This discrepancy is difficult to explain as and FLCs have similar functions. of Didox sFLCs to the incidence of ESRD and death (mean follow-up for death 6.0 years). Results After adjustment for baseline eGFR, there was no significant association between monoclonal excess of sFLCs and risk of ESRD or mortality. Baseline log and log concentrations were positively associated with ESRD risk, but these associations seemed to be due JNKK1 to correlations with eGFR (per 1 SD higher concentration: adjusted hazard ratio 1.05 [95% confidence interval 0.88 to 1 1.26] and 0.99 [0.83 to 1 1.19], respectively). For mortality, after adjustment for eGFR plus markers of cardiac damage, there was weak evidence of an association with , but not , sFLC concentration (fully adjusted hazard ratio 1.33 [95% confidence interval 1.05 to 1 1.67] per 1 Didox SD higher concentration). Conclusions Associations between monoclonal and polyclonal excess of sFLCs and risk of ESRD are explained by the correlation between these measures and renal function. We found only weak evidence of an association between polyclonal excess of sFLC concentration and mortality. Introduction In Western populations, about 5% to 10% of the adult population has an estimated GFR (eGFR) less than 60 ml/min per 1.73 m2 (10.6 g/dl; 0.001). There were no significant differences in baseline renal function or cardiac damage ( em i.e. /em , troponin T or NT-proBNP) between the MGUS+ and MGUS? groups. Both kappa and lambda concentrations were significantly related to several baseline clinical and laboratory measurements (Supplementary Tables 1 and 2), but several of these associations were explained in large part by their association with eGFR (Supplementary Table 3). Table 1. Baseline clinical characteristics in the CRIB cohort thead valign=”bottom” th rowspan=”2″ colspan=”1″ /th th align=”center” valign=”middle” rowspan=”2″ colspan=”1″ Completeness of data /th th align=”center” valign=”middle” rowspan=”2″ colspan=”1″ All /th th align=”center” colspan=”2″ rowspan=”1″ MGUS status hr / /th th align=”center” valign=”middle” rowspan=”2″ colspan=”1″ em P /em /th th align=”center” rowspan=”1″ colspan=”1″ MGUS? /th th align=”center” rowspan=”1″ colspan=”1″ MGUS+ /th /thead Number of people36432935Age, years100%61.2 (14.4)60.9 (14.4)64.1 (13.9)0.21Estimated GFRa, ml/min/1.73m2100%21.9 (10.7)22.1 (10.8)20.8 (10.2)0.49Number (%) of men100%236 (64.8%)212 (64.4%)24 (68.6%)0.63Disease history????Vascular disease100%161 (44.2%)142 (43.2%)19 (54.3%)0.21????Diabetes Mellitus100%64 (17.6%)58 (17.6%)6 (17.1%)0.94????Left Ventricular Hypertrophyb96%68 (19.5%)58 (18.4%)10 (30.3%)0.10Renal diagnosis????Glomerulonephritis100%90 (24.7%)81 (24.6%)9 (25.7%)0.98c????Diabetes100%30 (8.2%)28 (8.5%)2 (5.7%)C????Hypertension100%52 (14.3%)47 (14.3%)5 (14.3%)C????Cystic disease100%29 (8.0%)27 (8.2%)2 (5.7%)C????Obstructive/pyelonephritis100%31 (8.5%)28 (8.5%)3 (8.6%)C????Other known cause100%47 (12.9%)41 (12.5%)6 (17.1%)C????Unknown/unavailable100%85 (23.4%)77 (23.4%)8 (22.9%)CMedication????Any antihypertensive100%301 (82.7%)274 (83.3%)27 (77.1%)0.36????Aspirin100%95 (26.1%)87 (26.4%)8 (22.9%)0.65????Vitamin D100%128 (35.2%)117 (35.6%)11 (31.4%)0.63????Calcium100%83 (22.8%)73 (22.2%)10 (28.6%)0.39????Iron100%94 (25.8%)86 (26.1%)8 (22.9%)0.67????Erythropoietin100%35 (9.6%)30 (9.1%)5 (14.3%)0.32????Folic acid/B Vitamins100%45 (12.4%)40 (12.2%)5 (14.3%)0.72Smoking status????Never100%135 (37.1%)124 (37.7%)11 (31.4%)0.16c????Ex100%183 (50.3%)167 (50.8%)16 (45.7%)C????Current100%46 (12.6%)38 (11.6%)8 (22.9%)CEthnicity????White100%318 (87.4%)288 (87.5%)30 (85.7%)0.26c????Black100%22 (6.0%)18 (5.5%)4 (11.4%)C????Asian100%24 (6.6%)23 (7.0%)1 (2.9%)CPhysical measurements????Weight, kg99%76.1 (16.6)76.1 (16.6)76.8 (16.3)0.79????Height, m100%1.69 (0.09)1.69 (0.09)1.69 (0.09)0.84????Waist:hip ratio97%0.90 (0.11)0.90 (0.11)0.91 (0.07)0.76????Body mass