Can citrate therapy prevent nephrolithiasis?

This prospective study was done to help determine whether or not oral citrate therapy can elevate urinary citrate levels and reduce the incidence of recurrent calcium stones in patients with hypocitraturia (urinary citrate less than 320 mg/24 hr). The treatment group (Group I) consisted of 10 patients treated with oral citrate and hydration. The control group (Group II) was treated with hydration alone. In Group I, the new stone formation rate (stones per patient year) fell from 1.17 +/- 0.26 to 0.45 +/- 0.32 (p = 0.07) and the twenty-four-hour urinary citrate excretion rose from 69 +/- 14 mg to 473 +/- 96 mg (p = 0.002). In Group II, the new stone formation rate fell from 0.9 +/- 0.25 to 0.27 +/- 0.13 (p = 0.03). The twenty-four-hour urinary citrate excretion increased, though not significantly, from 166 +/- 21 mg to 326 +/- 77 mg (p = 0.06). We conclude that oral citrate therapy can significantly increase urinary citrate levels in patients with recurrent stones associated with hypocitraturia but that oral citrate therapy and hydration were no better than hydration alone in reducing the incidence of recurrent stones.

The haemodynamic effects of correction of anaemia in haemodialysis patients using recombinant human erythropoietin.

STUDY OBJECTIVE: To evaluate the acute and long-term haemodynamic response to recombinant human erythropoietin (rHuEpo) correction of chronic anaemia in haemodialysis-supported patients. DESIGN: Prospective analysis of randomly chosen patients undergoing the multicentre phase III clinical recombinant erythropoietin trial. SETTING: Chronic haemodialysis patients supported in one of two dialysis centres of a large urban tertiary referral centre. PATIENTS: Thirteen of the 59 patients who met the criterion for participation in the multicentre clinical phase III trial of recombinant erythropoietin were randomly chosen. Mean age (42.6 years), and time on dialysis (3.4 years) was representative of the study population. Ten patients were receiving antihypertensive therapy, which remained unchanged throughout the study. INTERVENTIONS: Haemodynamic testing was done in a fasting state, in the supine position, utilising radionuclide angiocardiography. Plasma volume was determined by 125I-labelled serum albumin. Echocardiographic and hormonal evaluations were also performed at each haemodynamic evaluation. All testing was done immediately prior to first dose of drug, upon reaching target haematocrit, and at 6 months and 1 year of continued non-anaemia. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure did not seem to change at any of the study periods, while total peripheral resistance did drop at target (34 +/- 2.5 vs 27.2 +/- 3.2 microns2, P = 0.05). Cardiac output (5.6 +/- 0.5 vs 7.6 +/- 0.8 l/min, P = 0.005) and stroke volume (77 +/- 9.6 vs 116 +/- 15.4 ml, P = 0.005) also rose at this same period but returned to baseline during later periods. Ejection fraction increased over baseline at both target and 1 year study points (50 +/- 2.7 vs 57.7 +/- 3 vs 63 +/- 4.3, P = 0.05) while the haematocrit was increased at target (21.8 +/- 0.9 vs 35.6 +/- 1.0, P less than 0.0005), and maintained at this new level throughout the study. Total blood volume (118 +/- 6.7 vs 100.4 +/- 8.1 ml/cm, P less than 0.05) and plasma volume (150 +/- 8.2 vs 108.5 +/- 9.4 ml/cm, P less than 0.001) decreased at 1 year. CONCLUSION: Recombinant human erythropoietin is effective in correcting the anaemia of chronic renal failure. Any haemodynamic changes which may be induced seem to occur early in the course of therapy, are different from those changes induced by blood transfusions, and tend to return to baseline with continued treatment.

Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial.

