Quantifying urine protein is critical for detecting and monitoring kidney disease. However, screens for proteinuria are unable to detect low levels of albuminuria. For this reason, our institution has long measured urinary total protein and osmolality on routine urinalysis specimens (RUS) and calculated a predicted 24-hour protein excretion (PER) based upon the protein to osmolality ratio (POR). Within the last decade, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been approved by the United States Food and Drug Administration (FDA) as a treatment for adults with type 2 diabetes mellitus, and these agents appear to be beneficial for many forms of proteinuric renal disease and confer renal protection. Therefore, we investigated whether the expected glucosuria and increase in urine osmolality while on SGLT2i would significantly alter the POR, and hence predicted PER, via a retrospective analysis of residual timed and randomly collected urine specimens. Between January 1st, 2014, until January 29th, 2025, 5820 patients with nearly contemporaneous (collected within one week of each other) timed collections and RUS were identified that included 5656 not on SGLT2i (Cohort A) and 164 patients prescribed SGLT2i (Cohort B). Total protein concentrations were assessed using a Roche Cobas c701 by using benzethonium chloride. The osmolality was determined via freezing point depression using a Precision Systems Inc Multi-OSMETTE, whereas glucose measurements were made using either an Arkray AX-4030 with AUTION Stick 9EB test strips or a Clinitek Status with Multistix 10 SG reagent strips. Predicted 24-hour protein results were then calculated from the POR using a published formula based upon prior clinical studies: 10(x·[log(protein/osmolality)]+y where x is 0.908 or 0.953 for males and females, respectively, and y is 2.8254 or 2.9739 for males and females, respectively. In Cohort A, there was good correlation between the predicted and measured 24-hour PER (Spearman correlation coefficient, ρ = 0.78), although the predicted PER underestimated the measured PER (Passing-Bablok regression, y = 1.54x-20.97 mg/24 hr). Importantly, a strong correlation (ρ = 0.93) and similar distribution (p=0.17) were found between the predicted and measured PER in Cohort B, with a much-reduced proportional bias (y = 1.06x+62.96 mg/24 hr). Furthermore, comparison of the difference between the predicted and measured PER between the two cohorts demonstrated the same prediction accuracy (p = 0.65), with a median difference (interquartile range) of 79 mg/24 hr (256) and 109 mg/24 hr (480) for Cohort A and B, respectively. Finally, a strong correlation (ρ = 0.85), similar distribution (p = 0.23), and little bias (y = 0.96x+28.14 mg/24 hr) existed between the predicted and measured PER for all patients with overt glucosuria (urine glucose ≥1000 mg/dL, n = 348). In summary, these data suggest that the established formula for predicted PER on RUS is equally valid for patients on or off SGLT2i, and that this result is a useful clinical estimating tool.

Background:Living kidney donation (KD) evaluation particularly focuses on glomerular filtration rate (GFR). Assessing GFR in living kidney donors can be done by estimation (eGFR) or measurement (mGFR). This study aims to evaluate the impact of eGFR equations, focusing on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation for donor eligibility screening and the reclassification of donors excluded by eGFR criteria to mGFR assessments. Methods:Retrospective, single-center observational study of 2512 kidney donors evaluated between 2011 and 2023, at the Mayo Clinic. We performed analyses and comparisons of 4 eGFR formulae and 2 mGFR methods in terms of performance, eligibility criteria according to Kidney Disease: Improving Global Outcomes guidelines/age-adjusted criteria, eligibility reclassification, and subgroup analyses. Results:The CKD-EPI 2021 resulted in a higher percentage of patients being eligible for KD (81.4%) and achieved the highest P10 (32%-34%) and P30 (87%-88%) across all mGFR methods. When patients were deemed eligible for donation by any eGFR formula, 95% retained this status on reassessment with mGFR. Conversely, when an eGFR formula classified a patient as ineligible, this was revised to be eligible in about 90% of cases on reassessment with mGFR, with a higher reclassification rate observed when the IoCl was used instead of CrCl. Conclusions:The CKD-EPI 2021 performs best for screening potential KD. If a KD is deemed ineligible by CKD-EPI 2021, there is a high likelihood that they will be reclassified as eligible when assessed with mGFR. This study strongly supports using mGFR in donor evaluations, especially when the eGFR does not meet the criteria to ensure equity of access to being a living donor.

