DEFINITIONS Table of Contents Table 1. LOINC Codes to Measure Egfr Table 2

SUPPLEMENTARY MATERIALS 1: DEFINITIONS Table of contents Table 1. LOINC codes to measure eGFR Table 2. LOINC codes to measure UACR Table 3. Definitions of selection criteria variables Table 4. Patient Characteristics during baseline Table 5. Clinical outcomes definitions

Table 1. LOINC codes to measure eGFR Variable Definition

33914-3 Glomerular filtration rate/1.73 sq M.predicted [Volume Rate/Area] in Serum or Plasma by Creatinine-based formula (MDRD)

48642-3 Glomerular filtration rate/1.73 sq M predicted among non-blacks [Volume Rate/Area] in Serum or Plasma by Creatinine-based formula (MDRD)

48643-1 Glomerular filtration rate/1.73 sq M predicted among blacks [Volume Rate/Area] in Serum or Plasma by Creatinine-based formula (MDRD)

50044-7 Glomerular filtration rate/1.73 sq M predicted among females [Volume Rate/Area] in Serum or Plasma by Creatinine-based formula (MDRD)

50210-4 Glomerular filtration rate/1.73 sq M.predicted [Volume Rate/Area] in Serum or Plasma by Cystatin-based formula

50384-7 Glomerular filtration rate/1.73 sq M.predicted [Volume Rate/Area] in Serum or Plasma by Creatinine-based formula (Schwartz)

62238-1 Glomerular filtration rate/1.73 sq M.predicted [Volume Rate/Area] in Serum or Plasma by Creatinine-based formula (CKD-EPI)

69405-9 Glomerular filtration rate/1.73 sq M.predicted [Volume Rate/Area] in Serum or Plasma

70969-1 Glomerular filtration rate/1.73 sq M predicted among males [Volume Rate/Area] in Serum or Plasma by Creatinine-based formula (MDRD)

76633-7 Glomerular filtration rate/1.73 sq M.predicted by Creatinine-based formula (MDRD) in Blood

77147-7 Glomerular filtration rate/1.73 sq M.predicted [Volume Rate/Area] in Serum, Plasma or Blood by Creatinine-based formula (MDRD)

Table 2. LOINC codes to measure UACR Variable Definition

9318-7 Albumin/Creatinine [Mass Ratio] in Urine

Table 3. Definitions of selection criteria variables Variable Definition

Age Continuous variable of age in years

Type 2 Diabetes One inpatient claim for ICD-9 diagnosis code 250.xx (any position) or diagnosis ICD-10 diagnosis code E11.xx (any position), or two outpatient claims for ICD 9 diagnosis code 250.xx (any position) or ICD-10 diagnosis code E11.xx (any position) at least 30 days apart but no more than 180 days apart eGFR laboratory result An eGFR result of <60 ml/min/1.73m^2 resulting from LOINC codes indicating kidney 33914-3, 48642-3, 48643-1, 50044-7, 50210-4, 50384-7, 62238-1, disease 69405-9, 70969-1, 76633-7, or 77147-7

UACR laboratory result A UACR result of ≥30 mg/g resulting from LOINC code 9318-7 indicating kidney disease

ESRD One claim for ICD-9 inpatient or outpatient diagnosis code 403.91, 404.92, 404.93, 585.5, 585.6, 586, 404.03, 404.13, 403.01, 403.11, 404.02, or 404.12 (any position) or ICD-10 inpatient or outpatient diagnosis code I12.0, I13.11, I13.2, N18.6, N19, Z91.15, Z94.0, or Z99.2 (any position)

DKD (general) One claim for ICD-9 inpatient or outpatient diagnosis code 250.4, 250.40, 250.42, 274.1, 285.21, 403, 403.00, 403.01, 403.10, 403.11, 403.90, 403.91, 404, 404.00, 404.01, 404.02, 404.03, 404.10, 404.11, 404.12, 404.13, 404.90, 404.91, 404.92, 404.93, 581.0, 581, 581.1, 590.0, 593.6, 581.2, 581.3, 581.8, 581.81, 581.89, 581.9, 582, 582.0, 582.1, 582.2, 582.4, 582.8, 582.81, 582.89, 582.9, 583, 583.0, 583.1, 583.2, 583.4, 583.6, 583.7, 583.8, 583.81, 583.89, 583.9, 585, 585.1, 585.2, 585.3, 585.4, 585.5, 585.6, 585.9, 593.9, 753.12, 753.13, or 753.14 (any position) or ICD-10 inpatient or outpatient diagnosis code D63.1, E08.22, E09.22, E10.22, E11.22, E11.2, E11.21, E11.29, E13.22, I12.9, I13.0, I13.1, I13.10, N08, N18, N18.1, N18.2, N18.3, N18.4, N18.5, or N18.9 (any position)

Kidney transplant One claim for ICD-9 inpatient or outpatient procedure code 55.51, 55.52, 55.53, 55.54, 55.61, or 55.69 (any position) or ICD-10 inpatient or outpatient diagnosis code 0TY00Z0, 0TY00Z1, 0TY00Z2, 0TY10Z0, 0TY10Z1, or 0TY10Z2 (any position) or HCPCs code 00862, 00868, 50300, 50320, 50323, 50325, 50327, 50328, 50329, 50340, 50360, 50365, 50370, 50380, or 50547 (Li et al, 2009)

Dialysis One claim for ICD-9 inpatient or outpatient diagnosis code V45.11, V45.12, V56, V56.0, V56.1, V56.2, V56.3, V56.31, V56.32 or V56.8 (any position) or ICD-9 inpatient or outpatient procedure code 39.95 or 54.98 (any position) or ICD-10 inpatient or outpatient diagnosis code Z91.15 or Z99.2 (any position) or CPT code 90935, 90937, 90945, or 90947 or revenue code 0800, 0801, 0802, 0803, or 0804 (Patel et al, 2013; Young et al, 2004)

HIV One claim for ICD-9 inpatient or outpatient diagnosis code 042.xx- 0.44.xx (any position) or ICD-10 diagnosis code inpatient or outpatient B20.x–B22.x, B24.x (any position) (Quan et al, 2005)

Sickle cell disease One claim for ICD-9 inpatient or outpatient diagnosis code 282.6, 282.60, 282.61, 282.62, 282.63, or 282.69 (any position) or ICD-10 inpatient or outpatient diagnosis code D57.00, D57.01, D57.02, D57.20, D57.211, D57.212, D57.219, D57.40, D57.411, D57.412, D57.419, D57.80, D57.811, or D57.819 (any position) (Shankar et al, 2005; Singh et al, 2018)

Nephrotic syndrome, One claim for inpatient or outpatient ICD-9 diagnosis code 581.xx including: focal (any position) or ICD-10 diagnosis code N04 or N04.xx (any glomerulosclerosis/focal position) sclerosing glomerulonephritis, membranoproliferative glomerulonephritis type 1/ diffuse membranoproliferative glomerulosclerosis

Chronic One claim for inpatient or outpatient ICD-9 diagnosis code 582.xx or glomerulonephritis, 583.xx(any position) or ICD-10 diagnosis code N03.xx or N07.xx nephritis, nephritic (any position) Syndrome, and nephropathy, including: membranous nephropathy, IgA nephropathy/Berger’s disease, rapidly progressive, systemic lupus erythematosus nephritis, interstitial nephritis/pyelonephritis from analgesic abuse, chronic/acute interstitial nephritis

Polyarteritis nodosa and One claim for inpatient or outpatient ICD-9 diagnosis code 446.xx allied conditions (any position) or ICD-10 diagnosis code M30, M30.0, or M30.8 (any (Wegener’s position) granulomatosis)

Obstructive and reflux One claim for inpatient or outpatient ICD-9 diagnosis code 592.9, uropathy or urolithiasis 599.6x (any position) or ICD-10 diagnosis code N20.9, N13.xx (any position)

Chronic One claim for inpatient or outpatient ICD-9 diagnosis code 590.0xx pyelonephritis/reflux 593.7x (any position) or ICD-10 diagnosis code N11.1, N13.729 (any nephropathy position)

Renal artery occlusion One claim for inpatient or outpatient ICD-9 diagnosis code 362.32, or renal artery stenosis 440.1 (any position) or ICD-10 diagnosis code I70.1, H34.239 (any position)

Polycystic kidneys One claim for inpatient or outpatient ICD-9 diagnosis code 753.1x (adult type) (any position) or ICD-10 diagnosis code Q61.2 (any position)

Renal tumour One claim for inpatient or outpatient ICD-9 diagnosis code 189.0 (any (malignant) position) or ICD-10 diagnosis code C64.9 (any position)

Gouty nephropathy One claim for inpatient or outpatient ICD-9 diagnosis code 274.1x (any position) or ICD-10 diagnosis code M10.3x (any position)

Vasculitis One claim for inpatient or outpatient ICD-9 diagnosis code 447.6 (any position) or ICD-10 diagnosis code I77.6 (any position)

Renal agenesis, One claim for inpatient or outpatient ICD-9 diagnosis code 753.xx dysgenesis, and (any position) or ICD-10 diagnosis code Q60.x (any position) hypoplasia

Multiple myeloma One claim for inpatient or outpatient ICD-9 diagnosis code 203.xx (any position) or ICD-10 diagnosis code C90.xx (any position)

Tubular necrosis One claim for inpatient or outpatient ICD-9 diagnosis code 584.5 (any position) or ICD-10 diagnosis code N17.0x (any position)

Table 4. Patient Characteristics during baseline Variable Definition

Age 18-24, 25-39, 40-54,55-69, 70-89, ≥90

Gender Male, Female

Race White, Asian, Black, Hispanic, Unknown

Region Northeast: { CT, MA, ME, NH, NJ, NY, VT, RI, PA } Midwest: { IL, IN, MI, IA, KS, MN, MO, NE, ND, SD, OH, WI } South: { DE, DC, FL, GA, MD, NC, AL, SC, VA, KY, MS, TN, WV, AR, LA, OK, TX } West: { AZ, CO, ID, NM, MT, NV, AK, UT, WY, CA, HI, OR, WA }

Provider Specialty Endocrinologist, Nephrologist, Cardiologist, Urologist, (Internal Medicine Specialist or Family Medicine/General, or Internist/General Internist or General Practitioner or General Practice Specialist)

Charlson Deyo Continuous variable indicating index, which includes the following comorbidity score comorbidity categories defined using ICD codes: AIDS, congestive heart failure, COPD, dementia, hemiplegia and paraplegia, myocardial infarction, peripheral vascular disease, rheumatologic disease, stroke, peptic ulcer disease, renal disease, cancer, liver disease, diabetes (Deyo, Cherkin, Ciol, 1992)

Hypertension ICD-9 inpatient or outpatient diagnosis code 401.x-405.x (any position) or ICD-10 inpatient or outpatient diagnosis code I10.x-I13.x or I15.x (any position) (Tonelli et al, 2015)

