Subsequent urinary stone events are predicted by the magnitude of urinary oxalate excretion in enteric hyperoxaluria.

Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited. Therefore, we assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate. Mean ± standard deviation age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6-73.0) mg/24 h and 81 patients had one or more stone event during a median follow-up time of 4.9 (2.8-7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event. Thus, these data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group. BACKGROUND: Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited. METHODS: We assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate. RESULTS: Mean ± SD age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6-73.0) mg/24 h and 81 patients had ≥1 stone event during a median follow-up time of 4.9 (2.8-7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event. CONCLUSIONS: These data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group.

End Point Considerations for Clinical Trials in Enteric Hyperoxaluria.

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown. Currently, there are no US Food and Drug Administration-approved therapies for enteric hyperoxaluria, and it is unclear what end points should be used to evaluate the efficacy of new drugs and biologics for this condition. This study represents work of a multidisciplinary group convened by the Kidney Health Initiative to review the evidence supporting potential end points for clinical trials in enteric hyperoxaluria. A potential clinical outcome is symptomatic kidney stone events. Potential surrogate end points include ( 1 ) an irreversible loss of kidney function as a surrogate for progression to kidney failure, ( 2 ) asymptomatic kidney stone growth/new stone formation observed on imaging as a surrogate for symptomatic kidney stone events, ( 3 ) urinary oxalate and urinary calcium oxalate supersaturation as surrogates for the development of symptomatic kidney stone events, and ( 4) plasma oxalate as a surrogate for the development of the clinical manifestations of systemic oxalosis. Unfortunately, because of gaps in the data, this Kidney Health Initiative workgroup was unable to provide definitive recommendations. Work is underway to obtain robust information that can be used to inform trial design and medical product development in this space.

Randomized Placebo-Controlled Trial of Reloxaliase in Enteric Hyperoxaluria.

BACKGROUND: Enteric hyperoxaluria is caused by increased intestinal oxalate absorption and can lead to kidney stones, chronic kidney disease, and kidney failure. Reloxaliase is an orally administered recombinant enzyme that degrades oxalate along the gastrointestinal tract, thereby preventing its absorption. METHODS: We randomly assigned participants with enteric hyperoxaluria to reloxaliase or placebo, three to five times per day with food for 4 weeks. The primary end point was percent change from baseline in 24-hour urinary oxalate (UOx) excretion during weeks 1 to 4. Secondary end points included the proportion of participants with more than a 20% reduction in 24-hour UOx and an efficacy assessment in the bariatric surgery subgroup. RESULTS: A total of 115 patients underwent randomization. The 24-hour UOx decreased from a baseline geometric mean of 83.2 to 67.4 mg/24 hr during weeks 1 to 4 in reloxaliase-treated participants. Corresponding data for placebo-treated participants were 84.2 to 78.1 mg/24 hr. Estimates from the mixed-effect model repeated-measures (MMRM) analysis showed a 22.6% reduction in geometric mean UOx during weeks 1 to 4 for reloxaliase and 9.7% for placebo, a difference of 14.3 percentage points (95% confidence interval [CI], 4.9 to 22.8; P=0.004). A 20% or greater reduction in 24-hour UOx was observed in 48.3% of reloxaliase-treated participants and 31.6% of placebo-treated participants (P=0.06). In the bariatric surgery subgroup, MMRM analysis showed a 21.2% reduction in geometric mean UOx for reloxaliase and a 6.0% reduction for placebo, for a difference of 16.2 percentage points (95% CI, 4.2% to 26.7%). Adverse events occurred in 69% of reloxaliase-treated participants versus 53% of individuals taking placebo and were most commonly gastrointestinal. All but one of the adverse events were grade 1 or 2 in severity; no reloxaliase-treated participants discontinued the study. CONCLUSIONS: Reloxaliase treatment for 4 weeks reduced UOx excretion in patients with enteric hyperoxaluria; adverse events were relatively common, but not dose-limiting. These data establish the foundation for a clinical trial to determine the impact of reloxaliase on nephrolithiasis in patients with enteric hyperoxaluria. (Funded by Allena Pharmaceuticals; ClinicalTrials.gov number, NCT03456830.)