BACKGROUND:The performance of estimated glomerular filtration rate (eGFR) among patients with heart failure (HF) may be worse than in the general population due to a higher prevalence of confounding factors affecting creatinine and cystatin C. Studies in this area are scarce and not stratified by type of HF. We evaluated the performance of current creatinine and cystatin C equations (eGFRcr, eGFRcys, and eGFRcrcys) compared with measured GFR (mGFR) among patients with HF stratified by ejection fraction. METHODS:We pulled data on Mayo Clinic patients with an mGFR performed for clinical indications from 2011 to 2023, with serum creatinine and cystatin C measured within 7 days and an echocardiogram performed up to 1 year before the mGFR date. HF was identified by the presence of International Classification of Diseases codes within 1 year before the mGFR and subgrouped into ejection fraction (EF) ≥50% (HFEF≥50%, n=182) or <50% (HFEF<50%, n=115) and compared with no-HF controls (n=1871). CKD-EPI (and EKFC) eGFRcr, eGFRcys, and eGFRcrcys equations were calculated and compared for bias (mGFR minus eGFR) and accuracy (1-P30, proportion of people with ≥30% difference between eGFR and mGFR). CIs were generated by bootstrapping. RESULTS:The HF groups were characterized by older age, higher proportion of males, more diabetes, higher creatinine, and higher cystatin C than controls. In terms of bias, eGFRcr overestimated mGFR to a greater extent in both HF groups compared with controls, whereas eGFRcys and eGFRcrcys showed similar bias in both HF groups and controls. In the HF groups, cystatin C-based equations were more accurate than eGFRcr, particularly within HFEF<50% (1-P30 of 28% and 34% for CKD-EPI eGFRcys and eGFRcrcys, respectively, versus 60% for eGFRcr), whereas eGFRcrcys was more accurate in controls. The CKD-EPI and EKFC equations were overall convergent, showing similar results. CONCLUSIONS:Among patients with HF, eGFRcr demonstrates inferior performance (more bias and less accuracy) compared with cystatin C-based eGFRs, with this effect being more pronounced in those with HFEF<50%.

Pancreas transplantation alone (PTA) is a beta cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m(2), and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m(2)) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

PURPOSE To report on CheckMate 627 (ClinicalTrials.gov identifier: NCT02832167 ), a phase II adaptive basket design trial of nivolumab in uncommon advanced/metastatic tumors. METHODS Adults with previously treated advanced/metastatic malignancies received nivolumab 240 mg once every 2 weeks for eight cycles, followed by nivolumab 480 mg once every 4 weeks. The primary end point was investigator-assessed objective response rate (ORR). In addition to observed ORRs, model-adjusted ORRs were estimated via Bayesian analysis in patients who completed ≥28 weeks of follow-up, to correct for variability inherent in multitumor studies. This adaptive model allowed for borrowing of information from other tumors demonstrating similar ORR and evaluation of nivolumab treatment effect versus historical standard-of-care (SOC) controls. Nivolumab was considered to have met the criteria for ORR superiority in a group if there was ≥80% posterior probability of ORR with nivolumab exceeding ORR with historical SOC control treatment in that group. RESULTS The study included 25 tumor groups (n = 239), with 24 groups included in the Bayesian ORR analysis (efficacy was reported but not modeled in the other group that contained a mix of tumor types). The poorly differentiated neuroendocrine tumor (PD-NET) group (n = 20) met the prespecified criterion for ORR superiority with a 93% probability of the model-adjusted ORR with nivolumab (22% [95% CI, 8 to 44]) exceeding the respective historical SOC ORR of 10.0%. The observed ORR was 30.0% (95% CI, 11.9 to 54.3). There were no new safety signals for nivolumab. CONCLUSION Nivolumab showed evidence of antitumor activity in patients with advanced/metastatic PD-NET in CheckMate 627. The results of this study support the use of an adaptive basket design for identification of rare cancers responsive to immunotherapy.

