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Clinical Nephrology |
* United States Renal Data System Coordinating Center and Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana; and Division of Nephrology, Maine Medical Center, Portland, Maine
Address correspondence to: Dr. Jay L. Xue, United States Renal Data System, 914 South 8th Street, Suite D-206, Minneapolis, MN 55404. Phone: 612-337-8979; Fax: 612-347-5878; jxue{at}usrds.org
Received for publication June 28, 2005. Accepted for publication January 15, 2006.
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Abstract |
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Introduction |
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Very few data have been published regarding the incidence of ARF. An often-cited incidence rate (4.9%) was obtained using single-hospital data collected in 1979 (2). Investigators from the same group reported a higher incidence rate (7.0%) using single-center data 17 yr later (3). With a similar definition of ARF, another study reported that 0.9% of patients presented with ARF at hospital admission (4). No study has been conducted to assess the possibility of change in incidence rates of ARF using multiple-year data.
Despite advances in medical techniques during the past several decades, mortality in patients with ARF remains high. Depending on patient characteristics as well as criteria used for the definition of ARF, of those who develop ARF while in the hospital, 25 to 80% die before discharge (3,5–7). No study using national data has been conducted to determine whether mortality outcomes of patients with ARF have changed over time.
Given the absence of an epidemiologic study of ARF using national data, we decided to study ARF using a 5% sample of US hospitalized Medicare beneficiaries for the years 1992 to 2001. The objectives of the study were to determine the incidence and mortality of ARF in hospital settings.
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Definitions
ARF was determined on the basis of ICD-9-CM diagnosis codes, coded as either the principal or a secondary diagnosis. Those with renal failure, as defined by registration with the US Renal Data System for ESRD treatment, were excluded. In the ICD-9-CM, ARF is defined as "the sudden, severe onset of inadequate kidney function." Five subcodes (584.5, 584.6, 584.7, 584.8, and 584.9) under a main code (584) are used to designate ARF. The validity of ARF in claims data has been evaluated (8). Positive predictive value was 88% in ARF defined by 50% increase of serum creatinine from the baseline and 87% in ARF recorded by ICD-9-CM codes (8).
In Medicare inpatient claims, each admission was assigned one code for the principal diagnosis and as many as nine codes for secondary diagnoses. We scrutinized all principal and secondary diagnosis codes for codes that denoted ARF. For many admissions, fewer than nine secondary diagnosis codes were indicated. In this study, any of nine secondary code positions could have been used to indicate a secondary diagnosis of ARF.
We also determined intensive care unit (ICU) stay, sepsis, other acute organ dysfunction, and renal dialysis during the hospital stay. In Medicare claims, renal dialysis was indicated by revenue center codes (0800 to 0809) and ICD-9-CM procedure codes (3995 and 5498). ICU stay is indicated by revenue center codes (0200 to 0209). Revenue codes are documented for reimbursement purposes, with coding accuracy having been verified before payment was made. Sepsis and acute organ dysfunction were indicated by ICD-9-CM diagnosis codes, which have been used in previous studies (9,10). In this study, acute organ dysfunction pertained to cardiovascular, respiratory, hepatic, hematologic, and neurologic dysfunction (see Appendix 1 for codes for organ dysfunction associated with sepsis).
Patient demographics were recorded in the Medicare Enrollment Denominator File as well as in Medicare claims. Race and ethnicity included white, black, Hispanic, Native American, and Asian American. Because of a small number of records for minorities, we combined Hispanic, Native American, and Asian American into an "other" group. Therefore, in this study, white and black patients were non-Hispanic white and non-Hispanic black, respectively.
The Medicare Enrollment Denominator File includes information on Medicare beneficiary entitlement status, as taken from administrative enrollment records. This file is an abbreviated version of the Medicare Enrollment Database. The Denominator File includes the date of death. All deaths are required to be reported to the Social Security Administration by statute and are reported to the Centers for Medicare and Medicaid Services.
Statistical Analyses
All data that were used in this study were collected from hospitalized patients (Medicare inpatient claims). We conducted discharge-level analyses of incidence and mortality. All admissions, regardless of whether the patient died during hospitalization or survived to discharge, were included in the study. Design of the study and analysis of the data at the discharge level were conducted using the National Hospital Discharge Survey (10,11).