Resistant hypertension Prescription claims for four or more unique antihypertensive medications or combination medications with the following NDC generic names: benazepril hydrochloride, captopril, enalapril, maleate, fosinopril sodium, lisinopril, moexipril, perindopril, quinapril hydrochloride, ramipril, trandolapril, candesartan, eprosarta, mesylate, irbesarten, losartan potassium, telmisartan, valsartan, acebutolol, atenolol, betaxolol, bisoprolol fumarate, carteolo, hydrochloride, metoprolol tartrate, metoprolol, succinate, nadolol, penbutolol sulfate, pindolol, propranolol hydrochloride, solotol hydrochloride, timolol maleate, chlorthalidone, chlorothiazide, hydrochlorothiazide, indapamide, metolazone, amiloride hydrochloride, triamterene, furosemide, bumetanide, amlodipine besylate, bepridil, diltiazem hydrochloride, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, verapamil hydrochloride, Spironolactone, Eplerenone, doxazosin mesylate, prazosin hydrochloride, terazosin hydrochloride, methyldopa, alpha methyldopa, clonidine hydrochloride, guanabenz acetate, guanfacine hydrochloride, guanadrel, guanethidine, monosulfate, Reserpine, hydralazine hydrochloride, minoxidil, nadolol/bendroflumethiazide (American College of Cardiology, 2017; Braam et al, 2012)

Hyperlipidemia ICD-9 inpatient or outpatient diagnosis code 272.0-272.4 (any position) or ICD-10 inpatient or outpatient diagnosis code E78.0-E78.5 (any position) (Bellows et al, 2017)

Obesity (as identified ICD-9 inpatient or outpatient diagnosis code 278.xx (any position), via ICD codes and ICD-10 inpatient or outpatient diagnosis code E66.xx, Z68.3x or procedure codes) Z68.4x (any position), or HCPCS procedure code G0447 or G0473 (ACOG, 2017)

Microvascular Diabetic neuropathy : ICD 9 inpatient or outpatient diagnosis code complications disease 250.6x and/or 357.2 (any position) (Boulanger, 2009) or ICD-10 inpatient or outpatient diagnosis code E11.4x Diabetic retinopathy: ICD-9 inpatient or outpatient diagnosis code 362.xx (any position) or ICD-10 inpatient or outpatient diagnosis code E08.3x, E11.3x, or E13.3x (any position) Diabetic nephropathy: ICD-9 diagnosis code (inpatient or outpatient, any position) 250.40, 250.42, or 583.xx or ICD-10 diagnosis code (inpatient or outpatient, any position) E11.21, E13.21, E08.21, N07.xx, or N08 (Fleet et al, 2013)

Atrial fibrillation ICD-9 inpatient diagnosis code 427.31 (primary or secondary position) or ICD-10 inpatient diagnosis code I48.0, I48.1, I48.2 or I48.91 (primary or secondary position) (Chronic Conditions Data Warehouse, 2017)

Coronary artery disease ICD-9 inpatient or outpatient diagnosis code 410.x, 411.1, 412, 413.9 (any position) or ICD-10 inpatient or outpatient diagnosis code I20.0, I21.x, I22.x, I24.x, I25.1x-I25.2, I25.8x-I25.9 (any position)

Peripheral vascular ICD-9 inpatient or outpatient diagnosis code 093.0, 437.3, 440.x, disease 441.x, 443.x, 447.1, 557.1, 557.9, or V43.4 (any position) or ICD-10 inpatient or outpatient diagnosis code 70.x, I71.x, I73.xx, I77.1, I79.0, I79.2, K55.1, K55.8, K55.9, Z95.8, or Z95.9 (Quan et al, 2005)

Acute Coronary Myocardial infarction: Syndrome ICD-9 inpatient or outpatient diagnosis code 410.xx (any position) or ICD-10 inpatient or outpatient diagnosis code I21.xx or I22.xx (any position) Unstable Angina: ICD-10 inpatient or outpatient diagnosis code I20.xx (any position)

Anemia ICD-9 inpatient or outpatient diagnosis code 280.x-281.x, 285.21 or 285.9 (any position) or ICD-10 inpatient or outpatient diagnosis code D50.x-D53.x, D63.1, or D64.9 (any position) (Sun et al, 2017)

Hyperkalemia ICD-9 inpatient or outpatient diagnosis code 276.7 (any position) or ICD-10 inpatient or outpatient diagnosis code E87.5 (any position) or potassium test result of >5.5 mEq/L resulting from LOINC codes 12812-4, 12813-2, 22760-3, 2823-3, 2824-1, 29349-8, 42569-4, 51618-7, 6298-4, 75940-7, 77142-8 or CPT procedure code 84132

Hypokalemia ICD-9 inpatient or outpatient diagnosis code 276.8 (any position) or ICD-10 inpatient or outpatient diagnosis code E87.6 (any position) or potassium test result of <3.5 mEq/L resulting from LOINC codes 12812-4, 12813-2, 22760-3, 2823-3, 2824-1, 29349-8, 42569-4, 51618-7, 6298-4, 75940-7, 77142-8 or CPT procedure code 84132

Hyponatremia ICD-9 inpatient or outpatient diagnosis code 276.1 (any position) (Shea et al., 2008; Movig et al., 2003) or ICD-10 inpatient or outpatient diagnosis code E87.1 (Gandhi et al., 2017)

Angina Pectoris ICD-9 inpatient or outpatient diagnosis code 413 or 414.0x (any position) or ICD-10 inpatient or outpatient diagnosis code I20.9 or I25.1x or I25.7x (any position)

Stroke ICD-9 inpatient diagnosis code 430.x-431.x, 433.x1, 434.x1 or 436.x (any position) or ICD-10 inpatient diagnosis code I60.x, I61.x-I63.x or I67.89 (any position) (Andrade et al, 2012; Sacco et al, 2013)

Myocardial infarction ICD-9 inpatient or outpatient diagnosis code 410.xx (any position) or ICD-10 inpatient or outpatient diagnosis code I21.xx or I22.xx (any position) (Sun et al, 2017; American Diabetes Association 2018)

Sleep apnea ICD-9 inpatient or outpatient diagnosis code 327.23, 780.51, 780.53 or 780.57 (any position) or ICD-10 inpatient or outpatient diagnosis code G47.30, G47.33 or G47.39 (any position) (AFHSC, 2015)

Depression ICD-9 inpatient or outpatient diagnosis code 296.2, 296.3, 298.0, 300.4, 309.0, 309.1, 309.28 or 311 (any position) or ICD-10 inpatient or outpatient diagnosis code F20.4, F31.3–F31.5, F32.x, F33.x, F34.1, F43.21 or F43.23 (any position) (Quan et al, 2005; Townsend, Walkup, Crystal, 2012)

Fatigue & sleep related ICD-9 inpatient or outpatient diagnosis code 780.7x, 300.5x, 780.50, disorders 780.52, 780.54-780.56, 780.58-.59, 307.4x, 327.0x, 327.1x,(any position) or ICD-10 inpatient or outpatient diagnosis code R53.1, R53.8x, F48.8, F51.02, F51.09, F51.01, F51.03, F51.04, F51.05, F51.19, F51.11, F51.12, F51.13, F51.8, G47.0x, G47.1x, G47.2x, G47.4x, G47.5x, G47.6x, G47.8, G47.9, G93.3 (any position)

Pain disorders ICD-9 inpatient or outpatient diagnosis code 720.xx, 721.2x to 721.9x, 722.1x to 722.3x, 722.5x, 722.6x, 722.70, 722.72, 722.73, 722.80, 722.82, 722.83, 722.90, 722.92, 722.93, 724.xx, 729.1x, 780.96, 338.xx, 307.80, 053.1x, 250.6x, 307.8x, 323.xx, 335.20, 335.34, 336.9x, 337.1x, 337.2x, 338.3x, 339.xx, 340.xx, 341.xx, 346.0x to 346.9x, 350.xx, 351.xx, 353.xx to 356.xx, 357.2x, 358.xx, 524.6x, 577.1x, 696.xx, 714.xx, 715.xx, 719.xx, 720.xx, 721.0x to 722.4x, 722.71, 722.81, 722.91, 723.1x, 724.4x, 728.0x, 729.0x, 729.2x, 729.5x, 784.0x, 786.5x, 789.xx, 733.99, 733.14, 780.71, 820.8x, 820.9x, 951.4x, 952.xx, 953.4x, or 955.5x to 955.7x (any position) or ICD-10 inpatient or outpatient diagnosis code E08.42, E09.42, E11.42, E13.42, G04.xx, G05.xx, G35, G36.xx, G37.xx, G43.xx, G44.xx, G50.xx, G51.xx, G54.xx, G56.xx, G57.xx, G58.7, G60.xx, G89.xx, G90.xx, G95.xx, G99.xx, M05.xx, M06.xx, M12.xx, M26.6xx, M43.xx, M45.xx, M46.xx, M47.xx, M48.xx, M50.xx, M51.xx, M53.xx, M54.xx, M60.xx, M79.xx, M96.1, R07.xx, R10.xx, R16.xx, R19.xx, R51, R52, F45.4x, B02.2x, S04.1x, S14.1x, S24.1x, S34.1x, S34.3x, S44.xx, S54.xx, S64.xx, or S74.xx (any position)

Edema ICD-9 inpatient or outpatient diagnosis code 782.3 (any position) or ICD-10 inpatient or outpatient diagnosis code R60.x (any position) (Chinali et al, 2010)

Chronic ICD-9 inpatient or outpatient diagnosis code 416.8, 416.9, 490.x– lung/pulmonary disease 505.x, 506.4, 508.1, or 508.8 (any position) or ICD-10 inpatient or outpatient diagnosis code I27.8, I27.9, J40.x–J47.x, J60.x–J67.x, J68.4, J70.1, or J70.3 (any position)

Respiratory failure ICD-9 inpatient diagnosis code 518.5x, 518.81, 518.83 or 518.84 (any position) or ICD-10 inpatient diagnosis code J96.xx (any position) (Behrendt, 2000)

Heart Failure ICD-9 inpatient or outpatient diagnosis code 398.91, 402, 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, or 428.xx or ICD-10 inpatient or outpatient diagnosis code I09.81, I11.0, I13.0, I13.2, I50.1. I50.20, I50.21, I50.22, I50.23, I50.30, I50.31, I50.32, I50.33, I50.40, I50.41, I50.42, I50.43, or I50.9 in the primary or secondary position

Table 5. Health care resource utilization outcomes Variable Definition

Count of Inpatient Count of any events within the inpatient confinement that do not visits have discharge status codes 02, 03, 04, 05, 43, 51, 61, 62 63, 64, 65, 66, 70, 71, 72, or NA

Count of Outpatient Count of events with any ICD-9 or ICD-10 outpatient diagnosis code visits (any position) and type of service “office visit” or “outpatient” (any position) occurring on different days or revenue codes 0456, 0516, 0526

Count of Emergency Count of events with any ICD-9 or ICD-10 diagnosis code (any room visits position) and type of service code FAC_OP.ER or PROF.ER (any position) or revenue code 0450, 0451, 0452, 0456, 0459 or 0981

Duration of inpatient Sum of duration of all events related to ICD-9 or ICD-10 inpatient stay diagnosis code within the inpatient confinement (any position)

Count of number of Count of number of unique NDC generic names across the follow up different medications period (generic names) prescribed

Table 6. Cost outcomes Variable Definition

Total cost Sum of standard cost amounts of medical services in occurrence of inpatient visits, urgent care visits, outpatient visits, and ER visits, and prescription claims in occurrence of pharmacy dispensing during follow-up.

