Comparison of peritoneal dialysis and hemodialysis after kidney transplant failure.

BACKGROUND: Patients with a failed kidney transplant represent a unique chronic kidney disease population that is increasing in number and is at high risk of morbidity and mortality. Among transplant-naïve patients, those treated with peritoneal dialysis (PD) show an early survival advantage compared with those treated with hemodialysis (HD). But any advantage of PD after allograft failure is unknown. The aim of this study was to investigate the clinical outcomes of patients with failed allografts according to the type of dialysis modality. METHOD: We reviewed medical records of patients who initiated dialysis after kidney transplant failure from November 1982 to May 2011. Demographics features, clinical data, and survival outcomes were compared between PD and HD patients who had experienced allograft failure. RESULTS: The 182 patients with failed allografts showed the most common cause to be chronic rejection. The median duration of function before allograft failure was 74.0 months. After allograft failure, 145 (79.7%) patients returned to HD and 37 (20.3%) to PD. Twenty-three patients (12.6%) died over the median 69.1 months duration of follow-up. During the observation period, 16 HD (11%) and 7 PD (8.9%) patients died. The survival rates of PD patients at 1 year were 91.2% and 84.4%, respectively, at 1 and 3 years, and those of HD patients 94.8% and 88.9%. There was no significant difference in the survivals of the 2 groups. CONCLUSIONS: The study suggests that the outcome of patients starting PD after kidney transplant failure was similar to those starting HD. Therefore, PD can be regarded to be a good treatment option for patients returning to dialysis after kidney transplant failure.

Apoptosis in endothelial cells by cyclosporine.

OBJECTIVES: The immunosuppressive drug cyclosporine (CsA) is a potent agent widely used after organ transplantations and to treat various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity, which are influenced by the degree of the endothelial damage. Several studies have demonstrated CsA treatment to directly induce apoptosis in several cell types. Thus, CsA may induce endothelial damage via activation of proapoptotic proteins. The present study was undertaken to investigate the effects of CsA on apoptosis of endothelial cells using human umbilical vein endothelial cells. METHODS: Proliferation was measured by using the Cell Counting Assay Kit after cells were exposed to CsA (0 L, 10 L, 30 L, 50 L or 100 µg/mL). Apoptotic cells were identified by fluorescence microscopy of 4', 6-diamidino-2-phenylidole-stained nuclei. Western blot analysis was done for poly(ADP-ribose) polymerase (PARP), p27, p53 and caspase. RESULTS: Cell viability decreased dependent on the CsA concentration. CsA treatment group showed chromatin condensation and nuclear fragmentation. CsA produced a dose-dependent induction of p27 and reduction of procasapase-3. CsA treatment induced the degradation of 116-kDa PARP into an 89-kDa fragment. CONCLUSIONS: CsA induced apoptosis of endothelial cells.

Elevated fibroblast growth factor 23 levels as a cause of early post-renal transplantation hypophosphatemia.

BACKGROUND: Hypophosphatemia is a common complication after renal transplantation. Hyperparathyroidism has long been thought to be the cause, but hypophosphatemia can persist after high parathyroid hormone (PTH) levels normalize. Furthermore, calcitriol levels remain inappropriately low after transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor 23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed prospective study to investigate if FGF-23 early after renal transplantation contributes to hypophosphatemia. METHODS: We measured FGF-23 levels before and at 1, 2, 4, and 12 weeks after transplantation in 20 renal transplant recipients. Serum creatinine, calcium (Ca), phosphate (Pi), intact PTH (PTH), and 1,25-dihydroxy vitamin D (1,25(OH)(2)VitD) were measured at the same time. RESULTS: FGF-23 levels decreased by 97% at 4 weeks after renal transplantation (PRT) (7,471 ± 11,746 vs 225 ± 295 pg/mL; P < .05) but were still above normal. PTH and Pi levels also decreased significantly after renal transplantation, and Ca and 1,25(OH)(2)VitD slightly increased. PRT hypophosphatemia of <2.5 mg/dL developed in 15 (75%) and 12 (60%) patients at 4 weeks and 12 weeks respectively. Compared with nonhypophosphatemic patients, the levels of FGF-23 of hypophosphatemic patients were higher (303 ± 311 vs 10 ± 6.9 pg/mL; P = .02) at 4 weeks PRT. FGF-23 levels were inversely correlated with Pi (r(2) = 0.406; P = .011); PTH was not independently associated with Pi (r(2) = 0.132; P = .151). CONCLUSIONS: FGF-23 levels decrease dramatically after renal transplantation. During the early PRT period, Pi rapidly decreased, suggesting that FGF-23 is cleared by the kidney, but residual FGF-23 may contribute to the PRT hypophosphatemia. FGF-23, but not PTH levels, was independently associated with PRT hypophosphatemia.

