New Perspectives in Chronic Renal Insufficiency
Defining a renal anemia management period,☆☆

https://doi.org/10.1053/ajkd.2000.19927Get rights and content

Abstract

Estimates of the prevalence of anemia during chronic renal insufficiency (CRI) vary depending on how anemia is defined. An analysis of patients beginning dialysis in the United States found that 67% had a hematocrit of less than 30% and 51% had a hematocrit of less than 28%. The anemia of CRI, therefore, appears to be prevalent even as it is underrecognized and undertreated—despite the widespread realization that there is much to be gained by treatment with recombinant human erythropoietin, with little risk of accelerating the progression of kidney disease. It is difficult to separate the effects of anemia in CRI from those of other comorbid conditions, but it is clear that anemia is a strong predictor of mortality and cardiac morbidity. Correction of anemia would be expected to negate the contribution of anemia to the mortality and cardiac morbidity associated with CRI. While this hypothesis is well-validated in hemodialysis patients, data in the population with CRI are preliminary but encouraging. Recent small prospective studies have established that treatment of anemia with recombinant human erythropoietin can reverse some degree of the cardiac morphological changes seen in CRI. While awaiting the results of large long-term clinical trials, the concept of the renal anemia management period (RAMP) draws attention and focus to the need for proactive and aggressive treatment of anemia among patients with CRI. The RAMP is defined as the period of time after the onset of CRI during which anemia develops, requiring diagnosis and treatment. Treatment of anemia during the RAMP has the potential to ameliorate, or even prevent, significant future morbidity in patients with CRI.

Section snippets

Overview

In nephric anemic dialysis patients, the mean baseline values of EPO (19 to 30 mU/mL) are much lower than those observed in healthy patients with the same degrees of anemia. Thus, although the kidney at end-stage renal disease (ESRD) continues to produce some EPO despite effective cessation of excretory function, it is incapable of augmenting EPO production in response to an appropriate hypoxic stimulus.4 Although few data are available on sequential EPO levels in patients with CRI, EPO

Pathogenesis

The persistent observations of “inappropriately” low EPO levels in virtually all cases of kidney disease14 indicate that the predominant factor in the anemia of kidney failure is the inadequate production of endogenous EPO by diseased kidneys. Shortened RBC survival may also play a role but is probably more instrumental in determining the severity of anemia. Kidney disease thus affects the RBC mass by interfering with both RBC production and life span through disruption of the kidney’s

The manifestations and implications of anemia in CRI

Very few studies have directly addressed the manifestations and implications of anemia in CRI. This may be because it is almost impossible to distinguish between the clinical effects of anemia and those due to mild azotemia and because anemia and the other concurrent comorbidities of CRI (eg, disturbances in divalent ion metabolism or subtle imbalances in electrolyte or acid-base status) can impact negatively on clinical status. Partial information, however, can be gleaned from longitudinal

The renal anemia management period (RAMP) and the impact of treatment

As described, the anemia of CRI is prevalent, occurring in a significant percentage of CRI patients; it is underrecognized, as a significant percentage of patients entering treatment for ESRD are also anemic (sometimes severely so); and it is undertreated, in that anemia responds to currently available therapeutic options that apparently are not being used often or effectively enough. Consequently, we propose the establishment and widespread recognition of a RAMP, defined as the period of time

Unanswered questions and research needs

There has been a strong tendency, as noted by Lindberg et al in this supplement (pp. S52-S61), to extrapolate results from rHuEPO trials in hemodialysis patients to other patient populations. In this era of evidence-based medicine, therapeutic and economic decisions based on such extrapolations clearly are no longer acceptable. The research agenda of the next decade must address questions that are unique to the anemia of CRI patients: What is the definition of anemia in patients with kidney

Conclusion

Anemia, an underrecognized and undertreated concomitant of CRI, is associated with significant clinical and functional consequences. Moreover, during the CRI period there is strong evidence for detrimental effects on QOL, exercise tolerance, and related factors that impact activities of daily living. In addition, it is indirectly linked to cardiac morphologic and functional changes, most specifically LVH and progression of LVMI abnormalities.

However, the most ominous effect of the anemia of CRI

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    Supported by an unrestricted educational grant from Amgen, Inc.

    ☆☆

    Address reprint requests to Anatole Besarab, MD, Professor of Medicine, West Virginia University Department of Medicine, Robert C. Byrd Health Science Center, PO Box 9165, Morgantown, WV 26506. E-mail: [email protected]

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