About 50% of renal cell carcinoma patients initially present with a regional or distant metastatic disease. Attempts to treat metastatic renal cell carcinomas have been directed at cytokine-based immunotherapy. Response rates of interleukin-2-based immunotherapy of 5 to 29% have been reported in this disease. Immunization as a mechanism to recruit host antitumor responses is increasingly being described as a potentially effective and less toxic approach for the treatment of metastatic and high-risk primary cancers. An autologous renal cell cancer vaccine has been applied at our institution for the prevention of recurrence or metastasis in locally advanced cases for more than one year. Herein, two metastatic renal cell carcinoma cases, which failed to show a response to initial immunotherapy or chemoradiotherapy, which were successfully treated with IL-2 (Aldesleukin) and interferon-alpha as autologous cancer vaccine adjuvants is reported.
Carcinoma, Renal Cell* ; Chemoradiotherapy ; Humans ; Immunization ; Immunotherapy* ; Interferon-alpha ; Interleukin-2 ; Neoplasm Metastasis ; Recurrence ; Vaccines

PURPOSE: To evaluate the effects of autologous tumor vaccine alone or in combination with dendritic cell vaccines, as a method of stimulating antigen-presenting cells in patients with a locoregionally confined renal cell carcinoma (RCC) or metastatic disease. MATERIALS AND METHODS: Twenty-seven patients with RCC pathological stages II to IV were treated with autologous tumor cell vaccine, either with or without dendritic cell vaccine. Interleukin 2 (IL-2) based immunotherapy was also applied to the patients with metastatic disease. Immunomagnetic beads were used to isolate CD14+ monocytes from patient or donor in dendritic cell preparations. IL-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) were used for maturation of dendritic cells. Flow cytometry evaluations were performed for dendritic cell maturation and changes in the immunological profiles following our treatment. RESULTS: Both the isolation of CD14+ monocyte, using Immunomagnetic beads, and the maturation of dendritic cells, using IL-4 and GM-CSF stimulation, were effective. Tumor immunological profiles showed increased CD3 and CD56 populations after treatment. Side effects related with vaccine were minimal and tolerable. Patients were stratified by the purpose for the vaccination; 8 patients for post-nephrectomy adjuvant therapy and 19 for adjuvant immunotherapy of a metastatic disease. All 8 patients in the former showed a disease free state, while only one of the 19 in the latter group remained in complete remission, while 6 showed short-term responses. CONCLISIONS: Autologous RCC vaccine, combined with or without dendritic cell vaccine, might be effective in the suppression of tumor recurrence in locoregionally confined RCC, although a longer follow-up will be required. These vaccines should be further developed to reach their therapeutic purpose in metastatic RCC.
Antigen-Presenting Cells ; Carcinoma, Renal Cell* ; Colony-Stimulating Factors ; Dendritic Cells* ; Flow Cytometry ; Follow-Up Studies ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunotherapy ; Interleukin-2 ; Interleukin-4 ; Monocytes ; Recurrence ; Tissue Donors ; Vaccination ; Vaccines*

BACKGROUND: Currently, the dosage of tacrolimus used after transplantation is based on the patient's body weight. However, there is a low correlation between body weight and body composition in kidney transplant recipients. In this study, we evaluate the pharmacokinetics of tacrolimus according to body composition in 18 Korean kidney transplant recipients with stable graft function. METHODS: Body composition parameters were calculated using bioelectrical impedance analysis. Pharmacokinetic profiles were determined 0, 1, 2, 3, and 4 hours after treatment with tacrolimus and were compared between high- and low-level median body composition groups. The values of C0, C1, C2, C3, and C4 were used in determining an abbreviated area under the curve (AUC) for tacrolimus. RESULTS: The mean body mass index (BMI) and body composition values were as follows: BMI, 24.3 kg/m2; lean mass, 49.8 kg; and fat mass, 17.4 kg. There were no statistical differences in pharmacokinetic profiles between groups with different BMIs. However, the C0 and C4 in the high-fat group were significantly elevated compared with those of the low-fat group (P=0.024 and 0.031, respectively). Furthermore, the C0, C2, C3, and C4 and the AUC were significantly different between the two lean mass groups (P=0.007, 0.038, 0.047, 0.015, and 0.015, respectively). Other variables, such as waist circumference and arm muscle circumference, did not differentiate between the pharmacokinetic profiles of tacrolimus. CONCLUSION: Taken together, these data suggest that tacrolimus dose monitoring based on body composition may provide adequate dosage leading to favorable long-term outcomes.
Adipose Tissue ; Area Under Curve ; Arm ; Body Composition ; Body Mass Index ; Body Weight ; Electric Impedance ; Kidney ; Muscles ; Tacrolimus ; Transplants ; Waist Circumference