Background Anti-programmed cell death protein 1 antibodies plus multikinase inhibitors have shown encouraging activity in several tumour types, including colorectal cancer. This study assessed regorafenib plus nivolumab in patients with microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.Methods This single-arm, open-label, multicentre phase 2 study enrolled adults from 13 sites in the USA with previously treated advanced microsatellite stable/mismatch repair-proficient metastatic colorectal cancer. Eligible patients had known extended RAS and Bostatus, progression or intolerance to no more than two (for extended RAS mutant) or three (for extended RAS wild type) lines of systemic chemotherapy and an Eastern Cooperative Oncology Group performance status of 0 or 1. Regorafenib 80 mg/day was administered orally for 3 weeks on/1 week off (increased to 120 mg/day if 80 mg/day was well tolerated) with intravenous nivolumab 480 mg every 4 weeks. Primary endpoint was objective response rate. Secondary endpoints included safety, overall survival, and progression-free survival. Exploratory endpoints included biomarkers associated with antitumour activity. Patients who received at least one dose of study intervention were included in the efficacy and safety analyses. Tumour assessments were carried out every 8 weeks for the first year, and every 12 weeks thereafter until progressive disease/end of the study, and objective response rate was analysed after all patients had met the criteria for primary completion of five post-baseline scans and either 10-months' follow-up or drop out. This trial is registered with ClinicalTrials.gov, number NCT04126733.Findings Between 14 October 2019 and 14 January 2020, 94 patients were enrolled, 70 received treatment. Five pa-tients had a partial response, yielding an objective response rate of 7% (95% CI 2.4-15.9; p = 0.27). All responders had no liver metastases at baseline. Median overall survival (data immature) and progression-free survival were 11.9 months (95% CI 7.0-not evaluable) and 1.8 months (95% CI 1.8-2.4), respectively. Most patients (97%, 68/70) experienced a treatment-related adverse event; 51% were grade 1 or 2, 40% were grade 3, 3% were grade 4, and 3% were grade 5. The most common (>= 20%) events were fatigue (26/70), palmar-plantar erythrodysesthesia syndrome (19/70), maculopapular rash (17/70), increased blood bilirubin (14/70), and decreased appetite (14/70). Higher baseline expression of tumour biomarkers of immune sensitivity correlated with antitumour activity.Interpretation Further studies are warranted to identify subgroups of patients with clinical characteristics or bio-markers that would benefit most from treatment with regorafenib plus nivolumab.Funding Bayer/Bristol Myers Squibb.Copyright (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BACKGROUND:The National Kidney Foundation recently endorsed the refit Chronic Kidney Disease Collaboration (CKD-EPI) equation for estimated glomerular filtration rate (eGFR) using creatinine, age and sex [2021 eGFRCr(AS)] without a coefficient for race. We evaluated the impact of adopting the 2021 eGFRCr(AS) equation or a variation of the 2009 CKD-EPI eGFR equation without race [2009 CKD-EPI eGFRCr(ASR-NB)] compared to the original CKD-EPI eGFR [2009 eGFRCr(ASR)].METHODS:The studied population included patients with a clinically ordered iothalamate clearance (n = 33 889). Bias was assessed as the difference between measured and estimated GFR, P30 was defined as the percentage of estimates within 30% of measured GFR, and concordance was determined according to relevant clinical thresholds.RESULTS:Among Black patients, the median bias for 2009 eGFRCr(ASR), 2009 eGFRCr(ASR-NB), and 2021 eGFRCr(AS) was -1.32 mL min-1 (1.73 m2)-1 (95CI -2.46 to -0.26), -8.81 mL min-1 (1.73 m2)-1 (95CI -9.93 to -7.58), and -6.08 mL min-1 (1.73 m2)-1 (95CI -7.18 to -4.92), respectively. The median bias among non-Black patients was -0.15 m min-1 (1.73 m2)-1 (95CI -0.84 to -0.08) for 2021 eGFRcr(AS) compared to -3.09 mL min-1 (1.73 m2)-1 (95CI -3.17 to -3.03) for the 2009 eGFRCr(ASR). P30 and concordance were not significantly different in either racial group. The net reclassification improvement at a measured GFR <20 mL min-1 (1.73 m2)-1 was 6.4% (95CI 0.36 to 12.4) for Black patients and -5.1% (95CI -6.0 to -4.1) for non-Black patients using the 2021 eGFRCr(AS) equation.CONCLUSIONS:Overall, the change in reported eGFR was minimal. However, these changes led to significant reclassification improvements at lower eGFR, which will indirectly improve equitable access to CKD resources.

