• Korean Journal of Clinical Pharmacy
• /
• v.13 no.1
• /
• pp.1-4
• /
• 2003

Cyclosporine (CsA) has become well established as a potent immunosuppressive agent in the renal transplantation. However, therapy is complicated by large intraindividual and interindividual variability in pharmacokinetics of CsA and frequent undesirable clinical outcomes such as graft rejection and nephrotoxicity. The objective of this study was to determine the CsA trough blood concentrations that were associated with acute graft rejection and renal toxicity in renal transplant patients. Also, the ability of the current recommendation of therapeutic range for CsA to prevent graft rejections and CsA-associated renal toxicity was assessed. The clinical courses of the patients on CsA as an immusuppressive agent for preventing the graft rejection with renal ransplantation performed at Seoul National University Hospital from January 1995 to September 1998 were retrospectively reviewed. Total of 78 patients were included and three of them were retransplantation cases. Twenty-two acute episodes of rejection were identified, but only 16 episodes were clinically significant. Of these all the episodes occurred during the first month after transplantation except one. Mean daily doses of CsA were $427.2\pm72.1,\;352.6\pm56.8,\;308.62\pm48.3\;and\;268.47.1\;mg$ at posttransplant 1, 3, 6, and 12 months, respectively. Mean CsA whole blood though levels were $259.8\pm36.2,\;238.5\pm39,\;200.8\pm45.8\;and\;161.9\pm25.8\;ng/ml$ at posttransplant 1, 3, 6 and 12 months, respectively. Mean daily doses/weight were $7.9\pm1,\;6.4\pm1,\;5.3\pm0.7\;and\;4.6\pm0.7\;mg/kg$ at posttransplant 1, 3, 6 and 12 months, respectively. CsA doses decreased significantly as months progressed (p<0.001). During the first month after transplantation, only $12.5\%$ of the patients in rejection group had CsA concentration in therapeutic range, and 87.5, 93.8, and $100\%$ were within the therapeutic range at posttransplant 3, 6, and 12 months, respectively. These results suggested that CsA concentrations of $250\sim300\;ng/ml$ might be appropriate for preventing the acute rejection during the first posttransplant month.

• The Journal of the Korea Contents Association
• /
• v.12 no.9
• /
• pp.250-256
• /
• 2012

Disease, such as osteopenia, osteoporosis, etc caused by reduced bone density are common to women after menopause and as the social medical cost increases due to osteoporosis fractures the medical interest in bone density reduction has increased. The bone density reduction is observed even for renal failure patients, due to their decreased ability to synthesize vitamin D which leads to bone fibrosis because of deficiency in calcium absorption. Thus renal failure patients not only suffer from kidney dysfunction, but also are exposed to complications, such as osteoporosis, due to reduced bone density. This research observed the change in bone density of patients receiving renal failure treatment and analyzed the change in bone density before and after kidney transplantations. Subjects were 214 renal failure patients at the department of nephrology Busan B General Hospital. The change in bone density was studied for subjects with and without kidney transplantation according to their age and sex. The research showed improvement or maintenance of bone density for subjects that received kidney transplantation, but showed a tendency of consistent decrease in bone density for subjects without kidney transplantation. Kidney transplantation can be considered as the best cure for renal failure patients, and this researched confirmed that bone density can be improved through kidney transplantation. Thus, this study can also be used as data for preventing complications due to renal failures.

