Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non‐diabetic chronic renal failure

Abstract

Although the DN patients have inappropriately low EPO levels for the severity of their anaemia, they can mount an appropriate EPO response to moderate hypoxia. The mechanism underlying the EPO-deficient anaemia present in some diabetic patients remains unclear.

Lower haemoglobin level and subsequent decline in kidney function in type 2 diabetic adults without clinical albuminuria

“…Haemoglobin concentrations were found to be significantly decreased in patients with microalbuminuria compared to patients with normoalbuminuria [3]. Autonomic neuropathy has been postulated to play a role in erythropoietin dysregulation in diabetic patients [9,10]. In addition, nutrient deficiencies including iron, folate, and vitamin B12, or undetected malignant diseases or anaemia of chronic inflammation (formally termed anaemia of chronic diseases) [25] may contribute to anaemia in diabetic subjects.…”

“…However, the precise mechanisms of anaemia in diabetic patients are unknown, and a decline in haemoglobin concentrations appears to occur earlier in diabetic patients with nephropathy than in patients with non-diabetic kidney diseases [2][3][4][5][6][7]. In addition to erythropoietin deficiency due to tubulointerstitial changes, which is an early morphological alteration of diabetic nephropathy [8], autonomic neuropathy [9,10] and increased serum advanced glycation end-products [11] may participate in the pathogenesis of anaemia in diabetic kidney disease.…”

Anaemia in diabetes: is there a rationale to TREAT?

“…In fact, endogenous erythropoietin production has been suggested as a possible marker of the severity of tubulointerstitial damage in diabetes [19]. However, the fact that patients with diabetes and anaemia are able to mount an appropriate response to acute hypoxia [23], suggests that the cells which produce erythropoietin are not simply lost in diabetes. Rather that the 'tissue oxygenationerythropoietin-Hb' feedback mechanism may operate at a lower set-point in the diabetic tubule and peritubular milieu.…”

Hif-1

“…In principle, this could be because the EPO-producing cells are lost, because they experience higher levels of oxygen for a given hematocrit, or because the relationship between local oxygenation and EPO production is altered. Some clues as to how EPO is dysregulated in renal disease come from clinical observations that EPO production is commonly maintained in patients with inherited or acquired cystic disease and is impaired early in some patients with diabetes and in patients with primary autonomic neuropathy (93)(94)(95). Even in patients who are treated with dialysis, the remnant kidneys produce some EPO, and before the advent of recombinant EPO, it was widely recognized that removal of the native kidneys increased transfusion requirements.…”