Difficulty in differential diagnosis for renal cancer with microscopic papillary architecture: overlapped pathological features among papillary renal cell carcinoma (RCC), mutinous tubular and spindle cell carcinoma, and unclassified RCC. Lessons from a Japanese multicenter study.

OBJECTIVES: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. METHODS: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. RESULTS: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years. CONCLUSION: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.

Clinical Outcomes in Patients With Metastatic Papillary Renal-Cell Carcinoma: A Multi-Institutional Study in Japan.

BACKGROUND: Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC. PATIENTS AND METHODS: This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed. RESULTS: Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016). CONCLUSION: Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings.

Angiogenic, inflammatory and immunologic markers in predicting response to sunitinib in metastatic renal cell carcinoma.

The objective of this prospective study was to identify baseline angiogenic and inflammatory markers in serum as well as the baseline levels of immune cells in whole blood to predict progression-free survival in patients with metastatic renal cell carcinoma treated with sunitinib. Blood samples were collected at baseline in all 90 patients to analyze serum angiogenic and inflammatory markers together with peripheral blood immunological marker. The association between each marker and sunitinib efficacy was analyzed. Univariate and multivariate Cox proportional model analyses were used to assess the correlation between those markers with survival. Baseline levels of interleukin-6, interleukin-8, high sensitivity C-reactive protein and myeloid-derived suppressor cells were significantly higher in patients who progressed when compared with those with clinical benefit. Analysis by the Cox regression model showed that baseline interleukin-8, high sensitivity C-reactive protein and percentage of T helper type 1 cells were significantly associated with progression-free survival in univariate analysis. Furthermore, in multivariate analysis, those three markers were independent indices to predict progression-free survival. In conclusion, angiogenic (interleukin-8), inflammatory (interleukin-6, high sensitivity C-reactive) and immunologic (myeloid-derived suppressor cells, percentage of T helper type 1 cells) markers at baseline would predict the response to sunitinib therapy and/or disease progression in patients with metastatic renal cell carcinoma.

Rapid Progressive Disease After Nivolumab Therapy in Three Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: Rapid progressive disease (RPD), accelerated tumour growth immediate after the initiation of immune checkpoint inhibitor therapy, has been reported in melanoma and lung cancer. Herein, we describe 3 cases of RPD during the initial phase of nivolumab treatment for metastatic renal cell carcinoma. PATIENTS AND METHODS: The first and second patients received nivolumab in the fourth-line setting. The third patient received nivolumab therapy as third-line treatment. RESULTS: The first patient developed severe respiratory failure due to carcinomatous lymphangiosis 14 days after initiation of nivolumab therapy. The second patient developed leg paraplegia due to rapid growth of the metastatic tumour at the sixth thoracic vertebrae 5 days later. The third patient developed grade 4 hypercalcemia due to RPD on day 3. CONCLUSION: Clinicians should be aware of RPD during the initial phase of nivolumab therapy, especially in patients with critical lesions in the late-line setting.

Clinical efficacy and prognostic factors of tumor progression in Japanese patients with advanced renal cell carcinoma treated with sorafenib.

OBJECTIVE: Result of clinical trial for registration purpose is often difficult to generalize because of its limited population in number and inclusion criteria. METHODS: To understand the efficacy of sorafenib under daily medical practice, we retrospectively investigated therapeutic outcomes of 175 Japanese patients with advanced renal cell carcinoma treated with sorafenib at 15 centers. RESULTS: The objective response rate and disease control rate were 15.4 and 77.1%, respectively, being similar to those in the Phase II study in Japanese patients (19.4 and 73.6 months). Any tumor shrinkage was observed with 53% of patients, while tumor control without growth was in 61%. Lung lesions were more sensitive to sorafenib than other lesions, in terms of any tumor shrinkage (54%) and the extent of maximal shrinkage, while tumor control was better in lymph node metastases (77%) than in lung (69%). Liver was worse in any tumor shrinkage (35%), tumor control (55%) and the extent of tumor growth. Slightly, shorter median overall survival of 21.1 months compared with Phase II clinical trial (25.3 months) is likely to be attributable to different patient population, because median overall survival was improved to 26.4 months when the population was matched to that in Phase II trial. Univariate and multivariate analyses identified prognostic factors for worse overall survival, including intermediate and poor Memorial Sloan-Kettering Cancer Center risk, Eastern Cooperative Oncology Group performance status ≥1, the presence of non-clear cell component and the presence of liver metastasis. CONCLUSIONS: In conclusion, the present study confirmed the efficacy of sorafenib in the real-world setting on advanced renal cell carcinoma.