Pathophysiology and Treatment of Enteric Hyperoxaluria.

Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative-sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.

Ferumoxytol for treating iron deficiency anemia in CKD.

Iron deficiency is an important cause of anemia in patients with chronic kidney disease (CKD), but intravenous iron is infrequently used among patients who are not on dialysis. Ferumoxytol is a novel intravenous iron product that can be administered as a rapid injection. This Phase III trial randomly assigned 304 patients with CKD in a 3:1 ratio to two 510-mg doses of intravenous ferumoxytol within 5 +/- 3 d or 200 mg of elemental oral iron daily for 21 d. The increase in hemoglobin at day 35, the primary efficacy end point, was 0.82 +/- 1.24 g/dl with ferumoxytol and 0.16 +/- 1.02 g/dl with oral iron (P < 0.0001). Among patients who were not receiving erythropoiesis-stimulating agents, hemoglobin increased 0.62 +/- 1.02 g/dl with ferumoxytol and 0.13 +/- 0.93 g/dl with oral iron. Among patients who were receiving erythropoiesis-stimulating agents, hemoglobin increased 1.16 +/- 1.49 g/dl with ferumoxytol and 0.19 +/- 1.14 g/dl with oral iron. Treatment-related adverse events occurred in 10.6% of patients who were treated with ferumoxytol and 24.0% of those who were treated with oral iron; none was serious. In summary, a regimen of two doses of 510 mg of intravenous ferumoxytol administered rapidly within 5 +/- 3 d was well tolerated and had the intended therapeutic effect. This regimen may offer a new, efficient option to treat iron deficiency anemia in patients with CKD.

Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy.

IgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time course for progression to ESKD. The aim of this Kidney Health Initiative project was to identify surrogate end points that could serve as reliable predictors of a treatment's effect on long-term kidney outcomes in IgAN and be used as a basis for approval. Proteinuria was identified as the most widely recognized and well studied risk factor for progression to ESKD in IgAN. The workgroup performed a critical review of the data on proteinuria reduction as a surrogate end point for a treatment's effect on progression to ESKD in IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death. We conclude that data support the use of proteinuria reduction as a reasonably likely surrogate end point for a treatment's effect on progression to ESKD in IgAN. In the United States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.

Safety of ferumoxytol in patients with anemia and CKD.

BACKGROUND: Iron deficiency anemia is a common complication in patients with chronic kidney disease (CKD). Currently available intravenous (IV) iron replacement therapies have either inconvenient regimens of administration or adverse event profiles that limit their utility in the outpatient setting. Ferumoxytol is a novel, semisynthetic, carbohydrate-coated, superparamagnetic iron oxide nanoparticle that is administered IV as an injection. The main objective of this study was to assess the safety of ferumoxytol for the treatment of patients with CKD stages 1 to 5 and 5D. STUDY DESIGN: Phase 3, randomized, double-blind, placebo-controlled, crossover, multicenter study of a single 510-mg dose of ferumoxytol versus saline as placebo. SETTING & PARTICIPANTS: 750 patients with CKD stages 1 to 5 and 5D. INTERVENTION: An IV injection of either 17 mL of ferumoxytol or saline placebo over 17 seconds on day 0 and the alternate agent on day 7. OUTCOMES & MEASUREMENTS: Descriptive comparison of adverse events, laboratory tests, and vital signs. RESULTS: Of 750 randomly assigned patients with CKD, 60% were not on dialysis therapy. 713 patients received ferumoxytol, and 711 received placebo. There were 420 adverse events reported; 242 in 152 patients (21.3%) with ferumoxytol and 178 in 119 patients (16.7%) with placebo. The incidence of related adverse events was 5.2% with ferumoxytol and 4.5% with placebo. The most common related adverse events after each treatment included symptoms related to the injection/infusion site, dizziness, pruritus, headache, fatigue, and nausea. Serious adverse events occurred in 21 patients (2.9%) after ferumoxytol and 13 patients (1.8%) after placebo. Serious related adverse events were observed in 1 patient (0.1%) after each treatment. There was no meaningful decrease in blood pressure after administration of ferumoxytol or placebo. LIMITATIONS: Follow-up was 7 days after each study treatment. CONCLUSIONS: Ferumoxytol is well tolerated and has a safety profile similar to placebo in anemic patients with CKD stages 1 to 5 and 5D.

