Deficient erythropoietin (EP) production is thought to be a key factor in the pathogenesis of the anemia of end-stage renal disease. We describe the interrelationships between radioimmunoassayed plasma EP levels, reticulocyte counts corrected for anemia (CRC) and hematocrit (HCT) under challenge by hemorrhage, transfusions and hemodialysis in 32 chronically-hemodialyzed patients. Spontaneous hemorrhage resulted in a decrease in HCT (P = 0.001) and increases in both EP (P = 0.006) and CRC levels (P = 0.0065). Transfusions of two units of packed red cells into each of 16 patients suppressed EP (P = 0.0004) and CRC (P less than 0.0001) after about 28 and 42 hours, respectively. Repeat transfusions after one to 27 days resulted in similarly significant suppressions of both EP and CRC, except the CRC remained on higher levels for prolonged periods of times. Within a few hours after each transfusion of 2,3-diphosphoglycerate-poor red cells, both EP (P = 0.009) and CRC (P = 0.007) increased temporarily between one to 18 and three to 38 hours, respectively. Hemodialysis resulted in alkalinization (P = 0.008) of blood but not in changes of EP or CRC counts. The data show that, with the EP-HCT feedback loop persisting, increased endogenous hormone levels elicit erythropoietic responses, and that the regulation of EP levels may involve determinants such as oxy-deoxyhemoglobin interactions.

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Forty patients with metastatic, recurrent, or unresectable renal cell carcinoma were entered into a study of the therapeutic efficacy of adoptive immunotherapy using periodate (IO4-) and interleukin-2 (IL2)-activated autologous leukocytes and continuous infusion low-dose IL2. Patient survival was also examined. The first 15 consecutive patients were enrolled in protocol A without an IL2 priming phase and the following 25 patients were entered in protocol B where a 5-day priming phase was initiated before leukapheresis. A maintenance regimen consisted of either 3 x 10(6) units of recombinant interferon-alpha (rIFN-alpha), three times per week only or together with leukapheresis and infusion of IO4-/IL2-activated cells and 2 days of continuous infusion IL2 per month. Thirty-four patients completed the protocol treatment. Four patients were removed from the study owing to rapid tumor progression and two patients died while receiving treatment. The clinical response rate was 22%: two patients had a complete response and five patients had a partial response. Among the 25 patients who had no clinical response, 11 patients had either a mixed response or stabilization. Neither response, response duration, nor site response correlated with the total dose of IL2 administered or the number of activated killer cells infused. Patients who received maintenance therapy had longer survival times than patients who did not receive such therapy. All toxicity and side effects associated with IL2 treatment were transient and resolved after discontinuation of the drug. Patients on maintenance therapy tolerated both rIFN-alpha and monthly infusions of activated killer cells and IL2 well. This study confirms the concept of adoptive immunotherapy as a new treatment approach for advanced renal cell carcinoma and suggests that maintenance therapy may prolong survival time.

The applicability of the ethanol dilution (ED) technique for total body water (TBW) determination in uremic patients was studied. 73 TBW measurements were performed on 28 patients. As the basic parameters underlying the ED technique showed nearly normal values (Widmark factor r = 0.722 ± 0.0786, normal =0.710 ± 0.090 g/kg; β₆₀ =0.121 ± 0.037, normal = 0.140 ± 0.018 g/kg × 60 min; ‘rectilinear’ course ofthe blood ethanol elimination curve), the ED technique for TBW measurements is well applicable to uremic patients. Subclinical hyperhydration was diagnosed (TBW = 57.88 ± 8.08% of body weight, normal = 52.6 ± 5.4%) in 61% ofthe cases.