[The prevalence, influencing factors and prognosis of abnormal serum potassium levels in patients with chronic kidney disease].

Objective: To estimate the prevalence of hyperkalemia and hypokalemia in patients with chronic kidney disease (CKD), analyze the influencing factors and explore the impact on disease prognosis. Methods: A total of 3 190 patients with CKD stage 1-4 from 39 tertiary clinical centers in China between November 2011 and December 2016 were recruited. The baseline characteristics of the patients were collected through face-to-face questionnaire investigation, physical examination and laboratory test. Meanwhile, the data of patient's end-stage renal disease, cardiovascular disease events and deaths were obtained up to December 2017 through active monitoring. The patients were categorized into three groups based on their baseline level of serum potassium (hypokalemia:<3.5 mmol/L, normal range: 3.5-<5.0 mmol/L, hyperkalemia: ≥5 mmol/L). Multi-nominal logistic regression was employed to evaluate the association between clinical characteristics and the presence of hyperkalemia or hypokalemia. The competing risk-based subdistribution Cox proportional hazards regression was used to assess the association between baseline level of serum potassium and various outcomes. Results: The mean age of the patients was (50±14) years, with a male rate of 57.6% (1 839/3 190) and a majority of glomerulonephritis (59.7%, 1 668/2 792). Patients with CKD stage 3-4 accounted for 70.8% (2 260/3 190), and the mean level of serum potassium was (4.4±0.7) mmol/L. The prevalence of hypokalemia and hyperkalemia was 3.7% (n=118) and 17.6% (n=561), respectively. In the multivariable adjusted analysis, presence of history of cardiovascular disease (OR=0.33, 95%CI: 0.13-0.83, P=0.019) and estimated glomerular filtration rate (OR=0.95, 95%CI: 0.91-0.98, P=0.001) were inversely associated with hypokalemia, while use of thiazide or loop diuretic (OR=2.06, 95%CI: 1.51-2.81, P<0.001) and estimated glomerular filtration rate (OR=1.13, 95%CI: 1.12-1.16, P<0.001) were positively associated with hyperkalemia. After adjusting for relevant cardiovascular and renal risk factors, the result only showed a significant association between hypokalemia and risk of all-cause mortality (HR=2.12, 95%CI: 1.06-4.24, P=0.034). Conclusions: Hypokalemia and hyperkalemia were not rare in patients with CKD in China, with the latter more prevalent. Hypokalemia was independently associated with the risk of death.

The associations of endothelial and podocyte injury in proliferative lupus nephritis: from observational analysis to in vitro study.

Our study aims to evaluate the endothelial cell-podocyte crosstalk in proliferative lupus nephritis (LN). The semi-quantification scores of glomerular endothelial cell injury and the foot process width (FPW) were processed in 110 proliferative LN patients. Podocytes were stimulated with LN-derived IgG. Glomerular endothelial cells were treated with podocyte-conditioned medium (PCM), and then podocytes were incubated with endothelial cell-conditioned medium (ECM). The levels of vascular endothelial growth factor-A (VEGF-A) in PCM and endothelin-1 in ECM were analyzed, and the injury of podocyte and glomerular endothelial cells were further evaluated. The pathological score of glomerular endothelial cell injury was correlated with FPW in LN complicated with thrombotic microangiopathy. In vitro study showed the following: 1. Stimulation of podocytes by IgG from LN led to decline in the expression of nephrin with cytoskeleton rearrangement, and reduction of VEGF-A levels. 2. Exposure of glomerular endothelial cells to PCM incubated with LN-derived IgG (PCM-LN) induced more endothelin-1 secretion and disruption of intercellular tight junction. 3. Exposure of podocytes to ECM stimulated with PCM-LN could induce cytoskeleton redistribution with decrease of nephrin. In conclusion, the pathological glomerular endothelial cell lesions were associated with FPW and the VEGF-endothelin-1 system might play a critical role in the endothelial cell-podocyte crosstalk in LN.

[Clinical characteristics of cardiomyopathies complicated with ventricular thrombosis].