Peristomal pagetoid spread of urothelial carcinoma of the ureter.

Patients with ostomy including urinary stoma often develop peristomal complications, especially skin damage. The patient in this case was a 69-year old female with a history of urothelial carcinoma of the bladder and left ureter who underwent transurethral resection of a bladder tumor, nephroureterectomy and cystectomy combined with ureterocutaneostomy. Later, she had recurrence of urothelial carcinoma in the remaining ureter that spread to the peristomal epidermis, with a skin appearance resembling Paget's disease. We report this case based on its clinical significance since we believe it is the first description of this condition in the literature.

[Neobladder-rectal fistula as early postoperative complication of radical cystectomy and orthotopic neobaldder construction].

We report a case of neobladder-rectal fistula that developed as an early postoperative complication of radical cystectomy and orthotopic neobladder construction procedures. A 75-year-old man underwent a radical cystectomy and orthotopic neobladder construction using Studer's method for locally invasive bladder cancer (cT2N0M0). The patient had severe watery diarrhea on postoperative day 20, and was diagnosed with a neobladder-rectal fistula based on cystography findings. We inserted a Foley catheter into the neobladder, and performed conservative treatment. Four months after development of the fistula, cystography revealed that it had spontaneously closed. A neobladder-rectal fistula is an extremely rare complication, with no other known reports. Herein, we present this case of neobladder-rectal fistula and discuss its formation, diagnosis and treatment, along with reference to previous reports of neobladder-vaginal fistulas.

[Pseudosarcomatous myofibroblastic proliferation of the bladder-case report].

A 66-year-old man with a history of sporadic von Recklinghausen' s disease was treated for pseudosarcomatous myofibroblastic proliferation in the bladder. The patient had a history of repetitive recurrence of bladder carcinoma requiring transurethral resection (TUR) 4 times and 1 course of intravesical BCG instillation. Three months after the fourth TUR, an intravesical solid mass 4 cm in diameter was detected. Suspicion of recurrent bladder carcinoma led to a fifth TUR procedure. Pathological findings showed submucosal growth of myofibroblasts with myxoidal stroma and we made a diagnosis of Pseudosarcomatous myofibroblastic proliferation. The patient was well with no evidence of recurrence after 1 year.

A study of plasma bicalutamide concentrations in hemodialysis patients.

Bicalutamide is an anti-androgen that is used worldwide to treat prostate cancer (CaP). However, there are no data on blood bicalutamide concentrations in hemodialysis (HD) patients with CaP. Therefore, we investigated the plasma levels of bicalutamide during the peridialysis period in this population. The study group included 5 HD patients with CaP who had been treated with bicalutamide (80 mg/day) for at least 3 months. Blood samples were taken during and between HD sessions and the plasma concentrations of the active R enantiomer (R-bicalutamide) were assessed using an HPLC assay. The plasma R-bicalutamide levels on the non-dialysis day were measured in 2 patients (patients 1 and 2) immediately before dosing and 8 and 24 h after dosing. These levels were 18,730, 19,090 and 19,420 ng/ml (patient 1), and 4,522, 4,581, and 5,296 ng/ml (patient 2), respectively. The mean plasma levels of R-bicalutamide in all 5 subjects just before HD, and 2 and 4 h after the start of HD were 8,726, 9,354 and 10,068 ng/ml, respectively. These results show that bicalutamide does not accumulate and is not diluted in the blood circulation of HD patients when given at the normal dosage used in the general population.

Perioperative outcomes of laparoscopic radical nephrectomy for renal cell carcinoma in patients with dialysis-dependent end-stage renal disease.

The aims of this study were: (i) to analyze the perioperative outcomes of laparoscopic radical nephrectomy for renal cell carcinoma in patients with dialysis-dependent end-stage renal disease and (ii) to reveal perioperative management problems that are unique to these patients. Between June 2004 and June 2011, laparoscopic radical nephrectomy was performed in 39 patients who had renal cell carcinoma and dialysis-dependent end-stage renal disease. The operative outcomes of these patients were compared with the operative outcomes of 104 non-end-stage renal disease patients with sporadic renal cell carcinoma who underwent laparoscopic radical nephrectomy during the same period. Laparoscopic surgery was completed in thirty-eight end-stage renal disease patients. One patient was converted to open surgery because of an intraoperative injury to the inferior vena cava. This patient was excluded from the analysis. The mean operative time was 240 min; blood loss, 157 mL; and postoperative hospital stay, 9.6 days. Postoperative complications were observed in six patients, as follows: retroperitoneal hematoma and abscess in one patient, thrombosis of the arteriovenous fistula in three patients, pneumonia in one patient, and gastrointestinal bleeding in one patient. Eleven patients required blood transfusions. There was no significant difference between the end-stage renal disease patients and the non-end-stage renal disease patients in the mean operative time or the amount of blood loss. In conclusion, laparoscopic radical nephrectomy is feasible for dialysis-dependent end-stage renal disease patients, as well as for non-end-stage renal disease patients; however, end-stage renal disease patients may have a higher probability of experiencing non-life-threatening complications.