Historical comparison of prophylactic ganciclovir for gastrointestinal cytomegalovirus infection in kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) can cause morbidity in kidney transplant recipients. The gastrointestinal (GI) tract is a major target for CMV disease. The aim of this study was to evaluate the benefit of ganciclovir prophylaxis on GI CMV infection in intermediate-risk CMV seropositive transplant recipients. METHODS: Since January 2009, intravenous ganciclovir (5 mg/kg, twice daily) was administered for 14 days after kidney transplantation in 41 patients. The historical control group consisted of 45 patients who received kidney transplantations between January 2007 and December 2008. To evaluate the effects of prophylaxis on GI CMV infection, we performed routine endoscopic examinations with mucosal biopsies at the time of transplantation as well as 1, 3, and 6 months thereafter. RESULTS: The average age of the 86 studied patients was 43.7 ± 10.6 years (range = 14-63) and the male-to-female ratio 1:1.3. Forty-three (50%) patients underwent deceased donor transplantations and 84 (97.7%) patients were CMV seropositive at that time. The incidence of GI CMV infection was significantly lower among the prophylaxis than the historical control group (24.4% vs 48.9%, P = .026). Patient age, numbers of deceased donors, and tacrolimus trough levels at 1 and 3 months posttransplant were significantly lower in the prophylaxis than the historical control group. Logistic regression analysis revealed ganciclovir prophylaxis to be the only significant risk factor for GI CMV infection. CONCLUSION: Prophylactic treatment with ganciclovir decreased the incidence GI CMV infection among seropositive kidney transplant recipients.

Utilization of power plant bottom ash as aggregates in fiber-reinforced cellular concrete.

Recently, millions tons of bottom ash wastes from thermoelectric power plants have been disposed of in landfills and coastal areas, regardless of its recycling possibility in construction fields. Fiber-reinforced cellular concrete (FRCC) of low density and of high strength may be attainable through the addition of bottom ash due to its relatively high strength. This paper focuses on evaluating the feasibility of utilizing bottom ash of thermoelectric power plant wastes as aggregates in FRCC. The flow characteristics of cement mortar with bottom ash aggregates and the effect of aggregate type and size on concrete density and compressive strength were investigated. In addition, the effects of adding steel and polypropylene fibers for improving the strength of concrete were also investigated. The results from this study suggest that bottom ash can be applied as a construction material which may not only improve the compressive strength of FRCC significantly but also reduce problems related to bottom ash waste.

The production of reactive oxygen species in tacrolimus-treated glial cells.

OBJECTIVE: After organ transplantation, some patients suffer from mild neurological symptoms, such as tremor, to severe complications, including seizures and encephalopathy. These neurological side effects can be caused by immunosuppressants such as tacrolimus. However, the mechanism of encephalopathy by tacrolimus is not fully understood. METHODS: We measured the production of reactive oxygen species (ROS) in glioma cells after tacrolimus treatment. Tacrolimus added to glioma cells was incubated for 60 minutes at 37 degrees C. The production of ROS was evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2',7'-dichlorofluorescin using VICTOR3TM multilabel counter. RESULTS: Tacrolimus resulted in the production of the ROS in glioma cells. The production of the ROS was increased in time-dependent fashion. CONCLUSIONS: These findings indicated that the tacrolimus may contribute the neurological side effects by ROS production.

