Factors Associated With Proteinuria Assessment After Acute Kidney Injury Among US Veterans

To the Editor:

Acute kidney injury (AKI) is a common complication during hospitalization and is associated with an increased risk of chronic kidney disease (CKD) and new or worsening proteinuria.^1,2 Assessment of proteinuria after AKI provides prognostic information that helps risk-stratify patients for progressive CKD³ and identifies patients who may derive the greatest benefit from kidney-protective therapies, such as renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. We sought to characterize predictors of proteinuria testing within a year after AKI. Despite guidelines recommending post-AKI proteinuria assessment, only 6%-28% of AKI survivors have this checked at 3 months after discharge.4, 5, 6 Understanding of factors associated with post-AKI proteinuria assessment can inform implementation efforts to improve this metric.

We identified a retrospective cohort of AKI survivors within the Veterans Health Administration (VHA). The cohort included patients with established primary care within VHA who had AKI during a hospitalization from January 1, 2017 to October 31, 2023 and survived at least 1 year after hospital discharge (Item S1). Exclusion criteria included age <18 years or >85 years on date of AKI onset, baseline estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m²,⁷ dialysis before or within a year after hospitalization, and kidney transplant at any time though 1 year after index hospitalization. Because of uncertainty about interventions for proteinuria in stage 5 CKD, we also excluded eGFR <15 mL/min/1.73m² at hospital discharge. The outcome was spot proteinuria quantification (urine total protein- or albumin-creatinine ratio) within 1 year of discharge. To best capture laboratory orders done for post-AKI care, we did not include urine dipstick, which may be ordered for other indications. We used a multivariable logistic regression model predicting proteinuria assessment with 18 covariates (Table 1), performed in R version 4.4.1 (R Foundation). We determined the proportions of patients with proteinuria assessments among those who saw a nephrologist, cardiologist, endocrinologist, or primary care physician in the year after discharge.

Table 1.

Baseline Characteristics of Cohort

Characteristic	All N = 109,335	No proteinuria check n = 71,034	Proteinuria check n = 38,301
Demographicsa
Age (y), mean ± SD	66.8 ± 10.3	66.4 ± 10.8	67.6 ± 9.4
Male sex, n (%)	102,732 (94.0)	66,459 (93.6)	36,273 (94.7)
Race
Black, n (%)	27,811 (25.4)	18,223 (25.7)	9,588 (25.0)
Other, n (%)	9,852 (9.0)	6,315 (8.9)	3,537 (9.2)
White, n (%)	71,672 (65.6)	46,496 (65.5)	25,176 (65.7)
Hispanic ethnicity, n (%)	6,995 (6.4)	4,275 (6.0)	2,720 (7.1)
Baseline conditions and kidney health
Baseline proteinuria, KDIGOb, n (%)
0	33,642 (30.8)	19,327 (27.2)	14,315 (37.4)
1	18,674 (17.1)	9,140 (12.9)	9,534 (24.9)
2	9,207 (8.4)	3,675 (5.2)	5,532 (14.4)
Missing	47,812 (43.7)	38,892 (54.8)	8,920 (23.3)
Baseline CKD stage, n (%)
eGFR ≥60 mL/min/1.73m2	85,012 (77.8)	58,893 (82.9)	26,119 (68.2)
Stage 3a, eGFR 45-59 mL/min/1.73m2	14,980 (13.7)	8,210 (11.6)	6,770 (17.7)
Stage 3b, eGFR 30-44 mL/min/1.73m2	7,640 (7.0)	3,325 (4.7)	4,315 (11.3)
Stage 4, eGFR 15-29 mL/min/1.73m2	1,703 (1.6)	606 (0.9)	1,097 (2.9)
Outpatient eGFR decline ≥30% in 5 years prior to AKIc, n (%)	9,064 (8.3)	4,254 (6.0)	4,810 (12.6)
Baseline diabetes status, n (%)
No evidence of diabetes	44,729 (40.9)	36,395 (51.2)	8,334 (21.8)
Diabetes codes present, A1c missing	54 (0)	45 (0.1)	9 (0)
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c < 6%d	11,656 (10.7)	7,882 (11.1)	3,774 (9.9)
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c 6%-6.4%d	11,093 (10.1)	6,497 (9.1)	4,596 (12.0)
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c 6.5%-7.9%d	22,844 (20.9)	11,111 (15.6)	11,733 (30.6)
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c ≥8%d	18,959 (17.3)	9,104 (12.8)	9,855 (25.7)
Baseline heart failure, n (%)	37,504 (34.3)	22,704 (32.0)	14,800 (38.6)
Baseline CAD, n (%)	50,121 (45.8)	30,686 (43.2)	19,435 (50.7)
Baseline PVD, n (%)	24,923 (22.8)	15,057 (21.2)	9,866 (25.8)
Baseline prior stroke, n (%)	16,630 (15.2)	10,842 (15.3)	5,788 (15.1)
Baseline hypertension, n (%)	91,124 (83.3)	57,067 (80.3)	34,057 (88.9)
Baseline prior or active cancer, n (%)	45,511 (41.6)	29,374 (41.4)	16,137 (42.1)
SGLT2i use before AKIe, n (%)	5,016 (4.6)	2,204 (3.1)	2,812 (7.3)
ACEi/ARB use before AKIe, n (%)	60,440 (55.3)	35,712 (50.3)	24,728 (64.6)
AKI severity and discharge eGFR
AKI maximum stage, n (%)
1, serum creatinine 150%-199% of baseline	73,523 (67.2)	47,908 (67.4)	25,615 (66.9)
2, serum creatinine 200%-299% of baseline	23,924 (21.9)	15,351 (21.6)	8,573 (22.4)
3, serum creatinine ≥300% of baseline or dialysis-related billing codes	11,888 (10.9)	7,775 (10.9)	4,113 (10.7)
Discharge eGFR, n (%)
eGFR ≥60 mL/min/1.73m2	60,884 (55.7)	43,736 (61.6)	17,148 (44.8)
eGFR 45-59 mL/min/1.73m2	21,741 (19.9)	13,843 (19.5)	7,898 (20.6)
eGFR 30-44 mL/min/1.73m2	17,351 (15.9)	9,403 (13.2)	7,948 (20.8)
eGFR 15-29 mL/min/1.73m2	9,359 (8.6)	4,052 (5.7)	5,307 (13.9)

