High levels of a hematopoiesis inhibitor in renal failure raise erythropoietin needs

from medicontext.co.il

WESTPORT, CT (Reuters Health) – Elevated levels of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a physiologic inhibitor of hematopoiesis, can occur in chronic renal failure patients and increase their erythropoietin requirements. Angiotensin-converting enzyme (ACE) inhibitor use can also produce elevated AcSDKP levels.

French investigators led by Dr. Vincent Praloran, from the Universitי Victor Segalen Bordeaux in Limoges, measured the AcSDKP plasma levels of 176 patients with chronic renal failure and 51 healthy subjects. The renal failure group included 120 patients who received hemodialysis and 56 patients who did not. Eighteen patients in the hemodialysis group and 21 patients in the nondialysed group received ACE inhibitors.

Chronic renal failure patients had substantially higher AcSDKP levels than control subjects, the authors found. ACE inhibitor-treated patients had levels that were fourfold higher than those of other patients. Hemodialysis was associated with a significant reduction in AcSDKP levels and in AcSDKP half-life.

A significant but weak direct correlation between AcSDKP levels and erythropoietin needs was noted in hemodialysis patients overall, the researchers state. A much stronger association was found in the subset of patients who received ACE inhibitors.

The current findings suggest that AcSDKP is a uremic toxin, similar to other hematopoiesis inhibitors described in the literature that can produce erythropoietin resistance at high levels, Dr. Praloran's team point outs out.

Dr. Iain C. Macdougall, from the Department of Renal Medicine at King's College Hospital in London, comments that the current report not only provides "interesting data to suggest why some patients receiving ACE inhibitors might be less responsive to erythropoietin, but it also provides a putative mechanism whereby ACE inhibitors but not angiotensin II blockers could cause this effect."

In his editorial, Dr. Macdougall suggests that it might be worthwhile trying angiotensin II blocker therapy in renal patients who clearly need some form of therapy but who seem to have developed ACE inhibitor-induced erythropoietin resistance.

Am J Kidney Dis 2001;38:510-517,649-651

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