[Renal epithelioid angiomyolipoma with malignant behavior].

The patient was a 22-year-old woman with a history of tuberous sclerosis who complained of abdominal distention. Computed tomography showed bilateral renal masses with minimal fat tissue that were unlike classical angiomyolipoma (AML), as well as enlargement of the paraaortic lymph nodes, pleural effusion, and ascites, similar to other advanced malignant neoplasms such as renal cell carcinoma and renal sarcoma. We performed a left nephrectomy to relieve the symptoms. A pathological examination revealed that the tumor was composed of polygonal epithelioid cells positive for both αSMA and HMB-45, as well as spindle-shaped cells, while immunoreactivity proved the tumor to be an eAML, a subtype of AML with malignant potential. Although the patient was scheduled for postoperative adjuvant chemotherapy, her condition worsened and she died on postoperative day 24 before receiving chemotherapy. We discuss this case with reference to previous reports.

Key predictive factors of axitinib (AG-013736)-induced proteinuria and efficacy: a phase II study in Japanese patients with cytokine-refractory metastatic renal cell Carcinoma.

BACKGROUND: Axitinib (AG-013736) is an oral, selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2 and 3. This phase II study investigated axitinib efficacy, safety and biomarkers in Japanese patients with cytokine-refractory metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: In an open-label, multicentre study, 64 patients received an axitinib starting dose of 5mg twice daily. RESULTS: Objective response rate (ORR) was 50.0% and median progression-free survival (PFS) was 11.0 months per independent review committee. Common treatment-related adverse events were hypertension (84%; 70% grade ≥3), hand-foot syndrome (75%; 22% grade ≥3) and diarrhoea (64%; 5% grade ≥3). Eighteen patients (28%) developed proteinuria ≥2g/24h and required dose reduction or treatment interruption/discontinuation. Proteinuria was a major cause for treatment discontinuation. Baseline urine protein levels were associated with development of proteinuria ≥2g/24h (hazard ratio [HR]=5.457, P=0.0035 in patients with baseline proteinuria ≥1+ versus <1+). Baseline urine protein levels correlated more strongly with axitinib-related proteinuria than other baseline renal function test values or blood pressure. Patients with greater decreases in soluble VEGFR-2 concentrations had significantly higher ORR and longer PFS than those with smaller decreases (ORR: 64.5% versus 37.5%, P=0.045; median PFS: 12.9 months versus 9.2 months, HR=0.42, P=0.01). CONCLUSIONS: Axitinib showed significant antitumour activity and was well tolerated in Japanese mRCC patients. Baseline proteinuria and soluble VEGFR-2 levels may be key indicators of axitinib-induced proteinuria and efficacy, respectively.

Postoperative renal function after partial nephrectomy for renal cell carcinoma in patients with pre-existing chronic kidney disease: a comparison with radical nephrectomy.

We assessed whether adequately functioning parenchyma is preserved in patients with pre-existing chronic kidney disease (CKD) after partial nephrectomy (PN) compared with those who underwent radical nephrectomy (RN). A total of 95 patients with pre-existing CKD who underwent curative surgery for pathological T1a-T2N0M0 renal cell carcinoma with a follow-up period of 12 months or more were the subject of the present study. Of these, 51 patients underwent RN, and 44 PN. Renal function was assessed by using the estimated glomerular filtration rate (e-GFR). We classified the subjects into two groups according to the preoperative e-GFR: preoperative e-GFR 45-59 mL/min/1.73 m(2) (68 patients); and 30-44 mL/min/1.73 m(2) (27 patients). In the former group, the probability of freedom from new onset of e-GFR <45 mL/min/1.73 m(2) stemmed from the significant difference between the PN and RN groups (P = 0.006; PN: 2 years 64%; RN: 2 years 22%). In contrast, in the latter group, the probability of freedom from new onset of e-GFR <30 mL/min/1.73 m(2) was not associated with a significant difference between PN and RN group (P = 0.80). Overall survival and the number of the patients who went on to develop end-stage renal disease requiring renal replacement therapy between PN and RN were not significantly different in each group. Death from renal cell carcinoma was not noted in either group. PN could significantly prevent development to late-stage CKD in patients with preoperative e-GFR 45-59 mL/min/1.73 m(2) compared with RN. Patients with preoperative e-GFR 30-44 mL/min/1.73 m(2) should be reviewed in a more strict study.

