Presence of a Failed Kidney Transplant in Patients Who Are on Hemodialysis Is Associated with Chronic Inflammatory State and Erythropoietin Resistance JUAN M. LO ´ PEZ-GO ´ MEZ,* ISABEL PE ´ REZ-FLORES,* ROSA JOFRE ´ ,* DIANA CARRETERO,* PATROCINIO RODRI ´ GUEZ-BENITEZ,* MAITE VILLAVERDE,* RAFAEL PE ´ REZ-GARCI ´ A,* GEORGE M. NASSAR, † ENRIQUE NIEMBRO, ‡ and JUAN CARLOS AYUS § Departments of *Nephrology and ‡ Pathology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; † Department of Nephrology, Baylor College of Medicine, and Renal Research Inc., The Kidney Institute, Houston, Texas; and § Department of Nephrology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas Abstract. Patients returning to hemodialysis (HD) after failure of their kidney transplant suffer from high morbidity and mortality rates. It is common practice to keep failed kidney transplants in place. It is not known if these failed kidney transplants induce an inflammatory state that contributes to morbidity and mortality. In a single facility, patients starting on HD with failed kidney transplant were identified (Group A) and screened for the presence of chronic inflammatory state. Those with clinical symptoms attributed to the failed allograft (Group A1) were not offered transplant nephrectomy unless deemed necessary during follow-up. Their clinical and labora- tory data were followed up for 6 months. Similar data were obtained from a group of incident HD patients (Group B). Forty-three patients had a failed Kidney transplant (Group A). Of these, 29 comprised Group A1 and 14 Group A2. Group B comprised 121 patients. In comparison with Group B, Group A exhibited worse anemia and erythropoietin resistance index (ERI), had lower serum albumin and prealbumin, and higher CRP. Group A1 had lower Hb and higher ferritin, CRP, and ESR in comparison with Group A2. Following transplant ne- phrectomy, Group A1 had improvement in ERI, serum albu- min, prealbumin, ferritin, fibrnogen, CRP, and ESR. At 6 months, Group A1 had higher Hb and serum albumin levels, and lower CRP and ERI in comparison with Group A2. Group B parameters showed no change during follow-up. Patients returning to HD following failure of their kidney transplant suffer from a chronic inflammatory state. Resection of failed transplants in symptomatic patients is associated with amelio- ration of markers of chronic inflammation. Transplant nephrec- tomy should be considered a treatment option for patients with failed kidney transplants, especially if they exhibit signs and symptoms of chronic inflammatory state. Patients who return to hemodialysis (HD) with a failed kidney transplant are being increasingly recognized as a group of patients with high rates of morbidity and mortality (1–3). Recent data show that the annual adjusted death rates for patients after kidney transplant failure is threefold higher than that of patients with a functioning kidney transplant (1). Car- diovascular and infectious events are most common causes of death, but the exact reasons for such high mortality and mor- bidity rates are just beginning to receive attention (1–3). Failed kidney transplants may undergo resection in patients who develop intense pain at the transplant site as a result of uncontrolled immune-mediated rejection. Otherwise, it is com- mon practice to keep failed kidney transplants in place despite loss of kidney function. Consequences of leaving such failed kidney transplants in place have not been well studied. We have recently demonstrated that HD patients, with occult in- fection of their failed arteriovenous grafts (AVG), experience a chronic inflammatory state (4 –9). This characterized by a constellation of signs and symptoms that include failure to thrive, hypoalbuminemia, erythropoietin-resistant anemia, high plasma C-reactive protein (CRP) levels, and increased morbid- ity and mortality (4 –20). Resection of these AVG with occult infection led to resolution of the chronic inflammatory state and general improvement of health (4 –9). Influenced by these observations, we hypothesized that failed kidney transplants, by virtue of being a site of persistent immune-mediated reac- tivity, may similarly be inducing a chronic inflammatory state. We also hypothesized that resection of the failed kidney trans- plants is associated with amelioration of the chronic inflam- matory state. In this study, we examined the hypothesis that failed kidney transplants are associated with a chronic inflammatory state. We selected a large HD facility and identified all patients who Received January 31, 2004. Accepted June 15, 2004. Correspondence to Dr. Juan Carlos Ayus, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, MC #7882, San Antonio, TX 78229-3900. Phone: 713-942-8434; Fax: 713-942-9342; E-mail: ayus@uthscsa.edu 1046-6673/1509-2494 Journal of the American Society of Nephrology Copyright © 2004 by the American Society of Nephrology DOI: 10.1097/01.ASN.0000137879.97445.6E J Am Soc Nephrol 15: 2494–2501, 2004