Supplementary Information for: Predictors of chronic kidney disease in type 1 diabetes: a longitudinal study from the AMD Annals initiative.
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1 Supplementary Information for: Predictors of chronic kidney disease in type 1 diabetes: a longitudinal study from the AMD Annals initiative. Authors: Pamela Piscitelli 1, Francesca Viazzi 2 ; Paola Fioretto 3, Carlo Giorda 4 ; Antonio Ceriello 5,6 ; Stefano Genovese 6 ; Giuseppina Russo 7 ; Pietro Guida 8 ; Roberto Pontremoli 2 and Salvatore De Cosmo 1. 1 Department of Medical Sciences, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy; 2 Università degli Studi and IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy; 3 Department of Medicine, University of Padova, Padova, Italy. 4 Diabetes and Metabolism Unit ASL Turin 5, Chieri (TO), Italy; 5 Institut d'investigacions Biomèdiques August Pii Sunyer (IDIBAPS) and Centro de Investigación Biomédicaen Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; 6 U.O. Diabetologia e Malattie Metaboliche, Multimedica IRCCS, Sesto San Giovanni, Milano, Italy; 7 Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 8 Associazione Medici Diabetologi, Rome, Italy. 1. Fig. S1: Flow diagram for selection of study patients. 2. Fig. S2: Figure that illustrates the hierarchical tree of glomerular filtration rate (egfr) <60 ml/min/1.73m2 risk during follow-up.
2 1-Supplemental Figure S1 5,486 patients aged 18 years with type 1 diabetes and 5-year renal follow-up from 137 clinics Patients excluded according to: 552 missing data about treatment 1,061 patients with baseline albuminuria or egfr<60 ml/min/1.73m 2 43 with egfr<60 ml/min/1.73 m 2 in the previous measure if baseline egfr < 90 ml/min/1.73 m lacking a second egfr measurement before the excluded for missing duration of diabetes or in any baseline measurement about HbA1c, Triglycerides, HDL, LDL, or blood pressure 2,656 from 118 clinics constitute the study population
3 2-Supplemental Figure S2
4 Supplementary Tables Supplementary Table S1 Multivariate analysis for the occurrence of 5-year renal outcome. egfr <60 CKD ml/min/1.73m2 Albuminuria Odds Ratio (95%CI) p Odds Ratio (95%CI) p Odds Ratio (95%CI) p Male sex 1.07 ( ) ( ) ( ) Age (by 10 years) 1.07 ( ) ( ) < ( ) Known duration of diabetes (by 10 years) 1.09 ( ) ( ) ( ) BMI (Kg/m 2 ) ( ) ( ) ( ) ( ) ( ) ( ) egfr below 90 by 10 ml/min/1.73 m ( ) < ( ) < ( ) HbA1c 7% 1.04 ( ) ( ) ( ) Triglycerides 150 mg/dl 1.44 ( ) ( ) ( ) HDL <40M <50F mg/dl 1.20 ( ) ( ) ( ) LDL 100 mg/dl 0.75 ( ) ( ) ( ) Blood Pressure 140/85 mmhg 1.22 ( ) ( ) ( ) Retinopathy Non-proliferative 1.18 ( ) ( ) ( ) Proliferative 1.66 ( ) ( ) ( ) Lipid-lowering treatment 1.10 ( ) ( ) ( ) Antihypertensive treatment 1.83 ( ) ( ) ( ) Treatment with ACE-Is/ARBs 0.97 ( ) ( ) ( ) Aspirin 0.84 ( ) ( ) ( ) Insulin pump 0.94 ( ) ( ) ( ) Complete case analysis SUA in the top gender-specific quintile 0.90 ( ) ( ) ( ) Smokers 1.75 ( ) ( ) ( ) <0.001 See Table 1 legend for abbreviations.