Cytokine array after cyclosporine treatment in rats.

OBJECTIVES: Long-term treatment with cyclosporine (CsA) results in chronic nephrotoxicity, which is known to be mediated by several cytokines including transforming growth factor-betal. Cytokines are known to play an important role in innate immunity, apoptosis, angiogenesis, cell growth, and differentiation. They are known to be involved in most disease processes, including cancer, cardiac disease, and nephrotoxicity. To evaluate changes of cytokines in a rat model of CsA-induced chronic nephrotoxicity, we performed a cytokine array. METHODS: Experiments were performed on two groups of rats; normal control group and CsA-treated group. Cytokine array in rat serum was performed using Cytokine Antibody Array I kit from RayBiotech. RESULTS: Serum creatinine, urine creatinine, and creatinine clearance increased in the CsA-treated group. Among the several cytokines, the expressions of the lipopolysaccharide-induced CXC chemokine (LIX), monocyte chemoattractant protein 1 (MCP-1), nerve growth factor (beta-NGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the CsA-treated group were increased above that of cytokines in the control group. The density of the LIX in controls was 0.62, and in the CsA-treated group was 1.24. The density of the MCP-1 in controls was 0.68, and in CsA-treated, 1.43. The density of the beta-NGF in controls was 0.62, and that in CsA-treated, 1.24. The density of the TIMP-1 in controls 1.13, and in CsA-treated, 1.40. CONCLUSIONS: Our data suggested that among several cytokines elevated levels of the LIX, MCP-1, beta-NGF, and TIMP-1 are the contributing factors to CsA-induced nephropathy.

Effects of tacrolimus on antioxidant status and oxidative stress in glioma cells.

OBJECTIVES: After organ transplantation, some patients suffer from mild neurologic symptoms, ranging from tremor to severe complications, including seizures and encephalopathy. Among the immunosuppressants, tacrolimus can cause neurologic side effects. However, the mechanisms of encephalopathy by tacrolimus are not fully understood. We measured the antioxidant status, hydrogen peroxide level, and malondialdehyde level in glioma cells after tacrolimus treatment. METHODS: The production of hydrogen peroxide was determined by the modified xylenol orange method. The amount of malondialdehyde was measured by the thiobarbituric acid assay, which is based on malondialdehyde reaction with thiobarbituric acid to give a red species absorbing at 535 nm. Total antioxidant status (TAS) was measured using TAS kits (NX2332). RESULTS: Tacrolimus resulted in dose- and time-dependent increases in the production of hydrogen peroxide by glioma cells. The antioxidant status decreased in the glioma cells after tacrolimus treatment. Malondialdehyde level was unchanged in the glioma cells after tacrolimus treatment. CONCLUSIONS: Increased production of reactive oxygen species and decreased antioxidant status by tacrolimus in glioma cells may contribute to neurologic side effects.

Basiliximab does not reduce the early rejection incidence in high-risk kidney recipients under tacrolimus-based immunosuppression.

This study sought to evaluate the benefit of addition of basiliximab to tacrolimus-based immunosuppression among high-risk renal transplantations. We retrospectively analyzed the clinical data of the basiliximab induction group (n = 55) and a risk-matched control group (n = 57). Graft survivals rates at 1, 3, and 5 years were 100%, 98.1%, and 91.8%, respectively, for the control and 96.2%, 93.9%, and 76.4%, respectively, for the basiliximab group (P = .083). Patient survivals rates at 1, 3, and 5 years were 98.3%, 98.3%, and 98.3%, respectively, for the control group and 98.2%, 94.2%, and 94.2%, respectively, for the basiliximab group (P = .277). Biopsy-proven acute rejection (AR) within 12 months occurred among 24.6% and 18.2% for the control and induction groups, respectively (P = .492). Serum creatinine levels at 1, 3, 6, and 12 months were 1.23 +/- 0.30, 1.38 +/- 0.41, 1.47 +/- 0.61, and 1.44 +/- 0.67 mg/dL, respectively, among the control and 1.24 +/- 0.28, 1.40 +/- 0.38, 1.40 +/- 0.36, and 1.63 +/- 1.62 mg/dL, respectively, among the induction group. In conclusion, this study showed that the addition of basiliximab to tacrolimus-based immunosuppression did not further improve the results of high-risk kidney transplantations in terms of reducing AR, prolonging graft survival, or improving renal function.

