Add-on anticholinergic therapy for residual nocturia in patients with lower urinary tract symptoms receiving α1-blocker treatment: a multi-centre, prospective, randomised study.

PURPOSE: To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume. RESULTS AND LIMITATIONS: Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged. CONCLUSIONS: A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

Genetic polymorphisms of CYP17A1 in steroidogenesis pathway are associated with risk of progression to castration-resistant prostate cancer in Japanese men receiving androgen deprivation therapy.

BACKGROUND: Hormone ablation therapy is the standard therapy for prostate cancer; however, there are large individual differences in the duration of response to the therapy. We investigated, in this retrospective multicenter study, the association between genetic polymorphic variations in steroidogenesis-related genes and the risk of progression to castration-resistant prostate cancer (CRPC) in Japanese patients after androgen deprivation therapy. METHODS: Two hundred and fourteen Japanese patients with prostate cancer who were receiving androgen deprivation therapy were enrolled in this study. We investigated 22 single-nucleotide polymorphisms (SNPs) from 8 genes related to steroidogenesis. The SNPs were assayed by polymerase chain reaction (PCR)-based methods. The different genotypes in this cohort were analyzed according to a case-control status of progression to CRPC at the median duration of hormonal therapy. A logistic regression method with adjustments for patients' characteristics was applied for the analysis.After applying the logistic regression method, we performed Cox regression analysis, following Kaplan-Meier and log-rank analyses. RESULTS: In the logistic regression analysis four genetic polymorphisms, rs743572, rs6162, rs6163, and rs1004467, in the CYP17A1 gene were significantly associated with a risk of progression to CRPC (p < 0.05). Cox regression analysis for these SNPs showed an association of risk of progression to CRPC with the rs743572 genotype (p = 0.02, odds ratio [OR] 0.43, 95 % confidence interval [CI] 0.22-0.85). CONCLUSION: The genetic backgrounds for CYP17A1 genes could influence the progression of prostate cancer to CRPC after androgen deprivation therapy.

Vardenafil and resveratrol synergistically enhance the nitric oxide/cyclic guanosine monophosphate pathway in corpus cavernosal smooth muscle cells and its therapeutic potential for erectile dysfunction in the streptozotocin-induced diabetic rat: preliminary findings.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are very effective agents for erectile dysfunction; however, specific patient populations are hard to treat. The efficacy of PDE5 inhibitors is limited because a minimum amount of nitric oxide (NO) is necessary. Resveratrol, a plant polyphenol, is reported to activate endothelial NO synthase (eNOS) through activation of sirtuin 1. We previously reported that human corpus cavernosal smooth muscle cells (CCSMCs) express eNOS and synthesize cyclic guanosine monophosphate (cGMP) via the NO/cGMP pathway. AIM: To investigate the ability of resveratrol and/or vardenafil to increase cGMP in an in vitro model using CCSMCs and to improve erectile function in an in vivo rat model of streptozotocin (STZ)-induced diabetes. METHODS: CCSMCs were treated with resveratrol and/or vardenafil. Twenty male Sprague-Dawley rats were randomly divided into five groups (N = 4 in each group): age-matched controls, diabetic controls, and diabetic rats treated with resveratrol, vardenafil, or both in combination for the last 4 weeks of an 8-week period of diabetes induction. MAIN OUTCOME MEASURES: Intracellular cGMP measurement, intracovernous pressure (ICP)/mean arterial pressure (MAP) ratio, and smooth muscle/collagen ratio. RESULTS: Intracellular cGMP level was elevated by resveratrol treatment in CCSMCs. The combination treatment of resveratrol and vardenafil had a synergistic effect. Diabetic rats showed impairment of erectile function. Treatment with either resveratrol or vardenafil improved ICP/MAP ratio, and combination therapy with resveratrol and vardenafil had a synergistic effect in improvement of ICP/MAP. CONCLUSIONS: Treatment with either resveratrol or vardenafil elevated cGMP level in CCSMCs and improved erectile function in STZ-induced diabetic rats. Furthermore, a synergistic effect was observed in vitro and in vivo. Resveratrol or combination therapy of resveratrol and vardenafil can improve erectile function in which NO release is impaired, although further study is needed to confirm the results.

α(1)-adrenoceptor blocker naftopidil improves sleep disturbance with reduction in nocturnal urine volume.