A new indicator of favorable prognosis in locally advanced renal cell carcinomas: gamma delta T-cells in peripheral blood.

BACKGROUND: Although human γδ T-cells that express Vγ2Vδ2-bearing T-cell receptor (Vγ2Vδ2 T-cells) have recently received considerable attention in the development of novel cancer immunotherapies, consensus has not yet been reached regarding the physiological relevance of this T-cell subset in the context of cancer immunosurveillance. Clinical trials of adoptive immunotherapy using autologous Vγ2Vδ2 T-cells have been applied to patients with advanced renal cell carcinoma (RCC) and some clinical benefits have been reported. In the present study, we investigated the correlation between the proportion of γδ T-cells in peripheral before surgery in patients with locally advanced RCC and those clinical outcomes. PATIENTS AND METHODS: Of 41 patients who underwent surgery for RCC, 13 patients had stage III disease without metastasis. These stage III patients were stratified into two groups based on the peripheral γδ T-cell proportion being greater or less than 8.7% before surgery and were followed up for up to 137 months (median 129 months). RESULTS: Remarkably, an obvious difference was found in the overall survival and cause-specific survival rate between the two groups. In 6 patients with a higher proportion of γδ T-cells, one patient had lung metastasis, but there were no cancer-related deaths. In contrast, 5 out of 7 patients with a lower proportion of γδ T-cells died during the study and 4 out of 7 patients died due to RCC. CONCLUSION: An increase in the proportion of peripheral γδ T-cells is a favorable prognostic factor for patients with locally advanced RCC.

Clinical results and pharmacokinetics of sorafenib in chronic hemodialysis patients with metastatic renal cell carcinoma in a single center.

OBJECTIVE: We investigated the safety and feasibility of sorafenib in patients with end-stage renal disease undergoing hemodialysis by examining the influence of pharmacokinetic parameters to their benefit and also the occurrence of drug-related adverse events of sorafenib. METHODS: Ten patients with metastatic renal cell carcinoma undergoing hemodialysis received sorafenib. Initial dose was 200 mg once daily, and the dose was increased up to the maintenance dose of 200 mg twice daily. The pharmacokinetic study was performed after a steady state was reached with 200 mg twice daily in six patients. RESULTS: Complete response occurred in one patient, partial response in three, stable disease in four and progressive disease in two. Median progression-free survival was 6.3 months. Serious adverse events were found in nine patients, including a Grade 5 subarachnoid hemorrhage and a Grade 4 cerebellar hemorrhage. In the pharmacokinetic study, the geometric mean of maximum concentration and area under the curve from 0 to 10 h of plasma concentration were similar on the day of hemodialysis and the day off hemodialysis. These data were lower than those from Japanese people with healthy kidneys and normal kidney function. There was no association between objective response or the occurrence of serious adverse events and pharmacokinetic parameters. CONCLUSIONS: Treatment with sorafenib of patients with metastatic renal cell carcinoma undergoing hemodialysis appears to be feasible, but we express some concern about the higher incidence of serious adverse events even with the reduced dose. However, clinical efficacy was not compromised.

A rare benign genitourinary tumor in a Japanese male: urinary retention owing to aggressive angiomyxoma of the prostate.

Close examination of a 67-year-old Japanese man, who complained of persistent nocturia, revealed that a semitransparent polypoid tumor had developed from the bladder neck to the prostatic urethra obstructing the internal urethral meatus, which resulted in excessive urinary retention and post-renal dysfunction. The tumor was resected by a transurethral procedure and a pathological examination of specimens revealed aggressive angiomyxoma (AAM) of the prostate. AAM usually develops in the intrapelvic and perineal organs of females. So far as we know, this is the second case of primary prostatic AAM reported in the English literature, and is the first case where the patient encountered urethral obstruction.

Template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract: impact on patient survival.