Abbreviations: AKI, acute kidney injury; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CAD, coronary artery disease; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; PVD, peripheral vascular disease; SD, standard deviation; SGLT2i, sodium-glucose cotransporter-2 inhibitor.

^aDemographics defined as reported in the electronic health records, including Other race(s) if multiple races listed or if neither Black nor White race.

^bProteinuria scale derived from KDIGO scale. 0: urine albumin-creatinine ratio <30 mg/g or protein-creatinine ratio <150 mg/g; 1: urine albumin-creatinine ratio 30-300 mg/g or protein-creatinine ratio 150-500 mg/g; 2: urine albumin-creatinine ratio >300 mg/g or protein-creatinine ratio >500 mg/g.

^cBaseline CKD progression was defined by dividing the baseline eGFR by the mean of the 3 oldest eGFR values from 2-5 years before the index hospitalization.

^dBaseline hemoglobin A1c defined by the mean of the 3 most recent A1c measurements before the index hospitalization.

^eMedication use before AKI defined in the 6 months preceding the index hospitalization.

We identified 109,335 patients meeting eligibility criteria. Quantified proteinuria was assessed after AKI in 35% (n = 38,301) of patients. Although not the study outcome, 37% (n = 40,536) of eligible patients had positive protein on urinalysis in the year after AKI. Among those who saw a nephrologist within VHA during the year after discharge (n = 18,375, 17% of cohort), 68% had proteinuria assessed; among those who saw a cardiologist (n = 44,087, 40% of cohort), endocrinologist (n = 15,779, 14% of cohort), or primary care (n = 105,488, 96% of cohort), 41%, 55%, and 36% had proteinuria assessed after AKI, respectively. Factors associated with higher odds of proteinuria assessment included prescription of sodium-glucose cotransporter-2 inhibitors or renin-angiotensin-aldosterone system inhibitors before hospitalization, male sex as recorded in VA electronic health records, elevated baseline proteinuria, reduced baseline and discharge eGFR levels, and diabetes (Table 2). Factors associated with lower odds of proteinuria assessment included increased age, Black race, no prior proteinuria assessment, heart failure, peripheral vascular disease, and stroke. When date was added to the model, odds of testing was associated with an increase of 5% per year (odds ratio 1.05, P < 0.0001).

Table 2.