index, kg/m299%26.6 (5.0)26.6 (5.0)26.8 (4.7)0.84????SBP, mmHg99%151.1 (21.9)151.4 (22.0)148.4 (20.8)0.45????DBP, mmHg99%83.8 (11.6)83.7 (11.9)84.2 (9.4)0.82 Open in a separate window Values are mean with SD in parentheses or number of subjects with percentage (%) in parentheses. CRIB, Chronic Renal Impairment in Birmingham; SBP, systolic BP; DBP, diastolic BP; MGUS, monoclonal gammopathy of uncertain significance, defined in this table as the presence of a monoclonal M-band on immunofixation electrophoresis and/or a serum free light chain ratio 0.37 or 3.17. aGFR was estimated using the simplified Modification of Diet in Renal Disease equation. Individuals receiving renal replacement therapy at baseline (either dialysis or a renal transplant) were excluded from the study. bBased on an electrocardiographic study. cSingle test across Didox all groups. Table 2. Baseline laboratory values in the CRIB cohort thead valign=”bottom” th rowspan=”2″ colspan=”1″ /th th align=”center” valign=”middle” rowspan=”2″ colspan=”1″ Completeness of data /th th align=”center” valign=”middle” rowspan=”2″ colspan=”1″ All /th th align=”center” colspan=”2″ rowspan=”1″ MGUS status hr / /th th align=”center” valign=”middle” rowspan=”2″ colspan=”1″ em P /em /th th align=”center” rowspan=”1″ colspan=”1″ MGUS? /th th align=”center” rowspan=”1″ colspan=”1″ MGUS+ /th /thead Number of people36432935Kidney function????Creatinine, umol/L100%263 (192C403)262 (190C402)283 (210C431)0.63????Cystatin C, mg/L95%3.0 (2.1C4.0)2.9 (2.1C3.9)3.3 (2.7C4.1)0.12????Urinary albumin:creatinine ratio, mg/mmoL80%56.9 (10.1C145.6)56.2 (10.1C147.6)62.0 (10.2C124.2)0.75????Symmetric dimethylarginine, umol/L100%1.39 (1.06C1.92)1.37 (1.03C1.92)1.50 (1.25C1.99)0.41????Urea, mmol/L100%18.9 (8.9)18.8 (8.9)19.6 (8.2)0.64????Urate, umol/L96%448 (117)447 (119)458 (94)0.58Cardiac damage????N-terminal pro-B-type natriuretic peptide, ng/L100%532 (238C1882)519 (240C1799)629 (180C2843)0.62????Number with elevated troponin T ( =0.01 g/L)100%81 (22.3%)70 (21.3%)11 (31.4%)0.17Endothelial function????Asymmetric dimethylarginine, umol/L100%0.52 (0.46C0.58)0.52 (0.45C0.58)0.53 (0.48C0.62)0.12????Arginine, umol/L100%178 (152C202)179 (152C203)169 (147C190)0.33????Von Willebrand factor, IU/dl92%142 (31)141 (31)150 (39)0.14Lipids????Total cholesterol, mmol/L96%5.62 (1.27)5.63 (1.27)5.55 (1.31)0.73????HDL cholesterol, mmol/L79%1.26 (0.41)1.26 (0.41)1.24 (0.50)0.79Inflammation & nutrition????C-reactive protein, mg/L94%4.34 (1.35C9.69)4.36 (1.33C9.53)3.97 (1.74C13.00)0.65????Albumin, g/L100%41.7 (4.5)41.8 (4.4)40.8 (5.1)0.22????Fibrinogen, g/L89%3.48 (0.80)3.47 (0.79)3.56 (0.87)0.53????Interleukin 6, ng/L90%3.9 (2.1C7.9)3.9 (2.1C7.8)4.5 (2.3C9.1)0.59????Tumour necrosis factor-alpha, ng/L97%17.0 (5.5)17.0 (5.3)17.1 (6.7)0.93Calcium and phosphate homeostasis????Calcium, mmol/L100%2.34 (2.26C2.43)2.34 (2.26C2.43)2.30 (2.18C2.39)0.11????Phosphate, mmol/L96%1.36 (1.18C1.59)1.36 (1.18C1.58)1.36 (1.18C1.67)0.91????25 hydroxy vitamin D3, nmol/L95%43.9 (28.7C57.8)44.2 (29.7C58.0)33.3 (21.9C48.1)0.02????1,25 dihydroxy vitamin D3, pmol/L88%61.9 (43.8C82.2)62.5 (46.0C83.2)48.0 (36.4C70.2)0.01????Intact parathyroid hormone, pmol/L86%14.5 (8.0C24.6)13.8 (7.5C24.2)20.8 (12.0C30.6)0.11????Whole parathyroid hormone, pmol/L90%7.9 (4.5C13.8)7.4 (4.4C13.4)10.9 (6.9C16.3)0.04B vitamins????Serum folate, nmol/L94%16.5 (11.3C25.8)16.5 (11.3C25.8)15.9 (11.1C27.2)0.95????Red cell folate, nmol/L88%487 Didox (374C698)488 (367C707)433 (390C671)0.82????Vitamin B12, pmol/L94%333 (241C441)331 (245C436)349 (225C460)0.90????Homocysteine, umol/L99%20.3 (15.8C26.3)19.9 (15.5C25.5)24.2 (18.6C30.2)0.03Rheological markers????Soluble P selectin, ug/L91%55.0 (45.0C75.0)55.0 (45.0C75.0)57.0 (47.5C76.5)0.48????Haemoglobin, g/dl97%12.1 (2.0)12.2 (2.0)10.6 (1.9) 0.001 Open in a separate window Values are mean with SD or median with interquartile range in parentheses or.