STUDY OBJECTIVE: To determine the effectiveness and safety of recombinant human erythropoietin (rHuEpo). PATIENTS: Hemodialysis patients (333) with uncomplicated anemia (hematocrit less than 0.30). All received rHuEpo intravenously, three times per week at 300 or 150 U/kg body weight, which was then reduced to 75 U/kg and adjusted to maintain the hematocrit at 0.35 +/- 0.03 (SD). RESULTS: The baseline hematocrit (0.223 +/- 0.002) increased to 0.35, more than 0.06 over baseline within 12 weeks in 97.4% of patients. Erythrocyte transfusions (1030 within the 6 months before rHuEpo therapy) were eliminated in all patients within 2 months of therapy. Sixty-eight patients with iron overload had a 39% reduction in serum ferritin levels after 6 months of therapy. The median maintenance dose of rHuEpo was 75 U/kg, three times per week (range, 12.5 to 525 U/kg). Nonresponders had complicating causes for anemia, myelofibrosis, osteitis fibrosa, osteomyelitis, and acute or chronic blood loss. Adverse effects included myalgias, 5%; iron deficiency, 43%; increased blood pressure, 35%; and seizures, 5.4%. The creatinine, potassium, and phosphate levels increased slightly but significantly. The platelet count increased slightly but there was no increase in clotting of vascular accesses. CONCLUSIONS: The anemia of hemodialysis patients is corrected by rHuEpo resulting in the elimination of transfusions, reduction in iron overload, and improved quality of life. Iron stores and blood pressure must be monitored and treated to maintain the effectiveness of rHuEpo and to minimize the threat of hypertensive encephalopathy.

Recombinant human erythropoietin correction of anemia. Dialysis efficiency, waste retention, and chronic dose variables.

A clinical review of patients who were treated with recombinant human erythropoietin was undertaken to evaluate the effect of partial correction of anemia upon dialysis function and waste retention. Assessment of possible variables that might influence the dosage response was also undertaken, both in a retrospective and prospective manner. Finally, a chart review of patients' symptoms while on dialysis was done to evaluate the effect of correction of anemia. Hematologic improvement was noted in all patients placed on hormone therapy with the correction of hemoglobin and hematocrit. There was no effect on white cell count, although a slight change in the differential was noted at target and one year; platelets rose to a new steady state. Dialysis efficiency was decreased slightly for urea and markedly for creatinine, probable reflecting the distribution characteristics of the latter. Retention of urate, phosphorus, and potassium was noted at target, with a drop toward usual serum levels with minimal dialysis prescription change. Variables such as age, gender, race, and dialysis prescription were compared in an effort to establish dosage variation, but no statistically significant changes were seen. There was an inverse trend in dosage, however, with increasing dialysis efficiency. Patients also seemed to be more tolerant of their dialysis treatments when nonanemic, compared to when anemic. While there is retention of some substances with improvement of anemia, the levels were easily corrected with adjustment of the dialysis prescription. No definite relationship could be seen in any of the variables studied and hormone dose requirements. Attention must be paid to adequate dialysis prescription in the erythropoietin treated patient.

Renal transplantation: results in hemodialysis patients previously treated with recombinant human erythropoietin.

The eventual commonplace use of recombinant human erythropoietin (r-HuEPo) for the treatment of the anemia associated with chronic renal failure will have definite consequences in the dialysis supported patient. The effect of this nonanemic state on renal transplantation, both in the early posttransplant period as well as the waiting period, was examined in this study. Thirteen of 16 patients who were treated with the hormone and subsequently underwent cadaveric renal transplantation (Tx) were compared to control transplant patients from a typical chronic renal patient population. There seemed to be no difference in the length of hospital stay, need for dialysis support post-Tx, or severity of acute post-Tx renal failure as measured by the days of dialysis support given. Furthermore, there seemed to be no evidence of marrow unresponsiveness to endogenous erythropoietin produced by the functioning allograft, so that after an initial fall in hemoglobin and hematocrit, these parameters returned to normal levels at three to six months. HLA antibody production was also tracked over the course of chronic r-HuEPo therapy, and the response followed one of three patterns: (a) initially very high (100%) or very low (less than 15%) and showed no change; (b) moderate to high reactivity fell to lower levels with time; or (c) some stimulation noted without recent blood transfusions. Thus, patients entering end-stage renal failure without having been exposed to transfusions can be maintained in a low antibody state and perhaps increase the cadaveric kidneys available to them. Therefore, r-HuEPo therapy in patients who will subsequently undergo transplantation seems to have no deleterious effect on patient morbidity, or transplant outcome.(ABSTRACT TRUNCATED AT 250 WORDS)