OBJECTIVES: To examine the mechanism underlying improvements in nocturia by α(1)-blockers, we investigated whether the α(1)-blocker naftopidil acts on nocturia with sleep disturbance using a frequency/volume chart (FVC). METHODS: A total of 56 male patients with lower urinary tract symptoms were enrolled. The inclusion criteria were as follows: eight or more points on the I-PSS; three or more points on the I-PSS score for nocturia; and prostate volume larger than 20 ml. Patients received 50 mg of naftopidil once daily for 4 weeks, and non-responders received 75 mg for another 4 weeks. All patients were examined, and their data entered into FVC for 2 days before and after administration of naftopidil. Quality of sleep was also evaluated using modified Pittsburgh sleep quality index (PSQI). RESULTS: Patients with sleep quality scores of three or four were assigned to sleep disturbance group (n = 33), while those with scores of less than three were assigned to non-disturbance group (n = 23). After administration of naftopidil, total I-PSS decreased and nocturia score decreased from 3.5 to 2.6 (P < 0.01). Total mean score of modified PSQI in sleep disturbance group became significantly lower after administration of naftopidil (from 16.9 to 14.0; P < 0.01). Naftopidil significantly decreased nocturnal urine volume, resulting in a decrease in the nocturnal polyuria index in both sleep disturbance and non-disturbance groups. CONCLUSION: These results suggest that α(1)-blockers have the ability to normalize sleep disorders. Naftopidil improved nocturnal polyuria regardless of the presence of sleep disturbance, meaning that it might directly reduce nocturnal urine production.

Long-term outcome of pediatric renal transplantation: a single center experience.

Renal transplantation is the optimal treatment for pediatric end-stage renal disease. We examined 51 children <20 yr old who underwent a total of 52 living-donor renal transplantations at Osaka University Hospital between 1972 and 2004. The mean age at transplantation was 13.7 (3-19 yr). The mean duration of follow-up was 16.5 yr. The five-, 10-, and 20-yr patient survival rates following renal transplantation were 94%, 90%, and 87%, respectively. The five-, 10-, and 20-yr graft survival rates were 76%, 65%, and 48%, respectively. A double-drug regimen was used before 1987; this was replaced by a triple-drug regimen including a calcineurin inhibitor in 1988. The five-, 10-, and 20-yr graft survival rates after 1988 (89%, 80%, and 60%, respectively) were higher than those before 1987. Growth was examined among patients <15 yr old at the time of surgery, and height standard deviation (SD) scores (Z-scores) were analyzed in 14 patients who displayed favorable renal function after transplantation. At the time of transplantation, mean SD score (SDS) was -2.39, and mean final adult SDS was -1.79. Rates of patient and graft survival after renal transplantation were mostly favorable. Future goals must include overcoming chronic rejection and establishing a steroid discontinuation protocol to improve growth.

Lower urinary tract symptoms and erectile dysfunction associated with depression among Japanese patients with late-onset hypogonadism symptoms.

The aim of this study was to investigate the relation between lower urinary tract symptoms (LUTS), erectile dysfunction (ED) and depression in Japanese patients with late-onset hypogonadism (LOH) symptoms. The study comprised 87 Japanese patients with LOH symptoms (>27 points on the Aging Males Symptoms Scale). Thirty-four patients were diagnosed as having depression and the remaining 53 patients were diagnosed as not having depression by the Mini International Neuropsychiatric Interview. We compared the International Index of Erectile Function (IIEF) 5, International Prostate Symptom Score (IPSS), IPSS quality-of-life (QOL) index, King's Health Questionnaire (KHQ), endocrinological data, and free uroflow study between depression and non-depression patients and performed multiple logistic regression analysis. IIEF5 scores of depression patients were significantly lower than those of non-depression patients. In KHQ, only the category of general health perceptions was significantly higher in depression patients than non-depression patients. However, IPSS, QOL index, and endocrinological and uroflowmetric data showed no significant difference between the groups. Multiple logistic regression analysis revealed moderate and severe ED to be risk factors for depression. However, LUTS are not related to depression. Moderate and severe ED is correlated with depression, whereas LUTS are not related to depression in Japanese LOH patients.

Change in cytokine levels after administration of saikokaryuukotsuboreito or testosterone in patients with symptoms of late-onset hypogonadism.