Data were analyzed using SAS (SAS Institute, Inc., Cary, NC). Proportion data were analyzed using the 
2 test. By-year rates for ARF and deaths were standardized to the 2000 data, with adjustment for age, gender, and race (12). Odds ratios (OR) for likelihood of ARF, sepsis, ICU stay, other acute organ failure, and death within 90 d after the date of hospital admission were analyzed using logistic regression.
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Results |
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The overall rate of ARF during the study period was 23.8 cases per 1000 discharges. Older patients were more likely to have ARF than those who were younger. Average ARF rates during the study period were 18.5, 20.8, 25.8, and 28.6 cases per 1000 discharges for age groups 
64, 65 to 74, 75 to 84, and 
85 yr, respectively. In men and women, the average ARF rates during the 10 yr were 28.3 and 20.0 cases per 1000 discharges, respectively. In white and black patients and patients of other races, the average ARF rates between 1992 and 2001 were 22.3, 34.4, and 24.3 cases per 1000 discharges, respectively.
Standardized ARF rates increased annually by approximately 11% (P < 0.0001), from 14.6 cases per 1000 discharges in 1992 to 36.4 cases per 1000 discharges in 2001 (Figure 1). Such an increase was present in subgroups that were defined on the basis of age, gender, and race. The increase of ARF incidence from 1992 to 2001 was also confirmed (P < 0.0001) by logistic regression after adjustment for age, gender, and race. The increase was observed when ARF was coded either as the principal diagnosis or as a secondary diagnosis and when dialysis was and was not required (Figure 2).
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Discussion |
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Earlier studies have observed multiple episodes of ARF in the same individuals (2,3), a phenomenon also found in our study. The majority (85%) of discharges in our study had only one hospital admission with ARF. Considering our 10-yr period, 15% of discharges with more than one episode of ARF is not surprising. When we examined ARF incidence by separating single from multiple episodes, the increases in ARF occurrence were similar in both categories over the 10 yr.
ARF was strongly associated with older age, male gender, and black race. Several studies have reported older individuals to be at a higher risk for ARF (3,16–18), which is not surprising because kidney function declines in the elderly. Our finding of increased risk for ARF in men is consistent with the finding of a multicenter study by Liano et al. (19) and the findings in patients with sepsis (10). However, in patients with heart disease, the findings are less clear. A recent study of patients who had had open-heart surgery found women to be at increased risk for ARF (20). Fortescue et al. (21) reported no difference in risk for ARF between men and women who had coronary bypass surgery. Further research seems needed to determine the incidence of ARF in patients with heart disease.
Very few studies have assessed racial differences regarding the incidence of and outcomes related to ARF, probably because of the difficulty of enrolling adequate numbers of minorities in a single-center or even a multicenter study. In a study of patients who had had open-heart surgery, white patients were found to have a lower risk for ARF defined broadly, but no racial differences were found in risk for ARF when ARF was defined more strictly, as requiring dialysis (20). In this study, we found black patients to be at a higher risk for ARF than those of other races. We also found that black patients were more likely to have sepsis and other acute organ failure than white patients. These differences between black and white patients were supported by a recent study (22). Further study is needed to determine the mechanisms of the racial differences.
Our finding that discharges with ARF had a higher in-hospital death rate than those without ARF is consistent with previous findings (18,23,24). The higher in-hospital death rate in ARF discharges was probably due to severe sickness, which requires intensive care (5,7,25). Longer hospital stays in ARF discharges also suggest severe illness. In addition, the severe sickness of ARF discharges was consistent with their other organ system failures. Other studies have indicated that comorbid conditions or surgical complications only partly account for the mortality difference between patients with and without ARF (23,24). Multiple organ failures primarily contributed to high mortality in patients with ARF and were strong predictors of death (6,26). In our study, when the logistic regression model included other organ failure, ARF was still significant for death, suggesting that ARF is an independent predictor of death.
Severity of illness also may account for the difference in in-hospital death rate that we found between discharges with ARF coded as the principal diagnosis and those with ARF coded as a secondary diagnosis. Most of the discharges with ARF coded as the principal diagnosis had ARF as the cause for hospital admission, whereas discharges with ARF as a secondary diagnosis had another cause for admission; this suggests that the latter discharges had disease in other organ systems, with the kidney as a secondary complication. The difference in severity of illness between ARF coded as the principal and as a secondary diagnosis is supported by the increase in intensive care and other acute organ failure. This finding is consistent with reports that patients with "community-acquired ARF" (i.e., patients in whom ARF was given as the cause for hospital admission) had a lower death rate than those with hospital-acquired ARF (4,27). Community-acquired ARF typically is related to volume disorders (especially volume depletion), with or without concomitant use of nonsteroidal anti-inflammatory drugs or angiotensin-converting enzyme inhibitors, and usually is reversible (4).
