Outcomes of Kidney Transplant Recipients With Posttransplant Genitourinary Infectious Complications: A Single Center Study.

OBJECTIVES: Long-term outcomes of kidney transplant recipients with postoperative genitourinary tract infections are not well characterized. In this single center retrospective study, we aimed to investigate the long-term effects of early posttransplant genitourinary infections under a protocol that included 1 month of antibiotic prophylaxis on graft failure and patient outcomes. MATERIALS AND METHODS: Electronic medical records of 1752 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. Of these, 344 patients had postoperative genitourinary tract infections within 6 months of transplant. Infections included urinary tract infections, recurrent urinary tract infections, and pyelonephritis. All patients received 1-month of treatment with antibiotic prophylaxis for genitourinary infections after graft placement. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. RESULTS: In the 344 patients with postoperative infections, the most common cause was Escherichia coli (34.9%). Kaplan-Meier graft survival results showed no significant differences (P = .08) among those with and those without postoperative urinary tract infections; however, patient survival (P = .01) was significantly different. Multivariate analysis demonstrated no significant trend regarding graft failure (hazard ratio: 1.28; 95% confidence interval, 0.95-1.71; P = .09) or patient death (hazard ratio: 1.33; 95% confidence interval, 0.98-1.79; P = .06) in patients with and without genitourinary infections. The major cause of graft failure was infection in the infection cohort (17.4%). CONCLUSIONS: Kidney transplant recipients who develop urinary tract infections within 6 months of transplant may be at increased risk of graft failure or patient death; however, further studies are needed to elucidate the relationship between posttransplant infections and long-term outcomes.

Outcomes of Kidney Transplant Recipients With Percutaneous Ureteral Interventions: A Single-Center Study.

BACKGROUND: Long-term outcomes of kidney transplantation recipients with percutaneous ureteral management of transplant ureteral complications are not well characterized. METHODS: Electronic records of 1753 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. One hundred thirty-one patients were identified to have undergone percutaneous ureteral management, with placement of percutaneous nephrostomy tube or additional intervention (nephroureteral stenting and/or balloon dilation). Indications for intervention included transplant ureteral stricture or ureteral leak. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. RESULTS: Kaplan- Meier graft survival (P = 0.04) was lower in patients with percutaneous ureteral intervention for transplant ureteral complication. Graft survival at 1, 5, and 10 years was 94.3% 78.3%, and 59.1% for no intervention and 97.2%, 72.1%, and 36.2% for intervention cohort. Patient survival (P = 0.69) was similar between cohorts. Multivariate analysis demonstrated no association with graft failure (hazard ratio, 1.21; 95% confidence interval, 0.67-2.19; P = 0.53) or patient death (hazard ratio, 0.56; 95% confidence interval, 0.22-1.41; P = 0.22) in intervention group. The major cause of graft failure was infection for percutaneous ureteral intervention group (20.4%) and chronic rejection for those without intervention (17.3%). CONCLUSIONS: Kidney transplant recipients with percutaneous ureteral interventions for ureteral complications do not have a significant difference in graft and patient survival outcomes. Therefore, aggressive nonoperative management can be confidently pursued in the appropriate clinical setting.

Long-Term Outcomes of Kidney Transplant Recipients with Bladder Dysfunction: A Single-Center Study.

BACKGROUND: Long-term outcomes of kidney transplantation recipients with bladder dysfunction or prior bladder surgery are not well characterized. MATERIAL AND METHODS: Electronic records of 1753 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. We found that 1652 recipients had normal bladder function, 80 had bladder dysfunction, and 21 had bladder substitute or urinary diversion. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. RESULTS: Kaplan-Meier graft survival (p=.11) and patient survival (p=.18) were lower in recipients with bladder surgery but not statistically significant. Multivariate analysis demonstrated inferior graft survival (HR 3.57, 95% CI 1.06-12.1, p =0.04) and a trend towards inferior patient survival (HR 3.19, 95% CI .71-14.5, p=0.13) in reci-pients with bladder surgery. The major cause of graft failure was chronic rejection for normal function (17.1%) and bladder dysfunction (28.5%), and infection for bladder surgery (28.5%). Post-operative urinary infectious and surgical complications were higher in recipients with bladder dysfunction (35%) and substitutes (52.3%) compared with normal function (12.8%). CONCLUSIONS: Kidney transplant recipients with prior bladder surgery have an increased risk of graft failure and an increased risk of infectious urinary complications. These risks should be considered in recipient selection and post-transplant management.

Paradoxical protection from atherosclerosis and thrombosis in a mouse model of sickle cell disease.

Sickle cell disease (SCD) is associated with vascular complications including premature stroke. The role of atherothrombosis in these vascular complications is unclear. To determine the effect of SCD on atherosclerosis and thrombosis, mice with SCD along with controls were generated by transplantation of bone marrow from mice carrying the homozygous sickle cell mutation (Hbb(hßs/hßs) ) or wild-type mice (Hbb(+/+) ) into C57BL6/J or apolipoprotein E deficient (Apoe(-/-) ) recipient mice. At the time of sacrifice, 23-28 weeks following bone marrow transplantation, anaemia, reticulocytosis, and splenomegaly were present in mice receiving Hbb(hßs/hßs) bone marrow compared with control mice. Analysis of atherosclerosis involving the aortic root revealed reduced atherosclerotic lesion area with reduced macrophage content and increased collagen content in Apoe(-/-) , Hbb(hßs/hßs) mice compared to Apoe(-/-) , Hbb(+/+) mice. In a carotid thrombosis model, the time to thrombosis was prolonged in Hbb(hßs/hßs) mice compared to Hbb(+/+) mice. This apparent protective effect of SCD on atherosclerosis and thrombosis was diminished by inhibition of heme oxygenase-1 (HMOX1) using zinc protoporphyrin IX. We conclude that SCD in mice is paradoxically protective against atherosclerosis and thrombosis, highlighting the complexity of vascular events in SCD. This protective effect is at least partially mediated by induction of HMOX1.

Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes.

Sickle cell disease (SCD) is a hematologic disorder caused by a missense mutation in the adult ß-globin gene. Higher fetal hemoglobin (HbF) levels in red blood cells of SCD patients have been shown to improve morbidity and mortality. We previously found that nuclear receptors TR2 and TR4 repress expression of the human embryonic ε-globin and fetal γ-globin genes in definitive erythroid cells. Because forced expression of TR2/TR4 in murine adult erythroid cells paradoxically enhanced fetal γ-globin gene expression in transgenic mice, we wished to determine if forced TR2/TR4 expression in a SCD model mouse would result in elevated HbF synthesis and thereby alleviate the disease phenotype. In a "humanized" sickle cell model mouse, forced TR2/TR4 expression increased HbF abundance from 7.6% of total hemoglobin to 18.6%, accompanied by increased hematocrit from 23% to 34% and reticulocyte reduction from 61% to 18%, indicating a significant reduction in hemolysis. Moreover, forced TR2/TR4 expression reduced hepatosplenomegaly and liver parenchymal necrosis and inflammation in SCD mice, indicating alleviation of usual pathophysiological characteristics. This article shows that genetic manipulation of nonglobin proteins, or transcription factors regulating globin gene expression, can ameliorate the disease phenotype in a SCD model animal. This proof-of-concept study demonstrates that modulating TR2/TR4 activity in SCD patients may be a promising therapeutic approach to induce persistent HbF accumulation and for treatment of the disease.