The purpose of this study was to evaluate plasma cytokine levels after treatment with saikokaryukotsuboreito (SKRBT), which is a herbal medicine, or androgen replacement treatment (ART), for patients with late-onset hypogonadism (LOH)-related symptoms. Thirty-one patients over 40 years of age with LOH-related symptoms were included in this study. SKRBT was given orally three times daily to a total of 7.5 g/day for 15 eugonadal patients and ART was give to 16 hypogonadal patients by intramuscular injection of testosterone enanthate at 125 mg each time every 2 weeks. Plasma levels of testosterone and 18 cytokines, as well as LOH-related symptoms scored according to the Aging Males' Symptoms (AMS) scale, were compared before and more than 2 months after treatment. In the ART group, the total AMS score was decreased and testosterone was increased significantly after treatment. No cytokine variables were altered significantly after the treatment. In the SKRBT group, although the total AMS score was significantly decreased, testosterone did not change. From the evaluation of cytokines, a significant increase was found in interleukin (IL)- 8, IL-13, interferon-gamma and tumour necrosis factor-alpha. We conclude that SKRBT might improve LOH-related symptoms in eugonadal patients through the beneficial effect of cytokines, a mechanism that is quite different from ART.

Why does atorvastatin inhibit renal crystal retention?

Recently, we reported that atorvastatin prevents renal tubular cell injury by oxalate and inhibits renal crystal retention. In this study, we investigated the mechanism by which atorvastatin inhibits renal crystal retention. Male Sprague-Dawley rats were separated into four experimental groups, and the ethylene glycol model of hyperoxaluria and the atorvastatin treatment model were analyzed. To clarify the mechanism by which atorvastatin inhibits renal crystal retention, the removed kidneys were used for the quantitative analysis of superoxide dismutase (SOD) and catalase. The subunits of the NADPH oxidase system were evaluated using real-time polymerase chain reaction analysis. Furthermore, the level of transforming growth factor-ß (TGF-ß) in kidney tissue was compared in each group. Atorvastatin treatment increased the SOD and catalase level compared with the stone-forming control group. Atorvastatin treatment decreased the expression of NOX-1 mRNA. Furthermore, the level of TGF-ß was suppressed by atorvastatin treatment. We found that atorvastatin have inhibited calcium oxalate (CaOX) urolithiasis formation. We hypothesize that the mechanism of action of atorvastatin involves inhibiting TGF-ß and NADPH oxidase, and increasing the SOD and catalase level. We believe that atorvastatin will be helpful in the treatment of CaOX urolithiasis.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

OBJECTIVE: To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. METHODS: Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. RESULTS: Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. CONCLUSIONS: The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Effect of sex hormones on crystal formation in a stone-forming rat model.

Sex hormones have substantial effects on crystal formation in the rat kidney through oxalate metabolism and oxidative cell damage. Testosterone is a promoter and estradiol an inhibitor of such crystal formation. The development of new medications related to sex hormones or GO are anticipated for sufferers of recurrent urolithiasis.

[Two cases of bladder cancer with hereditary nonpolyposis colorectal cancer].

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by an excess of extracolonic malignancies including those of the urinary tract. We report two cases of bladder tumor associated with HNPCC. The reported cases were compatible for Amsterdam criteria II for HNPCC. It is important to obtain a family history of cancer in patients with urothelial carcinoma. A patient with a strongly positive cancer history must be carefully examined for HNPCC and HNPCC associated cancers.

[A case report of retrocaval ureter associated with right ureteral tumors].

A case of retrocaval ureter associated with right ureteral tumor in a 70-year-old male is reported. The diagnosis was confirmed by CT and RP. Retroperitoneoscopic nephroureterectomy was performed. The histology of the tumor was urethelial carcinoma. After 20 months, there was neither evidence of recurrence nor metastasis. To our knowledge, this is the 11th case of retrocaval ureter associated with upper urinary tract tumors.

5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer.

Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

Decreased infiltration of macrophage scavenger receptor-positive cells in initial negative biopsy specimens is correlated with positive repeat biopsies of the prostate.