• Journal of Veterinary Clinics
• /
• v.28 no.1
• /
• pp.63-70
• /
• 2011

To consider the iliac fossa as the vascular anastomosis site of kidney transplantation for the short-term study of acute rejection in pigs. Twelve domestic pigs weighing 39~48 kg underwent heterotopic renal allgraft transplantation. The experimental animals were divided into 2 groups in terms of renal vascular anastomosis site; the external iliac artery and vein were used in iliac fossa model (n = 6), the abdominal aorta and the caudal vena cava inferior to the kidney were used in abdominal cavity model (n = 6). Renal function was evaluated by daily measurement of plasma creatinine and BUN concentrations. The experiments' health including postoperative complications was also assessed daily for 8 days after transplantation. After euthanazation gross and histopathologic analysis was performed. All six pigs in iliac fossa model developed neuropraxia and lameness of the ipsilateral pelvic limb. However, no necrosis was observed in any pigs. In the abdominal cavity model, durations of both the surgical operation and the vascular anastomosis were significantly longer than those in the iliac fossa model. Furthermore, ischemia injury of the transplanted kidney was increased in abdominal cavity model, which induced accelerated-acute immune response from day 4 after transplantation. Despite of pelvic limb complication, the iliac fossa model showed more advantages including not only less ischemia time related to easy vascular anastomosis, but also less immune response during the acute rejection period. The results indicate that the iliac fossa model may be appropriate to the study of acute rejection in porcine kidney transplantation.

• Journal of Veterinary Clinics
• /
• v.26 no.1
• /
• pp.29-35
• /
• 2009

This study was to determine the effects of ascorbic acid and alpha-tocopherol on the attenuation of an ischemia-reperfusion injury (IRI) after renal auto-transplantation in a pig model. In the treatment group, three pigs were subjected to a renal auto-transplantation followed by the administration of ascorbic acid and alpha-tocopherol and the flushing of ascorbic acid plus hepa-saline solution. Otherwise, the control group used only flushing of hepa-saline solution. Blood samples were collected from these pigs for measurement of serum blood urea nitrogen (BUN) and creatinine values on the day before surgery and day 1, 3, 5 and 7 after surgery. The kidneys were taken for histopathological evaluation following euthanasia on day 14 after surgery. Serum creatinine and BUN values showed a significantly difference between control and treatment group on day 1, 3 and 5 (P<0.05). In histopathologic findings, treatment group showed less damage than that of the control group on the basis of renal tubular damage. As a result, this study suggests that the exogenous ascorbic acid and alpha-tocopherol pretreatment therapy with ascorbic acid irrigation-aspiration has a role of attenuation of renal I/R injury and recovery of renal function in a pig transplantation model.

• Kidney Research and Clinical Practice
• /
• v.37 no.4
• /
• pp.414-417
• /
• 2018

Disseminated adenovirus infection can result in high mortality and morbidity in immunocompromised patients. Here, we report the case of a 10-year-old renal allograft recipient who presented with hematuria and dysuria. Adenovirus was isolated from his urine. His urinary symptoms decreased after intravenous hydration and reduction of immunosuppressants. However, 2 weeks later he presented with general weakness and laboratory tests indicated renal failure necessitating emergency hemodialysis. Adenovirus was detected in his sputum; therefore, intravenous ganciclovir and immunoglobulin therapy were initiated. Renal biopsy revealed diffuse necrotizing granulomatous tubulointerstitial nephritis compatible with renal involvement of the viral infection. Adenovirus was detected in his serum. Despite cidofovir administration for 2 weeks, adenovirus was also detected in the cerebrospinal fluid, resulting in generalized tonic-clonic seizure. The patient died 7 weeks after the onset of urinary symptoms. Adenovirus should be considered in screening tests for post-renal transplantation patients who present with hemorrhagic cystitis.

• Childhood Kidney Diseases
• /
• v.23 no.2
• /
• pp.67-76
• /
• 2019

Kidney disease is a major global health issue. Hemodialysis and kidney transplantation have been used in the clinic to treat renal failure. However, the dialysis is not an effective long-term option, as it is unable to replace complete renal functions. Kidney transplantation is the only permanent treatment for end-stage renal disease (ESRD), but a shortage of implantable kidney tissues limits the therapeutic availability. As such, there is a dire need to come up with a solution that provides renal functions as an alternative to the current standards. Recent advances in cell-based therapy have offered new therapeutic options for the treatment of damaged kidney tissues. Particularly, cell secretome therapy utilizing bioactive compounds released from therapeutic cells holds significant beneficial effects on the kidneys. This review will describe the reno-therapeutic effects of secretome components derived from various types of cells and discuss the development of efficient delivery methods to improve the therapeutic outcomes.