Objective: To summarize the clinical characteristics of cardiomyopathy complicated with ventricular thrombosis. Methods: The clinical data of inpatients suffered from cardiomyopathy complicated with ventricular thrombosis in Fuwai Hospital between January 2015 and May 2019 were analyzed retrospectively. Results: A total of 125 cases were reviewed, and 24.8% were female. Dilated cardiomyopathy was the most common disease (62.4%), followed by arrhythmogenic right ventricular cardiomyopathy (ARVC) (13.6%) and hypertrophic cardiomyopathy (11.2%). There were 74.4% thrombosis in left ventricle, 12.8% in right ventricle and 12.8% in biventricle. The proportions of right ventricle thrombosis were higher in ARVC than in other cardiomyopathies (52.9% vs 6.5%, P<0.01). The majority suffered from cardiac function New York Heart Association (NYHA) Class Ⅲ (45.6%) and class Ⅳ (39.2%). The ratio of NYHA Class Ⅳ was higher in female patients than in male ones (25.8% vs 10.6%, P<0.05). In lab detection, positive results of D-Dimer and N terminal-pro B type natriuretic peptide (NT-proBNP) accounted for 72.8% and 97.6%, respectively. There were 2.5% patients died in the hospital or discharged because of the worsening of illness, the chances were higher in female than male patients (9.7% vs 0, P<0.01). Among these patients, one succumbed to massive ischemic stroke caused by ventricular thrombus detachment under standard anticoagulation therapy. Conclusions: Dilated cardiomyopathy is the most common cardiomyopathy complicated with ventricular thrombosis. The most common location of thrombosis is left ventricle. Right ventricle thrombosis is more common in ARVC. The majority suffer from moderate or severe cardiac dysfunction. Higer proportion of female patients suffer from anemia, severe condition and poor prognosis.

Plasma ADAMTS-13 activity in proliferative lupus nephritis: a large cohort study from China.

Objectives The aim of this study was to investigate plasma ADAMTS-13 activity in patients with proliferative lupus nephritis and to evaluate the role of clinical, laboratory and pathological features, especially the vascular lesions in lupus nephritis. Methods Plasma samples from 163 class III and IV lupus nephritis patients confirmed by biopsy examinations and 98 normal controls were collected. ADAMTS-13 activity was evaluated by a residual collagen binding assay. IgG autoantibodies against ADAMTS-13 were detected by ELISA using recombinant ADAMTS-13 as a solid-phase ligand. Levels of vWF were measured by ELISA. Their associations with clinical, laboratory and pathological features were further assessed. Results Plasma ADAMTS-13 activity in lupus nephritis patients was significantly lower than that in normal controls (84 ± 21% vs. 90 ± 13%, p = 0.005). IgG ADAMTS-13 autoantibodies were detected in only three patients. The plasma level of vWF was significantly higher in the lupus nephritis group than in normal controls (1.00 ± 0.79 vs. 0.70 ± 0.30, p = 0.025). Plasma ADAMTS-13 activity was negatively correlated with the level of serum creatinine and proteinuria ( r = -0.354, p < 0.001; r = -0.200, p = 0.011, respectively). Patients with a higher level of ADAMTS-13 activity had significantly higher levels of factor H (401.51 ± 183.01 µg/ml vs. 239.02 ± 155.45 µg/ml, p = 0.005). Plasma ADAMTS-13 activity was negatively associated with total pathological AI scores ( r = -0.326, p < 0.001), endocapillary hypercellularity ( r = -0.419, p < 0.001), cellular crescents ( r = -0.274, p < 0.001), subendothelial hyaline deposits ( r = -0.266, p = 0.001), interstitial inflammatory cell infiltration ( r = -0.304, P < 0.001), tubular atrophy ( r = -0.199, p = 0.011), acute glomerular vascular lesions ( r = -0.344, p < 0.001) and acute renal vascular lesions ( r = -0.338, p < 0.001). No association was found between level of vWF and plasma ADAMTS-13 activity ( r = 0.033, p = 0.671). Low level of ADAMTS-13 activity was a risk factor for renal outcomes ( p = 0.039, HR = 0.047, 95% CI: 0.120-1.005). Conclusions Decreased ADAMTS-13 activity was found in patients with proliferative lupus nephritis, and plasma ADAMTS-13 activity was closely associated with renal injury indices, especially pathological vascular scores. The role of ADAMTS-13 in the disease remains to be further investigated.

Composite urinary biomarkers to predict pathological tubulointerstitial lesions in lupus nephritis.

