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Background: The efficacy of partial nephrectomy (PN) in setting of pT3a pathologic-upstaged renal cell carcinoma (RCC) is controversial. We compared oncologic and functional outcomes of radical nephrectomy (RN) and PN in patients with upstaged pT3a RCC., Patients and Methods: This was a multicenter retrospective analysis of patients with cT1-2N0M0 RCC upstaged to pT3a postoperatively. The primary outcome was recurrence-free survival, with secondary outcomes of overall survival and de novo estimated glomular filtration rate (eGFR) < 60. Multivariable analysis was performed to identify predictive factors for oncologic outcomes. Kaplan-Meier analyses (KMA) were obtained to elucidate survival outcomes., Results: A total of 929 patients had pT3a upstaging (686 [72.6%] RN; 243 [25.7%] PN; mean follow-up, 48 months). Tumor size was similar (RN 7.7 cm vs. PN 7.3 cm; P = .083). PN had decreased ΔeGFR (6.1 vs. RN 19.4 mL/min/1.73m 2 ; P < .001) and de novo eGFR < 60 (9.5% vs. 21%; P = .008). Multivariable analysis for recurrence showed increasing RENAL score (hazard ratio [HR], 3.8; P < .001), clinical T stage (HR, 1.8; P < .001), positive margin (HR, 1.57; P = .009), and high grade (HR, 1.21; P = .01) to be independent predictors, whereas surgery was not (P = .076). KMA revealed 5-year recurrence-free survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 79%, 74%, 70%, and 51%, respectively (P < .001). KMA revealed 5-year overall survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 64%, 65.2%, 56.4%, and 55.2%, respectively (P = .059)., Conclusions: In pathologically upstaged pT3a RCC, PN did not adversely affect risk of recurrence and provided functional benefit. Surgical decision-making in patients at risk for T3a upstaging should be individualized and driven by tumor as well as functional risks., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Chronic kidney disease (CKD) is classified according to cause, glomerular filtration rate, and proteinuria. Identification of proteinuria with urinalysis (UA) is less accurate than quantification via other methods. We investigated factors leading to discordant UA findings when compared against paired albumin-to-creatinine ratio (ACR) testing., Methods: Four thousand three hundred and twenty-three UAs were grouped by proteinuria level (A1-A3); concordance with ACR was examined. Classification of UA with confounding factors (UA+CF) or without (UA-CF) was based on CF that resulted in >10% increase in false-positive proteinuria readings. The presence of ≥3+ blood, ≥3+ leukocyte esterase, any ketonuria, specific gravity ≥1.020, ≥1+ urobilinogen, ≥2+ bilirubin, ≥2+ bacteria, ≥3 RBC/hpf (high powered field), ≥10 WBC/hpf, and/or ≥6 epithelial cells/hpf led to UA+CF classification., Results: Proteinuria was determined to be present in 14.1% by UA dipstick and 24.9% by ACR. Using ACR as the standard, overall concordance was 80.4%, with 17.2% false-negatives and 2.3% false-positives by UA. UA+CF represented 55.6% of UA overall (n = 2404), and 98.0% of those false-positive for proteinuria. High specific gravity and hematuria are the strongest predictors of false positives. For A2 proteinuria (30-300 mg/g, 1+,2+,3+ on UA) UA-CF had a higher negative predictive value (NPV) (99.8%) than UA+CF (77.6%); NPV for A3 proteinuria (>300 mg/g, 4+ on UA) was 100% for UA-CF and UA+CF., Conclusion: Additional abnormalities were noted in >50% of outpatient UAs indicating proteinuria. Given the significant proportion of patients having a false-positive UA for proteinuria when these CFs were present, we recommend that such patients undergo