• Journal of Veterinary Clinics
• /
• v.19 no.3
• /
• pp.299-302
• /
• 2002

Selectins are differentially expressed carbohydrate binding proteins involved in the initiation of tissue inflammation by mediating the rolling and tethering of leukocytes on the vascular endothelium. This primary event in initiation of inflammation, as occurs during reperfusion injury, can be therapeutically targeted using selectin inhibitors, which generally block binding of sLex to E-, P-, and L-selectins. The objective of this study was to determine the role of selectins in renal ischemia/reperfusion injury after kidney transplantation. Canine kidneys were subjected to 60-min warm ischemia, flushed with UW solution, cold stored for 24 h, and autotransplanted into the nephrectomized donor. Renal autografts were monitored for 7 days by serum creatinine in the first study and by histology and myeloperoxidase activity after 4-hour reperfusion in the second study. In each study, one group of animals received TBC1269 (selectin inhibitor) and the other received saline vehicle. Serum creatinine rose quickly after transplantation and was not different between the groups. TBC1269 abolished a reperfusion-induced 2-fold increase in renal cortex neutrophil infiltration and improved histologic signs of ischemia after 4 hours of reperfusion. Selectin blockade does not improve the course of injury caused by warm renal ischemia. A minor benefit associated with the inhibition of early inflammation during reperfusion after kidney transplantation seems to occur.

• Childhood Kidney Diseases
• /
• v.4 no.1
• /
• pp.84-91
• /
• 2000

Purpose: To improve the recovery of growth deficit after renal transplantation in children, we analysed the factors affecting height growth after renal transplantation. Methods: We reviewed medical records of fifty-six children in whom height data were available for three years after transplantation. All height data were converted into Z-scores. We analyzed the effects of sex, age at transplantation, cumulative mean steroid dose for 3 years, serum creatinine levels, height at transplantation, donor source and history of prior dialysis on patients' z-scores and delta Zs. Results: The Z-scores at transplantation were lower in patients of younger age (P=0.007). When baseline Z-scores were lower, the delta Zs were higher (P<0.01), but the Z-scores after transplantation were still lower (P<0.001). According to the analysis of the partial correlation coefficients, Z-scores and delta Zs at 1 year after transplantation were higher in groups of younger age and of lower steroid dosages (P<0.05). The delta Zs at 6 month and 1 year after transplantation were lower in the group with abnormally higher serum creatinine (P<0.05). There was no difference in Z-scores between groups of different genders, donor sources, and histories of previous dialysis. Conclusion: The children of younger age, on lower steroid dosage, with less growth retardation at transplantation, and with normal graft function had better height growth recoveries after renal transplantation.

• Clinical and Experimental Pediatrics
• /
• v.54 no.8
• /
• pp.317-321
• /
• 2011

Children who suffer from steroid-resistant nephrotic syndrome (SRNS) require aggressive treatment to achieve remission. When intravenous high-dose methylprednisolone fails, calcineurin inhibitors, such as cyclosporine and tacrolimus, are used as the first line of treatment. A significant number of patients with SRNS progress to end-stage renal disease if remission is not achieved. For these children, renal replacement therapy can also be problematic; peritoneal dialysis may be accompanied by significant protein loss through the peritoneal membrane, and kidney allograft transplantation may be complicated by recurrence of SRNS. Plasmapheresis and rituximab were initially used for treatment of recurrent SRNS after transplantation; these are now under consideration as rescue therapies for refractory SRNS. Although the prognosis of SRNS is complicated and unfavorable, intensive treatment in the early stages of the disease may achieve remission in more than half of the patients. Therefore, timely referral of pediatric SRNS patients to pediatric nephrology specialists for histological and genetic diagnosis and treatment is highly recommended.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.5
• /
• pp.413-423
• /
• 2021

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague-Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.