This Month in AJKD

Article Outline

• Thrombocytosis, Iron Depletion, Epoetin, and Mortality in ESRD
• Progression of Kidney Disease in CKD Patients
• Estimated GFR Reporting in the United States
• Blood Pressure Variability in Hemodialysis Patients
• Spontaneous Dissection of Segmental Arteries

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Thrombocytosis, Iron Depletion, Epoetin, and Mortality in ESRD 

See Streja et al, pages 727-736; and Littlewood, pages 642-644.

Recent studies have indicated a potential link between the relative state of iron depletion and higher mortality in patients with kidney failure treated by long-term hemodialysis. One hypothesis is that the increased risk of mortality with higher epoetin dosing may reflect the effects of thrombocytosis induced by relative iron depletion. In this issue, Streja et al explore this hypothesis in a retrospective study of over 40,000 hemodialysis patients at a large US dialysis provider. Thrombocytosis, defined as a platelet count of greater than 300 x 10⁹/L, was present in 15% and was associated with a 30% higher weekly dose of epoetin, lower transferrin saturation, and lower serum ferritin concentration. In fully adjusted models, thrombocytosis was associated with an increased risk of mortality at all hemoglobin levels, and, notably, adjusted 3-year risk of mortality in patients with hemoglobin greater than or equal to 13 g/dL was 21% higher in patients with thrombocytosis but no different in patients without thrombocytosis when compared to a reference group with hemoglobin of 11 to 12 g/dL. An editorial by Dr Littlewood notes that the results presented by Streja and colleagues suggest that increased use of intravenous iron to prevent iron deficiency could reduce the incidence of reactive thrombocytosis and hence reduce thrombotic complications and mortality; however, he stresses that the mechanism of increased mortality risk with higher-dose epoetin remains uncertain and that these findings, while supporting a novel and interesting hypothesis, require further investigation.

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Progression of Kidney Disease in CKD Patients 

See Johnson et al, pages 653-660; Levin et al, pages 661-671; and Kurth and Glynn, pages 635-637.

In this issue, 2 articles present prediction models for the progression of kidney disease: one classifies patients with chronic kidney disease (CKD) into risk levels for adverse outcomes, and another identifies and describes individual determinants of kidney disease progression, dialysis, and death. In the 1st article, Johnson et al derived and internally validated a risk score to predict the 5-year risk for developing kidney failure in an unreferred clinical population (the Kaiser Permanente Northwest health maintenance organization) with stage 3 to 4 CKD (n = 9,782). This score easily obtained demographic and laboratory characteristics, including age, sex, estimated glomerular filtration rate (eGFR), diabetes, anemia, and hypertension. In this population 3.3% initiated dialysis or underwent transplantation, 32% died without prior dialysis or transplantation, and 10% left the health maintenance organization before completing 5 years of follow up. The risk score had excellent discrimination, correctly identifying individuals developing or not developing kidney failure 89% of the time with effective calibration. In the 2nd article, Levin et al describe the risk factors for progression to kidney failure in stage 4 CKD patients referred to nephrologists in British Columbia, Canada (n = 4,231). In this population, 25% initiated dialysis or received a kidney transplant within 2 years, while only 7% died. Risk factors for more rapid progression of kidney disease included younger age, male sex, higher eGFR, higher systolic and diastolic blood pressure, lower hemoglobin, higher phosphorus and parathyroid hormone levels, greater proteinuria, and non-use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, while risk factors for death included older age, lower diastolic blood pressure, lower hemoglobin, and higher phosphorus and parathyroid hormone levels. An editorial by Drs Kurth and Glynn stresses that the logical next step following risk factor identification and development of prediction models is the design and implementation of future studies to evaluate how this knowledge can prevent disease.

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Estimated GFR Reporting in the United States 

See Accetta et al, pages 778-787; and Miller, pages 645-648.

While routine laboratory reporting of estimated glomerular filtration rate (eGFR) may help clinicians better detect kidney disease, the current national prevalence of eGFR reporting in clinical laboratories is unknown. In this issue, Accetta et al report results of the National Kidney Disease Education Program (NKDEP) 2006 to 2007 survey of 6,350 clinical laboratories in the United States. They found that, of laboratories reporting serum creatinine values, only 38.4% report eGFR (laboratories associated with physician offices, 25.8%; hospitals, 43.6%; independent, 38.9%; community clinics, 47.2%; health fair/insurance/public health, 45.5%; and other, 43.2%), and that laboratories vary greatly in their conventions for reporting of serum creatinine values. An editorial by Dr Miller, Chair of the NKDEP Laboratory Working Group, reviews the progress of creatinine standardization and updates the status eGFR reporting. According to the June 2008 Chemistry Survey by the American College of Pathologists, 70% of clinical laboratories were reporting eGFR and 77% of those laboratories were reporting eGFR each time the serum creatinine was measured.

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Blood Pressure Variability in Hemodialysis Patients 

See Brunelli et al, pages 716-726; and Jafar and Ebrahim, pages 638-641.

Blood pressure variability (BPV) is one putative risk factor for cardiovascular disease and mortality among hemodialysis patients; however, dialysis patients have extremely variable blood pressure, leading to difficulty identifying a single metric that best captures overall risk in this population. In this issue, Brunelli et al perform a retrospective cohort study of patients from the ArMORR cohort to identify a valid measure of long-term BPV in dialysis patients and to determine if an association between BPV and all-cause mortality exists. They found that, among 4 candidate BPV metrics, only the average residual–intercept ratio, an easily calculable metric of BPV that can distinguish between BPV and temporal blood pressure trend, adequately distinguished BPV from absolute blood pressure level and temporal blood pressure trend. In the primary analysis, each 1-SD increase in systolic and diastolic BPV was associated with adjusted hazard ratios (95% confidence intervals) for all-cause mortality of 1.13 (1.03 to 1.23) and 1.15 (1.06 to 1.26), respectively. An editorial by Drs Jafar and Ebrahim further examines the practice of BPV measurement in the general population and in dialysis patients, and whether or not it is of prognostic value.

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Spontaneous Dissection of Segmental Arteries 

See Yamanouchi et al, pages 788-791.

AJKD has developed a new feature designed to illustrate applications and interpretations of imaging in clinical nephrology. In this issue, Yamanouchi et al present the first Imaging Teaching Case, describing a spontaneous isolated renal segmental arterial dissection without obvious underlying etiology. A previously healthy 48-year-old man presented with the symptoms of sudden onset of flank pain, nausea, and vomiting. However, other typical findings of renal artery dissection and subsequent infarct, including hypertension, hematuria, and increased levels of lactate dehydrogenase, were absent. In this Imaging Teaching Case, Yamanouchi et al describe the role for diffusion-weighted magnetic resonance imaging (DWI) to detect ischemic lesions early in the clinical course. DWI is effective for confirming the diagnosis of acute renal segmental infarction in the absence of definitive laboratory findings. AJKD encourages its readers to submit Imaging Teaching Cases for publication. Further information can be found at www.editorialmanager.com/ajkd/AuthInstr.html.

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