Overview of vaccination in chronic kidney disease.

Infections are a major cause of death in end-stage renal disease (ESRD) patients, second only to cardiovascular disease, and also contribute to significant morbidity in patients with earlier stages of chronic kidney disease (CKD). Vaccines are a strategy to attempt to reduce morbidity related to infections. Patients with CKD and ESRD may not respond as well to vaccines as patients without kidney failure, but adequate seroresponse with standard or augmented regimens for vaccinations against influenza, hepatitis B, pneumococcus, and varicella have been documented. Influenza, in particular, seems to provide adequate protection with standard dosing regimens. Despite somewhat reduced effectiveness of certain vaccines in patients with CKD, there is emerging evidence of benefit to vaccination in these populations. However, vaccination rates are relatively low. Given the accumulating evidence of benefit, continuing quality improvement programs focused on increasing vaccination rates in patients with all levels of CKD are needed.

Intractable anemia among hemodialysis patients: a sign of suboptimal management or a marker of disease?

BACKGROUND: Most incident hemodialysis (HD) patients who initiate dialysis therapy with anemia usually can achieve a hemoglobin (Hb) level of 11 g/dL or greater (> or =110 g/L) within a few months of the initiation of recombinant human erythropoietin (EPO) therapy. However, patients unable to achieve this level may be at greater risk for adverse outcomes. Whether intractable anemia is a modifiable problem or a marker for other conditions is unclear. This question was addressed in a cohort of 130,544 incident HD patients from 1996 to 2000 who were administered EPO regularly. METHODS: Medicare claims data were used to determine demographic characteristics, comorbidities, hospitalizations, and related events. Patients who did not achieve an Hb level of 11 g/dL or greater (> or =110 g/L; n = 19,096; 14.6%) during months 4 to 9 after dialysis therapy initiation were compared with those who did. RESULTS: Patients unable to achieve an Hb level of 11 g/dL (110 g/L) were younger and more often of nonwhite race. In addition, these patients had more comorbid conditions; experienced more hospitalizations with longer stays, more infectious hospitalizations, and more catheter insertions; and were administered more blood transfusions. EPO was administered in higher and increasing doses during the years of study among patients with intractable anemia compared with those with an Hb level of 11 g/dL or greater (> or =110 g/L), likely denoting increasing attempts to correct anemia over the years. CONCLUSION: It is apparent that incident HD patients unable to achieve an Hb level of 11 g/dL or greater (> or =110 g/L) have a greater disease burden. The independent association of intractable anemia with such future outcomes as cardiovascular events and hospitalizations remains to be determined.

Effect of comorbidity on the increased mortality associated with early initiation of dialysis.

BACKGROUND: Current recommendations for initiating dialysis therapy are based on level of kidney function and clinical evidence of uremia. Several studies reported no benefit in patient survival from initiating dialysis therapy with a greater glomerular filtration rate (GFR). Whether this is explained by a greater comorbidity burden or detrimental effect of early initiation remains unclear. We thus undertook an evaluation of the impact of comorbidity on the association between GFR at initiation and death. METHODS: Data from the Center for Medicare & Medicaid Services were used to derive 3 incident dialysis populations: (1) general population aged 18+ years, (2) older patients aged 67+ years, and (3) a "low-risk" subgroup without diabetes, heart failure, or atherosclerotic heart disease. A Cox proportional hazard regression technique was used. RESULTS: Greater GFR at initiation of dialysis therapy was associated with a greater risk for death in all populations, and sequential adjustment for additional covariates attenuated the effect. Patients in the general dialysis population who initiated dialysis therapy at a GFR greater than 10 mL/min/1.73 m2 (>0.17 mL/s) had a 42% increased risk for death compared with patients with a GFR less than 5 mL/min/1.73 m2 (<0.08 mL/s) at initiation of dialysis therapy after adjusting for all covariates. In the older and healthier populations, adjusted increased risks were 25% and 39%, respectively. CONCLUSION: Patients initiating dialysis therapy at greater GFRs have an increased risk for death not fully explained by comorbidity. Additional research is required to determine the reasons for poor survival in patients who start dialysis therapy with significant residual renal function.