ACR confirmatory testing, according to a clinical algorithm for the incorporation of UA results into the management of CKD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare renal function and survival outcomes in patients with baseline chronic kidney disease (CKD) stage 2 undergoing partial (PN) or radical nephrectomy (RN), as nephron-sparing surgery is considered to be elective in this group., Methods: Retrospective analysis of patients with CKD stage 2 and T1/T2 renal mass undergoing PN or RN from 2001 to 2015. Patients were stratified into substage CKD 2a or CKD 2b and analyzed between types of surgery. Primary outcome was overall survival (OS), eGFR < 45 at last follow-up was the secondary outcome. Multivariable analysis (MVA) was conducted for predictors of eGFR < 45 and OS. Kaplan-Meier analyses were conducted for freedom from eGFR < 45 and OS., Results: 1213 patients analyzed (CKD 2a 609/CKD 2b 604) on MVA, RN (OR 3.68, p = 0.001) and CKD 2b (OR 3.3, p = 0.002) were independently associated with development of eGFR < 45 at last follow-up and RN (OR 3.76, p = 0.005) and eGFR < 45 (OR 2.51, p = 0.029) were associated with decreased OS. Kaplan-Meier analyses revealed that patients with CKD 2a/PN had the highest 5-year freedom from eGFR < 45 (94.3%) compared to CKD 2a/RN patients (91.5%), CKD2b/PN patients (87.6%) and CKD 2b/RN patients 82.0% (p < 0.001). Kaplan-Meier analyses for OS demonstrated that patients with CKD 2a/PN had significantly greater 5-year OS (97.6%) compared to CKD 2a/RN patients (95.2%), CKD 2b/PN patients (93.2%), and CKD 2b/RN patients (92.4%, p = 0.043)., Conclusions: Patients with baseline CKD stage 2, particularly CKD 2b and undergoing RN, are at increased risk of GFR < 45, which was associated with decreased OS. In patients with CKD 2b, a nephron-sparing strategy is indicated and should be prioritized when feasible.

Purpose: The GG (Grade Group) system was introduced in 2013. Data from academic centers suggest that GG better distinguishes between prostate cancer risk groups than the Gleason score (GS) risk groups. We compared the performance of the 2 systems to predict pathological/recurrence outcomes using data from the MUSIC (Michigan Urological Surgery Improvement Collaborative)., Materials and Methods: Patients who underwent biopsy and radical prostatectomy in the MUSIC from March 2012 to June 2017 were classified according to GG and GS. Outcomes included the presence or absence of extraprostatic extension, seminal vesical invasion, positive lymph nodes, positive surgical margins and time to cancer recurrence (defined as postoperative prostate specific antigen 0.2 ng/ml or greater). Logistic and Cox regression models were used to compare the difference in outcomes., Results: A total of 8,052 patients were identified. When controlling for patient characteristics, significantly higher risks of extraprostatic extension, seminal vesical invasion and positive lymph nodes were observed for biopsy GG 3 vs 2 and for GG 5 vs 4 (p <0.001). Biopsy GGs 3, 4 and 5 also showed shorter time to biochemical recurrence than GGs 2, 3 and 4, respectively (p <0.001). GGs 3, 4 and 5 at radical prostatectomy were each associated with a greater probability of recurrence compared to the next lower GG (p <0.001). GG (vs GS) had better predictive power for extraprostatic extension, seminal vesical invasion, positive lymph nodes and biochemical recurrence., Conclusions: GG at biopsy and radical prostatectomy allows for better discrimination of recurrence-free survival between individual risk groups than GS risk groups with GGs 2, 3, 4 and 5 each incrementally associated with increased risk.