Acute colitis associated with dengue fever in a renal transplant recipient.

Dengue fever is a significant health problem for international travelers to all endemic area. Dengue fever is characterized by a sudden onset of fever, headache, rash, myalgia, and joint pain. Infection with the dengue virus is detrimental to a immunosuppressed renal transplant patients. Herein we report a 29-year-old woman living-related renal transplant recipient returning from Southeast Asia with dengue fever presenting as acute colitis. The patient traveled to Southeast Asia for 1 week. She developed watery diarrhea in the second week after the onset of symptoms of dengue fever. Laboratory findings were leukopenia, thrombocytopenia, and elevated serum transaminase levels. Sigmoidoscopic features showed nonspecific acute colitis. She improved after 10 days of hospitalization with intensive supportive care and continuous tacrolimus monotherapy. Altered clinical symptoms are manifested in immunologically naïve adults. Manifestation of unusual symptoms does not exclude dengue virus infection in renal transplant recipients.

Rectal carcinoid tumor in a renal transplant patient.

Malignancy represents a leading cause of morbidity and mortality in patients with a long-term surviving graft. Carcinoid tumor is a common primary endocrine tumor in the general population that is rare in transplant recipients. Our present report focused on a 48-year-old man who received immunosuppressive therapy based on cyclosporine and steroids. Twelve years after renal transplantation, he suffered watery diarrhea and abdominal discomfort. Colonoscopy showed a hard, sessile mass at 5 cm from the anal verge; endoscopic ultrasound showed a 13-mm homogenous hypoechoic mass. Upon endoscopic biopsy, the histological examination revealed a carcinoid tumor. Immunosuppresion was reduced and we performed endoscopic mucosal resection of the rectum. His clinical course has been good with no demonstrated recurrence.

Case of adult mumps infection after renal transplantation.

Viruses are the most common cause of opportunistic infections, important complications of transplantation. Mumps infection in renal transplant recipients is uncommon. This report focused on a 23-year-old woman who received immunosuppressive therapy based on tacrolimus, prednisolone, and mycophenolate mofetil for renal transplantation. Sixteen months after transplantation, she was admitted with pain and swelling in both infra-auricular areas. Laboratory findings demonstrated positive mumps IgM and IgG antibodies and an increased serum amylase level. Computed tomography revealed both parotid glands to be diffusely enlarged. After the diagnosis of mumps parotitis, the patient's immunosuppression was reduced and the clinical course was satisfactory.

Delayed presentation of arteriovenous fistula and pseudoaneurysms in a renal transplant patient 10 years after percutaneous allograft biopsy.

A 51-year-old man was admitted with microscopic hematuria at 10 years after living donor renal transplantation. In order to distinguish between acute tubular necrosis and acute rejection, a graft biopsy was performed under ultrasound guidance at 1 month posttransplantation. Doppler sonography revealed 3 pulsatile cystic masses and an arteriovenous fistula (AVF) in the lower kidney pole. Selective transplant renal angiography revealed 3 pseudoaneurysms with an AVF supplied by a lobular artery in the lower pole. The diagnosis was AVF with pseudoaneurysm, which developed secondary to percutaneous renal allograft biopsy. Interventional treatment was performed because of the high risk for pseudoaneurysm rupture. The AVF and pseudoaneurysms were treated successfully by percutaneous transluminal embolization; renal function remained stable after embolization.