Uteroglobin(UG) is an anti-inflammatory/immunomodulatory protein secreted by the epithelial cells of vertebrates. Targeted disruption of UG rendered mouse glomerulonephritis resembling IgA nephropathy(IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and genetic polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide from the transcription initiation site of UG exon 1 would impact the progression of IgAN. PCR-RFLP was instituted to determine the genetic polymorphism in 60 patients with IgAN. Other measures like SSCP and direct sequencing were also adopted for the verification of polymorphic sites. Seventeen patients with IgAN(28%) were homozygous for adenine at position 38(38AA), 26 patients(43%) were heterozygous(38AG), and 17 patients(28%) were homozygous for the polymorphism(38GG), which was similar to the pattern obtained from the 60 normal controls. The amount of daily proteinuria, presence of hypertension, the level of IgA, and the amount of IgA-fibronectin(FN) complexes was similar between the genotypes. Serum IgA-FN level did not influence the progression of disease. However, 8 out of 17 patients (47%) with the AA genotype had progressive disease(PD), 10 of 26 patients(38%) with the AG genotype had PD, and only 1 of 17 patients(6%) with GG homozygocity had PD after 94+/-30.1 months of follow-up(mean+/-S.D.). The odds ratio for the progression of renal disease in patients with the AA genotype was 14.93(p=0.0355) and in patients with AG genotype was 12.94(p=0.0496) compared with patients have the GG genotype. Moreover, serum creatinine at the time of kidney biopsy was higher in patients with AA and AG genotypes than in patients with the GG genotype(1.5+/-0.69 : 1.3+/-0.53 : 1.0+/-0.31mg/dL; AA : AG : GG; p=0.0137 AA vs. GG; p=0.0269 AG vs. GG). Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN.
5' Untranslated Regions* ; Adenine ; Animals ; Binding Sites ; Biopsy ; Creatinine ; Epithelial Cells ; Exons* ; Genotype ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Humans ; Hypertension ; Immunoglobulin A* ; Kidney ; Mice ; Odds Ratio ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational ; Proteinuria ; Sequence Analysis ; Transcription Factors ; Transcription Initiation Site ; Uteroglobin* ; Vertebrates

Background: The effect of each health-related quality of life (HRQOL) component on hemodialysis prognosis has not been well studied. We aimed to investigate the clinical factors associated with HRQOL and the effect of HRQOL after dialysis initiation on long-term survival in an Asian population. Methods: A total of 568 hemodialysis patients were included from a nationwide prospective cohort study. HRQOL was evaluated using the Kidney Disease Quality of Life (KDQOL) Short FormTM 1.3 at 3 months after dialysis initiation. The effect of each KDQOL item score on mortality was analyzed. Multivariable Cox analysis was performed after adjusting for age, sex, modified Charlson comorbidity index, and causes of primary kidney disease. Results: Old age, diabetes mellitus, high comorbidities, and low serum albumin levels were associated with poor physical health status. Decreased urine output was associated with both poor physical and mental health status.The scores of 3 indices in the kidney disease domain (effect of kidney disease, social support, and dialysis staff encouragement) showed significant associations with mortality, as did the 3 indices (physical function, physical role limitation, and body pain) in the physical health domain. Neither the 4 indices in the mental health domain nor the mental composite score showed a significant association with mortality. However, a high physical composite score was associated with decreased overall patient mortality (P = 0.003). The effect of physical composite score on survival was prominent among young or middle-aged groups. Conclusion Poor physical health status 3 months after hemodialysis start correlates significantly with overall mortality.

Background: The effect of each health-related quality of life (HRQOL) component on hemodialysis prognosis has not been well studied. We aimed to investigate the clinical factors associated with HRQOL and the effect of HRQOL after dialysis initiation on long-term survival in an Asian population. Methods: A total of 568 hemodialysis patients were included from a nationwide prospective cohort study. HRQOL was evaluated using the Kidney Disease Quality of Life (KDQOL) Short FormTM 1.3 at 3 months after dialysis initiation. The effect of each KDQOL item score on mortality was analyzed. Multivariable Cox analysis was performed after adjusting for age, sex, modified Charlson comorbidity index, and causes of primary kidney disease. Results: Old age, diabetes mellitus, high comorbidities, and low serum albumin levels were associated with poor physical health status. Decreased urine output was associated with both poor physical and mental health status.The scores of 3 indices in the kidney disease domain (effect of kidney disease, social support, and dialysis staff encouragement) showed significant associations with mortality, as did the 3 indices (physical function, physical role limitation, and body pain) in the physical health domain. Neither the 4 indices in the mental health domain nor the mental composite score showed a significant association with mortality. However, a high physical composite score was associated with decreased overall patient mortality (P = 0.003). The effect of physical composite score on survival was prominent among young or middle-aged groups. Conclusion Poor physical health status 3 months after hemodialysis start correlates significantly with overall mortality.