Factors Associated With Proteinuria Assessment

Characteristic	Odds of proteinuria assessment (OR)	95% CI
Demographicsa
Age (y), mean ± SD	0.92b	0.91-0.94
Male sex, n (%)	1.08	1.02-1.15
Race
Black, n (%)	0.90	0.87-0.93
Other, n (%)	0.99	0.94-1.04
White, n (%)	Ref.
Hispanic ethnicity, n (%)	1.02	0.96-1.07
Baseline conditions and kidney health
Baseline proteinuria, KDIGOc, n (%)
0	Ref.
1	1.10	1.06-1.15
2	1.24	1.18-1.30
Missing	0.39	0.38-0.40
Baseline CKD stage, n (%)
eGFR ≥60 mL/min/1.73m2	Ref.
Stage 3a, eGFR 45-59 mL/min/1.73m2	1.45	1.10-1.20
Stage 3b, eGFR 30-44 mL/min/1.73m2	1.30	1.22-1.39
Stage 4, eGFR 15-29 mL/min/1.73m2	1.46	1.29-1.65
Outpatient eGFR decline ≥30% in 5 years prior to AKId, n (%)	1.12	1.06-1.18
Baseline diabetes status, n (%)
No evidence of diabetes	Ref.
Diabetes codes present, A1c missing	1.16	0.56-2.41
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c <6%e	1.62	1.54-1.70
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c 6%-6.4%e	2.22	2.12-2.33
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c 6.5%-7.9%e	2.93	2.82-3.05
Diabetes codes present or pre-AKI A1c ever ≥6.5%, baseline A1c ≥8%e	2.95	2.83-3.08
Baseline heart failure, n (%)	0.95	0.92-0.98
Baseline CAD, n (%)	0.99	0.96-1.02
Baseline PVD, n (%)	0.93	0.90-0.96
Baseline prior stroke, n (%)	0.80	0.77-0.83
Baseline hypertension, n (%)	1.03	0.98-1.07
Baseline prior or active cancer, n (%)	1.01	0.98-1.04
SGLT2i use before AKIf, n (%)	1.37	1.28-1.45
ACEi/ARB use before AKIf, n (%)	1.25	1.21-1.29
AKI severity and discharge eGFR
AKI maximum stage, n (%)
1, serum creatinine 150%-199% of baseline	Ref.
2, serum creatinine 200%-299% of baseline	0.99	0.95-1.02
3, serum creatinine ≥300% of baseline or dialysis-related billing codes	0.98	0.94-1.03
Discharge eGFR, n (%)
eGFR ≥60 mL/min/1.73m2	Ref.
eGFR 45-59 mL/min/1.73m2	1.28	1.24-1.33
eGFR 30-44 mL/min/1.73m2	1.72	1.65-1.79
eGFR 15-29 mL/min/1.73m2	2.38	2.24-2.52

Abbreviations: AKI, acute kidney injury; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CI, confidence interval; CAD, coronary artery disease; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; OR, odds ratio; PVD, peripheral vascular disease; SD, standard deviation; SGLT2i, sodium-glucose cotransporter-2 inhibitor.

^aDemographics defined as reported in the electronic health records, including Other race(s) if multiple races listed or if neither Black nor White race.

^bOdds ratio per 10 years of increased age at time of AKI onset.

^cProteinuria scale derived from KDIGO scale. 0: urine albumin-creatinine ratio <30 mg/g or protein-creatinine ratio <150 mg/g; 1: urine albumin-creatinine ratio 30-300 mg/g or protein-creatinine ratio 150-500 mg/g; 2: urine albumin-creatinine ratio >300 mg/g or protein-creatinine ratio >500 mg/g.

^dBaseline CKD progression was defined by dividing the baseline eGFR by the mean of the three oldest eGFR values from 2-5 years before the index hospitalization.

^eBaseline hemoglobin A1c defined by the mean of the three most recent A1c measurements before the index hospitalization.

^fMedication use before AKI defined in the 6 months preceding the index hospitalization.

The lower odds of testing in older and Black individuals and those without diabetes we observed are consistent with prior Medicare data.⁶ We also observed a dose-response effect for proteinuria measurement with more severely reduced eGFR at discharge but not with baseline CKD stage nor AKI stage; these findings may reflect closer attention to more recent kidney function after AKI compared with prehospital kidney function.

Our finding that male sex was predictive of proteinuria testing is contrary to observations in other populations. Although proteinuria testing did not differ by sex among Medicare beneficiaries,⁶ among Canadian AKI-survivors female sex was associated with higher likelihood of proteinuria assessment.⁴ These discrepant findings may be related to use of claims-based definitions for AKI,⁶ which are less sensitive in females,⁸ and inclusion of urine dipstick in the outcome definition,⁴ which may be confounded by differential rates of testing for non-AKI diagnoses by sex (ie, urinary tract infection). Although we cannot infer causation in this study, some factors we found associated with lower likelihood of proteinuria testing (heart failure, peripheral vascular disease, and stroke) may signify more comorbid patients in whom frailty and limited mobility may present additional barriers to outpatient laboratory testing. Finally, the suboptimal proteinuria testing across specialties highlights opportunities to improve rates of post-AKI proteinuria assessment regardless of specialty.

Study strengths include a creatinine-based AKI definition and a large national sample. Limitations include potentially reduced generalizability to nonveteran populations and the potential of temporal effects during the COVID pandemic. We were not able to determine the specialty of individual providers ordering the proteinuria test; however, our aim was to examine the prevalence of proteinuria testing across patient populations (ie, cardiology patients and endocrinology patients). Finally, excluding patients with eGFR <15 mL/min/1.73m² at discharge may select for a healthier population compared to the overall CKD population. As the benefits and safety of antiproteinuric agents after AKI continue to be demonstrated, identifying proteinuria in AKI survivors is critical to addressing potentially modifiable risk factors in this high-risk population.

Supplementary Materials

Supplementary File (PDF)

Item S1. Additional Methods