Correlational studies on insulin resistance and leptin gene polymorphisms in peritoneal dialysis patients

Objective(s):The aim of the study was to investigate the relationship between insulin resistance (IR) and leptin (LEP) gene polymorphisms in peritoneal dialysis (PD) patients. Materials and Methods: From July 1, 2011 to August 1, 2011, patients who received chronic PD were chosen and divided into three groups (DM, high HOMR-IR, and low HOMR-IR). Two PCR products of LEP were sequenced and aligned and the distribution of polymorphisms was analyzed using χ2 analysis. In addition, serum leptin level, PD conditions, and biochemical parameters according to different genotype of G-2548A and A19G were statistically analyzed (P-valu

Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.

Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an important role in disease progression of LN

Comparison of baseline characteristics in patients with active LN and inactive LN.

<p>SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; eGFR, estimated glomerular filtration rate; ESR, erythrocyte sedimentation rate; hs-CRP, high sensitive C reaction protein; TG, total glycerin; TC, total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; ds-DNA, double-strain DNA.</p><p>Comparison of baseline characteristics in patients with active LN and inactive LN.</p

Clinical characteristics of LN patients and healthy controls.

<p>SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; eGFR, estimated glomerular filtration rate; ESR, erythrocyte sedimentation rate; hs-CRP, high sensitive C reaction protein; TG, total glycerin; TC, total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; ds-DNA, double strain DNA.</p><p>Clinical characteristics of LN patients and healthy controls.</p

Clinical manifestations of proliferative LN patients and Class V LN patients.

<p>SBP, systolic blood pressure; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; ESR, erythrocyte sedimentation rate; ds-DNA, double-strain DNA.</p><p>Clinical manifestations of proliferative LN patients and Class V LN patients.</p

Expression of renalase in glomerular macrophages in active proliferative LN.

<p>(A) Left panel—kidney immunohistochemical staining for renalase of a control subject (20X); Right panel kidney immunohistochemical staining for renalase of an active LN patient (20X), arrows indicate representative renalase expression in glomeruli; (B) immunofluorescent staining of representative kidney sections of a patient with active LN, Left panel–staining with anti-CD68 antibody, Middle left- staining with anti-renalase antibody, Middle right -: nuclear staining, Right panel- merged picture; (C) immunofluorescent staining of representative kidney sections of a patient with active LN, Left panel—staining with anti-CD34 antibody, Middle left—staining with anti-renalase antibody, Middle right-: nuclear staining, Right panel—merged picture; (D) immunofluorescent staining of THP–1 cells in culture; Left panel—staining with anti-CD68 antibody, Middle left—staining with anti-renalase antibody, Middle right-: nuclear staining, Right panel—merged picture.</p

Serum renalase differentiates patients with proliferative LN from Class V LN.

<p>(A) Serum renalase levels were significantly higher in proliferative LN patients compared to Class V LN patients. Each dot represents the data of an individual. (B) Receiver operator characteristic curve (ROC) was performed to assess serum renalase as a predictive marker for proliferative LN. AUC was 0.780 while sensitivity and specificity were 67.80% and 85.71%, respectively, using a cutoff of 54.81 μg/ml.</p

Serum renalase as a predictive marker for active LN.

<p>(A) The amount of serum renalase in subjects with active LN was significantly higher than in individuals with inactive LN. (B) Receiver operator characteristic curve (ROC) was performed to assess serum renalase as a predictive marker for active LN. The AUC was 0.906 using a cutoff value of 66.67 μg/ml while sensitivity was 87.5% and specificity was 89.2%.</p

Comparison of serum renalase levels in patients with active LN before and after immunosuppressive treatment.

<p>Serum renalase levels decreased significantly after six-month immunosuppressive treatment.</p