Changes And Significance Of Immunoglobulin Light Chains In Diabetic Nephropathy

Objective: Serum free light chains(FLCs) are part of the immunoglobulin produced by B cells. In recent years, studies have found their roles in the inflammatory response, and speculated that they may be predictive indexes of the inflammatory response in the autoimmune disease. Combined free light chain(cFLC) concentrations are raised by chronic inflammation or renal insufficiency, which are both features of type 2 diabetes. Studies have demonstrated that c FLC concentrations are elevated in patients with diabetes compared with healthy control subjects and were seen before overt signs of renal disease. These patients have more risks of mortality(especially cardiovascular disease caused) and end-stage renal disease(ESRD) than patients without CKD. The relationship between diabetic nephropathy(DN) severity and cardiovascular risk is continuous. The aim of our study is to investigate the relationships between cFLC and clinical indicators and renal renal pathological changes of DN.Methods: The study included 40 DN patients and 40 non-diabetic nephropathy patients in the nephrology department of the Second Hospital of Hebei Medical University from February 2014 to July 2015, respectively experiment and control group, which were exclued chronic inflammatory disease. The patients’ renal frozen section were saved, and blood samples are collected after centrifuged. Detailed clinical indicators including age, gender, smoking history, blood pressure, plus the first biochemistry(hemoglobin, electrolyte, creatinine, blood lipid, albumin, urinary protein, hsCRP, Hcy) were obtained. The eGFR of the patients was calculated by equation of CKD-EPI. The expression of λFLC andκFLC was detected by indirect immunofluorescence. While, we also abserved the renal pathological changes by common light microscope. The concentration levels ofλFLC andκFLC were determined through ELISA method.Results:1 The experiment group have higher levels of SBP(173±34 vs 129±24 mmHg) and Scr(124.8±24.6 vs 73.8±14.0μmol/L), respectively, the levels of eGFR are lower(72±34 vs 105±31ml/min per1.73m2). The differences all have statistical significance(P<0.05).2 All the patient have exclued recent infection,and the mean levels of hsCRP are in the normal range(0~8mg/L). While, the experiment group have higher levels than the control group(3.8±2.5 vs 1.1±2.8mg/L, P<0.05).3 The two groups have differences of Hcy, the experiment group have higher levels(15.31±2.26 vs 9.10±1.55μmol/L, P<0.05).4 The levels of cFLC(λFLC plusκFLC) of the experiment group are higher when they compare to the control group(55.24±9.24 vs 21.83±7.62 mg/L, P<0.05), but have no differences between the each type of DN.5 The expressed sites of FLC are different.The main sites of DN are glomerular mesangium and K-W node. The main site of membranous nephropathy is the glomerular capillary walls. The main site of IgA nephropathy is the glomerular mesangium.6 Referring to the parameters of glomerulus sclerosis rate, degrees of tubular atrophy and percentage of arteriosclerosis,the experiment group are much severer. Accordding to the pathologic classification of diabetic nephropathy tubulointerstitial lesions, typeⅠ DN scores 2-4 points, typeⅡ DN scores 2-5points, type Ⅲ DN scores 4-6 points, type Ⅳ DN scores 5-7 points. And there is no difference between each type, as well as cFLC.7 The results of correlation analysis between clinical indicators and cFLC:systolic blood pressure, creatinine, Hcy and hsCRP are positive correlation of cFLC(P<0.05), while eGFR and hemoglobin are negative correlation of cFLC(P<0.05). The results of correlation analysis between pathological changes and cFLC: the levels of cFLC increase along with the severity of glomerulus sclerosis and tubular atrophy,they have positive correlations(P<0.05). The eGFR shows negative correlation with the severity of glomerulus sclerosis and tubular atrophy(P<0.05). The scores of tubulointerstitial lesions shows positive correlations(P<0.05) with cFLC, and negative correlation with eGFR(P<0.05).Conclusions:1 The levels of cFLC show positive correlation with hsCRP and Hcy,and negative correlation with eGFR of DN patients, these results suggest cFLC could be a predictor of the risk of mortality(especially cardiovascular disease caused) of DN patients.2 The levels of cFLC show positive correlation with the scores of diabetic nephropathy tubulointerstitial lesions, which suggest that cFLC could be a predictor of the progression of DN.