Objective: To determine adherence to Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for frequency of testing and control of parathyroid hormone (PTH), calcium, and phosphorus levels among patients with chronic kidney disease (CKD).
Study Design: Retrospective cohort.
Methods: The analysis was performed with administrative claims data from large US managed care plans. Patients with CKD were identified based on claims and laboratory data. Patients were excluded if they were <18 years or >65 years old, had fewer than 18 months of continuous eligibility, or had renal cancer.
Results: A total of 793 patients were identified with CKD stages 3, 4, or 5 (n = 424, n = 212, and n = 157, respectively). Serum calcium testing was conducted according to guidelines (once a year) in a high percentage of patients with stage 3 CKD (91%); however, the percentage dropped among patients with stage 4 CKD (64%), for whom the guidelines recommend testing 4 times a year. Plasma PTH and serum phosphorus levels were tested infrequently. Among those tested, a high percentage of both stage 3 and 4 CKD patients were in K/DOQI target ranges for calcium and phosphorus. However, fewer than half of the patients tested had PTH values within the target ranges.
Conclusion: There remains substantial opportunity to improve the quality of care with respect to bone and mineral metabolism in patients with CKD.
(Am J Manag Care. 2007;13:620-625)
Levels of parathyroid hormone, calcium, and phosphorus progressively worsen with advancing kidney failure and result in a substantial proportion of patients having severe complications long before they begin renal replacement therapy.
Assessment of the frequency of testing and control of parathyroid hormone, calcium, and phosphorus levels found generally low adherence to the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for bone metabolism and disease.
Given the significant resource utilization among patients with chronic kidney disease and the lack of adherence to the K/DOQI guidelines, management of these patients can be substantially improved.
Patients with chronic kidney disease (CKD) who require treatment with dialysis have a much shorter life expectancy and consume much larger amounts of healthcare-related resources than persons in the general population. Annual mortality rates among patients receiving dialysis are approximately 21%, and more than half of the deaths are due to cardiovascular (CV) diseases.1 Hospitalization rates among dialysis recipients average between 1.8 and 2.4 admissions per year.1 As many as one third of these hospitalizations are from CV causes.1
Annual mortality rates also are higher among patients with stage 3 or 4 CKD compared with the general population. Mortality rates average 15.5% per year, or nearly three quarters as high as the mortality rate for patients undergoing dialysis.2 Cardiovascular disease not only is the leading cause of death among these patients but also accounts for a substantial proportion of their hospital admissions, as it does for patients undergoing dialysis.3,4 The adjusted risk of hospitalization increases progressively as renal function declines, ranging from a 14% greater risk in patients with stage 3 CKD and an estimated glomerular filtration rate (eGFR) between 45 and 59 mL/min to a 315% greater risk in patients with stage 5 CKD and an eGFR below 15 mL/min.5
Several important CV risk factors are present in patients with CKD, including hypertension, extracellular fluid volume overload, diabetes, glucose intolerance, dyslipidemia, and alterations in homocysteine metabolism.6-11 Unfortunately, these factors collectively fail to account fully for the very high morbidity and mortality rates from CV causes even when considered together with other established CV risks such as advanced age, male sex, obesity, and tobacco use.7,12,13 In this regard, disturbances in mineral metabolism have received considerable attention in recent years as potentially important nontraditional risk factors for CV disease among patients with CKD.14-18
Abnormalities in calcium and phosphorus metabolism are common among patients treated with dialysis regularly, and observational studies suggest that elevated serum calcium and phosphorus levels are associated with increases in all-cause and CV mortality. In some reports, elevated plasma parathyroid hormone (PTH) levels also have been linked to adverse clinical outcomes.19-23 Although less is known about the risks associated with these biochemical abnormalities among patients with stage 3 or 4 CKD, plasma PTH levels often are elevated, whereas serum calcium and phosphorus levels typically remain within the normal range until the GFR is less than 15-20 mL/min. Nevertheless, patients who underwent any assessment of mineral metabolism or secondary hyperparathyroidism (SHPT) before beginning dialysis had a 38% lower risk of death than those who did not undergo this assessment in multivariate adjusted models (odds ratio = 0.62; 95% confidence interval = 0.49, 0.80).24 Such findings suggest that patients with stage 3 and stage 4 CKD are a good target population for therapeutic interventions aimed at reducing CV morbidity and mortality among patients with end-stage renal disease.
The Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease provide recommendations about the frequency of biochemical testing to determine plasma PTH levels and the serum levels of calcium (Ca) and phosphorus (P), including calculated values for the calcium-phosphorus ion product in serum (Ca × P). Acceptable target ranges for these biochemical parameters also are delineated. The objectives of these guidelines are to improve the clinical management of patients with CKD, to minimize and/or prevent metabolic bone disease, and to reduce the risks of vascular calcification and CV disease.25 The current research was done to assess the clinical surveillance of patients with stage 3, 4, or 5 CKD by obtaining data about their medical care and examining adherence to the K/DOQI guidelines from a naturalistic, managed care perspective.
Administrative claims data from large managed care health plans within the United States were used for this study. The database included enrollment information, medical and prescription claims data, and laboratory test results. The abbreviated version of the Modification of Diet in Renal Disease (MDRD) equation was used to estimate GFR. Race was not included in the computation as it was not available in the data.
Patients with CKD were identified from June 1, 2002, to May 31, 2004, by review of medical claims and electronic laboratory data. Patients were required to have, within 90 days of each other, both a claim categorization for CKD and an eGFR of <60 mL/min. The date of the first of these 2 events was used as the index date (Figure). The 90-day period following the index date was used to determine the stage of CKD, which was based either on the lowest eGFR during the period or receiving regular dialysis (Figure). The CKD stages were mutually exclusive as defined by the K/DOQI system of classification, and the most advanced stage of CKD during the first 90 days after the index date was used to categorize patients:
• Stage 3: eGFR values ≥30 mL/min but <60 mL/min with no dialysis therapy.
• Stage 5: eGFR values <15 mL/min or regular dialysistherapy.
Current Procedural Terminology (CPT), UB-92, and International Classification of Diseases, Ninth Revision diagnosis and procedure codes were used to identify patients undergoing dialysis regularly.
Only patients with at least 6 months of data prior to the index date and at least 12 months of data after the index date were included in the analysis. The information available before the index date was used to determine comorbid conditions and medication utilization. The data available from the 12-month period after the index date were used to assess changes in eGFR, changes in medication utilization, and adherence to K/DOQI guidelines for the frequency of assessment of biochemical markers of mineral metabolism.
Patients were excluded from the study if they were younger than 18 or older than 65 years of age, or had fewer than 18 months of continuous eligibility. Patients with a diagnosis of renal cancer also were excluded.
A total of 793 patients satisfied the inclusion criteria for CKD: 424 with stage 3, 212 with stage 4, and 157 with stage 5 CKD (Table 1). The mean age of the patients was 51 years (SD = 10.0 years) and 39% were female. The percentage of females increased according to the stage of CKD. Most patients had substantial comorbidities (Table 1). Hypertension was present in approximately 76% of the patients, diabetes in 41%, CV disease in 33%, and anemia in 30%. The prevalence of anemia increased from 19% in stage 3 CKD to more than 50% in stage 5 CKD.
The utilization of medications in each category increased during the postindex period compared with the preindex period (Table 2).
Rates of hospitalizations during the postindex period ranged from 24% for stage 3 CKD to 50% for stage 5 CKD (Table 3). The percentage of patients seen by a nephrologist also increased as kidney function declined, rising from 69% in stage 3 CKD to 98% in stage 5 CKD.
In this naturalistic study, patients with CKD had substantial comorbidity and consumed considerable healthcarerelated resources over the 1-year postindex period. Mineral metabolism was generally not monitored with the frequency recommended in the K/DOQI guidelines. Measurements of serum calcium concentrations were obtained most often in accordance with the K/DOQI guidelines among patients with stage 3 CKD, but the proportion of patients monitored adequately was substantially lower at more advanced stages of CKD. A very small proportion of patients had plasma PTH levels measured according to the frequency recommended in the K/DOQI guidelines at any stage of CKD. The results thus indicate that the prevalence and severity of SHPT are underestimated in this patient population.