5 Supplementary Table S2. Baseline clinical characteristics and missing information of type 1 diabetes mellitus patients included or excluded from the study. Included Excluded Included Excluded n=2656 n=768 Missing, n (%) Missing, n (%) Male sex 1487 (56.0%) 447 (58.2%) - - Age (years) 44±14 42± Known duration of diabetes (years) 17±12 17±11-64 (8.3%) BMI (Kg/m 2 ) 24.4± ± (4.9%) 398 (51.8%) Serum creatinine (mg/dl) 0.84± ± egfr (ml/min/1.73 m2) 99±16 100± Serum uric acid (mg/dl) 3.8± ± (44.9%) 234 (30.5%) Serum uric acid in the top gender-specific quintile 275 (18.8%) 99 (18.5%) - - HbA1c (%) (mmol/mol) 7.7±1.3(60±9) 8.0±1.5(64±7) - 26 (3.4%) HbA1c 7% 1843 (69.4%) 566 (76.3%) - - Total cholesterol (mg/dl) 189±34 192±37 21 (0.8%) 114 (14.8%) Triglycerides (mg/dl) 84±56 86± (19.4%) Triglycerides 150 mg/dl 191 (7.2%) 39 (6.3%) - - HDL (mg/dl) 62±19 61± (18.6%) HDL <40M <50F mg/dl 294 (11.1%) 70 (11.2%) - - LDL (mg/dl) 110±31 115± (20.7%) LDL 100 mg/dl 1650 (62.1%) 425 (69.8%) - - Systolic BP (mmhg) 125±17 126± (77.5%) Diastolic BP (mmhg) 76±9 77±9-595 (77.5%) Blood Pressure 140/85 mmhg 779 (29.3%) 52 (30.1%) - - Retinopathy Non-proliferative 495 (18.6%) 171 (22.3%) - - Proliferative 152 (5.7%) 29 (3.8%) - - Smokers 357 (26.2%) 52 (25.7%) 1294 (48.7%) 566 (73.7%) Lipid-lowering treatment 416 (15.7%) 78 (10.2%) - - Treatment with statins 400 (15.1%) 72 (9.4%) - - Treatment with fibrates 9 (0.3%) 4 (0.5%) - - Antihypertensive treatment 534 (20.1%) 60 (7.8%) - - Treatment with ACE-Is/ARBs 484 (18.2%) 54 (7.0%) - - Aspirin 184 (6.9%) 25 (3.3%) - - Insulin pump 162 (6.1%) 49 (6.4%) year outcomes CKD 559 (21.0%) 120 (15.6%) - - egfr<60 ml/min/1.73 m2 115 (4.3%) 34 (4.4%) - - Albuminuria 477 (18.0%) 93 (12.1%) - -
6 egfr<60 and albuminuria 33 (1.2%) 7 (0.9%) - - See Table 1 legend for abbreviations.
7 Supplementary Table S3. Baseline clinical characteristics of patients identified in nodes of hirarchical tree for glomerular filtration rate <60 ml/min/1.73 m 2 and for albuminuria. Nodes of hirarchical tree for glomerular filtration rate <60 ml/min/1.73 m 2 Nodes of hierarchical tree for albuminuria n=101 n=149 n=123 n=318 n=1965 n=137 n=397 n=669 n=216 n=1237 Male sex 46 (45.5%) 47 (31.5%) 68 (55.3%) 164 (51.6%) 1162 (59.1%) 65 (47.4%) 249 (62.7%) 439 (65.6%) 101 (46.8%) 633 (51.2%) Known duration of diabetes (years) 26±15 20±12 26±14 35±6 12±8 27±14 21±12 15±10 15±10 15±11 BMI (Kg/m 2 ) 25.3± ± ± ± ± ± ± ± ± ±2.9 Serum creatinine (mg/dl) 0.99± ± ± ± ± ± ± ± ± ±0.16 egfr (ml/min/1.73m2) 68±4 69±4 87±7 96±11 104±14 71±6 99±12 99±16 101±16 101±16 Serum uric acid (mg/dl) 4.3± ± ± ± ± ± ± ± ± ±1.8 SUA in the top genderspecific quintile 23 (42.6%) 32 (30.5%) 10 (14.7%) 32 (20.4%) 178 (16.5%) 42 (48.8%) 41 (19.7%) 81 (21.1%) 12 (9.8%) 99 (14.9%) HbA1c (%) HbA1c (mmol/mol) 8.1±1.1 (65±11) 7.7±1.2 (60±10) 7.9±1.1 (86±11) 7.7±1.3 (60±9) 7.6±1.4 (59±8) 8.1±1.2 (65±10) 7.7±1.2 (60±10) 7.8±1.4 (61±8) 9.7±1.0 (82±12) 7.1±0.9 (54±13) HbA1c 7% 87 (86.1%) 107 (71.8%) 101 (82.1%) 234 (73.6%) 1314 (66.9%) 116 (84.7%) 305 (76.8%) 