Dynamics of erythropoiesis following renal transplantation

Abstract

We examined the temporal dynamics of the correction of anemia following renal transplantation in 65 recipients using a sensitive radioimmunoassay for erythropoietin to determine the effects of modern immunosuppressive agents, delayed graft function, and early acute rejection. Pretransplant mean erythropoietin (25.6 +/- 3.3 mU/ml) was only 25% of the expected value at the mean hematocrit of 27.2 +/- 0.7, and erythropoietin correlated positively with hematocrit (r = 0.37, P less than 0.05). Following onset of graft function, erythropoietin increased to 109 +/- 13 mU/ml and then decreased in a negative feedback fashion over the next several months. Delayed graft function was associated with delay in the assumption of this orderly process irrespective of the immunosuppressive regimen used. Cyclosporine A produced a biphasic response despite delayed graft function in recipients with underlying adult polycystic kidney disease. Correction of anemia required resumption of graft function. Onset of acute graft rejection within the first month posttransplantation (14 episodes in 11 patients) abrogated the hematopoietic response until the rejection was successfully reversed. We conclude that a major cause for the anemia of renal failure is subnormal production of erythropoietin. Following transplantation, anemia corrects in an orderly manner with restoration of the normal biofeedback process between erythropoietin and red cell mass. This process is delayed by failure of graft to function initially and interrupted by acute early rejection, re-commencing following successful reversal.

Role of excretory graft function for erythropoietin formation after renal transplantation

“…This temporal pattern confirms qualitatively and extends two previous studies, also employing radioimmunoassays, that demonstrated early increases of irEPO after RTX [5,7]. In contrast to Besarab et al [7], who found a typically a fourfold increase in EPO within the first 2 post-transplant weeks, increases were less pronounced, and only about two-to threefold in our patients. This difference may be related to various factors, including individual haemoglobin concentrations, immunosuppression and additional drug therapy.…”

“…Previous studies addressing the correction of anaemia after renal transplantation (RTX), have shown that increases in EPO levels precede the reticulocytosis and rise in haematocrit following RTX [5,6,7] and in some cases EPO rose as early as the first to third posttransplant day [5,7]. An investigation by Besarab ef al.…”

Report Card on Living Kidney Donation

“…A previous study by van Dullemen et al demonstrated that EPO production decreases and EPO resistance increases relative to the decline in renal excretory function (33). Even without a significant decline in renal excretory function, DGF, acute tubulointerstitial rejection (7,34), chronic rejection (34) and possibly long-term calcineurin inhibitor toxicity (35) may cause diminished EPO production.…”

“…Early PTA has been attributed to blood loss at the time of surgery, frequent blood draws, iron depletion (2,4,(6)(7)(8), the persistent effect of uremic toxins (6), low erythropoietin (EPO) levels (6,9,10), EPO resistance (6,(9)(10)(11)(12) and the negative effects of immunosuppression on erythropoiesis (13,14).…”

Posttransplantation Anemia

“…The underlying factors causing anemia in the setting of rejection may include suboptimal kidney function, more intensified immunosuppression, acute inflammation, or perhaps a chronic inflammatory state leading to EPO resistance. Acute rejection can lead to a rapid decrease in EPO levels that is reversible on treatment of rejection (43). Molecular studies have shown that inflammatory genes are upregulated in deceased-donor kidney biopsies in patients with PTA (44).…”