Cholesterol and Incident CKD Among Adults With Diabetes

In This Article

Abstract and Introduction

Abstract

Context: The relative importance of the control of different metabolic risk factors for the prevention of chronic kidney disease among patients with diabetes in real life conditions is insufficiently understood.

Objective: We evaluated the effect of the achievement of glycated hemoglobin A_1c (HbA_1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDLc) or non–high-density lipoprotein cholesterol (non-HDLc) goals (ABC goals) on the development of incident chronic kidney disease (iCKD) among patients with diabetes.

Methods: In a nationwide registry of all individuals diagnosed with diabetes assisted by the health system in Colombia, we analyzed the association between baseline or sustained goal achievement and development of iCKD over a 4-year follow-up. iCKD was defined as a new occurrence of an estimated glomerular filtration rate less than 60 mL/min/1.73 m², hemodialysis, peritoneal dialysis, or kidney transplant.

Results: The study included 998 790 adults with diabetes (56% female, mean age 59). There were 125 626 cases of iCKD. After adjustment for multiple confounders, a baseline SBP less than 130 mm Hg (odds ratio [OR] 0.79 [0.78–0.80]) and a baseline HbA_1c less than 7.0% (OR 0.86 [0.85–0.87]) were negatively associated with iCKD. Sustained achievement showed stronger negative associations with iCKD than just baseline achievement. Considering each goal separately, sustained non-HDLc less than 130 mg/dL had the strongest negative association with iCKD (OR 0.67 [0.65–0.69]). Patients who maintained the triple ABC goal over the entire follow-up had 32% (29–34) lower odds of developing CKD, 38% (34–42) if they additionally kept a normal body mass index (BMI). Sustained ABC control including a normal BMI was more strongly associated with a lower incidence of CKD in patients of Black race (OR 0.72 vs 0.89; P for interaction = .002).

Conclusion: At the country level, sustained achievement of ABC goals and most especially non-HDLc were associated with substantial reductions in iCKD.

Introduction

Chronic kidney disease (CKD) is a major health issue worldwide. Progressing CKD leads not only to end-stage renal disease (ESRD) but also to multiple adverse clinical outcomes, including cardiovascular disease, death, and disability.^[1] In sharp contrast to other noncommunicable diseases, CKD prevalence seems to be increasing over time. Recent studies from the Global Burden of Disease Collaboration estimate the global prevalence of CKD at 9.1%, an increase of almost 30% over the last 30 years.^[2] Low- or middle-income countries bear 80% of the disease burden from CKD.^[3]

Diabetes is currently the second leading cause of CKD and the top cause of ESRD.^[4] In 2019, type 2 diabetes was estimated to have caused 2.5 million incident CKD (iCKD) cases and more than 400 000 deaths. The risk of developing diabetic nephropathy does not follow closely the degree of hyperglycemia, especially among patients with type 1 diabetes,^[5] indicating that other disturbances must act synergistically with hyperglycemia to promote the development of glomerular and tubular changes that characterize CKD. These alterations include excess plasma free fatty acids, oxidative stress, vascular shear stress induced by transmitted systemic hypertension, impaired autoregulation, hyperperfusion or hypoperfusion, and activation of the renin-angiotensin-aldosterone system.^[6]

This multifactorial pathogenesis suggests that successful and continued control of the main risk factors may substantially affect the appearance of new CKD in people with diabetes. The positive and long-lasting effect of early glycemic control on the development of CKD has been proven for patients with type 1 diabetes in the Diabetes Control and Complications Trial—Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) study,^[7] and for patients with type 2 diabetes in the United Kingdom Prospective Diabetes Study (UKPDS).^[8] However, the associations between tight blood pressure or blood lipids control and the risk of iCKD have not been equally robust. This may be due to a host of factors, but it is important to note that treatment goals, pharmacological agents, and guideline adoption have all changed notably since the publication of these milestone trials.

With this background, we aimed to evaluate the association between the achievement of glycated hemoglobin A_1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDLc) or non–high-density lipoprotein cholesterol (non-HDLc) goals, the so-called ABC goals of diabetes, and the development of iCKD in a nationwide sample of nearly all patients with diabetes in the Colombian Health System. We also explored the differential effect of achieving these goals only at baseline vs sustaining them over time, and whether these associations differed in subgroups defined by race or body mass index (BMI).