Association between body mass index and CKD in apparently healthy men.

BACKGROUND: Overweight and obesity are well-established risk factors for cardiovascular disease and decline in kidney function in individuals with existing chronic kidney disease (CKD). Conversely, their association with the development of CKD is less clear. METHODS: We evaluated the association between body mass index (BMI) and risk for CKD in a cohort of 11,104 initially healthy men who participated in the Physicians' Health Study and provided a blood sample after 14 years. BMI was calculated from self-reported weight and height. We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study and defined CKD as GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). RESULTS: After an average 14-year follow-up, 1,377 participants (12.4%) had a GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). Higher baseline BMI was associated consistently with increased risk for CKD. Compared with participants in the lowest BMI quintile (<22.7 kg/m2), those in the highest quintile (>26.6 kg/m2) had an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.19 to 1.76; P trend <0.001) after adjusting for potential confounders. We found similar associations by using different categories of BMI. Compared with men who remained within a +/-5% range of their baseline BMI, those who reported a BMI increase greater than 10% had a significant increase in risk for CKD (OR, 1.27; 95% CI, 1.06 to 1.53). CONCLUSION: In this large cohort of initially healthy men, BMI was associated significantly with increased risk for CKD after 14 years. Strategies to decrease CKD risk might include prevention of overweight and obesity.

National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.

Hospitalization during advancing chronic kidney disease.

BACKGROUND: The care of patients with end-stage renal disease (ESRD) is associated with substantial costs to society, much of which is accounted for by a high rate of hospitalization. However, the influence of declining kidney function on hospitalization as ESRD approaches is not well understood. METHODS: We performed a retrospective cohort study of national data to evaluate the frequency of hospitalizations among patients with chronic kidney disease (CKD) who reached ESRD and had at least 2 years of Medicare eligibility before initiation of dialysis therapy. The study period for each patient extended from 2 years before to 6 months after the initiation of dialysis therapy. RESULTS: The study cohort was composed of 109,321 patients with a mean age of 75 years, all of whom initiated long-term dialysis therapy between 1995 and 1998. Mean hospitalization rate was 134 hospitalizations/1,000 patient-months at risk (PMAR). Hospitalization rates gradually increased as ESRD approached, peaking in the 3 months immediately after the initiation of dialysis therapy at 487 hospitalizations/1,000 PMAR. Cause-specific hospitalization rates mirrored this trend and were greatest for placement of vascular access and diagnoses related to cardiovascular (CVD) and infectious disease. CONCLUSION: Hospitalizations during CKD become more frequent with the approach of ESRD. The majority of these hospitalizations, both before and after the initiation of dialysis therapy, are caused by comorbidity related to CKD. These hospitalizations may be favorably impacted on by heightened attention to the prevention and management of CVD and timely placement of vascular access during CKD.

Predictors of ARF after cardiac surgical procedures.