e19165 Background: Cancer care is complex and requires synthesis of increasing amounts of clinical and financial data to optimize treatment decisions. The heightened differentiation of individual cancers, therapy sequencing, and increasing number of treatment options make it more challenging for oncologists to stay current. A survey showed that 82% of Network providers validated the utility of clinical evidence and decision-making assistance at the point-of-care. Providing education on efficacy, toxicity, and cost in the form of evidence tables (ET) as CDST may assist in value-based decision-making. Methods: We retrospectively reviewed utilization of ET developed to provide clinical and financial data about regimens included within the Value Pathways powered by NCCN. Thirty ET were embedded in the electronic health record (EHR) and posted on our intranet between June-December 2019, covering over 90% of cancers. Utilization was queried from roll out through January 2020. ET include a summary of primary literature (primary/secondary endpoints, adverse events) and monthly Medicare allowable reimbursement rates. ET are updated with each change to pathways and quarterly for cost updates. We also conducted a survey to understand provider ET utilization patterns. Results: Utilization was evaluated for 1,200 physicians across 470 sites that have access to ET. ET have been accessed 1178 times by 586 providers within the EHR and accessed 1363 times by 260 providers via intranet. Our rate of repeat users of the ET is 35% in the EHR and 97% on the intranet. A survey of 200 physicians after ET release showed that 19% of physicians use ET with every new chemotherapy start and an additional 50% refer to ET only if they are uncertain about the best option. Conclusions: Utilization patterns underscore the importance of ET as a CDST within the EHR and on the intranet. While early ET use is high, continued tracking of utilization and addition of content to assist in complex clinical decisions is a priority. Providers surveyed found that clinical informatics tools like ET are useful to enhance decision-making in complex cancer care. [Table: see text]

TPS8069 Background: Older patients and those with significant comorbidities have not attained outcomes seen in younger patients with classical Hodgkin lymphoma (cHL) and CD30-expressing peripheral T-cell lymphoma (PTCL). Five-year progression-free survival (PFS) was 30%–45% in older HL patients treated with combination chemotherapy versus 75%–80% in younger patients (Evens 2008; Proctor 2009). Similarly, when adjusted for age, a Charleston Comorbidity Index ≥2 was independently associated with worse overall survival (HR=1.63) and PFS (HR=1.54) (Ellin 2018). Brentuximab vedotin (BV, ADCETRIS), a CD30-directed antibody-drug conjugate, has robust activity in cHL patients refractory to several lines of chemotherapy. BV monotherapy in 27 cHL patients aged ≥60 years had a 92% objective response rate (ORR) and 73% achieved complete remission (Forero-Torres, 2015). BV was also active and well-tolerated in CD30-expressing PTCL patients with relapsed or refractory disease (Horwitz 2014). Frontline BV monotherapy may have the potential to be an active and well-tolerated treatment for cHL and PTCL patients who are older or have significant comorbidities, which are populations with high unmet need. Methods: This phase II, open-label study, SGN35-015 (NCT01716806), has added 2 cohorts to evaluate the efficacy and tolerability of BV monotherapy in treatment naive patients with cHL, (Part E), or CD30-expressing PTCL (Part F, n~50 each) who are unsuitable for conventional combination therapy due to comorbidity-related factors as determined by a Cumulative Illness Rating Scale (CIRS) score ≥10 or dependence on others for any instrumental activities of daily living. Eligible patients must also have an Eastern Cooperative Oncology Group (ECOG) performance status ≤3 and measurable disease ≥1.5 cm per radiographic techniques. BV (1.8 mg/kg) will be administered as a single intravenous infusion on day 1 of each 2-day cycle. Patients achieving a complete remission, partial remission, or stable disease will receive up to 16 cycles of treatment. Response will be assessed by blinded independent central review of spiral CT and PET scans at Cycles 2, 6, 11, and at end of treatment to be graded per Lugano 2014. The primary objective of these cohorts is to assess ORR of frontline therapy with single-agent BV in patients who have significant comorbidities. Clinical trial information: NCT01716806 .

