BACKGROUND/RATIONALE:
A substantial body of literature indicates that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) can be delayed and mortality decreased, through the use of angiotensin converting enzyme inhibitors (ACEIs) and/or angiotension receptor blockers (ARBs), lipid and blood pressure control, and management by nephrology specialists. However, there are no systematically collected data regarding guideline-concordant care provided to the veteran population with CKD.

OBJECTIVE(S):
Aim 1: To study K-DOQI/VA-DOD Chronic Kidney Disease Guideline care in VA patients with CKD and to evaluate predictors of the provision of guideline-concordant care. Objective 1.1: To estimate the proportions of VA patients with CKD who receive recommended guideline-concordant care. Objective 1.2: To evaluate potential predictors of the provision of guideline-concordant care, including patient sociodemographic factors, comorbidities, and specialty care. Objective 1.3: To evaluate potential predictors of nephrologist subspecialist care in VA patients with CKD taking into account CKD stage, medical comorbidities, and acuity of recognized renal disease.

Aim 2: To estimate incidence of first (incident) dialysis in VA patients with CKD and to evaluate potential predictors of incident dialysis. Objective 2.1: To estimate incidence of first (incident) dialysis, with separate estimates for planned (i.e., preceded by placement or attempted placement of permanent access) and emergency dialysis. Objective 2.2: To evaluate potential predictors of planned and emergency dialysis, including the provision of guideline concordant care.

Aim 3: To estimate mortality prior to dialysis in VA patients with CKD and to evaluate potential predictors of pre-dialysis mortality. Objective 3.1: To estimate mortality rates prior to dialysis in VA patients with CKD. Objective 3.2: To evaluate potential predictors of pre-dialysis mortality, including the provision of guideline-concordant care.

Aim 4. To process and evaluate available measures of micro/macroalbuminuria in VA patients with diabetes in order to determine their utility for identifying early stages (1 and 2) of CKD and for better characterizing CKD progression over time, and more specifically between races. Objective 4.1: Macro/microalbuminuria status (no proteinuria, microalbuminuria, and overt proteinuria) in patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2 will be associated with time to transition into CKD stage 3 and above (i.e., time to the first eGFR value below <60 mL/min/1.73m2), even with adjustment for various confounding variables. Objective 4.2: The combination of a baseline eGFR and microalbuminuria in patients with CKD stages 1 to 4 will predict transition into the next stage of CKD (ex: from stage 3 to stage 4 or above) and to dialysis better than either one of those two elements alone. Objective 4.3: The addition of microalbuminuria to a baseline eGFR will improve the prediction of subsequent eGFR decline better in African Americans than in Whites.

Aim 5. To study variability and trends in eGFR in VA patients with CKD and diabetes over time and evaluate patterns of eGFR progression as potential predictors of ESRD and pre-dialysis mortality. Objective 5.1: A pattern of eGFR decline with a high time-to-time variability will be associated with a higher risk of ESRD and pre-dialysis mortality compared to a pattern of similar eGFR decline over time but with less variability. Objective 5.2: African Americans compared to Whites will be associated with a pattern of eGFR decline with high time-to-time variability.


METHODS:
We developed a dynamic inception cohort of all veterans (both with and without diabetes) first identified as having CKD in FY99-02 based upon calculation of eGFR without prior dialysis. This cohort was followed through FY04, measuring processes and intermediate outcomes of ambulatory care and the occurrence of cardiovascular events, dialysis, and mortality, using merged VA and CMS datasets.

FINDINGS/RESULTS:
Prevalence of CKD by GFR criterion was 31.6%. Only 20.2% to 42.4% of individuals with CKD received a renal-related diagnosis code in either VA or Medicare records over one year. Specificity of renal codes ranged from 93.2% to 99.4%. CKD is a common co-morbidity for patients with diabetes in the VA system, but diagnosis codes in administrative records are insensitive markers for patients with CKD.