BACKGROUND: In a pilot study, a low preoperative serum ferritin level predicted increased risk for acute renal failure (ARF) after cardiopulmonary bypass. It was hypothesized that this may reflect a decreased ability to bind free iron and defend against oxidative stress. However, the pilot study was performed in a small number of patients (n = 30) operated on by a single surgeon. The purpose of this study was to validate whether the serum ferritin level predicts ARF in a larger sample. METHODS: The present study evaluated 120 patients who underwent procedures performed by eight surgeons at another tertiary referral center. Data were collected prospectively and included patient characteristics, laboratory studies, procedure types, and postoperative course. ARF was defined as a 25% or greater increase in creatinine level 48 hours after surgery. RESULTS: The frequency of ARF was 42%, but no patient required dialysis therapy. Preoperative serum ferritin levels did not differ in the groups with and without ARF (158 +/- 119 and 163 +/- 125 ng/mL, respectively), and rates of ARF did not differ when examined by ferritin quartiles. ARF was more frequent in those who underwent valve surgery (54% versus 35% in patients who did not undergo valve procedures; P = 0.044). The odds ratio for ARF after valve surgery was 2.58 (95% confidence interval, 1.06 to 6.29; P = 0.037), adjusted for longer times of surgery and aortic cross-clamp. Most excess ARF occurred in those who underwent aortic valve replacement (AVR; 62%; P = 0.014 versus nonvalve procedures). CONCLUSION: Low preoperative serum ferritin level was not confirmed to predict ARF after cardiac surgery. Valve procedures, particularly AVR, increased the risk for ARF.

Chronic kidney disease in the United States: an underrecognized problem.

The continued growth of the population with end-stage renal disease (ESRD) is partially related to the underrecognition of earlier stages of chronic kidney disease (CKD) and risk factors for the development of CKD. There are several published estimates of the prevalence of CKD in the United States. From Third National Health and Nutrition Examination Survey data it has been estimated that there are 6.2 million individuals with serum creatinine levels at or above 1.5 mg/dL, or 8.3 million individuals with decreased glomerular filtration rate (<60 mL/min/1.73 m (2)). Estimates of prevalence from a health maintenance organization study suggest that there are 4.2 million Americans with persistently elevated serum creatinine levels. In addition to the high prevalence, several studies have shown that CKD is associated with increased risk for cardiovascular disease, hospitalizations, and mortality. To promote earlier detection of CKD, The National Kidney Foundation Guidelines for CKD: Evaluation, Classification and Stratification, recommended screening individuals at increased risk for CKD, such as patients with diabetes, high blood pressure, and family history of kidney disease. Therapeutic interventions to delay progression and reduce comorbidity, such as cardiovascular disease, are more likely to be effective if they are implemented early in the course of CKD.

General medical care among patients with chronic kidney disease: opportunities for improving outcomes.

Suboptimal health care during advancing chronic kidney disease (CKD) may result in greater morbidity and cost once dialysis is started and may preclude future transplantation. Medicare data were examined for the prevalence of selected general health, diabetes, and CKD interventions in a national cohort of patients in the 2 yr before dialysis initiation and compared with a contemporaneous non-CKD cohort. A total of 24,778 individuals who were aged > or =67 yr composed the CKD cohort, and 1,046,136 individuals who were aged > or =67 yr did not have CKD. Among patients with diabetes and CKD, fewer than two thirds had claims for eye examinations, 75% for HbA(1C) testing, and 68% for lipid testing, with similar proportions in the non-CKD cohort. Among those without diabetes, 47 and 54% of the CKD and non-CKD cohorts, respectively, had claims for lipid testing. Fewer than 50 and 15% had claims for influenza and pneumococcal vaccination, respectively, with slightly lower proportions among patients with CKD. Claims for cancer tests were found for 14 to 41% and 29 to 52% of individuals with and without CKD, respectively, depending on the type of cancer. A greater proportion of patients with diabetes tended to have claims for tests in both cohorts. In the CKD cohort, claims for anemia testing and parathyroid hormone levels were available in fewer than 50 and 15%, respectively, and claims for permanent vascular access were found for only 30% of hemodialysis patients. This study provides further evidence that patients with CKD may not be receiving general health and CKD care according to current recommendations.

Atherosclerotic renovascular disease in United States patients aged 67 years or older: risk factors, revascularization, and prognosis.