Objective This study aimed to evaluate the clinical value of urinary biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein-1 (MCP-1) in lupus nephritis. Methods A total of 109 biopsy-proven lupus nephritis patients were included and 50 healthy individuals were used as normal controls. Urinary KIM-1, NGAL, and MCP-1 levels were measured by ELISA and their correlations with clinical and histological features were assessed. Receiver operating characteristic curves were performed and the Cox regression model was applied to identify prognostic factors associated with renal outcomes. Results Active lupus nephritis patients exhibited elevated urinary levels of KIM-1, NGAL, and MCP-1 compared with lupus nephritis patients in remission ( P < 0.001) and normal controls ( P < 0.001). The urinary KIM-1 level was correlated with pathological tubular atrophy ( r = 0.208, P < 0.05) and increased significantly in the presence of interstitial inflammatory lesions ( P = 0.031). Urinary KIM-1, NGAL, and MCP-1 levels were higher in patients with active tubulointerstitial lesions than in those with only chronic lesions ( P = 0.015, P = 0.230, and P = 0.086, respectively). A combination of KIM-1, NGAL, and MCP-1 was a good indicator for diagnosing active tubulointerstitial lesions (area under the curve: 0.796). The combination of KIM-1 and NGAL was identified as an independent risk factor for renal outcomes (hazard ratio = 7.491, P < 0.05). Conclusion Urinary KIM-1, NGAL, and MCP-1 levels were associated with kidney injury indices in lupus nephritis. The combination of the three biomarkers showed increased power in predicting tubulointerstitial lesions and renal outcomes.

Tubular basement membrane immune complex deposition is associated with activity and progression of lupus nephritis: a large multicenter Chinese study.

Tubulointerstitial injury is found frequently in lupus nephritis. Immune complex deposits can occur in the tubular basement membranes (TBMs), although its significance in lupus nephritis patients remains unclear. This study assessed the clinical and prognostic features of lupus nephritis patients with TBM deposits in a large Chinese multicenter cohort. Complete data were collected from 195 patients with renal biopsy-proven lupus nephritis diagnosed in the Peking University First Hospital as the discovery cohort. A total of 102 lupus nephritis patients were enrolled from another four centers as the validation cohort. The status of TBM deposits was retrospectively assessed using electron microscopy, and the associations of the deposits with clinical data, pathological characteristics and renal outcomes were further analyzed. The percentage of positive TBM deposits was nearly 30% in the lupus nephritis patients. Using immuno-gold labeling, we found that 10/10 patients were positive for IgG, 7/10 were C3d positive, 6/10 were C1q positive, and 1/10 were C4d positive. Patients with TBM deposits presented with more active features, including a higher SLEDAI score (SLE Disease Activity Index) ( p < 0.001), higher serum creatinine level ( p = 0.001) and lower serum C3 level ( p < 0.001). These patients also presented with higher scores for most renal pathological indices, including the total activity indices score ( p < 0.001) and total chronicity indices score ( p = 0.001). TBM deposits affected renal outcomes in the univariate Cox hazards regression analysis (HR = 4.2, 95% CI = 1.3-14.3, p = 0.02). In conclusion, TBM deposits were common in lupus nephritis patients and correlated closely with the clinical disease activity and renal outcome.

[Impact of anemia and chronic kidney disease on the risk of cardiovascular disease and all-cause mortality among diabetic patients].

OBJECTIVE: To explore the association between anemia and cardiovascular disease and all-cause mortality among diabetic patients, and whether the association is modified by the presence of chronic kidney disease (CKD). METHODS: Physical examination data of 8 563 patients with diabetes who met the inclusion and exclusion criteria between 2010 and 2011 were collected, based on the prospective cohort data of Kailuan study. The deadline of the follow-up was December 31, 2015, and the endpoints comprised all-cause mortality and cardiovascular disease. Survival analysis was performed by Kaplan-Meier method. Cox proportional hazards regression model was used to assess the association between anemia with or without CKD, and cardiovascular events and all-cause mortality after adjustment for confounding factors. RESULTS: The average age of the subjects was (57.3±10.3) years, of whom the patients with anemia accounted for 5.2%. The proportion of the patients with anemia combined with CKD was higher than that of the patients without anemia (27.2% vs. 20.8%, P=0.001). The median follow-up time was 4.9 years (interquartile range: 4.6-5.2 years). During the follow-up period, 559 patients died, and 434 patients had cardiovascular disease. Compared with the patients without anemia, the all-cause mortality rate of the patients with anemia was higher (3 220.3/100 000 person-years vs. 1 257.9/100 000 person-years, P<0.001). There was no statistically significant difference in the incidence of cardiovascular disease between the above two groups (999.8/100 000 person-years vs. 1 081.2/100 000 person-years, P>0.05). The mortality and incidence of cardiovascular disease among the patients with CKD were higher than those of the patients without CKD (2 558.3/100 000 person-years vs. 1 044.0/100 000 person-years, P<0.001; 1 605.9/100 000 person-years vs. 941.6/100 000 person-years, P<0.001). Results of Cox regression model showed that, after adjustment for confounding factors, the all-cause mortality risk increased by 95% in the diabetic patients with anemia (HR=1.95, 95% CI: 1.50-2.54). Anemia and CKD significantly increased the mortality risk among diabetic patients (HR=3.61, 95% CI: 2.48-5.26). The CKD patients without anemia had an increased risk of cardiovascular disease (HR=1.41, 95% CI: 1.13-1.74). CONCLUSION: Anemia is associated with an increased mortality risk in Chinese diabetic patients. Patients with CKD have an increased risk of cardiovascular disease and mortality. The all-cause mortality risk increases significantly in anemia patients with the presence of CKD, which indicates that we should focus on the prevention and treatment of diabetic patients with anemia and CKD.