Inpatient cost Sum of standard cost amounts of claims with inpatient confinement claim= “YES” within the medical services table during follow-up.

Outpatient cost Sum of standard cost amounts of medical services in occurrence of outpatient visits during follow up as defined in Table 5.

Emergency room cost Sum of standard cost amounts of medical services occurrence of emergency room visit with type of service code as FAC_OP.ER or PROF.ER or revenue code 0450, 0451, 0452, 0456, 0459 or 0981 during follow up.

Pharmacy cost Sum of standard cost amounts of prescription claims in occurrence of any pharmacy dispensing during follow up.

SUPPLEMENTARY MATERIALS 2: TABLES AND FIGURES

TABLE OF CONTENTS

Table 1. Distribution of T2D patients with newly recognized CKD according to KDIGO classification on cohort entry...... 3 Table 2. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by prevalent comorbidities...... 6 Table 3. Stratification by risk categories A-V for patients with T2D and incident CKD...... 11 Table 4. Number and percentage of patients with T2D and incident CKD, during a 365-day baseline period for stratification by risk categories A-V...... 13 Table 5. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories A-D (Stage of Albuminuria: A1) ...... 13 Table 6. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories E-K (Stage of Albuminuria: A2) ...... 15 Table 7. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories L-R (Stage of Albuminuria: A3) ...... 19 Table 8. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories S-V (Missing stage of Albuminuria) ...... 22 Table 9. Annual HCRU outcomes of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data. Results are stratified by relevant comorbidities...... 24 Table 10. Mean number of inpatient visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results ...... 26 Table 11. Mean number of outpatient visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results...... 27 Table 12. Mean number of emergency room visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results...... 28 Table 13. Mean number of unique medications filled per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results...... 28

1 Table 14. Mean duration (days) of all inpatient visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results...... 29 Table 15. Annual costs of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data. Results are stratified by relevant comorbidities...... 31 Table 16. Mean total cost per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results...... 32 Table 17. Mean inpatient costs per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results ...... 33 Table 18. Mean outpatient costs per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results ...... 34 Table 19. Mean emergency room costs per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results ...... 35 Table 20. Mean pharmacy costs per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results...... 36 Table 21. Mean pharmacy costs per person per year of commercially insured patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results...... 37 Table 22. Mean pharmacy costs per person per year of Medicare insured patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results...... 38

Figure 1. Health care resource utilization of T2D patients with newly recognized CKD identified in Optum CDM, 1 Jan 2008 – 31 Dec 2017, stratified by presence of baseline HF...... 4 Figure 2. Annualized count of inpatient hospitalizations PPPY among T2D patients with newly recognized CKD identified in Optum CDM, 1 Jan 2008 – 31 Dec 2017, stratified by KDIGO CKD stages...... 5

Table 1. Distribution of T2D patients with newly recognized CKD according to KDIGO classification on cohort entry.

Stage of DKD by eGFR classification (n=106,369)

G1 G2 G3a G3b G4 G5 Missing Stage of 10,237 1,884 145 44 A1 Albuminuria (9.6%) (1.8%) (0.1%) (0.04%) 4,863 6,777 4,803 1,240 158 20 10,065 A2 (4.6%) (6.4%) (4.5%) (1.2%) (0.2%) (0.02%) (9.46%) 833 1,249 1,113 421 91 7 1,980 A3 (0.8%) (1.2%) (1.1%) (0.4%) (0.1%) (0.01%) (1.86%) 47,090 11,855 1,364 130 Missing (44.3%) (11.2%) (1.3%) (0.1%) Abbreviations: T2D, Type 2 diabetes mellitus; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes

Albuminuria Stages: normal (A1), <30 mg/g; microalbuminuria (A2), 30-300 mg/g; macroalbuminuria (A3), >300mg/g CKD Stages by eGFR classification: CKD stage 1 (G1), >90 ml/min/1.73m2; CKD stage 2 (G2), 60-89 ml/min/1.73m2; CKD stage 3a (G3a), 45-59 ml/min/1.73m2; CKD stage 3b (G3b), 30-44 ml/min/1.73m2; CKD stage 4 (G4), 15-29 ml/min/1.73m2; CKD stage 5 (G5), <15 ml/min/1.73m2 Patients with ESRD, CKD, kidney transplant, or dialysis during the 365-day baseline period were excluded.

3 18.4

16.3

11.9 12.3

7.4

2.7 Count or number of days PPPY days of ornumber Count 1.3 0.3 0.7 0.6

Inpatient visits Outpatient visits ER Visits Different medications Duration of inpatient filled stay

No HF during baseline HF during baseline

Figure 1. Health care resource utilization of T2D patients with newly recognized CKD identified in Optum CDM, 1 Jan 2008 – 31 Dec 2017, stratified by presence of baseline HF.

Abbreviations: T2D, Type 2 diabetes mellitus; CKD, chronic kidney disease; HF, heart failure; ER, emergency room; KDIGO, Kidney Disease: Improving Global Outcomes; PPPY, per person per year

Patients with ESRD, CKD, kidney transplant, or dialysis during the 365-day baseline period were excluded.

Figure 2. Annualized count of inpatient hospitalizations PPPY among T2D patients with newly recognized CKD identified in Optum CDM, 1 Jan 2008 – 31 Dec 2017, stratified by KDIGO CKD stages.

Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; T2D, Type 2 diabetes mellitus

Patients with ESRD, CKD, kidney transplant, or dialysis during the 365-day baseline period were excluded.

5 Table 2. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by prevalent comorbidities.

No resistant Resistant No No HF Anemia HF during hypertension hypertension anemia during during baseline during during during baseline baseline (N=11,795) baseline baseline baseline (N=94,574) (N=19,761) (N=89,480) (N=16,889) (N=86,608) Demographics eGFR value on

CED 55.06 50.68 55.15 52.02 55.10 (15.83) 51.75 (13.44) -- Mean (SD) (15.77) (12.81) (15.96) (13.22) UACR value on

CED 181.47 207.72 231.33 182.41 189.88 176.06 (376.53) -- Mean (SD) (432.37) (413.81) (684.93) (440.73) (364.23) Age (years) 70.12 74.43 70.08 72.86 70.37 (13.06) 71.78 (11.81) -- Mean (SD) (12.84) (12.53) (12.85) (12.79) -- Median 70 [63, 77] 74 [67, 81] 71 [63, 78] 71 [65, 78] 70 [63, 77] 73 [66, 80] [IQR] Gender 41,049 5,214 39,231 7,032 39,601 (44.3%) 6,662 (39.4%) -- Male, n (%) (43.4%) (44.2%) (45.3%) (35.6%) -- Female, n 53,490 6,576 10,218 47,341 12,725 49,848 (55.7%) (%) (56.6%) (55.8%) (60.5%) (54.7%) (64.4%) -- Missing n 35 (0.0%) 5 (0.0%) 31 (0.0%) 9 (0.1%) 36 (0.0%) 4 (0.0%) (%) Race 54,391 7,007 50,178 11,220 51,760 (57.8%) 9,638 (57.1%) -- White, n(%) (57.5%) (59.4%) (57.9%) (56.8%) 3,517 3,093 252 (2.1%) 3,326 (3.7%) 443 (2.6%) 676 (3.4%) -- Asian, n(%) (3.7%) (3.6%) 10,308 1,557 9,213 2,652 9,112 (10.2%) 2,753 (16.3%) -- Black, n(%) (10.9%) (13.2%) (10.6%) (13.4%)

6 -- Hispanic, 12,604 1,308 11,449 2,463 11,968 (13.4%) 1,944 (11.5%) n(%) (13.3%) (11.1%) (13.2%) (12.5%) -- Unknown, 13754 1671 12675 2750 13314 (14.9%) 2111 (12.5%) n(%) (14.5%) (14.2%) (14.6%) (13.9%) Region -- Northeast, 9,284 1,251 7,582 2,953 9,049 (10.1%) 1,486 (8.8%) n(%) (9.8%) (10.6%) (8.8%) (14.9%) -- Midwest, 9,034 1,227 8,620 1,641 8,581 (9.6%) 1,680 (9.9%) n(%) (9.6%) (10.4%) (10.0%) (8.3%) 54,229 6,749 10,362 49,378 11,600 50,616 (56.6%) -- South, n(%) (57.3%) (57.2%) (61.4%) (57.0%) (58.7%) 21,676 2,515 20,683 3,508 20,875 (23.3%) 3,316 (19.6%) -- West, n(%) (22.9%) (21.3%) (23.9%) (17.8%) -- Missing, 351 (0.4%) 53 (0.4%) 359 (0.4%) 45 (0.3%) 345 (0.4%) 59 (0.3%) n(%) Provider

Specialty -- 2,279 2,076 Endocrinologist, 211 (1.8%) 2,135 (2.4%) 355 (2.1%) 414 (2.1%) (2.4%) (2.4%) n(%) -- Nephrologist, 303 (0.3%) 53 (0.4%) 273 (0.3%) 83 (0.5%) 267 (0.3%) 89 (0.5%) n(%) -- Cardiologist, 1,586 1,700 717 (6.1%) 1,795 (2.0%) 508 (3.0%) 603 (3.1%) n(%) (1.7%) (2.0%) -- General 45,851 5,653 42,704 8,800 Practitioner / 43,179 (48.3%) 8,325 (49.3%) (48.5%) (47.9%) (49.3%) (44.5%) Internist, n(%) -- Urologist, 229 (0.2%) 30 (0.3%) 229 (0.3%) 30 (0.2%) 208 (0.2%) 51 (0.3%) n(%) -- Inpatient 1,787 1,626 342 (2.9%) 1,720 (1.9%) 409 (2.4%) 503 (2.5%) facility, n(%) (1.9%) (1.9%) -- Outpatient 1,378 1,313 197 (1.7%) 1,305 (1.5%) 270 (1.6%) 262 (1.3%) facility, n(%) (1.5%) (1.5%) -- Missing, 50,843 6,628 47,396 10,075 48,085 (53.7%) 9,386 (55.6%) n(%) (53.8%) (56.2%) (54.7%) (51.0%) Comorbidity score Deyo comorbidity