Of 182,162 patients with Stage 3 or 4 CKD, 66% were dispensed ACE-I/ARB agents within a twelve month period from 1999-2000. The odds of receiving ACE-I/ARB agents were increased six-fold (odds ratio [OR] 5.81; 95% confidence interval [CI] 5.62-6.02; p < .0001) if potassium-wasting diuretics were dispensed, and increased 30% (OR 1.31; 95% CI 1.24 - 1.37; p < .0001) with nephrology care. The association of nephrology care with ACE-I/ARB agents disappeared when adjusted for diuretic use.

Of 39,044 patients, 70.0 %, 22.5 %, and 7.6 % had early stage 3, late stage 3, and stage 4 CKD, respectively; 3.1%, 9.5%, and 28.1% visited a nephrologist, respectively. The association of higher consistency of nephrologist visits and reduced mortality was consistent across CKD stages. Overall, higher consistency of nephrologist visits was associated with greater reduction of mortality: the adjusted hazard ratios (AHRs) were 0.80 (95% CI=0.66, 0.97), 0.67 (0.54, 0.84), and 0.44 (0.31. 0.61), respectively, when the groups of two, three, and four visits were compared to those who had no visits. One visit made no difference from no visits (AHR=1.02; 95% CI=0.89, 1.16). The consistency of outpatient nephrology care was independently associated in a graded fashion with lower pre-dialysis mortality for diabetic patients with moderately severe to severe CKD. However, only a minority of patients received care from a nephrologist.

We conducted a retrospective cohort study of 39,629 patients with diabetes and stage 3 to stage 5 chronic kidney disease, with a median follow-up period of 19.3 months during 1997 to 2000. The cohort consisted of 81.4% whites, 14.4% blacks, 2.2% Hispanics and 2% others.
The overall dialysis-free mortality was 11.2 per 100 person-years. Dialysis-free mortality was 11.1 for whites, 11.6 for blacks, 10.7 for Hispanics and 11.0 for others. When adjusted for age, sex, and comorbid conditions, blacks had a hazard ratio of 1.13 (95% CI, 1.05-1.21), Hispanics had a hazard ratio of 1.07 (95% CI, 0.90-1.27) and others had a hazard ratio of 1.11 (95% CI, 0.93-1.33) compared with whites. The findings were not explained by access to nephrologist care. Identifying possible mediating factors for the race/ethnicity differences in chronic kidney disease outcomes that can be improved by the health care system is critical to developing action plans to eliminate differences.

We identified acute kidney injury (AKI) events not requiring dialysis from laboratory data and classified them according to the ratio of the highest creatinine during the hospitalization to the lowest creatinine measured between 90 days before hospitalization and the date of discharge. We estimated mortality risks using multivariable Cox regression models adjusting for demographics, comorbidities, medication use, primary diagnosis of admission, length of stay, mechanical ventilation, and postdischarge estimated GFR (residual kidney function). The adjusted mortality risk associated with AKI was 1.41 (95% CI 1.39 to 1.43) and increased with increasing AKI stage: 1.36 (95% CI 1.34 to 1.38), 1.46 (95% CI 1.42 to 1.50), and 1.59 (95% CI 1.54 to 1.65; P < 0.001 for trend). In conclusion, AKI that does not require dialysis associates with increased long-term mortality risk, independent of residual kidney function, for patients who survive 90 days after discharge.

IMPACT:
Results from our study were the first to provide national estimates of the prevalence of chronic kidney disease among veterans with diabetes; to demonstrate racial differences in pre-dialysis mortality; and to evaluate the prevalence of renin angiotensin system inhibitors (RASI) treatment. Rates of guideline-concordant therapy with ACEI/ARBs was moderate (about two thirds of veterans) with differences by age (lower age worse). Nephrologist care improved the prescription rates of ACEI/ARBs, especially among younger veterans, possibly through the greater use of diuretic treatment. Consistency of nephrology care (defined as the number of quarters in which care was provided) was associated with a decrease in pre-dialysis mortality. Additionally, among hospitalized veterans, acute kidney injury is common (about 9.5%) and associated with high rates of post-discharge mortality. These results may have implications for sub-specialty care in the context of primary care redesign.