Another finding of our study is the decline in deaths within 90 d after hospital admission from 1992 to 2001, seen in both ARF and non-ARF discharges. Using the same criteria for defining ARF, Hou and colleagues (2,3) found a 25% death rate in a 1979 study and a 19% death rate in a 1996 study. McCarthy studied Mayo Clinic data on ARF patients who required intensive care and hemodialysis in two periods: 1977 to 1979 and 1991 to 1992 (28). Survival rates in hospital were 32% in the 1977 to 1979 period and 52% in the 1991 to 1992 period; 1-yr survival rates were 30 and 21% for the two periods, respectively. In our study, 1-yr death risk estimated by Cox regression also showed a declining trend during the study period (data not shown). The decline in death within 90 d after hospital admission from 1992 to 2001 that was found in this study not only reflects an improvement in hospital care but also suggests that patient mortality was not affected by the declining length of hospital stay during the study period. Since the 1982 implementation of the Prospective Payment System for Medicare, length of hospital stay continues to decline (29,30). A previous study reported that use of a fixed interval for death rather than inpatient death is reasonable (31).
Limitations of this study should be noted. This is a retrospective study using administrative data. Although use of ICD-9-CM codes for identification of ARF has been shown to be valid by a previous study (8), sensitivity was low (15%), suggesting that ARF that is recorded in Medicare claims is likely underreported. A recent study indicated that approximately 80% of patients with biochemical criteria for ARF were not identified by ICD-9-CM code (22). If these findings are applicable to the Medicare population, then the magnitude of underestimations in this study could be up to five- or six-fold. Given the definition of ARF in the ICD-9-CM ("the sudden, severe onset of inadequate kidney function") and the previous validation of disease codes in claims data (32,33), it is likely that the documentation of ARF and other conditions that were examined in this study was accurate; however, less severe ARF and other conditions may not have been coded. The possibility that ARF is underreported in Medicare claims has two main implications. First, the true incidence rate of ARF may be higher than that reported in this study. Second, outcomes from claims data may be overestimated; for example, the true mortality rate of ARF may be lower than that reported in this study because those with less severe ARF, unreported in Medicare claims, likely would have lower death risks. Another limitation of our study is that, because our data were analyzed at the discharge level, a potential for survivor bias could contribute to the decreasing 90-d mortality rate over time.
The increase in ARF from 1992 to 2001 may be attributable partially to changes in coding practices. Unfortunately, there is no reliable variable in claims data to test whether these practices have changed. Although there is evidence that associated conditions such as sepsis also are on the rise, without external validation, it is not possible to differentiate clearly real increases from changes in reporting practices. The change in coding practices could be driven by the change in Medicare reimbursement incentives. The smooth curve of rising ARF, however, does not support this notion because the change in reimbursement policy likely would result in a sudden increase or decrease in ARF. Furthermore, the rising trend of ARF that requires dialysis (Figure 2) cannot be linked plausibly with coding practices. In any case, the most recent data do suggest that the current level of ARF should be a cause for concern.
Preexisting kidney impairment likely has an impact on ARF occurrence as well. Patients with impaired kidney function may be more susceptible to risk factors for ARF; therefore, chronic kidney disease may be an important contributor to the increase in ARF that was found in this study. Impaired kidney function can be diagnosed in outpatient or inpatient settings. For investigation of the effect of impaired kidney function on the development of ARF, the impairment should be present first. Further research, with a study design that is different from the design of this study is needed for that purpose.
The main strength of this study is its use of a large sample that covered broad geographic areas, including all 50 US states and the District of Columbia. Medicare patients are older, and our results may not be generalizable to younger patients. However, the data used in this study were from a random sample of the Medicare population, and the results are highly representative of the older US population.
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Acknowledgments |
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We thank Beth Forrest, James M. Kaufmann, PhD, and Nan Booth, MSW, MPH, for assistance with manuscript preparation and editing.
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