7 score

-- Mean (SD) 2.07 (1.36) 3.92 (1.69) 2.23 (1.50) 2.51 (1.61) 2.15 (1.40) 2.86 (1.84) -- Median 2 [1, 3] 4 [3, 5] 2 [1, 3] 2 [1, 3] 2 [1, 3] 2 [1, 4] [IQR] Comorbidities Angina pectoris, 18,820 6,889 19,221 6,488 20,180 (22.6%) 5,529 (32.7%) n(%) (19.9%) (58.4%) (22.2%) (32.8%) Acute coronary 1,690 1,223 1,922 2,183 (2.4%) 730 (4.3%) 991 (5.0%) syndrome, n(%) (1.8%) (10.4%) (2.2%) 16,108 3,653 19,761 16,071 (18.0%) 3,690 (21.8%) 0 (0.0%) Anemia, n(%) (17.0%) (31.0%) (100.0%) Atrial fibrillation, 6,539 4,334 7,887 2,986 8,081 (9.0%) 2,792 (16.5%) n(%) (6.9%) (36.7%) (9.1%) (15.1%) Chronic 15,698 5,120 15,546 5,272 lung/pulmonary 16,911 (18.9%) 3,907 (23.1%) (16.6%) (43.4%) (17.9%) (26.7%) disease, n(%) Coronary artery 10,016 4,347 10,497 3,866 11,263 (12.6%) 3,100 (18.4%) disease, n(%) (10.6%) (36.9%) (12.1%) (19.6%) 8,889 1,737 7,804 2,822 8,907 (10.0%) 1,719 (10.2%) Depression, n(%) (9.4%) (14.7%) (9.0%) (14.3%) 8,108 3,066 7,909 3,265 8,066 (9.0%) 3,108 (18.4%) Edema, n(%) (8.6%) (26.0%) (9.1%) (16.5%) Fatigue & sleep 21,636 4,369 18,832 7,173 related disorders, 21,383 (23.9%) 4,622 (27.4%) (22.9%) (37.0%) (21.7%) (36.3%) n(%) Heart Failure, 11,795 8,142 3,653 0 (0.0%) 8,529 (9.5%) 3,266 (19.3%) n(%) (100.0%) (9.4%) (18.5%) Hyperkalemia, 1,742 1,533 515 (4.4%) 1,826 (2.0%) 431 (2.6%) 724 (3.7%) n(%) (1.8%) (1.8%) --Hyperkalemia 1,688 1,493 indicated by ICD 506 (4.3%) 1,771 (2.0%) 423 (2.5%) 701 (3.5%) (1.8%) (1.7%) codes, n(%) --Hyperkalemia indicated by lab 80 (0.1%) 23 (0.2%) 86 (0.1%) 17 (0.1%) 63 (0.1%) 40 (0.2%) values, n(%) Hypokalemia, 2,540 2,216 1,312 988 (8.4%) 2,553 (2.9%) 975 (5.8%) n(%) (2.7%) (2.6%) (6.6%) Hyponatremia, 1,674 631 (5.3%) 1,769 (2.0%) 536 (3.2%) 1,324 981 (5.0%)

8 n(%) (1.8%) (1.5%) Hyperlipidemia, 78,429 10,123 14,404 71,425 17,127 74,148 (82.9%) n(%) (82.9%) (85.8%) (85.3%) (82.5%) (86.7%) Hypertension , 83,893 11,215 16,302 76,705 18,403 78,806 (88.1%) n(%) (88.7%) (95.1%) (96.5%) (88.6%) (93.1%) Microvascular 29,484 4,692 27,065 7,111 28,299 (31.6%) 5,877 (34.8%) disease, n(%) (31.2%) (39.8%) (31.2%) (36.0%) Myocardial 1,178 946 (1.0%) 916 (7.8%) 1,358 (1.5%) 504 (3.0%) 684 (3.5%) infarction, n(%) (1.4%) 17,095 3,210 16,208 4,097 16,361 (18.3%) 3,944 (23.4%) Obesity, n(%) (18.1%) (27.2%) (18.7%) (20.7%) Pain disorders, 63,713 9,746 12,387 57,630 15,829 61,072 (68.3%) n(%) (67.4%) (82.6%) (73.3%) (66.5%) (80.1%) Peripheral 13,179 3,532 12,332 4,379 vascular disease, 13,446 (15.0%) 3,265 (19.3%) (13.9%) (29.9%) (14.2%) (22.2%) n(%) Resistant 13,623 3,266 16,889 13,199 3,690 hypertension, 0 (0.0%) (14.4%) (27.7%) (100.0%) (15.2%) (18.7%) n(%) Respiratory 1,257 1,249 884 (0.9%) 1,550 (1.7%) 591 (3.5%) 892 (4.5%) failure, n(%) (10.7%) (1.4%) Sleep apnea, 9,142 2,446 9,140 2,448 9,070 (10.1%) 2,518 (14.9%) n(%) (9.7%) (20.7%) (10.6%) (12.4%) 3,530 1,073 3,256 1,347 3,642 (4.1%) 961 (5.7%) Stroke, n(%) (3.7%) (9.1%) (3.8%) (6.8%) Concomitant medications 61,406 7,948 12,966 56,729 12,625 56,388 (63.0%) Statins, n (%) (64.9%) (67.4%) (76.8%) (65.5%) (63.9%) Anti-hypertensive agents 45,555 5,928 10,778 42,323 9,160 40,705 (45.5%) ACEIs, n (%) (48.2%) (50.3%) (63.8%) (48.9%) (46.4%) 22,941 3,126 20,938 5,129 18,713 (20.9%) 7,354 (43.5%) ARBs, n (%) (24.3%) (26.5%) (24.2%) (26.0%) Beta blockers, n 29,228 4,981 11,851 27,295 6,914 22,358 (25.0%) (%) (30.9%) (42.2%) (70.2%) (31.5%) (35.0%) Thiazide, 43,422 8,493 15,856 41,553 10,362 36,059 (40.3%) potassium- (45.9%) (72.0%) (93.9%) (48.0%) (52.4%)

9 sparing, and loop diuretics, n (%) Calcium Channel 29,415 3,983 12,328 26,767 6,631 21,070 (23.5%) Blockers, n (%) (31.1%) (33.8%) (73.0%) (30.9%) (33.6%) 2,592 2,002 3,338 1,256 2,543 (2.8%) 2,051 (12.1%) MRAs, n (%) (2.7%) (17.0%) (3.9%) (6.4%) Alpha blockers, n 2,840 2,664 479 (4.1%) 1,708 (1.9%) 1,611 (9.5%) 655 (3.3%) (%) (3.0%) (3.1%) Alpha-2 receptor 54 (0.1%) 12 (0.1%) 33 (0.0%) 33 (0.2%) 47 (0.1%) 19 (0.1%) agonists, n (%) Combined alpha 3,539 3,205 and beta 642 (5.4%) 1,462 (1.6%) 2,719 (16.1%) 976 (4.9%) (3.7%) (3.7%) blockers, n (%) Central agonists, 3 (0.0%) 0 (0.0%) 2 (0.0%) 1 (0.0%) 3 (0.0%) 0 (0.0%) n (%) Peripheral 1,660 1,698 adrenergic 629 (5.3%) 772 (0.9%) 1,517 (9.0%) 591 (3.0%) (1.8%) (2.0%) inhibitors, n (%) Glucose lowering agent classes 20,242 3,312 19,167 4,387 18,982 (21.2%) 4,572 (27.1%) Insulin, n (%) (21.4%) (28.1%) (22.1%) (22.2%) Dipeptidyl- Peptidase-4 12,071 1,248 10,868 2,451 11,090 (12.4%) 2,229 (13.2%) Inhibitor (DPP- (12.8%) (10.6%) (12.5%) (12.4%) 4i), n (%) Glucagon-like peptide-1 4,049 3,686 353 (3.0%) 3,669 (4.1%) 733 (4.3%) 716 (3.6%) Receptor Agonist (4.3%) (4.3%) (GLP1), n (%) Alpha Glucosidase 294 (0.3%) 42 (0.4%) 266 (0.3%) 70 (0.4%) 265 (0.3%) 71 (0.4%) Inhibitor, n (%) Sodium-glucose Cotransporter-2 2,359 2,215 155 (1.3%) 2,204 (2.5%) 310 (1.8%) 299 (1.5%) Inhibitors (2.5%) (2.6%) (SGLT2i), n (%) Thiazolidinedione 9,678 8,399 2,027 748 (6.3%) 8,712 (9.7%) 1,714 (10.1%) (TZD), n (%) (10.2%) (9.7%) (10.3%)

10 Sulfonylurea 30,816 3,796 28,376 6,236 28,084 (31.4%) 6,528 (38.7%) (SU), n (%) (32.6%) (32.2%) (32.8%) (31.6%) Biguanides 47,524 4,962 43,260 9,226 (monotherapy), n 42,970 (48.0%) 9,516 (56.3%) (50.3%) (42.1%) (49.9%) (46.7%) (%) Biguanides (mono- and 53,671 5,457 10,572 48,729 10,399 48,556 (54.3%) combination (56.8%) (46.3%) (62.6%) (56.3%) (52.6%) therapy), n (%) Bile acid sequestrants, n 832 (0.9%) 108 (0.9%) 765 (0.9%) 175 (1.0%) 761 (0.9%) 179 (0.9%) (%) Meglitinides, n 927 (1.0%) 132 (1.1%) 877 (1.0%) 182 (1.1%) 809 (0.9%) 250 (1.3%) (%) Number of different classes of glucose lowering agents -- Mean (SD) 1.47 (1.23) 1.33 (1.15) 1.42 (1.22) 1.65 (1.19) 1.46 (1.21) 1.40 (1.24) -- Median 1 [1, 2] 1 [0, 2] 1 [0, 2] 1 [1, 2] 1 [1, 2] 1 [0, 2] (IQR) Number of glucose lowering agents, categories 31,449 4,086 29,390 6,145 29,431 (32.9%) 6,104 (36.1%) ...1; n (%) (33.3%) (34.6%) (33.9%) (31.1%) 40,616 4,553 36,969 8,200 36,941 (41.3%) 8,228 (48.7%) ...>= 2; n (%) (42.9%) (38.6%) (42.7%) (41.5%) Abbreviations: SD, standard deviation; IQR, interquartile range; Dx, diagnosis; T2D, Type 2 diabetes mellitus; CKD, chronic kidney disease; ACEI, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blockers; HF, heart failure

Patients with ESRD, CKD, kidney transplant, dialysis, or other diagnoses which could cause CKD from causes other than T2D during the 365-day baseline period were excluded. Resistant hypertension is defined as 4 or more unique antihypertensive medication prescription claims within a 30-day period.

Table 3. Stratification by risk categories A-V for patients with T2D and incident CKD.

Stage of CKD by eGFR classification Stage 1 Stage 2 Stage 3a Stage 3b Stage 4 Stage 5 (>90 (60-89 (45-59 (30-44 (15-29 (<15 Missing ml/min/1.73 ml/min/1.73m2) ml/min/1.73m2) ml/min/1.73m2) ml/min/1.73m2) ml/min/1.73m2) m2) A1 Stage of (<30 A B C D Albuminuria mg/g) A2 (30- 300 E F G H I J K mg/g) A3 (>300 L M N O P Q R mg/g) Missin S T U V g

12 Table 4. Number and percentage of patients with T2D and incident CKD, during a 365-day baseline period for stratification by risk categories A-V.