Macrophage scavenger receptor (MSR)-positive inflammatory cells and tumor-associated macrophages (TAMs) have been reported to regulate the growth of various cancers. In this study, the infiltration of MSR-positive cells and TAMs was analyzed to predict the outcome of repeat biopsy in men diagnosed as having no malignancy at the first prostate biopsy. Repeat biopsy of the prostate was carried out in 92 patients who were diagnosed as having no malignancy at the first biopsy. Of these, 30 patients (32.6%) were positive for prostate cancer at the repeat biopsy. Tumor-associated macrophages and MSR-positive cells were immunohistochemically stained with mAbs CD68 and CD204, respectively. Six ocular measuring fields were chosen randomly under a microscope at x400 power in the initial negative biopsy specimens, and the mean TAM and MSR counts for each case were determined. No difference in TAM count was found between the cases with or without prostate cancer. By contrast, the MSR count in patients with cancer was significantly lower than that in patients without cancer at the repeat biopsy (P < 0.001). Logistic regression analysis indicated that the MSR count at first biopsy is a significantly better predictive factor for positive repeat biopsy than PSA velocity, interval between first and repeat biopsies, or TAM count. Decreased infiltration of MSR-positive cells in negative first biopsy specimens was correlated with positive findings in the repeat biopsy. The MSR count might be a good indicator for avoiding unnecessary repeat biopsies.

SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer.

Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.

Olfactory mucosal transplantation after spinal cord injury improves voiding efficiency by suppressing detrusor-sphincter dyssynergia in rats.

PURPOSE: Several recent studies showed that olfactory mucosal transplantation after spinal cord injury promotes extensive regeneration of the injured spinal cord. We examined the efficacy of olfactory mucosal transplantation for bladder dysfunction after spinal cord injury in rats. MATERIALS AND METHODS: In adult female rats the Th9-10 spinal cord was completely transected, followed by olfactory mucosal transplantation or gelatin sponge filling as the control. Each group was examined by cystometrogram and external urethral sphincter electromyogram. Calcitonin gene-related peptide and growth associated protein 43 double positive expression in the L6/S1 dorsal horn was evaluated by immunohistochemistry. Transplant sites were examined by immunohistochemistry with antibodies against neurofilament M and neuronal class III beta-tubulin. RESULTS: On cystometrogram voiding efficiency was significantly higher in the transplantation group than in controls. On external urethral sphincter electromyogram with simultaneous cystometrogram the transplantation group showed a larger ratio of interburst silent periods to burst activity duration and a greater number of high frequency oscillations. In the transplantation group calcitonin gene-related peptide and growth associated protein 43 double positive expression in the L6/S1 dorsal horn was less dense than in controls. The transplantation group showed strong neurofilament M and neuronal class III beta-tubulin expression at the transplant site. CONCLUSIONS: Olfactory mucosal transplantation after spinal cord injury weakened external urethral sphincter excessive bursting and increased the urethral opening to improve voiding efficiency. Olfactory mucosal transplantation may modify emergence of the spinal micturition reflex after spinal cord injury. Transplantation resulted in new axons growing at the transplant site, implying the possible existence of interneuron bridging across the injured spinal cord.

Orthosiphon grandiflorum has a protective effect in a calcium oxalate stone forming rat model.

This study amied to investigate the effects of Orthosiphon grandiflorum on the renal tubular cell injury induced by oxalate and the inhibitory effects of O. grandiflorum on urinary deposit formation in an animal model and compared the results with those from a potassium citrate treatment. Rats were divided into three groups: an untreated stone-forming group, an O. grandiflorum-treated stone-forming group and a potassium citrate-treated stone forming group. Ethylene glycol (0.5%) was administered to the rats during the last week, and vitamin D3 (0.5 mum) was force fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. Twenty-four hour urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope to determine the number of crystals. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. Oxidative stress was examined by 8-OHdG immunohistofluorescence. O. grandiflorum and potassium citrate have the ability to alkalinize urine. Among all groups, the number of crystal deposits and the level of 8-OHdG staining decreased significantly in the O. grandiflorum-treated stone forming group, as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the O. grandiflorum-treated stone-forming group, as compared with the untreated stone-forming group. The results indicate that O. grandiflorum has a significant inhibitory effect on crystal deposition in the calcium oxalate-stone-forming rat model.

Tumor multiplicity is an independent prognostic factor of non-muscle-invasive high-grade (T1G3) bladder cancer.