Kidney disease and injury is largely silent with few overt clinical manifestations until disease or injury is quite advanced. For this reason, laboratory testing is the mainstay of the assessment and monitoring of kidney injury or disease. A number of modalities have been used, some new, while others have been in place for many years. These laboratory testing modalities include routine urinalysis, assessment of proteinuria and albuminuria, markers of proximal tubule function and injury, and new markers for acute kidney injury. Additionally, several means are now available for the determination of glomerular filtration rate either through direct measurements using clearance markers or indirectly through empirically derived equations to estimate the glomerular filtration rate.

Introduction: Serum cystatin C increases earlier than creatinine during acute kidney injury. However, whether cystatin C decreases earlier during recovery is unknown. This retrospective study aimed to determine the temporal trend between creatinine and cystatin C in acute kidney injury. Methods: We identified hospitalized patients with nonoliguric acute kidney injury who had serial creatinine and cystatin C values measured between May 2015 and May 2016. Demographic and laboratory data, causes of acute kidney injury, and relevant comorbidity data were collected through chart review. Results: For the 63 identified patients, mean (SD) age was 58.7 (13.9) years; male sex, 62%; white race/ethnicity, 95%. Baseline median (range) creatinine was 1.1 (0.5-3.0) mg/dl; 13% were kidney transplant recipients and 37% received corticosteroids. Comorbidities included malignancy (38%), diabetes mellitus (33%), heart failure (19%), and thyroid disorder (16%). The cause of kidney injury was acute tubular necrosis in 71%, 61% had acute kidney injury stage III, and 33% required dialysis. Cystatin C began to decrease before creatinine in 68% of patients: 1 day earlier, 46%; 2 days earlier, 16%; and 3 days earlier, 6%. In 24% of cases, both began decreasing on the same day; in only 8%, cystatin C decreased after creatinine. Overall, cystatin C mean (95% confidence interval) decrease was 0.92 (0.65-1.18) days before creatinine (P < 0.001). Conclusion: In summary, cystatin C decreases before creatinine in most hospitalized patients with acute kidney injury. If confirmed in large prospective studies, these findings may have important management implications, possibly shortening hospital stay and reducing costs.

4016 Background: Pancreatic ductal adenocarcinomas exhibit high degree of desmoplasia with extensive connective tissue growth factor (CTGF) expression and extracellular matrix production. CTGF overexpression is associated with aberrant fibrous tissue in mouse model, in which progression of tissue adhesion was inhibited by pamrevlumab. We hypothesize that pamrevlumab, an anti-CTGF antibody, may influence resectability of locally advanced pancreatic cancer (LAPC) by inhibiting effects of CTGF. Methods: Pamrevlumab + gemcitabine/Nab-paclitaxel (G/N) (Arm A) vs G/N (Arm B) was given to treatment-naïve LAPC patients to improve resection rate and overall survival (OS). Patients (N = 37) were randomized 2:1 in Arm A vs Arm B. Patients who completed 6 cycles of treatment underwent resectability assessment per protocol criteria (NCCN, CA 19-9, PET, RECIST) and, if found eligible, underwent resection. No adjuvant therapy was given; second line therapy was administered per investigator discretion. Results: In the ITT population, a higher percentage of patients discontinued treatment in Arm B (46.2%) vs Arm A (25%), mainly due to disease progression or adverse events. More patients normalized PET in Arm A (35%) vs Arm B (23%). Thirty percent of patients overall had best objective RECIST response (CR + PR). More patients were eligible for surgery and were resected in Arm A vs Arm B; 70.8% vs 15.4% and 33.3% vs 7.7%, respectively. Improvement in OS was noted in patients eligible for surgery vs not (27.73 vs 18.40 months, p-value = 0.0766) and in patients resected vs not (NE vs 18.56 months, p-value = 0.0141). Progression-free survival showed similar trend (16.39 vs 10.09 months, p-value = 0.1049) and (16.39 vs 10.38 months, p-value = 0.3778), respectively. No increase in serious adverse events or delay in wound healing post-surgery was observed in Arm A vs. Arm B. Conclusions: These findings indicate that pamrevlumab may be a valuable addition to neoadjuvant therapy in LAPC without added toxicity. These results warrant a follow-on study in a larger patient population. Clinical trial information: NCT02210559.