Stage of CKD by eGFR classification (n=106,369) Stage 1 Stage 2 Stage 3a Stage 3b Stage 4 Stage 5 (>90 (60-89 (45-59 (30-44 (15-29 (<15 Missing ml/min/1.73m2) ml/min/1.73m2) ml/min/1.73m2) ml/min/1.73m2) ml/min/1.73m2) ml/min/1.73m2) Stage of A1 (<30 10,237 (9.62%) 1,884 (1.77%) 145 (0.14%) 44 (0.04%) Albuminuria mg/g) A2 (30- 10,065 300 4,863 (4.57%) 6,777 (6.37%) 4,803 (4.52%) 1,240 (1.17%) 158 (0.15%) 20 (0.02%) mg/g) (9.46%) A3 1,980 (>300 833 (0.78%) 1,249 (1.17%) 1,113 (1.05%) 421 (0.4%) 91 (0.09%) 7 (0.01%) mg/g) (1.86%) 47,090 11,855 1,364 (1.28%) 130 (0.12%) Missing (44.27%) (11.15%)

Table 5. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories A-D (Stage of Albuminuria: A1)

Risk Strata A Risk Strata B Risk Strata C Risk Strata D (G3A & A1) (G3B & A1) (G4 & A1) (G5 & A1) (N=10,237) (N=1,884) (N=145) (N=44) Demographics

Age (years)

-- Mean (SD) 71.22 (10.90) 73.64 (11.71) 75.24 (14.74) 68.45 (9.54) -- Median [IQR] 71 [65, 77] 73 [67, 79] 74 [67, 81] 70 [63, 74] Gender

-- Male, n (%) 4,011 (39.2%) 562 (29.8%) 34 (23.4%) 17 (38.6%) -- Female, n (%) 6,222 (60.8%) 1,321 (70.1%) 111 (76.6%) 27 (61.4%) -- Missing n (%) 4 (0.0%) 1 (0.1%) 0 (0.0%) 0 (0.0%) Race

-- White, n(%) 6,075 (59.3%) 1,125 (59.7%) 79 (54.5%) 20 (45.5%) -- Asian, n(%) 268 (2.6%) 40 (2.1%) 0 (0.0%) 2 (4.5%)

13 -- Black, n(%) 1,104 (10.8%) 215 (11.4%) 18 (12.4%) 0 (0.0%) -- Hispanic, n(%) 1,187 (11.6%) 235 (12.5%) 23 (15.9%) 9 (20.5%) -- Unknown, n(%) 974 (9.5%) 172 (9.1%) 15 (10.3%) 5 (11.4%) -- Missing, n(%) 629 (6.1%) 97 (5.1%) 10 (6.9%) 8 (18.2%) Region

-- Northeast, n(%) 667 (6.5%) 107 (5.7%) 10 (6.9%) 0 (0.0%) -- Midwest, n(%) 965 (9.4%) 204 (10.8%) 11 (7.6%) 1 (2.3%) -- South, n(%) 6,557 (64.1%) 1,178 (62.5%) 91 (62.8%) 1 (2.3%) -- West, n(%) 2,020 (19.7%) 391 (20.8%) 32 (22.1%) 41 (93.2%) -- Missing, n(%) 28 (0.3%) 4 (0.2%) 1 (0.7%) 1 (2.3%) Provider Specialty

-- Endocrinologist, n(%) 299 (2.9%) 50 (2.7%) 4 (2.8%) 1 (2.3%) -- Nephrologist, n(%) 14 (0.1%) 4 (0.2%) 0 (0.0%) 1 (2.3%) -- Cardiologist, n(%) 161 (1.6%) 34 (1.8%) 1 (0.7%) 0 (0.0%) -- General Practitioner / 5,151 (50.3%) 1,005 (53.3%) 75 (51.7%) 8 (18.2%) Internist, n(%) -- Urologist, n(%) 22 (0.2%) 2 (0.1%) 0 (0.0%) 0 (0.0%) -- Inpatient facility, n(%) 190 (1.9%) 37 (2.0%) 2 (1.4%) 0 (0.0%) -- Outpatient facility, n(%) 137 (1.3%) 23 (1.2%) 2 (1.4%) 32 (72.7%) -- Missing, n(%) 5,715 (55.8%) 1,100 (58.4%) 81 (55.9%) 42 (95.5%) Comorbidity score

Deyo comorbidity score

-- Mean (SD) 2.17 (1.41) 2.27 (1.47) 2.46 (1.55) 2.52 (1.37) -- Median [IQR] 2 [1, 3] 2 [1, 3] 2 [1, 3] 2 [2, 4] Comorbidities

Angina pectoris, n(%) 2,195 (21.4%) 462 (24.5%) 28 (19.3%) 6 (13.6%) Acute coronary syndrome, n(%) 235 (2.3%) 43 (2.3%) 4 (2.8%) 1 (2.3%) Anemia, n(%) 1,532 (15.0%) 314 (16.7%) 27 (18.6%) 4 (9.1%) Atrial fibrillation, n(%) 817 (8.0%) 168 (8.9%) 10 (6.9%) 4 (9.1%) Chronic lung/pulmonary disease, 1,784 (17.4%) 355 (18.8%) 31 (21.4%) 8 (18.2%) n(%) Coronary artery disease, n(%) 1,212 (11.8%) 213 (11.3%) 16 (11.0%) 4 (9.1%) Depression, n(%) 1,057 (10.3%) 191 (10.1%) 16 (11.0%) 4 (9.1%) Edema, n(%) 923 (9.0%) 210 (11.1%) 23 (15.9%) 4 (9.1%) Fatigue & sleep related disorders, 2,261 (22.1%) 405 (21.5%) 27 (18.6%) 6 (13.6%) n(%) Heart Failure, n(%) 822 (8.0%) 212 (11.3%) 13 (9.0%) 4 (9.1%) Hyperkalemia, n(%) 206 (2.0%) 41 (2.2%) 0 (0.0%) 0 (0.0%) Hypokalemia, n(%) 280 (2.7%) 60 (3.2%) 5 (3.4%) 2 (4.5%)

14 Hyponatremia, n(%) 161 (1.6%) 34 (1.8%) 2 (1.4%) 0 (0.0%) Hyperlipidemia, n(%) 8,698 (85.0%) 1,526 (81.0%) 117 (80.7%) 33 (75.0%) Hypertension , n(%) 9,145 (89.3%) 1,692 (89.8%) 131 (90.3%) 37 (84.1%) Microvascular disease, n(%) 3,284 (32.1%) 615 (32.6%) 46 (31.7%) 22 (50.0%) Myocardial infarction, n(%) 132 (1.3%) 26 (1.4%) 4 (2.8%) 0 (0.0%) Obesity, n(%) 1,917 (18.7%) 305 (16.2%) 24 (16.6%) 24 (54.5%) Pain disorders, n(%) 7,031 (68.7%) 1,331 (70.6%) 102 (70.3%) 31 (70.5%) Peripheral vascular disease, n(%) 1,515 (14.8%) 299 (15.9%) 25 (17.2%) 14 (31.8%) Resistant hypertension, n(%) 1,436 (14.0%) 388 (20.6%) 32 (22.1%) 2 (4.5%) Respiratory failure, n(%) 144 (1.4%) 46 (2.4%) 2 (1.4%) 2 (4.5%) Sleep apnea, n(%) 1,089 (10.6%) 196 (10.4%) 9 (6.2%) 3 (6.8%) Stroke, n(%) 373 (3.6%) 71 (3.8%) 5 (3.4%) 1 (2.3%) Abbreviations: CKD, chronic kidney disease; Dx, diagnosis; IQR, interquartile range; T2D, Type 2 diabetes mellitus; SD, standard deviation.

Patients with ESRD, CKD, kidney transplant, dialysis, or other diagnoses which could cause CKD from causes other than T2D during the 365-day baseline period were excluded from Cohort 1. Resistant hypertension is defined as 4 or more unique antihypertensive medication prescription claims within a 30-day period.

Table 6. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories E-K (Stage of Albuminuria: A2)

Risk Strata Risk Risk Strata K Risk Strata E Risk Strata F Risk Strata G Risk Strata I H Strata J (eGFR missing (G1 & A2) (G2 & A2) (G3A & A2) (G4 & A2) (G3B & A2) (G5 & A2) & A2) (N=4,863) (N=6,777) (N=4,803) (N=158) (N=1,240) (N=20) (N=10,065) Demographics

Age (years)

66.15 56.78 (11.51) 69.18 (10.99) 72.78 (12.08) 75.06 (12.42) 74.95 (13.14) 66.05 (13.67) -- Mean (SD) (15.38) -- Median [IQR] 68 [57, 75] 57 [49, 66] 70 [63, 75] 73 [66, 79] 74 [68, 81] 74 [67, 83] 68 [56, 72] Gender

3,814 2,673 (55.0%) 2,196 (45.7%) 463 (37.3%) 37 (23.4%) 12 (60.0%) 5,656 (56.2%) -- Male, n (%) (56.3%) 2,961 2,189 (45.0%) 2,605 (54.2%) 776 (62.6%) 121 (76.6%) 8 (40.0%) 4,407 (43.8%) -- Female, n (%) (43.7%) -- Missing n (%) 1 (0.0%) 2 (0.0%) 2 (0.0%) 1 (0.1%) 0 (0.0%) 0 (0.0%) 2 (0.0%) Race

-- White, n(%) 1,840 (37.8%) 3,157 2,684 (55.9%) 704 (56.8%) 89 (56.3%) 14 (70.0%) 4,992 (49.6%)

15 (46.6%) -- Asian, n(%) 243 (5.0%) 275 (4.1%) 181 (3.8%) 34 (2.7%) 1 (0.6%) 0 (0.0%) 980 (9.7%) -- Black, n(%) 885 (18.2%) 879 (13.0%) 584 (12.2%) 129 (10.4%) 19 (12.0%) 1 (5.0%) 751 (7.5%) 1,476 1,245 (25.6%) 674 (14.0%) 192 (15.5%) 21 (13.3%) 3 (15.0%) 1,885 (18.7%) -- Hispanic, n(%) (21.8%) -- Unknown, n(%) 479 (9.8%) 595 (8.8%) 425 (8.8%) 107 (8.6%) 18 (11.4%) 1 (5.0%) 927 (9.2%) -- Missing, n(%) 171 (3.5%) 395 (5.8%) 255 (5.3%) 74 (6.0%) 10 (6.3%) 1 (5.0%) 530 (5.3%) Region

-- Northeast, n(%) 383 (7.9%) 546 (8.1%) 395 (8.2%) 109 (8.8%) 10 (6.3%) 0 (0.0%) 2,169 (21.5%) -- Midwest, n(%) 291 (6.0%) 374 (5.5%) 470 (9.8%) 144 (11.6%) 14 (8.9%) 2 (10.0%) 955 (9.5%) 4,306 3,338 (68.6%) 2,884 (60.0%) 706 (56.9%) 94 (59.5%) 9 (45.0%) 3,367 (33.5%) -- South, n(%) (63.5%) 1,542 836 (17.2%) 1,034 (21.5%) 274 (22.1%) 40 (25.3%) 9 (45.0%) 3,532 (35.1%) -- West, n(%) (22.8%) -- Missing, n(%) 15 (0.3%) 9 (0.1%) 20 (0.4%) 7 (0.6%) 0 (0.0%) 0 (0.0%) 42 (0.4%) Provider Specialty -- Endocrinologist, 223 (4.6%) 218 (3.2%) 157 (3.3%) 47 (3.8%) 7 (4.4%) 0 (0.0%) 319 (3.2%) n(%) -- Nephrologist, n(%) 7 (0.1%) 14 (0.2%) 8 (0.2%) 5 (0.4%) 3 (1.9%) 1 (5.0%) 36 (0.4%) -- Cardiologist, n(%) 28 (0.6%) 68 (1.0%) 111 (2.3%) 29 (2.3%) 6 (3.8%) 0 (0.0%) 121 (1.2%) -- General Practitioner 3,156 2,214 (45.5%) 2,374 (49.4%) 597 (48.1%) 75 (47.5%) 10 (50.0%) 3,329 (33.1%) / Internist, n(%) (46.6%) -- Urologist, n(%) 3 (0.1%) 10 (0.1%) 12 (0.2%) 5 (0.4%) 1 (0.6%) 0 (0.0%) 3 (0.0%) -- Inpatient facility, 47 (1.0%) 61 (0.9%) 79 (1.6%) 24 (1.9%) 2 (1.3%) 0 (0.0%) 154 (1.5%) n(%) -- Outpatient facility, 81 (1.7%) 112 (1.7%) 55 (1.1%) 21 (1.7%) 4 (2.5%) 6 (30.0%) 77 (0.8%) n(%) 3,479 2,478 (51.0%) 2,649 (55.2%) 692 (55.8%) 91 (57.6%) 16 (80.0%) 3,829 (38.0%) -- Missing, n(%) (51.3%) Comorbidity score