OBJECTIVE: Non-muscle-invasive high-grade (T1G3) bladder cancers have high potential for progression. The objective of this study is to clarify the clinicopathological factors affecting the outcome of T1G3 bladder cancer. METHODS: We retrospectively reviewed 60 cases of T1G3 bladder cancer between 1994 and 2006. The correlations of both intravesical recurrence and progression with prognostic factors, such as T stage, history of bladder cancer, multiplicity, concomitant carcinoma in situ, tumor size, intravesical instillation of bacillus Calmette-Guérin and intravesical chemotherapy, were evaluated by multivariate analysis with the Cox proportional hazards model. RESULTS: Median follow-up period was 52 months (4-105 months). Thirty-seven cases of intravesical recurrence (61.7%) were observed during follow-up. Two- and 5-year recurrence-free survival rates were 44.1% and 36.1%, respectively. Tumor multiplicity and instillation of bacillus Calmette-Guérin were significantly correlated with intravesical recurrence on multivariate analysis. Ten cases of progression (16.7%) were observed during the follow-up period. Two- and 5-year progression-free survival rates were 87.7% and 83.4%, respectively. Only tumor multiplicity was significantly correlated with progression on multivariate analysis. CONCLUSIONS: T1G3 cancers with multiple lesions showed high risks of intravesical recurrence and progression. Although bacillus Calmette-Guérin instillation reduced the risk of intravesical recurrence, no effect was observed on disease progression.

Utility of the Japanese GFR estimation equation for evaluating potential donor kidney function.

BACKGROUND: In Japan, the number of living kidney transplantations has increased each year, and an accurate evaluation of renal function must be conducted before donation to minimize the risk to donors. Recently, the Japanese Society of Nephrology issued a new equation for estimating glomerular filtration rate (eGFR) in Japanese people. This study compared the accuracy of eGFR and creatinine clearance (Ccr) values with that of inulin clearance (Cin) for assessing renal function in kidney donors. METHODS: Clinical data were analyzed for 85 potential living kidney donors who had undergone routine measured GFR (mGFR) and Ccr measurements from October 2006 to November 2008 at a single center. Inulin clearance, representing the mGFR, was determined by standard method. The eGFR was calculated as: eGFR = 194 x Scr(-1.094) x Age(-0.287) (for females, x0.739). RESULTS: Mean mGFR was 96.1 +/- 14.7 (range 67.8-126.8); mean eGFR, 72.6 +/- 12.7 (range 50.1-107.1); and mean Ccr, 117.3 +/- 22.4 (range 35.1-170.1), in units of ml/min/1.73 m(2) for each. Relative to mGFR, the correlation coefficient for Ccr was 0.496, and the mean difference between the two values was 21.1 ml/min/1.73 m(2) (23.2%), with a root-mean square error (RMSE) of 19.6. The correlation coefficient between eGFR and mGFR was 0.502, and the mean difference between the two values was -23.5 (23.7%), with a RMSE of 11.0. Bland-Altman plots showed that Ccr overestimated mGFR in 90.6% of cases, whereas eGFR underestimated mGFR in 95.3% of cases. CONCLUSION: Ccr and eGFR values did not accurately estimate mGFR in Japanese living kidney donors.

Post-transplant lymphoproliferative disorder following renal transplantation: a single-center experience over 40 years.

OBJECTIVES: To investigate post-transplant lymphoproliferative disorder (PTLD) following renal transplantation at our institution. METHODS: Medical records of 631 patients who underwent renal transplantation at Osaka University Hospital between March 1965 and December 2008 were reviewed. RESULTS: PTLD following renal transplantation was detected in 10 patients (five men, five women; mean age at transplantation, 38.5 years). Mean duration from renal transplantation to the onset of PTLD was 7.1 years (range, 5 months to 18 years, 9 months). Mean duration of observation was 3.9 years from the onset of PTLD. Immunosuppressant therapy comprised multidrug combination therapy, including cyclosporine in six patients and tacrolimus in four patients. In addition to a reduction in the immunosuppressant dose, which was performed in all patients, PTLD was treated with surgery in seven patients, radiotherapy in two patients, rituximab in five patients, and cytotoxic chemotherapy in four patients. A complete remission in eight patients and progressive disease in two were observed. At last follow up, seven patients were alive and five patients had functioning grafts. CONCLUSIONS: The incidence of PTLD following renal transplantation at our institution is 1.6% with onset occurring more than 5 years after transplantation in five patients. Consequently, with long-term renal graft survival now feasible, attention must be paid to detecting late-onset PTLD.