497 (74.3%) 216 (100.0%) 709 (57.3%) Total cholesterol (mg/dl) 194±37 196±35 192±31 195±30 187±35 192±34 191±34 200±38 187±31 183±31 Triglycerides (mg/dl) 96±42 86±46 79±29 78±37 85±61 92±42 91±68 133±73 61±13 59±14 Triglycerides 150 mg/dl 12 (11.9%) 11 (7.4%) 4 (3.3%) 14 (4.4%) 150 (7.6%) 12 (8.8%) 36 (9.1%) 143 (21.4%) 0 (0.0%) 0 (0.0%) HDL (mg/dl) 65±21 64±17 67±21 66±19 61±18 63±19 60±20 57±19 67±18 65±18 HDL <40M <50F mg/dl 10 (9.9%) 17 (11.4%) 12 (9.8%) 24 (7.5%) 231 (11.8%) 13 (9.5%) 58 (14.6%) 115 (17.2%) 15 (6.9%) 93 (7.5%) LDL (mg/dl) 111±36 114±31 108±28 114±28 109±31 111±30 113±31 117±34 108±29 106±28 LDL 100 mg/dl 58 (57.4%) 104 (69.8%) 75 (61.0%) 223 (70.1%) 1190 (60.6%) 89 (65.0%) 261 (65.7%) 473 (70.7%) 131 (60.6%) 696 (56.3%) Systolic BP (mmhg) 141±17 128±16 140±17 130±18 123±16 138±16 134±17 125±16 124±16 122±16 Diastolic BP (mmhg) 77±9 76±9 77±10 75±9 76±9 77±9 79±10 76±9 76±9 74±8 Blood Pressure 140/85 mmhg 64 (63.4%) 52 (34.9%) 73 (59.3%) 120 (37.7%) 470 (23.9%) 80 (58.4%) 193 (48.6%) 189 (28.3%) 61 (28.2%) 256 (20.7%) Non-proliferative retinopathy 22 (21.8%) 32 (21.5%) 36 (29.3%) 100 (31.4%) 305 (15.5%) 45 (32.8%) 101 (25.4%) 112 (16.7%) 44 (20.4%) 193 (15.6%) Proliferative retinopathy 11 (10.9%) 12 (8.1%) 20 (16.3%) 47 (14.8%) 62 (3.2%) 14 (10.2%) 41 (10.3%) 39 (5.8%) 13 (6.0%) 45 (3.6%) Smokers 5 (9.4%) 11 (15.5%) 10 (16.7%) 38 (25.9%) 293 (28.4%) 7 (10.1%) 52 (24.6%) 127 (37.1%) 23 (22.3%) 148 (23.2%) Lipid-lowering treatment 31 (30.7%) 29 (19.5%) 46 (37.4%) 70 (22.0%) 240 (12.2%) 60 (43.8%) 147 (37.0%) 92 (13.8%) 14 (6.5%) 103 (8.3%) Treatment with statins 29 (28.7%) 29 (19.5%) 45 (36.6%) 66 (20.8%) 231 (11.8%) 57 (41.6%) 142 (35.8%) 85 (12.7%) 14 (6.5%) 102 (8.2%) Treatment with fibrates 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (0.6%) 7 (0.4%) 2 (1.5%) 0 (0.0%) 6 (0.9%) 0 (0.0%) 1 (0.1%) Antihypertensive treatment 53 (52.5%) 39 (26.2%) 68 (55.3%) 104 (32.7%) 270 (13.7%) 137 (100.0%) 397 (100.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Treatment with ACE- Is/ARBs 50 (49.5%) 35 (23.5%) 60 (48.8%) 94 (29.6%) 245 (12.5%) 124 (90.5%) 360 (90.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Aspirin 24 (23.8%) 12 (8.1%) 32 (26.0%) 43 (13.5%) 73 (3.7%) 44 (32.1%) 79 (19.9%) 21 (3.1%) 3 (1.4%) 37 (3.0%) Insulin pump 2 (2.0%) 11 (7.4%) 0 (0.0%) 22 (6.9%) 127 (6.5%) 6 (4.4%) 26 (6.5%) 30 (4.5%) 14 (6.5%) 86 (7.0%)
8 5-year outcomes CKD 58 (57.4%) 45 (30.2%) 46 (37.4%) 76 (23.9%) 334 (17.0%) 70 (51.1%) 107 (27.0%) 155 (23.2%) 43 (19.9%) 184 (14.9%) egfr<60 ml/min/1.73 m2 40 (39.6%) 20 (13.4%) 21 (17.1%) 12 (3.8%) 22 (1.1%) 38 (27.7%) 16 (4.0%) 26 (3.9%) 4 (1.9%) 31 (2.5%) Albuminuria 32 (31.7%) 31 (20.8%) 31 (25.2%) 67 (21.1%) 316 (16.1%) 48 (35.0%) 96 (24.2%) 137 (20.5%) 39 (18.1%) 157 (12.7%) egfr<60 and albuminuria 14 (13.9%) 6 (4.0%) 6 (4.9%) 3 (0.9%) 4 (0.2%) 16 (11.7%) 5 (1.3%) 8 (1.2%) 0 (0.0%) 4 (0.3%) See Table 1 legend for abbreviations. Nodes are those identified in Supplemental Figure 2 and 3.
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