Table 1. Baseline characteristics of study participants
	Men (n = 433 219)	Women (n = 565 571)	Total (n = 998 790)
Age, y	59.0 (13.1)	59.8 (13.3)	59.5 (13.2)
Age group, %
< 40	7.4	6.9	7.1
40–49	15.1	13.4	14.1
50–59	27.9	28.8	28.4
60–69	28.0	27.6	27.8
70–79	16.0	16.6	16.3
≥ 80	5.6	6.8	6.3
Health insurance, %
Third-party	73.2	63.2	67.5
State	23.3	35.9	31.3
Special/Exceptional	1.5	0.9	1.2
Race, %
Black	6.6	7.6	7.2
Other	93.4	92.4	92.8
n for BMI	432 204	563 774	995 978
BMI	27.8 (4.8)	28.6 (5.6)	28.2 (5.3)
BMI category, %
Normal weight	20.6	20.2	20.4
Overweight	32.3	28.1	29.9
Obesity	47.2	51.7	49.7
n for BP	428 210	560 189	988 399
SBP, mm Hg	123.5 (13.6)	123.9 (13.9)	123.7 (13.7)
DBP, mm Hg	76.8 (8.7)	76.6 (8.7)	76.7 (8.7)
n for HbA_1c	367 129	467 269	834 398
HbA_1c, %	7.59 (2.2)	7.46 (2.1)	7.52 (2.1)
HbA_1c, mmol/mol	59	58	59
n for blood lipids	369 658	496 385	866 043
Non-HDLc, mg/dL	140.0 (45.6)	146.3 (46.1)	143.6 (46.0)
LDLc, mg/dL	106.2 (38.0)	113.0 (39.5)	110.1 (39.0)
CKD stage, %
1	65.7	60.8	63.0
2	34.3	39.2	37.0
Urinary albumin excretion, %
< 30 mg/g or < 20 mg/L	72.24	78.72	75.85
30–299 mg/g or 20–199 mg/L	23.24	18.12	20.38
≥ 300 mg/g or ≥ 200 mg/L	4.52	3.16	3.76
Hypertension, %	60.9	68.0	64.9

Data are means (SD) unless indicated otherwise. CKD stages were defined according to the KDIGO classification.
Abbreviations: BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; DBP, diastolic blood pressure; HbA_1c, glycated hemoglobin A_1c; KDIGO, Kidney Disease: Improving Global Outcomes; LDLc, low-density lipoprotein cholesterol; non-HDLc, non–high-density lipoprotein cholesterol; SBP, systolic blood pressure.

Table 2. Association between measures of diabetes control at baseline and incident chronic kidney disease
Measure of interest	Unadjusted OR	Adjusted OR	n for adjusted model
SBP < 130 mm Hg at baseline^a	0.74 (0.73–0.75)	0.79 (0.78–0.80)	755 844
HbA_1c < 7.0% at baseline^b	1.00 (0.98–1.01)	0.86 (0.85–0.87)	758 088
Non-HDLc < 130 mg/dL^c	1.18 (1.17–1.20)	1.05 (1.04–1.07)	758 285
LDLc < 100 mg/dL^c	1.17 (1.15–1.18)	1.09 (1.07–1.10)	752 056
Joint SBP, HbA_1c, and LDLc goal^d	1.03 (1.01–1.05)	0.94 (0.92–0.95)	719 010
Joint SBP, HbA_1c, LDLc, and BMI goal^e	1.06 (1.03–1.09)	0.88 (0.86–0.91)	719 010

Abbreviations: BMI, body mass index; HbA_1c, glycated hemoglobin A_1c; LDLc, low-density lipoprotein cholesterol; non-HDLc, non–high-density lipoprotein cholesterol; OR, odds ratio; SBP, systolic blood pressure.
^aAdjusted for sex, age, race (Black vs other), insurance type, BMI, baseline HbA_1c, and baseline non-HDL cholesterol.
^bAdjusted for sex, age, race (Black vs other), insurance type, BMI, baseline non-HDL cholesterol, and hypertension status.
^cAdjusted for sex, age, race (Black vs other), insurance type, BMI, baseline HbA_1c, and hypertension status.
^dAdjusted for sex, age, race (Black vs other), insurance type, and BMI.
^eAdjusted for sex, age, race (Black vs other), and insurance type.

