Development Of Renal Involvement Research Articles

The importance of M694V mutation in systemic lupus erythematosus; implications for its role in neutrophil extracellular traps associated renal involvement

Background: Systemic lupus erythematosus (SLE) is characterized by multisystem organ involvement. Enhanced neutrophil extracellular traps (NETs) formation and release as well as impaired clearance of NETs have been reported in SLE patients. Renal involvement is common in SLE which might be through deposition of immune complexes within the kidneys. M694V mutation is one of the hot spots of Mediterranean fever gene (MEFV). MEFV mutations have been previously reported in a number of auto-inflammatory and autoimmune diseases in Iranian patients. Objectives: This case-control study was aimed to evaluate the potential influences of M694V gene mutation in SLE disease and in development of renal involvement. Patients and Methods: Genotyping of 130 patients and 116 healthy controls was done for M694V mutation (rs61752717, c.2080A>G) using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) method. Results: Significant differences in the alleles and genotypes frequencies of M694V mutation between SLE patients and ethnically matched healthy controls were detected in this study (9.9% versus 2.4% P=0.000, OR [odds ratio]= 4.277, CI= 2.213-8.265). Furthermore a significant difference of renal involvement between M694V mutation carriers versus noncarriers (8.5% versus 10.4%, P=0.017, OR= 2.149, CI= 1.135- 4.072). Conclusions: The association between M694V mutation and SLE susceptibility was observed. Additionally, renal involvement was significant in SLE patients compared to controls. This finding probably is developed through NET-associated Dnase1 inhibition and maybe amyloidosis. This study may help to explain the nature of the inflammatory state in mutation carriers and assist to an accurate understanding of how it influences SLE pathogenesis.

Cut‐off values for serum matrix metalloproteinase‐9: Is there a threshold to predict renal involvement for Henoch–Schonlein purpura in children?

To clarify whether the level of matrix metalloproteinase-9 (MMP-9), tissue inhibitor matrix metalloproteinase-1 (TIMP-1) or the ratio of MMP-9/TIMP-1 was associated with the renal involvement in Henoch-Schonlein purpura (HSP); and to explore whether there existed early diagnostic measure for HSP nephritis (HSPN). Sixty-six patients with HSPN, 68 patients with HSP and 60 healthy children (control group) were enrolled into our study. Serum and urine samples before treatment were collected for detection. Compared with the HSP group and control group, serum MMP-9, TIMP-1 and ratio of MMP-9/TIMP-1 in the HSPN group were significantly higher (P<0.05 and P<0.01, respectively). Urine MMP-9, TIMP-1 and ratio of MMP-9/TIMP-1 in the HSPN group were obviously higher than those of the control group (P<0.05) and the HSP group (P<0.05). Receiver-operator curve (ROC) analysis was performed to obtain the area under the curve (AUC) and the AUC and its 95% confidence interval (CI) of serum MMP-9 were 0.97 and 0.95-0.99, respectively. The optimal cut-off point (sensitivity; specificity) of serum MMP-9 for diagnosing HSPN was 179.79 mg/L (0.96; 0.88). Levels of MMP-9, TIMP-1 and ratio of MMP-9/TIMP-1 in serum and urine were remarkably high in the patients with HSPN, but the serum MMP-9 was more sensitive. Serum MMP-9 may be associated with the occurrence and development of renal involvement in HSPN and become an important indicator for early diagnosis of HSPN.

Time to Renal Disease and End-Stage Renal Disease in PROFILE: A Multiethnic Lupus Cohort

BackgroundRenal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE).Methods and FindingsPROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic–demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcγRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model.ConclusionsFcγ receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Predictive value of IgG autoantibodies against C1q for nephritis in systemic lupus erythematosus.

Antibodies against C1q (C1qAb) have been demonstrated in the serum of patients with several immune complex diseases. Patients, particularly those with lupus nephritis, were found to have increased serum titres of IgG C1qAb in a cross-sectional analysis. In the present prospective study correlations were sought between serum titres of IgG C1qAb and clinical as well as laboratory parameters of disease activity in patients with systemic lupus erythematosus (SLE). Titres of IgG C1qAb in the serum of 68 SLE patients were measured serially during a three year period. At the same time clinical and laboratory parameters of disease activity were assessed. Increased titres of IgG C1qAb were found in the serum of 56% of SLE patients during the study. Significant correlations were found between increased titres of IgG C1qAb and renal involvement. Clinical signs of renal involvement were found to be associated with significant increases of serum titres of IgG C1qAb in the six months preceding this appearance. Fifty per cent of the increases in serum titres of IgG C1qAb were followed by the development of renal involvement. Elevated serum titres of IgG C1qAb were especially related to proliferative forms of glomerulonephritis. Furthermore, significant correlations were found between serum titres of IgG C1qAb and serum levels of immune complexes, levels of complement components, and titres of antibodies to DNA. The results suggest that IgG C1qAb play a pathogenic role in the development of lupus nephritis and that serial measurement of serum titres of IgG C1qAb is useful in the management of SLE patients.