Death and cardiovascular events after bacteriuria among adult women with chronic kidney disease

Figures & data

Figure 1 Survival analysis incorporating time-dependent and cumulative characteristics of the exposure (bacteriuria) and treatment among females with chronic kidney disease. The figure shows four hypothetical cohort members (A–D) with various cohort entry dates and variable numbers of infections and antibiotic treatment courses during the study period.

Notes: Survival analyses in this study treat the exposure dynamically, by incorporating both the timing and cumulative burden of infectious events (the first number in parentheses), as well as the cumulative treatment status (second number in each parenthesis) in multiple-determinant models. This is in contrast to more traditional “fixed” models in which exposure status is assigned based upon a single event at one point in time. With a dynamic model, the exposure status for each cohort member is fully characterized and updated over time.¹³

Table 1 Baseline characteristics of adult females with CKD, by outpatient bacteriuria and treatment status (2004–2009)

	Group 1 (n = 5796)	Group 2 (n = 451)	Group 3 (n = 428)	Group 4 (n = 132)	P-value
Age, years median (IQR)	71 (64, 77)	72 (63, 78)	72 (64, 77)	72 (63.5, 77)	0.63
White race, n (%)	5632 (97.2)	442 (98.0)	416 (97.2)	125 (94.7)	0.25
History of smoking, n (%)	1454 (25.1)	110 (24.4)	97 (22.7)	40 (30.0)	0.34
Hospitalization 6 months prior to index date, n (%)	147 (2.5)	8 (1.8)	31 (7.2)	7 (5.3)	<0.001
Charlson comorbidity score, n (%)					0.02
0	3049 (52.6)	198 (43.9)	209 (48.8)	70 (53.0)
1	1923 (33.2)	168 (37.3)	141 (32.9)	41 (31.1)
2	577 (10.0)	63 (14.0)	52 (12.2)	14 (10.6)
3+	247 (4.3)	22 (4.9)	26 (6.1)	7 (5.3)
Hypertension, n (%)	3429 (59.2)	259 (57.4)	243 (56.8)	69 (52.3)	0.3
Hyperlipidemia, n (%)	2568 (44.3)	197 (43.7)	159 (37.2)	50 (37.9)	0.02
Diabetes mellitus, n (%)	2252 (38.9)	197 (43.7)	192 (44.9)	50 (37.9)	0.02
Peripheral arterial disease, n (%)	131 (2.3)	14 (3.1)	15 (3.5)	1 (0.8)	0.16
Chronic obstructive pulmonary disease	473 (8.2)	45 (10.0)	33 (7.7)	8 (6.1)	0.42
History of cancer	400 (6.9)	36 (8.0)	38 (8.9)	14 (10.6)	0.15
Coronary artery disease	681 (11.8)	67 (14.9)	50 (11.7)	21 (15.9)	0.12
Dementia	68 (1.2)	9 (2.0)	9 (2.1)	2 (1.5)	0.2
Connective tissue disease	187 (3.2)	25 (5.5)	21 (4.9)	7 (5.3)	0.01
eGFR, mL/minute/1.73 m^2; median (IQR)	52.6 (44.6, 58.0)	53.0 (42.5, 59.7)	52.9 (42.4, 59.7)	52.1 (42.4, 61.0)	0.94
Proteinuria, n (%)					<0.001
Positive	955 (16.5)	94 (20.8)	80 (18.7)	22 (16.8)
Negative	1724 (29.7)	160 (35.5)	155 (36.2)	63 (47.7)
Test not ordered	3117 (53.8)	197 (43.7)	193 (45.1)	47 (35.6)
Serum albumin, g/dL; median (IQR)	4.2 (4.0, 4.4) n = 3674	4.2 (4.0, 4.4) n = 300	4.1 (3.9, 4.3) n = 271	4.1 (3.9, 4.3) n = 89	<0.001
Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, n (%)	2428 (41.9)	174 (38.6)	181 (42.3)	40 (30.3)	0.03
Beta blocker, n (%)	2448 (42.2)	197 (43.7)	169 (39.5)	62 (47.0)	0.40
HMG Co-A reductase inhibitors, n (%)	2585 (44.6)	189 (41.9)	182 (42.5)	45 (34.1)	0.06

Notes: Group 1: no urine culture order, or all urine culture orders resulted as “no growth”; Group 2: one or more positive urine cultures resulted, with an antibiotic prescription ordered within 90 days of each positive urine culture order date; Group 3: one or more positive urine cultures resulted, without an antibiotic prescription ordered within 90 days of each positive urine culture order date; Group 4: two or more positive urine cultures, with at least one treated and one not treated (with antibiotics) within 90 days of the urine culture order date; to convert serum albumin in g/dL to g/L, multiply by 10.

Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HMG Co-A, 3-hydroxy-3-methylglutaryl-coenzyme A; IQR, interquartile range.

Table 2 Crude rates (death and cardiovascular events) among adult females with CKD, by bacteriuria and treatment status

	Group 1 (n = 5796)	Group 2 (n = 451)	Group 3 (n = 428)	Group 4 (n = 132)
Deaths
Follow-up, median (IQR)	5.1 (3.3, 5.9)	5.3 (4.0, 6.1)	5.3 (3.9, 6.1)	5.6 (4.1, 6.2)
Person-years	25968.2	2198.7	2045.6	677.9
Events, n	635	50	81	18
Incidence rate (95% CI)^a	24.5 (22.6–26.4)	22.7 (17.2–30.0)	39.6 (31.8–49.2)	26.6 (16.7–42.1)
Composite cardiovascular eventb
Follow-up, median (IQR)	5.0 (3.0, 5.8)	5.0 (3.3, 6.0)	4.9 (3.0, 5.9)	5.4 (3.6, 6.2)
Person-years	25242.0	2049.9	1858.6	624.0
Events, n	366	74	81	26
Incidence rate^a	14.5 (13.1–16.1)	36.1 (28.7–45.3)	43.6 (35.1–54.2)	41.7 (28.4–61.2)

Notes: Group 1: no urine culture order, or all urine culture orders resulted in “no growth;” Group 2: one or more positive urine cultures resulted, with an antibiotic prescription ordered within 90 days of each positive urine culture order date; Group 3: one or more positive urine cultures resulted, without an antibiotic prescription ordered within 90 days of each positive urine culture order date; Group 4: two or more positive urine cultures, with at least one treated and one not treated (with antibiotics) within 90 days of the urine culture order date; ^aincidence rate: number of events per 1000 person-years;

b composite of hospitalization (primary discharge diagnosis) for myocardial infarction, congestive heart failure, cerebrovascular accident, or transient ischemic attack.

Abbreviations: CI, confidence interval; CKD, chronic kidney disease; IQR, interquartile range.

Table 3 Cox proportional hazard model for mortality and cardiovascular events among adult females with CKD, by treatment status after bacteriuria

	HR (95% CI)	P-value
Deaths
Unadjusted
Per cumulative treated infection	1.26 (1.08–1.47)	<0.001
Per cumulative untreated infection	1.86 (1.62–2.13)	0.004
Adjusteda
Per cumulative treated infection	0.96 (0.81–1.14)	0.62
Per cumulative untreated infection	1.56 (1.35–1.81)	<0.001
Composite cardiovascular eventb
Unadjusted
Per cumulative treated infection	1.34 (1.11–1.62)	<0.001
Per cumulative untreated infection	1.83 (1.52–2.19)	0.003
Adjusteda
Per cumulative treated infection	0.85 (0.67–1.09)	0.19
Per cumulative untreated infection	1.32 (1.05–1.65)	0.02

Notes:

a Adjusted for age at entry, race, smoking status, hospitalization 6 months prior to the index date, hospitalization during follow-up, CKD stage at entry, Charlson score, hyperlipidemia, diabetes, hypertension, peripheral arterial disease, chronic obstructive pulmonary disease, connective tissue disease, a history of cancer, coronary artery disease, proteinuria, and serum albumin;

b composite of hospitalization (primary discharge diagnosis) for myocardial infarction, congestive heart failure, cerebrovascular accident, or transient ischemic attack.

Abbreviations: CI, confidence interval; CKD, chronic kidney disease; HR, hazard ratio.

StrickerBHStijnenTAnalysis of individual drug use as a time-varying determinant of exposure in prospective population-based cohort studiesEur J Epidemiol201025424525120358262

 PubMed Web of Science ®Google Scholar