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.

A role for histamine in the pathogenesis of uremic pruritus was investigated in maintenance hemodialysis patients. Venous plasma histamine levels, as determined by radioenzymatic assay, were significantly higher (p less than 0.05) in hemodialysis patients with pruritus (368 +/- 103 pg/ml [mean +/- SEM], n = 6) than in those without pruritus (146 +/- 22 pg/ml, n = 5) and in normal controls (142 +/- 16, n = 5). Arteriovenous fistula histamine levels (202 +/- 52 pg/ml, n = 6) were significantly lower (p less than 0.05) than simultaneously drawn venous samples. Markedly elevated histamine-degrading enzyme (histaminase) activities were found in both hemodialysis patients with (2.95 +/- 0.18 pg histamine degraded/minute) and without (2.44 +/- 0.28) pruritus, but was undetectable in normal controls. Histaminase activities did not significantly differ in simultaneously drawn venous and fistula samples. With hemodialysis, histaminase activities fell significantly (p less than 0.01), whereas plasma histamine did not change. We further examined the effects of ketotifen, a putative mast cell stabilizer, on severe uremic pruritus. Five of five patients had significant (p less than 0.01) reductions in pruritus, as judged on a six-point pruritus index, after 8 weeks of drug (x = 2.3), as compared to conventional therapy (x = 5.9). Despite these improvements, no significant differences were noted in pre- versus post-drug plasma histamine levels, histaminase activities, or the histamine content per gram of skin biopsy specimen. These data support prior hypotheses that mast cell activation contributes to the pruritus of uremia.

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Our study demonstrates that high KDPI grafts behave more like moderate KDPI grafts (KDPI 35 - 85). Creatinine (Cr) greater than 2.0 mg/dL portends poorer long-term graft survival, and this outcome is similar amongst all recipients of KDPI > 35 allografts.
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We found that in kidney transplantation, more females donate. We analyzed transplant recipients for patterns of potential donor exclusion and found that equal proportions of male and female potential donors existed among first-degree biological relatives. More male recipients were married and therefore had more spousal potential donors. Among friends and non-first-degree relatives, significantly fewer males offered to donate to females. Equal proportions of female and male potential donors were excluded from donating for medical comorbidities, blood type incompatibility, recipient refusal, and potential donor reluctance. We concluded that female transplant candidates had fewer potential donors among spouses and opposite sex volunteers from friends and non-first-degree relatives.

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