Deyo comorbidity score

-- Mean (SD) 1.87 (1.24) 2.19 (1.37) 2.36 (1.52) 2.50 (1.52) 2.51 (1.49) 2.30 (1.45) 2.03 (1.32) -- Median [IQR] 2 [1, 3] 2 [1, 2] 2 [1, 3] 2 [1, 3] 2 [1, 3] 2 [1, 3] 2 [1, 4] Comorbidities

1,437 617 (12.7%) 1,346 (28.0%) 347 (28.0%) 33 (20.9%) 2 (10.0%) 1,972 (19.6%) Angina pectoris, n(%) (21.2%) Acute coronary 104 (2.1%) 187 (2.8%) 124 (2.6%) 34 (2.7%) 5 (3.2%) 1 (5.0%) 256 (2.5%) syndrome, n(%) Anemia, n(%) 506 (10.4%) 890 (13.1%) 798 (16.6%) 253 (20.4%) 35 (22.2%) 1 (5.0%) 1,449 (14.4%)

16 Atrial fibrillation, n(%) 178 (3.7%) 590 (8.7%) 555 (11.6%) 171 (13.8%) 20 (12.7%) 1 (5.0%) 793 (7.9%) Chronic lung/pulmonary 1,190 764 (15.7%) 949 (19.8%) 248 (20.0%) 28 (17.7%) 3 (15.0%) 1,695 (16.8%) disease, n(%) (17.6%) Coronary artery disease, 415 (8.5%) 964 (14.2%) 702 (14.6%) 189 (15.2%) 26 (16.5%) 1 (5.0%) 1,294 (12.9%) n(%) Depression, n(%) 512 (10.5%) 600 (8.9%) 423 (8.8%) 109 (8.8%) 16 (10.1%) 2 (10.0%) 863 (8.6%) Edema, n(%) 310 (6.4%) 487 (7.2%) 495 (10.3%) 156 (12.6%) 33 (20.9%) 1 (5.0%) 739 (7.3%) Fatigue & sleep related 1,252 875 (18.0%) 1,061 (22.1%) 290 (23.4%) 33 (20.9%) 4 (20.0%) 1,985 (19.7%) disorders, n(%) (18.5%) Heart Failure, n(%) 215 (4.4%) 524 (7.7%) 547 (11.4%) 192 (15.5%) 27 (17.1%) 2 (10.0%) 700 (7.0%) Hyperkalemia, n(%) 49 (1.0%) 105 (1.5%) 120 (2.5%) 33 (2.7%) 2 (1.3%) 0 (0.0%) 166 (1.6%) Hypokalemia, n(%) 112 (2.3%) 165 (2.4%) 139 (2.9%) 35 (2.8%) 4 (2.5%) 0 (0.0%) 225 (2.2%) Hyponatremia, n(%) 76 (1.6%) 133 (2.0%) 101 (2.1%) 25 (2.0%) 2 (1.3%) 0 (0.0%) 227 (2.3%) 5,560 1,005 3,871 (79.6%) 3,984 (82.9%) 112 (70.9%) 15 (75.0%) 8,410 (83.6%) Hyperlipidemia, n(%) (82.0%) (81.0%) 5,872 1,122 3,962 (81.5%) 4,322 (90.0%) 134 (84.8%) 17 (85.0%) 8,718 (86.6%) Hypertension , n(%) (86.6%) (90.5%) Microvascular disease, 2,620 1,498 (30.8%) 1,780 (37.1%) 488 (39.4%) 62 (39.2%) 8 (40.0%) 3,369 (33.5%) n(%) (38.7%) Myocardial infarction, 55 (1.1%) 85 (1.3%) 81 (1.7%) 20 (1.6%) 2 (1.3%) 1 (5.0%) 129 (1.3%) n(%) 1,597 1,433 (29.5%) 886 (18.4%) 207 (16.7%) 15 (9.5%) 6 (30.0%) 2,326 (23.1%) Obesity, n(%) (23.6%) 4,484 3,161 (65.0%) 3,264 (68.0%) 847 (68.3%) 107 (67.7%) 10 (50.0%) 6,506 (64.6%) Pain disorders, n(%) (66.2%) Peripheral vascular 1,221 495 (10.2%) 820 (17.1%) 234 (18.9%) 39 (24.7%) 4 (20.0%) 1,491 (14.8%) disease, n(%) (18.0%) Resistant hypertension, 368 (7.6%) 975 (14.4%) 842 (17.5%) 272 (21.9%) 42 (26.6%) 1 (5.0%) 1,161 (11.5%) n(%) Respiratory failure, n(%) 68 (1.4%) 99 (1.5%) 110 (2.3%) 38 (3.1%) 3 (1.9%) 0 (0.0%) 129 (1.3%) Sleep apnea, n(%) 630 (13.0%) 789 (11.6%) 509 (10.6%) 106 (8.5%) 19 (12.0%) 0 (0.0%) 1,110 (11.0%) Stroke, n(%) 113 (2.3%) 238 (3.5%) 218 (4.5%) 60 (4.8%) 6 (3.8%) 0 (0.0%) 358 (3.6%) Abbreviations: CKD, chronic kidney disease; Dx, diagnosis; IQR, interquartile range; T2D, Type 2 diabetes mellitus; SD, standard deviation.

18 Table 7. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories L-R (Stage of Albuminuria: A3)

Risk Strata Risk Strata Risk Strata Risk Strata Risk Risk Strata R Risk Strata O L M N P Strata Q (eGFR (G3B & A3) (G1 & A3) (G2 & A3) (G3A & A3) (G4 & A3) (G5 & A3) missing & A3) (N=421) (N=833) (N=1,249) (N=1,113) (N=91) (N=7) (N=1,980) Demographics

Age (years)

68.05 70.47 67.14 55.54 (11.75) 66.59 (11.70) 70.17 (12.65) 65.10 (14.47) -- Mean (SD) (12.91) (13.12) (10.02) -- Median [IQR] 66 [56, 74] 56 [48, 64] 67 [59, 74] 69 [61, 75] 70 [63, 77] 70 [62, 77] 69 [58, 74] Gender

-- Male, n (%) 532 (63.9%) 749 (60.0%) 605 (54.4%) 194 (46.1%) 40 (44.0%) 4 (57.1%) 1,207 (61.0%) -- Female, n (%) 301 (36.1%) 498 (39.9%) 506 (45.5%) 226 (53.7%) 50 (54.9%) 3 (42.9%) 773 (39.0%) -- Missing n (%) 0 (0.0%) 2 (0.2%) 2 (0.2%) 1 (0.2%) 1 (1.1%) 0 (0.0%) 0 (0.0%) Race

-- White, n(%) 309 (37.1%) 535 (42.8%) 545 (49.0%) 199 (47.3%) 43 (47.3%) 5 (71.4%) 936 (47.3%) -- Asian, n(%) 26 (3.1%) 44 (3.5%) 47 (4.2%) 10 (2.4%) 3 (3.3%) 0 (0.0%) 155 (7.8%) -- Black, n(%) 166 (19.9%) 207 (16.6%) 157 (14.1%) 60 (14.3%) 19 (20.9%) 0 (0.0%) 169 (8.5%) -- Hispanic, n(%) 223 (26.8%) 281 (22.5%) 185 (16.6%) 102 (24.2%) 12 (13.2%) 1 (14.3%) 414 (20.9%) -- Unknown, n(%) 78 (9.4%) 117 (9.4%) 110 (9.9%) 35 (8.3%) 11 (12.1%) 1 (14.3%) 203 (10.3%) -- Missing, n(%) 31 (3.7%) 65 (5.2%) 69 (6.2%) 15 (3.6%) 3 (3.3%) 0 (0.0%) 103 (5.2%) Region

-- Northeast, n(%) 64 (7.7%) 120 (9.6%) 88 (7.9%) 32 (7.6%) 9 (9.9%) 1 (14.3%) 385 (19.4%) -- Midwest, n(%) 79 (9.5%) 67 (5.4%) 93 (8.4%) 46 (10.9%) 8 (8.8%) 0 (0.0%) 197 (9.9%) -- South, n(%) 548 (65.8%) 836 (66.9%) 712 (64.0%) 250 (59.4%) 60 (65.9%) 3 (42.9%) 653 (33.0%) -- West, n(%) 142 (17.0%) 222 (17.8%) 219 (19.7%) 90 (21.4%) 14 (15.4%) 3 (42.9%) 735 (37.1%) -- Missing, n(%) 0 (0.0%) 4 (0.3%) 1 (0.1%) 3 (0.7%) 0 (0.0%) 0 (0.0%) 10 (0.5%) Provider Specialty

-- Endocrinologist, n(%) 37 (4.4%) 49 (3.9%) 30 (2.7%) 12 (2.9%) 1 (1.1%) 0 (0.0%) 80 (4.0%) -- Nephrologist, n(%) 0 (0.0%) 7 (0.6%) 4 (0.4%) 4 (1.0%) 0 (0.0%) 0 (0.0%) 8 (0.4%) -- Cardiologist, n(%) 7 (0.8%) 16 (1.3%) 24 (2.2%) 4 (1.0%) 2 (2.2%) 0 (0.0%) 20 (1.0%) -- General Practitioner / 411 (49.3%) 562 (45.0%) 518 (46.5%) 220 (52.3%) 48 (52.7%) 2 (28.6%) 678 (34.2%) Internist, n(%) -- Urologist, n(%) 0 (0.0%) 2 (0.2%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 3 (0.2%) -- Inpatient facility, n(%) 8 (1.0%) 15 (1.2%) 20 (1.8%) 14 (3.3%) 0 (0.0%) 1 (14.3%) 40 (2.0%) -- Outpatient facility, n(%) 16 (1.9%) 27 (2.2%) 19 (1.7%) 8 (1.9%) 1 (1.1%) 3 (42.9%) 22 (1.1%)

19 -- Missing, n(%) 455 (54.6%) 639 (51.2%) 583 (52.4%) 249 (59.1%) 51 (56.0%) 5 (71.4%) 796 (40.2%) Comorbidity score

Deyo comorbidity score

-- Mean (SD) 1.99 (1.26) 2.27 (1.43) 2.36 (1.48) 2.35 (1.35) 2.31 (1.21) 3.14 (1.77) 2.16 (1.37) -- Median [IQR] 2 [1, 3] 2 [1, 3] 2 [1, 3] 2 [1, 3] 2 [1, 3] 2 [1, 3] 3 [2, 5] Comorbidities