Polyoma virus-associated nephropathy and concurrent cytomegalovirus infection in the kidney transplant recipients.

INTRODUCTION: Cytomegalovirus (CMV) and polyoma virus BK (BKV) may both establish latency following primary infection. Frequent reactivation of these viruses can occur in the kidney transplant recipients. BKV may induce CMV gene expression by stimulating cellular regulator proteins or by its own gene regulator proteins. A high rate of concurrent CMV infections has been noted in kidney transplant recipients with polyoma virus-associated nephropathy (PVAN). METHODS: PVAN was identified in 10 of 191 patients who received kidney transplants between October 1998 and September 2003. PVAN was confirmed by allograft kidney biopsy. Four of the 10 patients were complicated by concurrent CMV infection. RESULTS: Two patients had only serological evidence of CMV infection and one patient had CMV gastritis. These three patients were treated with intravenous ganciclovir with good results. Disseminated ganciclovir-resistant CMV disease was demonstrated in the remaining patient. This 34-year-old kidney transplant recipient with PVAN died of multiorgan failure despite antiviral therapy with both ganciclovir and foscarnet. CONCLUSION: PVAN with concurrent CMV infection in kidney transplant recipients showed variable clinical courses including mortality. Further studies are needed to elucidate the influence of PVAN on the pathogenesis of CMV infection.

Cyclosporine-induced apoptosis in osteosarcoma cells.

INTRODUCTION: Posttransplant bone disease is one of the complications of cyclosporine (CsA), which is widely used as an immunosuppressive agent in the field of kidney transplantation. Cyclosporine treatment causes osteopenia as a result of altered bone turnover, but the pathogenic mechanisms of this process remain unclear. This study examined the ability of CsA to induce apoptosis in a rat osteoblast cell line. RESULTS: We induced apoptosis in rat osteoblastic ROS 17/2.8 cells by exposure to CsA. MTT assay showed that CsA exhibited significant cytotoxic effects on ROS 17/2.8 cells in a dose-dependent manner. Western blot analysis showed enhanced processing of caspase-8, Bax, and p53 after CsA treatment. Expression of cleaved poly (ADP-ribose) polymerase (PARP) was elevated by CsA treatment. Pro-caspase-3 and Bcl-2 proteins were decreased by CsA. CONCLUSIONS: These results suggested that CsA induced apoptosis of osteoblasts.

Primary immunosuppression with tacrolimus in kidney transplantation: three-year follow-up in a single center.

INTRODUCTION: The 1-year results of the phase III US Multicenter Trial comparing tacrolimus- and cyclosporine (Sandimmun)-based immunosuppressive therapy in kidney transplantation revealed a significant reduction in the incidence and severity of acute rejection episodes among patients maintained on tacrolimus. This retrospective, nonrandomized, single-center study represented 3-year data for patient and graft survival and safety in the tacrolimus-treated patients. METHODS: Among 97 consecutive kidney transplant recipients 41 who received tacrolimus and 56 cyclosporine-based immunosuppression were followed for 3 years for patient and graft survivals and for the incidence of acute rejection episodes as well as serious adverse events. RESULTS: The 3-year patient and graft survival rates for tacrolimus and cyclosporine were similar (91.0% vs 90.2%, 96.5% vs 95.0%). However, the incidence of acute rejection episodes was significantly lower in the tacrolimus (17.1%) compared with the cyclosporine group (35.7%, P = .043). There was a higher incidence of headache, posttransplant diabetes, and alopecia reported in the tacrolimus group, whereas hypertension, hypercholesterolemia, and hirsutism were more frequent in the cyclosporine group. The incidences of hand tremor, hyperkalemia, and viral infections were comparable in both groups. Two patients in the tacrolimus group were converted to cyclosporine due to nephrotoxicity and posttransplant diabetes, respectively, whereas 12 patients in the cyclosporine group were converted to tacrolimus as rescue therapy for acute rejection (41.7%), gingival hyperplasia (33.3%), nephrotoxicity (8.3%), neurotoxicity (8.3%), and hirsutism (8.3%), respectively. CONCLUSION: The 3-year results of tacrolimus treatment show excellent efficacy and safety in kidney transplantation. Due to different side-effect profiles, it is necessary to develop individualized immunosuppressive strategies in kidney transplant recipients.