OBJECTIVES: The benefit of lymphadenectomy (LND) in patients with urothelial carcinoma of the upper urinary tract (UCUUT) has remained controversial. The aim of this study was to examine the influence of the LND template and the total number of lymph nodes (LN) when increasing the number of patients undergoing complete dissection of regional nodes (CompLND). METHODS: A total of 109 UCUUT patients with clinically negative nodes underwent nephroureterectomy with concomitant lymphadenectomy at our center. Patients' survival was examined according to the type of LND and the number of removed LN. Univariate analysis was performed to find the cut-off value of LN influencing survival. RESULTS: Seventy-eight patients underwent CompLND. Incomplete lymphadenectomy was performed in an additional 41 patients. In the patients with pT2 or higher who were clinically negative for nodal metastasis, any cut-off value for the total number of LN removed showed no statistical significance. In contrast, CompLND had a significant impact on patient survival. The Cox proportional hazard model showed that CompLND was a significant factor after adjusting for adjuvant chemotherapy. The total number of removed LN was not significant. CONCLUSIONS: In patients with muscle-invasive clinical node-negative UCUUT, the number of LN removed shows minimal influence on their survival. In contrast, the influence of the particular type of lymphadenectomy is statistically significant. These findings suggest that the extent of lymphadenectomy should be determined by the template and not by the number of removed LN.

Contralateral metachronous tumor occurrence is more frequently associated with distant metastases or postoperative intrarenal recurrence in renal cell carcinoma patients.

OBJECTIVE: To analyze the prognosis of patients with sporadic bilateral renal cell carcinoma (RCC). METHODS: From January 1979 to December 2007, 984 patients with sporadic RCC underwent surgery at our department. Of these, 53 patients (5.7%) presenting with bilateral RCC were included in this retrospective analysis. RESULTS: Thirty-one of the 53 bilateral RCC patients had synchronous RCC, and 22 had metachronous RCC. Distant metastases by the time of the bilateral tumor occurrence were found in four patients (13%) in the synchronous group and in 10 patients (48%) in the metachronous group. No difference was found between the two groups in terms of overall survival. In contrast, survival after the second surgery in the metachronous group was significantly lower than that after the first surgery (P < 0.001) in the synchronous group (P = 0.02). In addition, the incidence of local recurrence after partial nephrectomy was higher in the metachronous group (26%) compared to the synchronous group (4%, P = 0.04) or the unilateral RCC patients (0.4%, P < 0.01). CONCLUSIONS: Metachronous occurrence of RCC in the contralateral kidney is associated with an unfavorable prognosis, suggesting that metachronous contralateral tumors might be metastasis of the original tumors. A stricter follow-up schedule is advisable for metachronous bilateral RCC patients.

A case of primary renal angiosarcoma.

A 78-year old man was diagnosed with a left bleeding renal cyst from CT scan results. Serial CT scans revealed the left kidney mass to be increasing in size and a new lesion in the liver. Renal cell carcinoma with liver metastasis was diagnosed and a radical nephrectomy performed. The initial pathological diagnosis was a benign chronic hematoma. However, the liver mass increased in size and multiplied, while another mass emerged in the twelfth thoracic vertebra with spinal paralysis and was immediately removed. Pathological findings for that specimen showed malignancy of stromal cell origin but low atypia. The renal specimen was re-evaluated using whole cross-section analysis and immunohistochemistry, and diagnosed as a primary renal angiosarcoma. Recombinant interleukin-2 therapy was started immediately; however, the patient died of metastatic disease 13 months after the initial operation. Although contrast imaging depicted the primary lesion as a non-specific hematoma with little focal pooling, and low-grade cytological atypia was shown pathologically, the angiosarcoma was extremely aggressive.

Minimal effect of cold ischemia time on progression to late-stage chronic kidney disease observed long term after partial nephrectomy.

OBJECTIVES: To assess the influence of cold ischemia on postoperative renal function and the new onset of late-stage chronic kidney disease during long-term follow-up after partial nephrectomy. METHODS: A total of 131 patients with renal tumors who underwent partial nephrectomy and were followed up for >or=12 months were included in the present study. Renal function was analyzed using the estimated glomerular filtration rate (e-GFR). RESULTS: We classified the subjects into 3 groups according to the length of cold ischemia time: group 1, 1-30 minutes; group 2, 31-60 minutes; and group 3, >60 minutes. Although the postoperative e-GFR was lower in group 3 than in groups 1 and 2, no significant difference was found among the 3 groups during long-term follow-up when preoperative CKD was absent. A cold ischemia time of >or=44 minutes significantly increased the probability of freedom from the new onset of an e-GFR of <45 mL/min/1.73 m(2), but this difference was minimal. Multivariate analysis showed that the preoperative e-GFR and the relative decrease of e-GFR at 1 year after surgery were the significant factors determining postoperative renal function. CONCLUSIONS: A cold ischemia time of >44 minutes appears to be a threshold influencing the new onset of late-stage CKD; however, it was not a significant factor on multivariate analysis. Thus, renal hypothermia appears to prevent the deterioration of renal function long term after surgery for patients undergoing a longer ischemia time.