Angina pectoris, n(%) 132 (15.8%) 305 (24.4%) 286 (25.7%) 92 (21.9%) 19 (20.9%) 1 (14.3%) 442 (22.3%) Acute coronary syndrome, 23 (2.8%) 43 (3.4%) 30 (2.7%) 9 (2.1%) 0 (0.0%) 0 (0.0%) 64 (3.2%) n(%) Anemia, n(%) 90 (10.8%) 194 (15.5%) 200 (18.0%) 65 (15.4%) 18 (19.8%) 2 (28.6%) 307 (15.5%) Atrial fibrillation, n(%) 26 (3.1%) 114 (9.1%) 111 (10.0%) 43 (10.2%) 9 (9.9%) 0 (0.0%) 180 (9.1%) Chronic lung/pulmonary 151 (18.1%) 220 (17.6%) 195 (17.5%) 73 (17.3%) 7 (7.7%) 1 (14.3%) 332 (16.8%) disease, n(%) Coronary artery disease, n(%) 87 (10.4%) 205 (16.4%) 158 (14.2%) 46 (10.9%) 5 (5.5%) 1 (14.3%) 285 (14.4%) Depression, n(%) 76 (9.1%) 113 (9.0%) 98 (8.8%) 31 (7.4%) 5 (5.5%) 1 (14.3%) 167 (8.4%) Edema, n(%) 73 (8.8%) 129 (10.3%) 118 (10.6%) 52 (12.4%) 16 (17.6%) 0 (0.0%) 178 (9.0%) Fatigue & sleep related 151 (18.1%) 257 (20.6%) 231 (20.8%) 86 (20.4%) 18 (19.8%) 2 (28.6%) 396 (20.0%) disorders, n(%) Heart Failure, n(%) 44 (5.3%) 114 (9.1%) 141 (12.7%) 54 (12.8%) 15 (16.5%) 0 (0.0%) 210 (10.6%) Hyperkalemia, n(%) 14 (1.7%) 22 (1.8%) 27 (2.4%) 12 (2.9%) 3 (3.3%) 0 (0.0%) 27 (1.4%) Hypokalemia, n(%) 19 (2.3%) 41 (3.3%) 32 (2.9%) 10 (2.4%) 3 (3.3%) 0 (0.0%) 55 (2.8%) Hyponatremia, n(%) 22 (2.6%) 32 (2.6%) 25 (2.2%) 13 (3.1%) 1 (1.1%) 0 (0.0%) 60 (3.0%) 1,005 681 (81.8%) 909 (81.7%) 318 (75.5%) 55 (60.4%) 4 (57.1%) 1,592 (80.4%) Hyperlipidemia, n(%) (80.5%) 1,115 1,010 706 (84.8%) 370 (87.9%) 72 (79.1%) 5 (71.4%) 1,789 (90.4%) Hypertension , n(%) (89.3%) (90.7%) Microvascular disease, n(%) 301 (36.1%) 547 (43.8%) 471 (42.3%) 186 (44.2%) 45 (49.5%) 2 (28.6%) 807 (40.8%) Myocardial infarction, n(%) 14 (1.7%) 24 (1.9%) 17 (1.5%) 5 (1.2%) 0 (0.0%) 0 (0.0%) 41 (2.1%) Obesity, n(%) 255 (30.6%) 309 (24.7%) 219 (19.7%) 79 (18.8%) 10 (11.0%) 2 (28.6%) 487 (24.6%) Pain disorders, n(%) 552 (66.3%) 852 (68.2%) 774 (69.5%) 285 (67.7%) 59 (64.8%) 5 (71.4%) 1,304 (65.9%) Peripheral vascular disease, 90 (10.8%) 255 (20.4%) 189 (17.0%) 67 (15.9%) 12 (13.2%) 0 (0.0%) 284 (14.3%) n(%) Resistant hypertension, n(%) 104 (12.5%) 219 (17.5%) 253 (22.7%) 95 (22.6%) 24 (26.4%) 0 (0.0%) 334 (16.9%) Respiratory failure, n(%) 20 (2.4%) 19 (1.5%) 18 (1.6%) 10 (2.4%) 0 (0.0%) 0 (0.0%) 38 (1.9%) Sleep apnea, n(%) 126 (15.1%) 140 (11.2%) 141 (12.7%) 53 (12.6%) 7 (7.7%) 1 (14.3%) 234 (11.8%) Stroke, n(%) 23 (2.8%) 58 (4.6%) 57 (5.1%) 18 (4.3%) 5 (5.5%) 0 (0.0%) 71 (3.6%)

Abbreviations: CKD, chronic kidney disease; Dx, diagnosis; IQR, interquartile range; T2D, Type 2 diabetes mellitus; SD, standard deviation.

20 Patients with ESRD, CKD, kidney transplant, dialysis, or other diagnoses which could cause CKD from causes other than T2D during the 365- day baseline period were excluded from Cohort 1. Resistant hypertension is defined as 4 or more unique antihypertensive medication prescription claims within a 30-day period.

21 Table 8. Patient characteristics of patients with T2D and incident CKD, during a 365-day baseline period. Characteristics are stratified by risk categories S-V (Missing stage of Albuminuria)

Risk Strata S Risk Strata U Risk Strata T Risk Strata V (G3A & UACR (G4 & UACR (G3B & UACR missing) (G5 & UACR missing) missing) missing) (N=11,855) (N=130) (N=47,090) (N=1,364) Demographics

Age (years)

-- Mean (SD) 72.10 (12.02) 74.59 (12.88) 75.24 (14.07) 71.05 (14.87) -- Median [IQR] 72 [65, 78] 74 [67, 81] 75 [67, 81] 70 [63, 78] Gender -- Male, n (%) 19,108 (40.6%) 3,881 (32.7%) 403 (29.5%) 65 (50.0%) -- Female, n (%) 27,965 (59.4%) 7,972 (67.2%) 959 (70.3%) 65 (50.0%) -- Missing n (%) 17 (0.0%) 2 (0.0%) 2 (0.1%) 0 (0.0%) Race

-- White, n(%) 29,633 (62.9%) 7,534 (63.6%) 824 (60.4%) 56 (43.1%) -- Asian, n(%) 1,194 (2.5%) 233 (2.0%) 31 (2.3%) 2 (1.5%) -- Black, n(%) 4,933 (10.5%) 1,367 (11.5%) 185 (13.6%) 17 (13.1%) -- Hispanic, n(%) 4,501 (9.6%) 1,084 (9.1%) 124 (9.1%) 35 (26.9%) -- Unknown, n(%) 4,390 (9.3%) 1,061 (8.9%) 125 (9.2%) 10 (7.7%) -- Missing, n(%) 2,439 (5.2%) 576 (4.9%) 75 (5.5%) 10 (7.7%) Region

-- Northeast, n(%) 4,203 (8.9%) 1,085 (9.2%) 144 (10.6%) 8 (6.2%) -- Midwest, n(%) 4,788 (10.2%) 1,394 (11.8%) 147 (10.8%) 11 (8.5%) -- South, n(%) 27,667 (58.8%) 6,873 (58.0%) 785 (57.6%) 60 (46.2%) -- West, n(%) 10,235 (21.7%) 2,446 (20.6%) 283 (20.7%) 51 (39.2%) -- Missing, n(%) 197 (0.4%) 57 (0.5%) 5 (0.4%) 0 (0.0%) Provider Specialty

-- Endocrinologist, n(%) 740 (1.6%) 196 (1.7%) 19 (1.4%) 1 (0.8%) -- Nephrologist, n(%) 150 (0.3%) 68 (0.6%) 20 (1.5%) 2 (1.5%) -- Cardiologist, n(%) 1,230 (2.6%) 377 (3.2%) 59 (4.3%) 5 (3.8%) -- General Practitioner / Internist, n(%) 23,882 (50.7%) 6,378 (53.8%) 763 (55.9%) 48 (36.9%) -- Urologist, n(%) 150 (0.3%) 41 (0.3%) 4 (0.3%) 1 (0.8%) -- Inpatient facility, n(%) 1,070 (2.3%) 321 (2.7%) 39 (2.9%) 5 (3.8%) -- Outpatient facility, n(%) 680 (1.4%) 188 (1.6%) 30 (2.2%) 31 (23.8%) -- Missing, n(%) 26,455 (56.2%) 7,122 (60.1%) 859 (63.0%) 85 (65.4%) Comorbidity score

22 Deyo comorbidity score

-- Mean (SD) 2.33 (1.58) 2.50 (1.65) 2.73 (1.74) 2.52 (1.81) -- Median [IQR] 2 [1, 3] 2 [1, 3] 2 [1, 4] 2 [1, 3] Comorbidities

Angina pectoris, n(%) 12,159 (25.8%) 3,388 (28.6%) 409 (30.0%) 31 (23.8%) Acute coronary syndrome, n(%) 1,319 (2.8%) 370 (3.1%) 59 (4.3%) 2 (1.5%) Anemia, n(%) 9,831 (20.9%) 2,837 (23.9%) 373 (27.3%) 35 (26.9%) Atrial fibrillation, n(%) 5,260 (11.2%) 1,633 (13.8%) 176 (12.9%) 14 (10.8%) Chronic lung/pulmonary disease, n(%) 9,777 (20.8%) 2,672 (22.5%) 314 (23.0%) 21 (16.2%) Coronary artery disease, n(%) 6,519 (13.8%) 1,771 (14.9%) 231 (16.9%) 19 (14.6%) Depression, n(%) 4,959 (10.5%) 1,215 (10.2%) 155 (11.4%) 13 (10.0%) Edema, n(%) 5,276 (11.2%) 1,691 (14.3%) 241 (17.7%) 19 (14.6%) Fatigue & sleep related disorders, n(%) 12,895 (27.4%) 3,361 (28.4%) 377 (27.6%) 32 (24.6%) Heart Failure, n(%) 5,602 (11.9%) 2,042 (17.2%) 295 (21.6%) 20 (15.4%) Hyperkalemia, n(%) 1,079 (2.3%) 302 (2.5%) 43 (3.2%) 6 (4.6%) Hypokalemia, n(%) 1,860 (3.9%) 423 (3.6%) 52 (3.8%) 6 (4.6%) Hyponatremia, n(%) 1,108 (2.4%) 249 (2.1%) 30 (2.2%) 4 (3.1%) Hyperlipidemia, n(%) 39,866 (84.7%) 9,656 (81.5%) 1,040 (76.2%) 95 (73.1%) Hypertension , n(%) 42,654 (90.6%) 10,891 (91.9%) 1,237 (90.7%) 107 (82.3%) Microvascular disease, n(%) 13,760 (29.2%) 3,757 (31.7%) 465 (34.1%) 43 (33.1%) Myocardial infarction, n(%) 916 (1.9%) 270 (2.3%) 39 (2.9%) 1 (0.8%) Obesity, n(%) 8,058 (17.1%) 1,928 (16.3%) 190 (13.9%) 28 (21.5%) Pain disorders, n(%) 33,239 (70.6%) 8,463 (71.4%) 964 (70.7%) 88 (67.7%) Peripheral vascular disease, n(%) 7,329 (15.6%) 2,046 (17.3%) 255 (18.7%) 27 (20.8%) Resistant hypertension, n(%) 7,495 (15.9%) 2,492 (21.0%) 323 (23.7%) 31 (23.8%) Respiratory failure, n(%) 1,025 (2.2%) 325 (2.7%) 41 (3.0%) 4 (3.1%) Sleep apnea, n(%) 5,191 (11.0%) 1,116 (9.4%) 106 (7.8%) 13 (10.0%) Stroke, n(%) 2,192 (4.7%) 649 (5.5%) 81 (5.9%) 6 (4.6%) Abbreviations: CKD, chronic kidney disease; Dx, diagnosis; IQR, interquartile range; T2D, Type 2 diabetes mellitus; SD, standard deviation.