BK virus infection in kidney transplant recipients.

INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV) has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV nephropathy is generally unfavorable, namely 50% of patients lose graft function. We herein report nine cases of BKV nephropathy after kidney transplantation. METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant patients received tacrolimus-based immunosuppression, and 31 received cyclosporine-based immunosuppression. Additionally, 88.2% of the patients received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There were nine cases of BKV nephropathy in kidney transplant recipients, an incidence of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and steroids. The median time to diagnosis of BKV infection was 7.8 months after transplantation. All patients experienced an elevated serum creatinine, which stabilized or decreased in seven patients with altered or decreased immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but serious complication after kidney transplantation, it should be included in the clinical differential of transplant dysfunction. In the absence of documented antiviral treatment, early diagnosis and judicious use of immunosuppressive agents is indicated to minimize the occurrence of BKV infection.

Viral infection following kidney transplantation: long-term follow-up in a single center.

INTRODUCTION: Viral infections are a leading cause of posttransplantation morbidity and mortality. The use of more potent immunosuppressive agents is responsible in part for the increasing incidence of some viral infections. This study summarized our experience with viral infections in 561 kidney transplant recipients. METHODS: The spectrum of viral infections in 561 consecutive kidney transplant recipients was examined retrospectively from November 1982 to November 2002. RESULTS: During a mean follow-up of 64.0 months, 193 virus infections in 156 of 561 kidney transplant recipients were recorded, an incidence of 34.2%. The most common viruses were cytomegalovirus (36.3%), varicella zoster virus (29.0%), herpes simplex virus (23.8%), BK virus (4.7%), hepatitis B virus (3.6%), and hepatitis C virus (2.6%). Among the CMV infections, 77.1% developed subclinical CMV infection and 22.9% had CMV disease. Generalized herpes zoster infection occurred in three cases and chicken pox in six cases. During a mean follow-up of 64.0 months, two of 159 patients died of CMV pneumonia. CONCLUSION: Viral infections among the kidney transplant recipients continue to be a major problem despite significant progress in understanding the pathogenesis of viral infection and the advent of antiviral therapy.

Comparison of bone morphogenetic protein receptors expression in the fetal and adult skin.

Wounds on fetal skin can be repaired without leaving scars until the second trimester, but after this period, skin wounds leave scars as in adults. It's known that certain growth factors such as TGF-beta, and bFGF are present at a very low levels during wound repair in fetal skin. These low levels of growth factors minimize inflammatory response and fibroblast proliferation at the wound site, which in turn inhibit collagen synthesis, and thus, allows scarless wound healing. Recently bone morphogenetic proteins (BMPs), one of the TGF-beta superfamily members, have been studied in the wound healing process. According to several studies, BMPs are related to the differentiation and growth of epithelial and mesenchymal cells, but the precise functions of BMPs and of BMP receptors on skin wound healing have not been elucidated. In this study, we investigated the expression pattern of BMP receptors in fetal skin during the second trimester and in adult skin by immunohistochemical staining and RT-PCR. BMP receptors were detected on the suprabasal epithelial cells and in the hair follicles in adult skin, but were not defected in the fetal skin except for the hair follicles. This was confirmed by confirming mRNA levels of BMP receptors by RT-PCR in both adult and fetal skins. In conclusion, BMPs and BMP receptors seem to be related to fetal and adult wound healing, and low levels of BMPs and BMP receptors during the second trimester seem to contribute to scarless wound healing in the fetus, as is TGF-beta during the second trimester.