Trends in anemia management in US hemodialysis patients 2004-2010.

BACKGROUND: There have been major changes in the management of anemia in US hemodialysis patients in recent years. We sought to determine the influence of clinical trial results, safety regulations, and changes in reimbursement policy on practice. METHODS: We examined indicators of anemia management among incident and prevalent hemodialysis patients from a medium-sized dialysis provider over three time periods: (1) 2004 to 2006 (2) 2007 to 2009, and (3) 2010. Trends across the three time periods were compared using generalized estimating equations. RESULTS: Prior to 2007, the median proportion of patients with monthly hemoglobin >12 g/dL for patients on dialysis 0 to 3, 4 to 6 and 7 to 18 months, respectively, was 42%, 55% and 46% declined to 41%, 54%, and 40% after 2007, and declined more sharply in 2010 to 34%, 41%, and 30%. Median weekly Epoeitin alpha doses over the same periods were 18,000, 12,400, and 9,100 units before 2007; remained relatively unchanged from 2007 to 2009; and decreased sharply in the patients 3-6 and 6-18 months on dialysis to 10,200 and 7,800 units, respectively in 2010. Iron doses, serum ferritin, and transferrin saturation levels increased over time with more pronounced increases in 2010. CONCLUSION: Modest changes in anemia management occurred between 2007 and 2009, followed by more dramatic changes in 2010. Studies are needed to examine the effects of declining erythropoietin use and hemoglobin levels and increasing intravenous iron use on quality of life, transplantation rates, infection rates and survival.

Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. Mutations in COL4A3 and COL4A4 are known to cause Alport syndrome (AS), thin basement membrane nephropathy, and to result in pathognomonic glomerular basement membrane (GBM) findings. Secondary FSGS is known to develop in classic AS at later stages of the disease. Here, we present seven families with rare or novel variants in COL4A3 or COL4A4 (six with single and one with two heterozygous variants) from a cohort of 70 families with a diagnosis of hereditary FSGS. The predominant clinical finding at diagnosis was proteinuria associated with hematuria. In all seven families, there were individuals with nephrotic-range proteinuria with histologic features of FSGS by light microscopy. In one family, electron microscopy showed thin GBM, but four other families had variable findings inconsistent with classical Alport nephritis. There was no recurrence of disease after kidney transplantation. Families with COL4A3 and COL4A4 variants that segregated with disease represent 10% of our cohort. Thus, COL4A3 and COL4A4 variants should be considered in the interpretation of next-generation sequencing data from such patients. Furthermore, this study illustrates the power of molecular genetic diagnostics in the clarification of renal phenotypes.

Pathophysiology of anemia and erythrocytosis.

An increasing understanding of the process of erythropoiesis raises some interesting questions about the pathophysiology, diagnosis and treatment of anemia and erythrocytosis. The mechanisms underlying the development of many of the erythrocytoses, previously characterised as idiopathic, have been elucidated leading to an increased understanding of oxygen homeostasis. Characterisation of anemia and erythrocytosis in relation to serum erythropoietin levels can be a useful addition to clinical diagnostic criteria and provide a rationale for treatment with erythropoiesis stimulating agents (ESAs). Recombinant human erythropoietin as well as other ESAs are now widely used to treat anemias associated with a range of conditions, including chronic kidney disease, chronic inflammatory disorders and cancer. There is also heightened awareness of the potential abuse of ESAs to boost athletic performance in competitive sport. The discovery of erythropoietin receptors outside of the erythropoietic compartment may herald future applications for ESAs in the management of neurological and cardiac diseases. The current controversy concerning optimal hemoglobin levels in chronic kidney disease patients treated with ESAs and the potential negative clinical outcomes of ESA treatment in cancer reinforces the need for cautious evaluation of the pleiotropic effects of ESAs in non-erythroid tissues.