nephrologists and pathologists, has been used to reach the recommendations. The management strategies discussed here apply to lupus nephritis in adults, particularly to those receiving care in the United States of America, and include interventions that were available in the United States as of April 2011.

While these recommendations were developed using rigorous methodology, guidelines do have inherent limitations in informing individual patient care; hence the selection of the term “recommendations.” While they should not supplant clinical judgment or limit clinical judgment, they do provide expert advice to the practicing physician managing patients with lupus nephritis.

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American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis

The pathologies of many infectious, autoimmune and malignant diseases are influenced by the profiles of cytokine production in pro-inflammatory (TH1) and anti-inflammatory (TH2) T cells. Interindividual differences in cytokine profiles appear to be due, at least in part, to allelic polymorphism within regulatory regions of cytokine gene. Many studies have examined the relationship between cytokine gene polymorphism, cytokine gene expression in vitro, and the susceptibility to and clinical severity of diseases. A review of the findings of these studies is presented. An on-line version featuring appropriate updates is accessible from the World Wide Web site, http://www.pam.bris.ac.uk/services/GAI/cytokine4.htm.

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Cytokine gene polymorphism in human disease: on-line databases.

The balance between IL-1 and IL-1Ra in disease.

Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles during kidney development, homeostasis and disease. In particular, miRNAs participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). Therefore, miRNAs represent potential new therapeutic targets for a debilitating disease that continues to increase in prevalence worldwide and for which fully effective therapies are lacking. Several lines of research aimed at improving common CKD diagnostic tools and avoiding invasive kidney biopsies have also identified circulating miRNAs as possible diagnostic and even prognostic biomarkers of kidney disease. This Review discusses current understanding of the function of miRNAs in CKD, focusing on functions specifically involved in the transforming growth factor β1 pathway, which is activated in CKD. miRNAs that, according to available evidence, seem to be involved in diabetic nephropathy, IgA nephropathy, lupus nephritis, polycystic kidney disease and graft rejection, are also discussed.

MicroRNAs in kidney physiology and disease

https://www.kidney-international.org/article/S0085-2538(15)56246-7/pdf

MiR-223 downregulation promotes glomerular endothelial cell activation by upregulating importin α4 and α5 in IgA nephropathy

Interleukin-1 receptor antagonist allele: Is it a genetic link between Henoch-Schönlein nephritis and IgA nephropathy?

SUMMARY:

Objective: To compare the effects, relapse ratio and outcomes between mycophenolate mofetil (MMF) and pulse intravenous cyclophosphamide (CTX) for the induction therapy in patients with crescentic lupus nephritis



Methodology:  This is a retrospective, controlled study Twenty-seven MMF therapeutic and twenty-five CTX therapeutic lupus patients with ≥50% crescent formation were enrolled in this study The general conditions, clinicopathological findings, remission and relapse ratio, and outcomes of them were compared



Results:  There was no significant difference of general condition and clinicopathological findings between MMF and CTX group At 12 months, the total remission ratio in MMF and CTX group were 731% and 696%, while the complete remission ratio in MMF group (538%) was significantly higher than that in CTX group (261%) The relapse ratio in MMF group (105%) was significantly lower than in CTX group (438%) Forty per cent of PR patients in CTX group suffered from relapse Until June 2005, the patients in CTX group received a follow time with 385 ± 212 (range 10∼80) months, and in MMF group the follow time was 411 ± 270 (range 12∼90) months Two patients in MMF group and two in CTX group entered into end stage renal failure The side effect of infection was more significant in CTX group



Conclusion:  Higher complete remission ratio and lower relapse ratio were observed in MMF group than in CTX group The side effect of infection was more infrequent in MMF group, which showed preferable security of MMF

Effects of mycophenolate mofetil for patients with crescentic lupus nephritis.

ObjectiveWe evaluated the role of a quality improvement initiative in improving clinical outcomes in peritoneal dialysis (PD).MethodsIn a retrospective analysis of 6 years of data from a hospital r...

/pdf/impact-of-continuous-quality-improvement-initiatives-on-53chza22v1.pdf

Impact of Continuous Quality Improvement Initiatives on Clinical Outcomes in Peritoneal Dialysis

Objective To investigate the prognosis of lupus nephritis (LN) and its influencing factors in patients with lupus nephritis in China. Methods A retrospective study was carried out in 86 patients followed up for at least 5 years. Clinical features, serological and immunological tests were investigated. Renal biopsies were performed at the beginning of the study and repeated in some cases during the follow-up period. All the 86 patients had serum creatinine (Scr) level less than 132.6 mumol/L at the initial presentation and were divided into three groups according to the level of Scr at the end of the study. Group I: the patients with normal renal function (Scr or = 530.4 mumol/L). Results Forty-seven patients reached clinical remission with normal renal function, 11 had with stabilization of renal function, although the systemic lupus erythematosis (SLE) activity relapsed repeatedly, while 28 subjects developed renal insufficiency after 60-170 (mean 88.12 +/- 28.23) months of observation. ESRF rate was 11.6% in this group of patients. Eight patients died (2 died of infections and 6 died of ESRF) during the follow-up period. At the beginning of the study the rates of hypertension, persistent anemia and hematuria in Group II were 50%, 70%, and 70% respectively, being much higher than those in Group I. The calculation of AI and CI in 60 patients revealed that there were 65% of patients with AI > or = 7 and 70% of patients with CI > or = 3 in Groups II and III, while in Group I there were only 32% of patients with AI > or = 7 and 19% of patients with CI > or = 3. Sixteen cases had pathologic class changed in 48 repeated biopsies. Seven cases changed to Class IV, 5 to Class II, 3 to Class V from other classes and one to class III from Class II. Conclusions Factors associated with the development of renal insufficiency in these lupus patients included hypertension, anemia and hematuria. Renal biopsy evaluation offered additional prognostic information and showed that patients with severe active and chronic histologic changes were at risk for developing renal insufficiency. During the clinical course, the renal classification of LN changed in certain patients, thus the histologic classification of renal morphology at initial presentation did not fully predict the outcome. Renal involvement is very common in systemic lupus erythematosis (SLE) patients. Lupus nephritis (LN) is the most common form of secondary renal disease in China. It has various and unpredictable clinical features. The risks associated with its treatment have challenged investigators to detect the factors which may influence the survival rate of patients with LN and to develop the rational approaches to therapy. Decades of intensive investigation at many centers around the world had underscored the predictive value of demographic, clinical and laboratory data prior to treatment. Controversies still existed due to the difference in environment, race and the selection criteria of patients as well as the method used to evaluate the outcome. There are still some factors which are thought to have an impact on the prognosis of LN. Most of the articles on the prognosis of patients with LN were reported from Europe and America either about Caucasian or African-American patients. The prognosis of LN and its influence in Chinese patients need more elucidation.

Yusheng Yu

Papers

MiR-223 downregulation promotes glomerular endothelial cell activation by upregulating importin α4 and α5 in IgA nephropathy

Interleukin-1 receptor antagonist allele: Is it a genetic link between Henoch-Schönlein nephritis and IgA nephropathy?

Effects of mycophenolate mofetil for patients with crescentic lupus nephritis.

Impact of Continuous Quality Improvement Initiatives on Clinical Outcomes in Peritoneal Dialysis

The prognosis of biopsy-proven lupus nephritis in chinese patients: long term follow-up of 86 cases.