A 3-year follow-up of a patient with acute renal failure caused by thrombotic microangiopathy related to antiphospholipid syndrome: case report.

Background Microvascular manifestations of antiphospholipid antibody syndrome in the kidneys include acute renal failure, thrombotic microangiopathy and hypertension. Therapy has been largely empiric. Case report A 49-year-old Chinese man presented with anuric acute renal failure without abundant proteinuria and heavy haematuria, but markedly low levels of urinary sodium, potassium and chlorine upon admission. On day 1 of hospitalization, his thrombocytopenia, anaemia and renal failure showed rapid progression. The presence of lupus anticoagulant and vascular ischaemia of the small vessels in renal arteriography were also observed. Anticoagulants, continuous renal replacement therapy, glucocorticoids and six sessions of plasma exchange were started. After the fourth plasma exchange (on day 20), his urine output increased and began to normalize. On day 25, haemodialysis was stopped and his general condition gradually improved. A renal biopsy was subsequently performed, and the histopathological diagnosis was thrombotic microangiopathy due to antiphospholipid antibody syndrome. A further 3-year follow-up showed that his haemoglobin level, platelet count and serum creatinine were within the normal range, with stable blood pressure. Conclusion Treatment modalities such as anticoagulation, immunosuppression and plasma exchange are likely to be necessary when severe acute renal failure combined with thrombotic microangiopathy present in nephropathy of antiphospholipid antibody syndrome.

Genetic variants in FH are associated with renal histopathologic subtypes of lupus nephritis: a large cohort study from China.

Objective Genetic variants in FH (complement factor H) were reported to associate with susceptibility to systemic lupus erythematosus (SLE). This study proposed that the genetic defects of FH in the susceptibility and in the development of lupus nephritis might be different. Methods This study enrolled 334 lupus nephritis patients, 269 SLE patients without clinical renal involvement and 350 controls. Two-step genotyping was performed. First, all the exons of the FH gene were fully sequenced in 100 lupus nephritis patients and 100 healthy controls. Second, genotyping of three common variants reported to be functional, rs1061170, rs800292 and rs6677604, was conducted in all the recruited individuals. Further, analysis of their associations with SLE/lupus nephritis susceptibility and the clinico-pathological parameters in the lupus nephritis group was performed. Results No significant differences were observed in allele and genotype frequencies of the three single nucleotide polymorphisms between lupus patients and controls. There was a significantly higher ratio of CC/CT genotypes of rs1061170 in lupus nephritis patients with class III than in the other two classes (class III vs. class IV vs. class V: 21.0% vs. 9.7% vs. 9.4%; P = .044). The rs6677604-GG genotype was observed to be associated with the absence of anti-ds DNA antibody ( P = .021), and the rs800292-TT genotype was associated with a higher level of circulating C3 ( P = 0.20) in lupus nephritis. Conclusion In an independent cohort, this is the first genetic association analysis focusing on FH genetic variants in Chinese lupus nephritis patients. It was found that the variants in the FH gene might affect the histopathologic subtypes and some clinical features of the disease.

Association of the IKZF1 5' UTR variant rs1456896 with lupus nephritis in a northern Han Chinese population.

