**4. Discussion**

CKD is a widespread health problem in the world and anemia is a common complication. Anemia conveys significant risk for cardiovascular disease, faster progression of renal failure and decreased quality of life.

Ferrokinetic studies provided on last decades important insights into human iron homeostasis in vivo. More recently, modern molecular biology and genetic studies of model organisms have extended our knowledge of normal iron biology and led to the identification of new key players in iron homeostasis and the detailed understanding of human iron disorders.

New insights in iron metabolism and the understanding of iron homeostasis, erythropoietin production and regulation and the relationships between mediators of inflammation and bone marrow erythropoiesis are modifying the traditional view on anemia, in special anemia of chronic disease. The anemia of CKD is among them, with the added burden of erythropoietin deficiency. Recent elucidations of specifically disrupted points of erythroid marrow function by inflammatory mediators, especially proinflammatory cytokines and inflammation-mediated induction of hepcidin, have improved our understanding of erythropoiesis-stimulating agents (ESAs) hyporesponsiveness.

These patients require a thorough evaluation to identify and correct causes of anemia other than erythropoietin deficiency. The mainstay of treatment of anemia secondary to CKD has become ESAs. The use of ESAs does carry risks and these agents need to be used judiciously. Iron deficiency often co-exists in this population and must be evaluated and treated. Correction of iron deficiency can improve anemia and reduce ESA requirements. Partial, but not complete, correction of anemia is associated with improved outcomes in patients with CKD.

Undoubtedly, the advent of ESA and various intravenous iron preparations has resulted in a much more effective management of anemia of CKD, allowing clinicians to maintain hemoglobin levels in certain desired ranges and to effectively treat iron deficiency. Among the emerging challenges are the risks associated with administering high ESA and iron doses, leading to elevated hemoglobin levels and iron overload. Goal-oriented treatment strategies targeting "desirable" hemoglobin and iron levels are now the norm in clinical nephrology.

Healthy ACD ACD/ IDA ACD/

LHD% 2.1 14.2 24.1 10.5 (0.9-4.1) (4.5-68.9) (5.1-68.9) (4.5-14.0)

> 20.3 (6.6)

Table 3. sTfR values, mean and standard deviation (SD) and LHD % values, median and 5th - 95th interquartiles in a group of 120 healthy subjects, 85 anemia of chronic disease patients

CKD is a widespread health problem in the world and anemia is a common complication. Anemia conveys significant risk for cardiovascular disease, faster progression of renal

Ferrokinetic studies provided on last decades important insights into human iron homeostasis in vivo. More recently, modern molecular biology and genetic studies of model organisms have extended our knowledge of normal iron biology and led to the identification of new key players in iron homeostasis and the detailed understanding of

New insights in iron metabolism and the understanding of iron homeostasis, erythropoietin production and regulation and the relationships between mediators of inflammation and bone marrow erythropoiesis are modifying the traditional view on anemia, in special anemia of chronic disease. The anemia of CKD is among them, with the added burden of erythropoietin deficiency. Recent elucidations of specifically disrupted points of erythroid marrow function by inflammatory mediators, especially proinflammatory cytokines and inflammation-mediated induction of hepcidin, have improved our understanding of

These patients require a thorough evaluation to identify and correct causes of anemia other than erythropoietin deficiency. The mainstay of treatment of anemia secondary to CKD has become ESAs. The use of ESAs does carry risks and these agents need to be used judiciously. Iron deficiency often co-exists in this population and must be evaluated and treated. Correction of iron deficiency can improve anemia and reduce ESA requirements. Partial, but not complete, correction of anemia is associated with improved outcomes in

Undoubtedly, the advent of ESA and various intravenous iron preparations has resulted in a much more effective management of anemia of CKD, allowing clinicians to maintain hemoglobin levels in certain desired ranges and to effectively treat iron deficiency. Among the emerging challenges are the risks associated with administering high ESA and iron doses, leading to elevated hemoglobin levels and iron overload. Goal-oriented treatment strategies targeting "desirable" hemoglobin and iron levels are now the norm in

30.8 (8.3)

sTfR (nmol/L) 15.1

failure and decreased quality of life.

**4. Discussion** 

human iron disorders.

patients with CKD.

clinical nephrology.

(2)

(ACD), 61 of them iron replete and 24 iron deficient (ACD/IDA).

erythropoiesis-stimulating agents (ESAs) hyporesponsiveness.

Iron replete

17.9 (6.1) The treatment of renal anemia with rHuEpo has improved the quality of life and outcome of hemodialysis patients. The efficacy of this therapy depends on the identification and correction of resistance factors, such as vitamin deficiency, inflammation, hyperparathyroidism. The major cause of resistance to rHuEpo is iron deficiency. The assessment of functional iron deficiency remains a daily challenge for nephrologists and their need to be careful of an appropriate use of the resources and the need to optimize patient treatment.

A better understanding of iron homeostasis enhance treatments for anemia. Subsequently, evidence-based diagnostic strategies must be developed, using both conventional and innovative laboratory tests, to differentiate between the various causes of distortions of iron metabolism.

Efforts have been made to evaluate some readily available and relatively inexpensive laboratory parameters as indirect markers of iron restricted erythropoiesis and iron availability in a clinical context influenced by inflammation and acute phase reaction.

The assessment of iron requirements and monitoring of therapy require accurate markers. It is desirable to seek alternative markers for iron status widely available. LHD% is related to iron availability for erythropoiesis in the previous weeks, derived from MCHC, it could be calculated in different hematological counters.

The data exposed show the reliability of LHD% in distinguishing iron deficient patients with and without inflammation. This parameter could help to the correct classification of patients with iron deficiency when the traditional markers become unreliable: it is particularly challenging the accurate assessment of iron status in chronically ill patients such as CKD.

LHD % correlates with the percentage of hypochromic erythrocytes as reported by Siemens analyzers (%Hypo) and comparing the results obtained for LHD% with those of sTfR the reliability of LHD% in distinguishing iron deficient patients with and without inflammation has been stated.

In conclusion, these results show that the new LHD% parameter is useful for diagnosing iron deficiency and a reliable parameter recognizing subsets of patients and therefore improving the diagnosis and management of anemia.The analysis of LHD% can be performed simultaneously in the course of routine blood counts, with no incremental costs and no additional needs of more blood sampling. In conjunction with standard blood cell counts and iron parameters could enable the diagnosis to be made rapid and accurately.

More prospective and longitudinal studies are needed in order to verify the results obtained, to determine their reliability for clinical purposes or whether the additional information provided could be used in managing the iron requirements of patients in different clinical situations.