23 Table 9. Annual HCRU outcomes of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data. Results are stratified by relevant comorbidities.

T2D and CKD diagnosis (N = 106,369 ) Anemia No HF during HF during No resistant Resistant No anemia during baseline baseline hypertension during hypertension during during baseline baseline (N=94574) (N=11795) baseline (N=89480) baseline (N=16889) (N=86608) (N=19761) HCRU Measures

Number of inpatient visits -- Mean count per 0.3 0.7 0.3 0.4 0.3 0.5 person per year Number of outpatient visits -- Mean count per 11.9 18.4 12.3 14.1 11.8 16.2 person per year Number of emergency room visits -- Mean count per 0.6 1.3 0.6 0.8 0.6 0.9 person per year Total duration of inpatient stays -- Mean duration per person per year 2.7 7.4 3 4 2.7 5.3 (days) Abbreviations: CKD, chronic kidney disease; HCRU, health care resource utilization; HF, heart failure; T2D, Type 2 diabetes mellitus.

All patients were required to have a minimum of 365 days of baseline enrollment prior to cohort entry. Patients included people aged 18 or older enrolled in the Optum CDM database. Patients with ESRD, CKD, kidney transplant, dialysis, or other diagnoses which could cause CKD from causes other than T2D during the 365- day baseline period were excluded from Cohort 1. Resistant hypertension is defined as 4 or more unique antihypertensive medication prescription claims within a 30-day period.

Table 10. Mean number of inpatient visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results

Mean number of inpatient visits (per Stage of CKD by eGFR classification person per year) Stage 1 Stage 2 Stage 3a Stage 3b Stage 4 Stage 5 (>90 ml/min/ (60-89 ml/min/ (45-59 ml/min/ (30-44 ml/min/ (15-29 ml/min/ (<15 ml/min/ Missing 2 2 2 2 2 2 1.73 ) 1.73 ) 1.73 ) 1.73m ) 1.73m ) 1.73m ) A1 Stage of (<30 0.2 0.3 0.3 0.2 Albuminuria mg/g) A2 (30- 300 0.2 0.2 0.3 0.4 0.5 0.9 0.2 mg/g) A3 (>300 0.3 0.3 0.4 0.5 0.7 1.2 0.3 mg/g) Missing 0.3 0.5 0.7 1.1 Abbreviations: ACR, albumin to creatine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HCRU, health care resource utilization; T2D, type 2 diabetes.

Index date of both cohorts was the next eGFR or UACR test that indicated kidney disease that occurred at least 90 days and at most 365 days after the first test indicating kidney disease. Patients were categorized according to the laboratory value used for cohort entry and the nearest laboratory value of the other test. If there is no other recent laboratory value the result is categorized as missing.

Table 11. Mean number of outpatient visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results.

Mean number of outpatient visits (per Stage of CKD by eGFR classification person per year) Stage 1 Stage 2 Stage 3a Stage 3b Stage 4 Stage 5 (>90 ml/min/ (60-89 ml/min/ (45-59 ml/min/ (30-44 ml/min/ (15-29 ml/min/ (<15 ml/min/ Missing 2) 2 2 2 2 2 1.73m 1.73m ) 1.73m ) 1.73m ) 1.73m ) 1.73m ) Stage of A1 (<30 11.7 13.4 13.1 10.9 Albuminuria mg/g) A2 (30- 10.1 11.1 13 13.9 14.3 26.8 10.5 300 mg/g) A3 (>300 11 12.2 13.4 14.5 17.4 16.4 11.7 mg/g) Missing 13 14.3 17.4 28.7 Abbreviations: ACR, albumin to creatine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HCRU, health care resource utilization; T2D, type 2 diabetes.

Table 12. Mean number of emergency room visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results.

Mean number of emergency room visits Stage of CKD by eGFR classification (per person per year) Stage 2 Stage 3a Stage 3b Stage 4 Stage 1 Stage 5 (60-89 (45-59 (30-44 (15-29 (>90 ml/min/ (<15 ml/min/ Missing ml/min/ ml/min/ ml/min/ ml/min/ 1.73m2) 1.73m2) 1.73m2) 1.73m2 1.73m2) 1.73m2) Stage of A1 (<30 0.5 0.7 0.6 1.2 Albuminuria mg/g) A2 (30-300 0.5 0.5 0.6 0.8 1 1.2 0.5 mg/g) A3 (>300 0.7 0.7 0.8 1 1.5 1.7 0.7 mg/g) Missing 0.7 0.9 1.2 1.3 Abbreviations: ACR, albumin to creatine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HCRU, health care resource utilization; T2D, type 2 diabetes.

Table 13. Mean number of unique medications filled per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results.

Mean number of unique medications filled (per Stage of CKD by eGFR classification person per year)

Stage 2 Stage 3a Stage 3b Stage 4 Stage 1 Stage 5 (60-89 (45-59 (30-44 (15-29 (>90 ml/min/ (<15 ml/min/ Missing 2 ml/min/ ml/min/ ml/min/ ml/min/ 2 1.73m ) 2 2 2 2 1.73m ) 1.73m ) 1.73m ) 1.73m ) 1.73m )

Stage of A1 (<30 12 13.4 13.7 9.7 Albuminuria mg/g)

A2 (30-300 12.4 12.4 12.9 13.8 14.2 11.5 12.3 mg/g)

A3 (>300 13.7 14 13.8 14.3 15.8 16.2 13.3 mg/g)

12.6 13.8 14.9 13.9 Missing Abbreviations: ACR, albumin to creatine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HCRU, health care resource utilization; T2D, type 2 diabetes. Index date of both cohorts was the next eGFR or UACR test that indicated kidney disease that occurred at least 90 days and at most 365 days after the first test indicating kidney disease. Patients were categorized according to the laboratory value used for cohort entry and the nearest laboratory value of the other test. If there is no other recent laboratory value the result is categorized as missing.

Table 14. Mean duration (days) of all inpatient visits per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data, categorized by eGFR and ACR laboratory results.

29 Mean duration of all inpatient visits (per person Stage of CKD by eGFR classification per year) Stage 2 Stage 3a Stage 3b Stage 4 Stage 1 Stage 5 (60-89 (45-59 (30-44 (15-29 (>90 ml/min/ (<15 ml/min/ Missing ml/min/ ml/min/ ml/min/ ml/min/ 1.73m2) 1.73m2) 1.73m2) 1.73m2) 1.73m2) 1.73m2) Stage of A1 (<30 1.5 2.6 2 0.7 Albuminuria mg/g) A2 (30-300 1.4 2.2 3.1 4.1 3.7 9.2 1.9 mg/g) A3 (>300 2.1 3.3 3.6 5.8 8.8 10.9 3.4 mg/g) Missing 3.3 5.6 9.1 9.1 Abbreviations: ACR, albumin to creatine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HCRU, health care resource utilization; T2D, type 2 diabetes.

Table 15. Annual costs of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, 365 days of follow up, or the end of data. Results are stratified by relevant comorbidities.

T2D and CKD diagnosis (N =106,369 ) Resistant No HF during HF during No resistant No anemia Anemia during hypertension baseline baseline hypertension during during baseline baseline during baseline (N=94,574) (N=11,795) baseline (N=89,480) (N=86,608) (N=19,761) (N=16,889) Cost Measures Total cost -- Mean cost per 21,844 41,952 23,230 28,266 21,971 33,127 person per year Inpatient cost

-- Mean cost per 6,139 16,116 6,886 9,008 6,292 11,338 person per year Outpatient care cost

-- Mean cost per 4,698 8,281 4,946 5,834 4,724 6,693 person per year Emergency room costs -- Mean cost per 947 2,108 1,040 1,249 979 1,490 person per year Pharmacy costs

-- Mean cost per 4,546 5,706 4,457 5,815 4,499 5,438 person per year Abbreviations: CKD, chronic kidney disease; HF, heart failure; T2D, Type 2 diabetes mellitus

Table 16. Mean total cost per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results.

Mean total cost (USD Stage of CKD by eGFR classification per person per year) Stage 1 Stage 2 Stage 3a Stage 3b Stage 4 Stage 5 (>90 (60-89 (45-59 (30-44 (15-29 (<15 ml/min/ Missing ml/min/ ml/min/ ml/min/ ml/min/ ml/min/ 2 1.73m ) 1.73m2) 1.73m2) 1.73m2) 1.73m2) 1.73m2) Stage of A1 (<30 18,756 22,037 20,407 17,432 Albuminuria mg/g) A2 (30- 18,529 19,902 24,283 26,871 31,085 110,210 18,386 300 mg/g) A3 (>300 22,998 25,487 29,562 33,263 45,428 34,755 22,630 mg/g) Missing 24,726 30,993 44,491 83,940

Abbreviations: ACR, albumin to creatine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; T2D, type 2 diabetes .

Table 17. Mean inpatient costs per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results

Mean inpatient costs (USD per person per Stage of CKD by eGFR classification year) Stage 1 Stage 2 Stage 3a Stage 3b Stage 4 Stage 5 (>90 (60-89 ml/min/ (45-59 ml/min/ (30-44 ml/min/ (15-29 ml/min/ (<15 ml/min/ Missing ml/min/ 1.73m2) 1.73m2) 1.73m2) 1.73m2) 1.73m2) 1.73m2) Stage of A1 (<30 3,979 5,828 4,079 1,659 Albuminuria mg/g) A2 (30-300 4,068 5,254 6,807 8,536 10,386 30,082 4,624 mg/g) A3 (>300 5,741 9,027 10,052 12,052 18,376 20,278 6,913 mg/g) Missing 7,485 11,764 19,272 20,495

Abbreviations: ACR, albumin to creatine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; T2D, type 2 diabetes;

Table 18. Mean outpatient costs per person per year of patients with T2D and incident CKD diagnosis followed until the occurrence of an outcome, death, discontinued enrollment, or 365 days of follow up, categorized by eGFR and ACR laboratory results

Mean outpatient costs (USD per person per Stage of CKD by eGFR classification year) Stage 1 Stage 2 Stage 3a Stage 3b Stage 4 Stage 5 (>90 ml/min/ (60-89 ml/min/ (45-59 ml/min/ (30-44 ml/min/ (15-29 ml/min/ (<15 ml/min/ Missing

1.73m2) 1.73m2) 1.73m2) 1.73m2) 1.73m2) 1.73m2) Stage of A1 (<30 4,344 5,384 5,232 2,116 Albuminuria mg/g) A2 (30-300 3,900 4,240 5,428 5,796 6,779 35,064 3,563 mg/g) A3 (>300 4,897 4,873 5,437 7,480 8,257 4,696 4,095 mg/g) Missing 5,317 5,846 9,575 40,409