S.B. Park

Mycophenolate mofetil-induced ischemic colitis

Anew immunosuppressive agent, mycophenolate mofetil (MMF), has proved to be effective in reducing the incidence of acute rejection in renal transplant recipients. 1‐ 4 Gastrointestinal side effects, especially diarrhea, are among its most common side effects. Gastrointestinal hemorrhage secondary to gastric and duodenal ulceration has also been described. However, the lower gastrointestinal hemorrhage due to colonic ulceration has rarely been reported in the literature. 5 To the best of our knowledge, there has been no reported case documenting the occurrence of MMF-induced ischemic colitis. We describe a case of ischemic colitis and hematochezia with the use of MMF in renal transplant recipients. CASE HISTORY A 49-year-old woman received a renal transplantation from her daughter. Initial immunosuppression consisted of cyclosporine (CyA), prednisolone, and MMF. The first rejection episode, which started 4 days after renal transplantation, was treated with steroid

The clinicopathological relevance of pretransplant anti-angiotensin II type 1 receptor antibodies in renal transplantation

Background Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been suggested as a risk factor for graft failure and acute rejection (AR). However, the prevalence and clinical significance of pretransplant AT1R-Abs have seldom been evaluated in Asia. Methods In this multicenter, observational cohort study, we tested the AT1R-Abs in pretransplant serum samples obtained from 166 kidney transplant recipients. Statistical analysis was used to set a threshold AT1R-Abs level at 9.05 U/mL. Results Pretransplant AT1R-Abs were detected in 98/166 (59.0%) of the analyzed recipients. No graft loss or patient death was reported during the study period. AT1R-Abs (+) patients had a significantly higher incidence of biopsy-proven AR than AT1R-Abs (-) patients (27.6 versus 10.3%, P = 0.007). Recipients with pretransplant AT1R-Abs had a 3.2-fold higher risk of AR within a year of transplantation (P = 0.006). Five study subjects developed microcirculation inflammation (score ≥2). Four of them were presensitized to AT1R-Abs. In particular, three patients had a high titer of anti-AT1R-Abs (>22.7 U/mL). Conclusions Pretransplant AT1R-Abs is an independent risk factor for AR, especially acute cellular rejection, and is possibly associated with the risk of antibody-mediated injury. Pretransplant assessment of AT1R-Abs may be useful for stratifying immunologic risks.

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.

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.

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.

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.

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.

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.

Resolution of uremic tumoral calcinosis in a patient on peritoneal dialysis with long-term low-calcium dialysate treatment

Tumoral calcinosis is a rare complication in uremic patients. An in-depth review of published literature suggests that most patients with uremic tumoral calcinosis do not respond to medical treatment. Here, we report the case of a patient on peritoneal dialysis who presented with infected multifocal masses on both hip joints and was successfully treated by medical intervention. The patient was diagnosed with uremic tumoral calcinosis by physical examination and radiologic imaging, and treated with low-calcium dialysis and a non-calcium phosphate binder, sevelamer, without increasing the dose of dialysis. At the 36-month follow-up, the majority of masses had disappeared and the patient was asymptomatic.

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.