Table 3. Association between measures of diabetes control at baseline and incident chronic kidney disease, by race
Measure of interest	Race				P for interaction
Measure of interest	Black		Other
Goal	Adjusted OR (95% CI)	n for model	Adjusted OR (95% CI)	n for model
SBP < 130 mm Hg^a	0.75 (0.70–0.81)	54 251	0.79 (0.78–0.81)	701 583	.15
HbA_1c < 7.0%^b	0.75 (0.70–0.79)	54 291	0.86 (0.85–0.88)	703 786	< .001
Non-HDLc < 130 mg/dL^c	1.18 (1.11–1.25)	54 291	1.04 (1.03–1.06)	703 983	< .001
LDLc < 100 mg/dL^c	1.15 (1.08–1.21)	54 854	1.08 (1.07–1.10)	697 191	.022
Joint SBP, HbA_1c, and LDLc goal^d	0.87 (0.81–0.94)	52 273	0.94 (0.92–0.96)	666 727	.050
Joint SBP, HbA_1c, LDLc, and BMI goal^e	0.72 (0.64–0.82)	52 273	0.89 (0.87–0.92)	666 727	.002

Abbreviations: BMI, body mass index; HbA_1c, glycated hemoglobin A_1c; LDLc, low-density lipoprotein cholesterol; non-HDLc, non–high-density lipoprotein cholesterol; OR, odds ratio; SBP, systolic blood pressure.
^aAdjusted for sex, age, insurance type, BMI, baseline HbA_1c, and baseline non-HDL cholesterol.
^bAdjusted for sex, age, insurance type, BMI, baseline non-HDL cholesterol, and hypertension status.
^cAdjusted for sex, age, insurance type, BMI, baseline HbA_1c, and hypertension status.
^dAdjusted for sex, age, insurance type, and BMI.
^eAdjusted for sex, age, and insurance type.

Table 4. Association between measures of diabetes control at baseline and incident chronic kidney disease, by body mass index category
Goal	BMI category						P for interaction
	Normal weight		Overweight		Obesity
	aOR (95% CI)	n for model	aOR (95% CI)	n for model	aOR (95% CI)	n for model
SBP < 130 mm Hg^a	0.80 (0.77–0.83)	155 901	0.82 (0.80–0.85)	246 096	0.76 (0.74–0.78)	353 847	.07
HbA_1c < 7.0%^b	0.84 (0.82–0.86)	156 668	0.88 (0.86–0.90)	246 677	0.86 (0.84–0.88)	354 743	.001
Non-HDLc < 130 mg/dL^c	1.02 (0.99–1.05)	156 729	1.04 (1.02–1.07)	246 727	1.08 (1.05–1.10)	354 829	< .001
LDLc < 100 mg/dL^d	1.04 (1.02–1.07)	154 138	1.09 (1.07–1.12)	241 114	1.10 (1.08–1.13)	356 804	< .001
Joint SBP, HbA_1c, and LDLc goal^e	0.89 (0.86–0.92)	146 829	0.97 (0.94–0.99)	231 054	0.94 (0.92–0.97)	341 127	.001

Abbreviations: aOR, adjusted odds ratio; BMI, body mass index; HbA_1c, glycated hemoglobin A_1c; LDLc, low-density lipoprotein cholesterol; non-HDLc, non–high-density lipoprotein cholesterol; SBP, systolic blood pressure.
^aAdjusted for sex, age, race (Black vs other), insurance type, baseline HbA_1c, and baseline non-HDL cholesterol.
^bAdjusted for sex, age, race (Black vs other), insurance type, baseline non-HDL cholesterol, and hypertension status.
^cAdjusted for sex, age, race (Black vs other), insurance type, baseline HbA_1c, and hypertension status.
^dAdjusted for sex, age, race (Black vs other) and insurance type.

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Strong Negative Association of Non-HDL Cholesterol Goal Achievement With Incident CKD Among Adults With Diabetes

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