William J. Gaughan

A 6-month study of low-dose recombinant human erythropoietin alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients

Two previous short-term studies (12 weeks and up to 16 weeks) that used androgens to supplement recombinant human erythropoietin (rHuEPO) for the treatment of the anemia associated with end-stage renal disease showed divergent results. Both studies were limited by their brief duration, since the hematopoietic effect of androgens does not peak until 5 months. Therefore, we conducted a 6-month, prospective, randomized trial comparing low-dose rHuEPO alone and in combination with androgens for the treatment of the anemia of end-stage renal failure. Nineteen anemic chronic hemodialysis patients were randomized into two groups. Group A (n = 10) received 1,500 U rHuEPO intravenously three times a week for 26 weeks. Group B (n = 9) received the same dose of rHuEPO plus nandrolone decanoate 100 mg intramuscularly weekly. Baseline transferrin saturation, serum ferritin, intact serum parathyroid hormone, plasma aluminum, and hematocrit levels were not significantly different between the groups. At study completion, both groups showed a significant increase in mean hematocrit compared with baseline (group A: 24.8% +/- 1.4% to 28.3% +/- 2.8%, P = 0.003; group B: 25.1% +/- 1.5% to 33.2% +/- 4.5%, P = 0.001). The increase in hematocrit in the rHuEPO plus androgen-treated group was statistically greater than in the rHuEPO-alone group (8.2% +/- 4.4% v 3.5% +/- 2.8%; P = 0.012). With the exception of mild discomfort at the injection site, there were no significant side effects from nandrolone. We conclude that the combination of low-dose rHuEPO and nandrolone decanoate is effective treatment for the anemia of end-stage renal failure.

National transplantation pregnancy registry: Report on outcomes in cyclosporine-treated female kidney transplant recipients with an interval from transplant to pregnancy of greater than five years

Successful renal transplantation enables previously infertile females to conceive and carry a pregnancy. Much of the reported data on posttransplantation pregnancy accrued before the advent of cyclosporine, when steroids and azathioprine were the mainstays of maintenance immunosuppression. One factor affecting pregnancy outcome in kidney recipients is the length of time from transplantation to conception or transplant interval. It has been recommended that patients wait at least 2 years posttransplantation to conceive, as transplant intervals of shorter duration have had less favorable outcomes. Some have suggested that extended transplant intervals (> 5 years) paradoxically result in adverse outcomes. We have extracted data on cyclosporine-treated recipients with transplant intervals longer than 5 years from the National Transplantation Pregnancy Registry, and report 17 pregnancies from 15 recipients (transplant interval, 5.9 +/- 0.9 years). There were 13 live births (76.5%) and four spontaneous abortions (23.5%). The mean gestational age was 37.7 +/- 2.04 weeks and mean birth weight was 2,753 +/- 679 g. Prematurity occurred in 30.8%, low birth weight in 15.4%, very low birth weight in 7.7%, and neonatal complications in 15.4%. There were no maternal or neonatal deaths. The mean serum creatinine before pregnancy was 1.31 mg/dL, and there was no significant change during or after pregnancy. There were no rejections during or up to 3 months postpartum. Graft survival at 2 years was 100%. We conclude that most pregnancy outcomes in cyclosporine-treated recipients with transplant intervals greater than 5 years are favorable for the newborn, recipient, and graft.

Safety Considerations: Breastfeeding after Transplant

Organ transplant is an effective treatment for end-stage organ failure. For women, restoration of organ function can restore fertility and the ability to successfully carry a pregnancy. Posttransplant pregnancies have been reported among recipients of all types of solid organ transplants via case and center reports plus registry data. Stable graft function is dependent on prevention of rejection, currently accomplished by using maintenance immunosuppressant medications, to which the fetus is exposed in utero. Common among neonatal outcomes in transplant recipients are preterm and low-birth-weight infants. Emotional, nutritional, and immunologic benefits of breastfeeding have been well-documented and could be valuable for these newborns. Concern must be directed at the effects of the childs exposure to immunosuppressive agents excreted into the breast milk. Breastfeeding could be considered in transplant recipients if it can be shown that the level of exposure does not result in risks to the newborn, immediately and throughout childhood. Despite concerns of health care professionals, some recipients have chosen to breastfeed. Breastfeeding after transplant must be approached with consideration of many issues, and the potential risks require further study. This review focuses on benefits of breastfeeding, common immunosuppressive agents used in organ transplant recipients, a summary of the reports of women who have breastfed their infants while on immunosuppressive therapy and the published studies on breastfeeding and immunosuppressive agents. Recommendations are provided to guide health care professionals to help mothers receiving immunosuppressive agents to make informed choices about breastfeeding their infants.

Ranitidine-Induced Acute Interstitial Nephritis With Epithelial Cell Foot Process Fusion

Although acute interstitial nephritis has been well described with the histamine H2-receptor antagonist cimetidine, we found only one previous case report of ranitidine-induced interstitial nephritis in the literature. We describe an additional patient who developed acute interstitial nephritis after taking ranitidine. Electron microscopy showed focal fusion of the epithelial cell foot processes that was not described in the previous report of ranitidine-induced interstitial nephritis.

Association of IgA nephropathy with Clostridium difficile colitis

Immunoglobulin A (IgA) nephropathy, the most common cause of glomerulonephritis worldwide, is usually idiopathic in origin and renal limited. Secondary IgA nephropathy has been associated with systemic disease, including such gastrointestinal tract disturbances as celiac sprue and inflammatory bowel disease. We describe gross hematuria and reversible acute renal failure from IgA nephropathy in a patient with cephalosporin-induced Clostridium difficile colitis. In addition to mesangial IgA and C3 deposition, renal histological examination showed glomerular bleeding, intratubular red blood cell casts, and acute tubular necrosis. To the best of our knowledge, this is the first report of an association between IgA nephropathy and C difficile colitis.

Serum bactericidal activity for Yersinia enterocolitica in hemodialysis patients: effects of iron overload and deferoxamine.

Human serum has been shown to be bactericidal for most strains of Yersinia enterocolitica. Systemic Y enterocolitica infections have been reported in iron-overloaded hemodialysis patients treated with deferoxamine. Both iron and deferoxamine are known to enhance the growth of Y enterocolitica. We inoculated sera from 12 hemodialysis patients whose serum ferritin levels ranged from 26 to 6,855 micrograms/mL (ng/mL), as well as three controls, with Yersinia organisms. After latencies of 0 to 24 hours, inoculated sera were then plated on blood agar. Bactericidal activity was demonstrated in all sera and the degree of activity did not correlate with ferritin levels. Bactericidal activity was also demonstrated in sera from three deferoxamine treated patients. We conclude that in vitro, sera of end-stage renal failure patients, with and without iron overload, are as bactericidal as control sera for Y enterocolitica and that deferoxamine therapy does not interfere with that bactericidal activity.