OBJECTIVES: Polymorphisms of IKAROS family zinc finger 1 (IKZF1) have been found to be associated with systemic lupus erythematosus (SLE) by genome-wide association studies (GWAS). The aim of the current study was to investigate the association between IKZF1 functional variants and lupus nephritis (LN) in a northern Han Chinese population and analyse their relationship with clinical and pathological phenotypes in LN. METHOD: The association between IKZF1 functional variants and LN was analysed for the lead variant rs1456896 with both GWAS and expression quantitative trait loci (eQTL) top hits in 500 LN patients and 500 healthy controls. Replication was conducted in an independent cohort comprising 798 LN patients and 704 healthy controls. Using the ENCODE (Encyclopedia of DNA Elements) databases, functional annotations and differential gene expression data were evaluated. RESULTS: A significant association between the single nuclear polymorphism (SNP) rs1456896 and susceptibility to LN was observed in the two different cohorts (p = 9.32 × 10-3 and p = 3.00 × 10-2) and reinforced in combination (p = 1.36 × 10-3). In silico analysis indicates that rs1456896 is a regulatory variant and lower mRNA expressions of IKZF1 were observed in both peripheral blood mononuclear cells (PBMCs) and renal biopsies from SLE patients compared to normal controls. Although patients with the protective genotype AA of rs1456896 seemed to have more pronounced clinical manifestations and a lower ratio of histological classes III and IV, no significant associations between rs1456896 genotypes and sub-phenotypes of LN were detected. CONCLUSIONS: Our results suggest that the rs1456896 A allele is associated with protective susceptibility to LN. However, this association did not seem to be implicated in the disease and histopathological severity of LN in the current population.

The dysfunctions of complement factor H in lupus nephritis.

OBJECTIVE: Our previous study showed that plasma levels of factor H (FH) were significantly decreased in patients with lupus nephritis and reflected lupus nephritis activity. The aim of this study was to further investigate in vitro biofunctions of plasma FH in patients with lupus nephritis. METHODS: FH was purified from the first run of plasma exchange in four active lupus nephritis patients and two non-renal involvement systemic lupus erythematosus (SLE) patients, and plasma from two healthy controls. Then, the biofunctions of the purified FH were analyzed. In addition, FH exons sequencing analysis was performed. RESULTS: Homogeneous FH was purified from the plasma fractions and the purity of the purified FH was comparable to the commercial FH. The abilities of FH binding with C3b and mCRP, and its protecting abilities from the lysis of sheep erythrocytes, from No. 3 and No. 4 lupus nephritis patients, decreased significantly compared with those in normal controls. The purified FH from lupus nephritis patients Nos. 2-4 could not induce the phagocytosis of late apoptotic cells significantly compared with normal controls. All four lupus nephritis patients had the known SNP rs1061147 (SCR5, A307A), rs1061170 (SCR7, Y402H), CM050194 (SCR20, S1191W) and CM010322 (SCR20, V1197A), which might be associated with the above dysfunctions. CONCLUSIONS: Dysfunctions of FH, including the regulations of complement alternative pathway and the clearance of apoptotic cells, were found in some active lupus nephritis patients, which were associated with their clinical phenotypes. The FH SNPs might contribute to the dysfunctions of FH in patients with lupus nephritis.

Statistical analysis of the relationship between IL-10 gene promoter polymorphisms and the development of coronary artery disease.

Here, we conducted a case-control study to investigate the association between IL-10 gene polymorphisms and development of CAD in a Chinese population. A total of 220 patients with CAD and 236 control subjects who visited the Zhengzhou People's Hospital between May 2012 and June 2014 were selected for this study. The IL-10-1082A/G and -592A/C polymorphisms were genotyped by polymerase chain reaction coupled with restriction fragment length polymorphism. The chi-squared test revealed a significant difference in the distributions of the IL-10-1082A/G genotypes (χ2 = 6.32, P = 0.04). This data was then statistically analyzed by logistic regression analysis; we observed revealed that the CC genotype of IL-10-1082A/G had a higher risk of CAD in comparison to the AA genotype (OR = 2.09, 95%CI = 1.11-3.97). Moreover, the C allele of IL-10-1082A/G had a 1.39 fold risk of CAD when compared with (OR = 1.39, 95%CI = 1.06-1.82). We did not observe any significant correlations between the IL-10-592A/C genetic variation and susceptibility to CAD. In conclusion, our study suggests that the IL-10-1082A/G genetic variation could influence the development of CAD in a Chinese population.

Interleukin-6 (IL-6) -174G/C genomic polymorphism contribution to the risk of coronary artery disease in a Chinese population.