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External Links for this Project

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PUBLICATIONS:

Journal Articles

1. Lafrance JP, Miller DR. Acute kidney injury associates with increased long-term mortality. Journal of the American Society of Nephrology : JASN. 2010 Feb 1; 21(2):345-52. [view]
2. Tiwari A, Tseng CL, Kern EF, Maney M, Miller DR, Pogach L. Facility variation in utilization of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with diabetes mellitus and chronic kidney disease. The American journal of managed care. 2007 Feb 1; 13(2):73-9. [view]
3. Kern EF, Maney M, Miller DR, Tseng CL, Tiwari A, Rajan M, Aron D, Pogach L. Failure of ICD-9-CM codes to identify patients with comorbid chronic kidney disease in diabetes. Health services research. 2006 Apr 1; 41(2):564-80. [view]
4. Tseng CL, Kern EF, Miller DR, Tiwari A, Maney M, Rajan M, Pogach L. Survival benefit of nephrologic care in patients with diabetes mellitus and chronic kidney disease. Archives of internal medicine. 2008 Jan 14; 168(1):55-62. [view]
5. Tseng CL, Lafrance JP, Lu SE, Soroka O, Miller DR, Maney M, Pogach LM. Variability in estimated glomerular filtration rate values is a risk factor in chronic kidney disease progression among patients with diabetes. BMC nephrology. 2015 Mar 25; 16(1):34. [view]

Conference Presentations

1. Tseng CL, Tiwari A, Kern EF, Miller DR, Maney M, Pogach L. African American race was related to higher risk of dialysis-free mortality among patients with diabetes and advanced chronic kidney disease. Paper presented at: Meharry Vanderbilt Alliance on Diabetes Health Disparities Annual Conference; 2007 Nov 12; Nashville, TN. [view]
2. Lafrance JP, Miller DR. Association of acute kidney injury with long-term mortality beyond post-discharge kidney function. Paper presented at: American Society of Nephrology Annual Meeting; 2009 Oct 20; San Diego, CA. [view]
3. Lafrance JP, Miller DR. Cyclooxygenase (COX)-2 selective and non-selective non-steroidal anti-inflammatory drugs and the risk of hypoglycemia. Paper presented at: American Society of Nephrology Annual Meeting; 2009 Oct 20; San Diego, CA. [view]
4. Tseng C, Lafrance JP, Lu SE, Soroka O, Miller DR, Maney M, Pogach LM. Does Variation in Estimated Glomerular Filtration Rate Predict Risk of Dialysis or Death in Patients with Chronic Kidney Disease. Poster session presented at: American Diabetes Association Annual Scientific Session; 2012 Jun 9; Philadelphia, PA. [view]
5. Tseng CL, Tiwari A, Kern EF, Miller DR, Maney M, Pogach LM. Evaluation of Administration of ACE Inhibitors and Angiotension Receptor Blockers among Diabetic Patients with Chronic Kidney Disease. Paper presented at: AcademyHealth Annual Research Meeting; 2006 Jun 1; Seattle, WA. [view]
6. Miller DR, Fincke BG, Zhang Q. health care utilization and expenditures associated with insulin glargine use. Paper presented at: Centers for Disease Control and Prevention Diabetes and Obesity Annual Conference; 2006 May 17; Denver, CO. [view]
7. Kern E, Tiwari A, Tseng CL, Miller D, Aron DC, Pogach LM. Prescription of Diuretics with Angiotensin System Inhibitors in Diabetes and Chronic Kidney Disease. Paper presented at: VA HSR&D National Meeting; 2006 Feb 1; Arlington, VA. [view]
8. Tseng, Tiwari, Kern, Miller DR, Maney, Pogach L. Race and dialysis-free mortality among patients with diabetes and advanced chronic kidney disease. Poster session presented at: VA HSR&D National Meeting; 2008 Feb 12; Baltimore, MD. [view]
9. Tseng CL, Kern E, Maney M, Tiwari A, Miller D, Pogach LM. Racial disparities in dialysis--free mortality and survival benefits of nephrologic care among Veteran Health Administration clinic users with chronic kidney diseases and diabetes. Paper presented at: Centers for Disease Control and Prevention Division of Diabetes Translation Annual Conference; 2007 Nov 14; Orlando, FL. [view]

DRA: Health Systems
DRE: Epidemiology
Keywords: Chronic disease (other & unspecified), Practice patterns, Quality assessment
MeSH Terms: none