BACKGROUND: Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS: Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic renovascular disease in the 2 years preceding December 31, 1999 (N= 1,085,250), followed until December 31, 2001. RESULTS: The incidence of atherosclerotic renovascular disease was 3.7 per 1000 patient-years. Major antecedent associations [P < 0.05, with adjusted hazards ratios (HR) > 1.5] included chronic kidney disease (adjusted HR 2.54), hypertension (2.42), peripheral vascular disease (2.00), and atherosclerotic heart disease (1.70). Adverse event rates after incident atherosclerotic renovascular disease greatly exceeded those in the general population (P < 0.0001): atherosclerotic heart disease, 303.9 per 1000 patient-years (vs. 73.5 in the general population); peripheral vascular disease, 258.6 (vs. 52.2); congestive heart failure, 194.5 (vs. 56.3); cerebrovascular accident or transient ischemic attack, 175.5 (vs. 52.9); death, 166.3 (vs. 63.3); and renal replacement therapy, 28.8 (vs. 1.3). Among atherosclerotic renovascular disease patients, 16.2% underwent a renal revascularization procedure, percutaneously in 96%. Revascularization was not associated with renal replacement therapy, congestive heart failure, or death but was associated with atherosclerotic heart disease (adjusted HR 1.42) (P= 0.004) and peripheral vascular disease (adjusted HR 1.38) (P= 0.002). CONCLUSION: Atherosclerotic renovascular disease is strongly associated with cardiovascular disease, both past and future. Absolute cardiovascular risk exceeds that of renal replacement therapy. Renal revascularization is used selectively and shows inconsistent associations with cardiovascular outcomes, renal replacement therapy, and death.

The value of vaccination in chronic kidney disease.

There has been much attention directed toward the high mortality of patients with end-stage renal disease (ESRD), with much of the focus on cardiovascular disease. However, infectious disease is the second most common cause of death in late-stage chronic kidney disease (CKD) patients. Although CKD patients are immunocompromised, some vaccines such as influenza, retain their efficacy and reduce infection rates with a standard immunization schedule. Other vaccines, such as hepatitis B and pneumococcal vaccines, require more frequent and/or higher doses to produce and maintain protective antibody levels. Attention has recently been given to the efficacy of influenza vaccination in ESRD patients in reducing morbidity and mortality. Centers with vaccination protocols have demonstrated reduced infection rates and resultant decreased morbidity and mortality. It could be extrapolated from this that widespread vaccination would reduce the total cost of ESRD patient care, and potentially improve patient well-being. However, vaccination appears to be underutilized in CKD patients, and it is a readily available intervention to improve outcomes.

Pharmacokinetics of oral micronized beta-estradiol in postmenopausal women receiving maintenance hemodialysis.

BACKGROUND: Although 11% of postmenopausal women with end-stage renal disease (ESRD) are prescribed hormone replacement therapy (HRT), the appropriate use remains poorly explored. Although there remains controversy surrounding the benefits of HRT, it may be of particular interest in this population, which has a high risk of bone loss and a fourfold increase in fracture risk compared to the general population. However, the appropriate dose of estrogen for use in postmenopausal women with ESRD is not known. The objective of this study was to evaluate the steady-state pharmacokinetics of oral micronized beta-estradiol in postmenopausal women with ESRD compared with postmenopausal women with normal renal function in order to determine equivalent dosing. METHODS: Six postmenopausal women with ESRD receiving maintenance hemodialysis and 6 healthy postmenopausal controls received 14 days of micronized beta-estradiol (1.0 mg for control, 0.5 mg for ESRD). Blood, urine, and dialysate samples were obtained during a dosage interval on day 14. Estradiol, estrone, albumin, and sex-hormone binding globulin (SHBG) concentrations were determined. Free estradiol concentrations were calculated using a previously described method. RESULTS: Women with ESRD had significantly lower serum albumin (610 +/- 31 micromol/L vs. 684 +/- 83 micromol/L) and SHBG (78 +/- 17 vs. 118 +/- 13 nmol/L) than control subjects. Total clearance of estradiol was not significantly different. Due to difference in binding, free estradiol concentrations were significant higher in ESRD women (53.2 +/- 17.7 pg/mL) than control women (43.5 +/- 8.7 pg/mL), despite receiving 50% of the dose. There was no significant difference in estrone concentrations. Clearance of both estradiol and estrone in the dialysate was minimal. CONCLUSION: Women with ESRD should receive approximately 50% of the dose typically prescribed to women without ESRD.