To investigate the role of IL-6 polymorphism (-174G/C and -572C/G) in the development of coronary artery disease (CAD), CAD patients (224) and control subjects (260) were recruited between January 2012 and December 2014. Genotyping at IL-6 -174G/C and -572C/G was conducted via polymerase chain reaction coupled to restriction fragment length polymorphism. Results indicated that several disease risk factors were significantly higher in CAD patients as compared to the control subjects. These factors include hypertension (χ2 = 20.03, P < 0.001), diabetes mellitus (χ(2) = 33.53, P < 0.001), tobacco smoking (χ(2) = 28.17, P < 0.001), body mass indexes (t = 11.39, P < 0.001), total cholesterol (t = 8.25, P < 0.001), low-density lipoprotein cholesterol (t = 7.24, P < 0.001), high-density lipoprotein cholesterol (t = 3.52, P < 0.001), and triglyceride (t = 6.09, P < 0.001). By unconditional logistic regression analysis, we observed that the CC genotype at IL-6 -174G/C was had a 2.32 (95%CI = 1.33-4.06) fold risk of developing CAD compared to the GG genotype. Moreover, IL-6 -174G/C polymorphism was positively associated with the risk of developing CAD in both dominant (OR = 1.63, 95%CI = 1.12-2.38; P = 0.01) and recessive models (OR = 2.18, 95%CI = 1.26-3.77; P = 0.001). However, no statistically significant association was observed between IL-6 -572C/G polymorphism and risk of CAD. In conclusion, IL-6 -174G/C polymorphisms are associated with the pathogenesis of CAD.

Neutrophil extracellular traps can activate alternative complement pathways.

The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative complement pathway on NETs in vitro was assessed by immunostain and confocal microscopy. Complement deposition on NETs were detected after incubation with magnesium salt ethyleneglycol tetraacetic acid (Mg-EGTA)-treated human serum. After incubation of serum with supernatants enriched in ANCA-induced NETs, levels of complement components in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Complement factor B (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b-9 on NETs incubated with heat-inactivated normal human serum (Hi-NHS) or EGTA-treated Hi-NHS (Mg-EGTA-Hi-NHS) were significantly less than that on NETs incubated with NHS or EGTA-treated NHS (Mg-EGTA-NHS). NETs induced by ANCA could activate the alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a and SC5b-9 concentration decreased from 800·42 ± 244·81 ng/ml, 7·68 ± 1·50 ng/ml, 382·15 ± 159·75 ng/ml in the supernatants enriched in ANCA induced NETs to 479·07 ± 156·2 ng/ml, 4·86 ± 1·26 ng/ml, 212·65 ± 44·40 ng/ml in the supernatants of DNase I-degraded NETs (P < 0·001, P = 0·008, P < 0·001, respectively). NETs could activate the alternative complement pathway, and might thus participate in the pathogenesis of AAV.

Plasma-soluble urokinase-type plasminogen activator receptor levels are associated with clinical and pathological activities in lupus nephritis: a large cohort study from China.

BACKGROUND: In this study, we detected plasma urokinase plasminogen activator (uPA) and soluble urokinase-type plasminogen activator receptor (uPAR) levels in Chinese lupus nephritis patients from a large cohort. The associations between plasma uPA and soluble uPAR and clinico-pathological characteristics were further analyzed. METHODS: The levels of plasma uPA and soluble uPAR were detected by ELISA in 202 patients with active lupus nephritis, 17 systemic lupus erythematosus (SLE) patients without renal involvement and 21 normal controls. RESULTS: There were no significant differences in the levels of the average plasma uPA among the lupus nephritis group, non-renal SLE group and normal control group (p = 0.129). The plasma-soluble uPAR level in the lupus nephritis group was significantly higher than that in the non-renal involvement SLE group (p = 0.004) and that in normal controls (p < 0.001). The plasma uPAR levels were positively associated with SLEDAI scores (r = 0.215, p = 0.007). In renal pathological data, there was significant difference of plasma-soluble uPAR levels among various pathological classes, which was the highest in the class IV group (p = 0.012). The level of plasma-soluble uPAR was found to be a risk factor for long-term renal outcomes in lupus nephritis by univariate survival analysis (p = 0.013, HR = 6.326, 95% CI: 1.466-27.298). CONCLUSIONS: Our study showed that the significantly increased plasma levels of soluble uPAR could be found in active lupus nephritis, and they were associated with some clinico-pathological features. Its involvement in the pathogenesis of lupus nephritis warrants further study.