Objective: To compare the prevalence of proteinuria in the urology clinic with other outpatient settings. Chronic kidney disease is classified according to cause, glomerular filtration rate, and proteinuria. Proteinuria may be more prevalent in patients with known chronic kidney disease, renal disorders (benign or malignant), or after urologic surgery., Methods: A cross-sectional study of 3 populations undergoing urinalysis (UA) testing was carried out: general outpatients (n = 20,334), urology outpatients (n = 5023), and kidney cancer patients (n = 1016). Proteinuria was classified under Kidney Disease: Improving Global Outcomes guidelines: A1 (<30 mg), A2 (30-300 mg), and A3 (>300 mg)., Results: Proteinuria was detected throughout a community-based health system in 8.6% of UA (8.2%: A2; 0.4%: A3). In comparison, 18.6% of urology office-performed UA had proteinuria (16.0%: A2, 2.5%: A3) (P < .0001 vs non-urology). Kidney cancer patients were more likely to have proteinuria (17.9%: A2, 3.8%: A3). The proportion with A3 was significantly higher in urology and kidney cancer patients when compared with other outpatients (each P < .0001), and in the kidney cancer subgroup compared with all urology patients (P < .0001). Additional abnormalities were frequently present on microscopic analysis of UA in the urology clinic, including hematuria (20.9%), pyuria (21.8%), and bacteriuria (3.1%)., Conclusion: The value of UA in the urology clinic as a screening test for proteinuria and other conditions appears high, with >56% having at least 1 abnormality. The population risk of proteinuria in the urology clinic is 18.5%, which is higher than that observed in non-urology clinics. Patients with kidney cancer appear more likely to have proteinuria than the average urology patient. We recommend evaluation of urology patients with UA to identify proteinuria., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Although it is commonly staged according to glomerular filtration rate, an international work group recommended classifying chronic kidney disease by cause, glomerular filtration rate and albuminuria. Data on nonsurgical patients with chronic kidney disease indicate proteinuria to be an independent predictor of renal function decrease and mortality. We evaluated whether preoperative proteinuria impacted survival in patients undergoing nephrectomy., Materials and Methods: An institutional registry was queried for information regarding preoperative creatinine/glomerular filtration rate and urinalysis in 900 patients, including 362 and 538 treated with partial and radical nephrectomy, respectively. Patients were grouped according to glomerular filtration rate level (G1 to G5), proteinuria level (A1 to A3) and chronic kidney disease risk classification (low to very high). Kaplan-Meier and Cox proportional hazards analyses of overall survival were performed., Results: The preoperative glomerular filtration rate was less than 60 ml/minute/1.73 m(2) in 30% of patients (median 73, IQR 56-91) and 20% of patients had baseline proteinuria. According to the KDIGO (Kidney Disease Improving Global Outcomes) classification 23% of patients were at moderately increased, 11% were at high and 8% were at very high risk for chronic kidney disease progression. Kaplan-Meier analysis revealed that the preoperative glomerular filtration rate, proteinuria and chronic kidney disease risk group were associated with poor overall survival. In Cox proportional hazard models accounting for age, gender, race, tumor size, clinical stage and surgery type the glomerular filtration rate, proteinuria and chronic kidney disease risk group were highly significant predictors of overall survival (p <0.0001)., Conclusions: Preoperative proteinuria is a significant predictor of overall survival in patients who undergo nephrectomy. Classification according to preoperative glomerular filtration rate and proteinuria more accurately predicts survival than using the glomerular filtration rate alone after accounting for cancer stage. This information supports routine evaluation of proteinuria in patients with kidney cancer., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Several studies suggest that aquaporin water channels can be identified in membranes by freeze-fracture electron microscopy. For this report, Chinese Hamster ovary cells were stably transfected with cDNAs encoding aquaporins 1-5. Measurement of the osmotic water permeability of the cells confirmed that functional protein was expressed and delivered to the plasma membrane. By freeze-fracture electron microscopy, a 20% increase in intramembrane particle (IMP) density was found in plasma membranes of cells expressing AQP2, 3 and 5, and a 100% increase was measured in AQP1-expressing cells, when compared to mock-transfected cells. On membranes of cells expressing AQP4, large aggregates of IMPs were organized into orthogonal arrays, which occupied 10-20% of the membrane surface. IMP aggregates were never seen in AQP2-transfected cells. Hexagonally packed IMP clusters were detected in approximately 5% of the membranes from AQP3-expressing cells. Particle size-distribution analysis of rotary shadowed IMPs showed a significant shift from 13. 5 (control cells) to 8.5 nm or less in AQP-expressing cells; size distribution analysis of unidirectionally shadowed IMPs also showed a significant change when compared to control. Some IMPs in AQP expressing cells had features consistent with the idea that aquaporins are assembled as tetramers. The results demonstrate that in transfected CHO cells, AQP transfection modifies the general appearance and number of IMPs on the plasma membrane, and show that only AQP4 assembles into well-defined IMP arrays.