A large proportion of patients with stage 3, 4, or 5 CKD had serum calcium and phosphorus levels that fell within the ranges considered acceptable according to the K/DOQI guidelines. That was not the case, however, for plasma PTH levels. Among those tested, fewer than 40% of patients with stage 3 CKD and fewer than a third of patients with stage 4 or 5 CKD were within the target range. Such findings indicate that the biochemical diagnosis of SHPT requires testing that is specific for PTH and that measurements of other biochemical parameters of mineral metabolism (including serum calcium and phosphorus concentrations) are grossly inadequate for identifying patients with this important clinical disorder.
The current results are consistent with data reported elsewhere. Several previous studies have documented that the frequency of biochemical testing for disturbances in mineral metabolism is both inconsistent and infrequent. Results from 1 study indicated that only 50% of patients with CKD had at least 1 measurement of serum phosphorus and only 12% had 1 or more measurements of plasma PTH during the 2 years before beginning dialysis.26 Others found that only 3.4% of 3014 patients had plasma PTH levels measured and only 0.3% had vitamin D levels measured during the year immediately prior to the start of dialysis.27 Moreover, only 20% of patients with stage 4 CKD who were followed by a nephrologist for 6 months or longer had plasma PTH levels that fell within the K/DOQI target range, whereas 91% of patients had acceptable serum calcium levels and 80% had acceptable serum phosphorus levels.28 The potential importance of these findings is underscored by the fact that patients with CKD who were evaluated for SHPT before beginning dialysis had a 38% lower risk of death than those who were not.24 The K/DOQI guidelines for bone metabolism and disease discussed in the current report were published initially in October 2003, which corresponds temporally with the latter portion of the observational period for this study. Additional work is needed to determine whether current practice differs substantially from that described herein and whether biochemical surveillance for abnormalities in mineral metabolism and SHPT is now more widespread following the release and dissemination of this set of recommendations.
The current study has several limitations. First, it was undertaken using an administrative claims database that only included patients with medical and prescription benefit coverage. As such, the results may not apply more generally to other populations. Second, the use of diagnostic codes to identify individuals with CKD and other comorbid conditions is not as rigorous as formal diagnostic assessments for determining health status. Third, the use of medical claims data alone does not provide information about quality of life, the functional status of patients, or clinical outcomes. Finally, the requirement for data gathered over an 18- month interval, which was comprised of a 6-month preindex period and a 12-month postindex period, likely excluded some patients with more severe disease who may not have survived long enough to be included in the current analysis, but who nonetheless consumed considerable healthcare resources. Despite these limitations, the results can be considered reliable because information from this database was validated adequately.
In conclusion, there is substantial opportunity to improve adherence to the K/DOQI guidelines for bone disease and metabolism among a high-risk group of patients with CKD who have high rates of healthcare resource utilization.
Author Affiliations: From HealthCore, Inc, Wilmington, Del (TH, MF); and Global Health Economics (BB, RB, BS) and Medical Affairs (WG), Amgen Inc, Thousand Oaks, Calif.
Funding Source: This study was supported by Amgen Inc.
Author Disclosure: The authors (BB, RB, BS, WG) are employees of Amgen. The authors (TH, MF) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter discussed in this article.
Authorship Information: Concept and design (TH, MF, BB, RB, BS); acquisition of data (TH, MF); analysis and interpretation of data (TH, MF, BB, RB, BS, WG); drafting of the manuscript (TH, BB, RB, WG); critical revision of the manuscript for important intellectual content (TH, MF, BB, RB, BS, WG); statistical analysis (TH); administrative, technical, or logistic support (BB, RB); and supervision (TH, BB, RB, BS).
Address correspondence to: Maxine Fisher, PhD, HealthCore, Inc, 800 Delaware Ave, 5th Fl, Wilmington, DE 19801-1366. E-mail: email@example.com.
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