Tryptophan-kynurenine ratio as a biomarker of bladder cancer.

OBJECTIVES: To investigate plasma and urinary kynurenine (KYN)-tryptophan (TRP) ratios in bladder cancer, expression of indoleamine 2,3-dioxygenase 1 (IDO1) in relation to tryptophan 2,3-dioxygenase (TDO2) in bladder tumour, and the correlation of KYN-TRP ratio with bladder tumour burden. METHODS: Metabotyping of the TRP-KYN metabolic axis was performed via a clinical case-control study. Expression of IDO1 and TDO2 was measured in human biopsied tissues. Correlational experiments between KYN-TRP ratio and bladder tumour were performed using a murine orthotopic prostate-specific antigen (PSA)-secreting MB49 bladder cancer model. RESULTS: We established for the first time that plasma TRP level was significantly decreased, while both plasma and urinary KYN-TRP ratios were significantly higher in bladder cancer patients, and expression level of IDO1 but not TDO2 was increased in human bladder tumour. We reported the positive correlation between IDO1 expression, KYN-TRP ratio, normalized PSA to creatinine, and bladder tumour burden in the murine model. CONCLUSION: Kynurenine-tryptophan ratio is a promising surveillance biomarker for bladder cancer, but would require further validation before clinical translation.

Postoperative risk of chronic kidney disease in radical nephrectomy and donor nephrectomy patients: a comparison and analysis of predictive factors.

INTRODUCTION: To compare baseline renal function and identify predictive factors in patients undergoing radical nephrectomy (RN) or donor nephrectomy (DN) and their risk of subsequent chronic kidney disease (CKD) after surgery. MATERIALS AND METHODS: A retrospective review of patients with no baseline CKD undergoing RN (n = 88) and DN (n = 58) from 2000 to 2008 was performed. Baseline and postoperative renal function (eGFR) was determined using the Modification of Diet in Renal Disease (MDRD) formula. CKD was defined as eGFR < 60 mL/min/1.73 m2 according to the National Kidney Foundation guidelines. RESULTS: Before surgery, patients undergoing RN and DN had a mean eGFR (+/- SD) of 83.5 +/- 17.4 and 92.9 +/- 17.0 mL/min/1.73 m2 respectively (p = 0.002). Patients with RN had significantly greater morbidities including hypertension (47.7%), diabetes (14.8%) and ischemic heart disease (12.5%) than DN (5.2%, 0% and 1.7% respectively) (all p < 0.05). Median follow up was 3.5 years. The relative hazard of developing CKD post RN compared with DN was 1.91 (95% CI 1.01 to 3.61, p = 0.040). The median time to CKD was 77 months (range 2-107) for RN and 100 months (range 11-105) for DN. Age, gender, comorbidities, radical nephrectomy and baseline kidney function were individual risk factors for CKD post nephrectomy. However, preoperative eGFR was the only independent prognostic factor on multi-variable analysis. CONCLUSIONS: Patients undergoing RN are distinctly different from kidney donors in terms of age, renal function and comorbidities. RN is not an independent predictive factor for CKD but the lower baseline renal function in RN patients significantly accelerates renal senescence in the uninephrectomy state.

Preoperative Renal Volume: A Surrogate Measure for Radical Nephrectomy-Induced Chronic Kidney Disease.

OBJECTIVES: Surgically induced chronic kidney disease (CKD) has been found to have less impact on survival as well as function when compared to medical causes for CKD. The aim of this study is to evaluate whether preoperative remaining kidney volume correlates with renal function after nephrectomy, which represents an individual's renal reserve before surgically induced CKD. METHODS: A retrospective review of 75 consecutive patients (29.3% females) who underwent radical nephrectomy (RN) (2000-2010) was performed. Normal side kidney parenchyma, excluding renal vessels and central sinus fat, was manually outlined in each transverse slice of CT image and multiplied by slice thickness to calculate volume. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. CKD is defined as eGFR < 60 mL/min/1.73 m(2). RESULTS: Mean preoperative normal kidney parenchymal volume (mean age 55 [SD 13] years) is 150.7 (SD 36.4) mL. Over median follow-up of 36 months postsurgery, progression to CKD occurred in 42.6% (n = 32) of patients. On multivariable analysis, preoperative eGFR and preoperative renal volume <144 mL are independent predictors for postoperative CKD. On Kaplan-Meier analysis, median time to reach CKD postnephrectomy is 12.7 (range 0.03-43.66) months for renal volume <144 mL but not achieved if renal volume is >144 mL. CONCLUSIONS: Normal kidney parenchymal volume and preoperative eGFR are independent predictive factors for postoperative CKD after RN and may represent renal reserve for both surgically and medically induced CKD, respectively. Preoperative remaining kidney volume may be an adjunct representation of renal reserve postsurgery and predict later renal function decline due to perioperative loss of nephrons.