677 Background: Napabucasin a first-in-class cancer stemness inhibitor in clinical development, suppresses cancer stemness by targeting Stat3-driven gene transcription. Preclinically, potent and broad-spectrum anti-cancer activity was observed in vitro and in vivo, alone and in combination with other agents. In a phase 1 study, napabucasin monotherapy was well tolerated with encouraging signs of anti-tumor activity at the RP2D of 500 mg BID. Methods: The current open-label, multi-center study includes phase II expansion in pts with refractory, K- Raswt mCRC to confirm safety and anti-tumor activity of napabucasin administered orally at 480mg BID in combination with panitumumab (6mg/kg bi-weekly). Results: 72 pts were enrolled, 48 pts were evaluable by RECIST of which 7 (15%) and 41 (85%) had 2 or >3 prior treatment lines, respectively. Of the 48 evaluable pts, 64.6% (31/48) were previously treated with an anti-EGFR agent. No new adverse events (AEs) were observed and most common AEs included grade 1/2 diarrhea, nausea, abdominal cramps, and vomiting. Among 48 pts enrolled who received RECIST evaluation, Disease Control Rate (DCR) was observed in 25 pts (52.1%) of which 3 pts achieved PR (6%) and 22 pts achieved SD (45%). Among 31 pts previously treated with anti-EGFR therapy, DCR was observed in 15 pts (48%) compared with DCR of 59% observed in 10 out of 17 anti-EGFR naïve pts receiving a scan. Conclusions: This phase II study confirmed that napabucasin can be safely combined with panitumumab at full dose and shows encouraging anti-tumor activity in pts with K- Ras wt mCRC, regardless of prior anti-EGFR exposure, suggesting that napabucasin may sensitize pts to repeat anti-EGFR therapy. Clinical trial information: NCT01776307. [Table: see text]

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.

Background: Iothalamate and iohexol are contrast agents that have supplanted inulin for the measurement of glomerular filtration rate (GFR) in clinical practice. Previous studies have noted possible differences in renal handling of these 2 agents, but clarity about the differences has been lacking. Study Design: Study of diagnostic test accuracy. Setting & Participants: 150 participants with a wide range of GFRs were studied in an outpatient clinical laboratory facility. Index Tests: Simultaneous urinary clearances of iothalamate, iohexol, and creatinine. Reference Test: None. Outcome: Relative differences between the urinary clearances. Iohexol and iothalamate in plasma and urine were assayed concurrently by a novel liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay. Results: Mean iohexol, iothalamate, and creatinine clearances were 52 6 28 (SD), 60 6 34, and 74 6 40 mL/min/1.73 m 2 , respectively. The proportional bias of iohexol to iothalamate urinary clearance was 0.85 (95% CI, 0.83-0.88) and was proportional across the GFR range. The mean proportional bias of iohexol clearance compared with creatinine clearance is 1.27 (95% CI, 1.20-1.34), whereas that of iothalamate clearance compared with creatinine clearance is 1.09 (95% CI, 1.03-1.15). Limitations: Lack of reference standard. Conclusions: This study reveals a significant and consistent difference between urinary clearances of iothalamate and iohexol. Comparison of studies reporting renal clearance measurements using iohexol versus iothalamate must account for this observed bias. Am J Kidney Dis. 67(1):49-55. a 2016 by the National Kidney Foundation, Inc.

We welcome the comments and interest of Drs Sterner, Bäck, and Nyman1Sterner G. Bäck S-E. Nyman U. Iohexol versus iothalamate for GFR measurement.Am J Kidney Dis. 2016; 67: 991Scopus (2) Google Scholar regarding our study.2Seegmiller J.C. Burns B.E. Schinstock C.A. et al.Discordance between iothalamate and iohexol urinary clearances.Am J Kidney Dis. 2016; 67: 49-55Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar We agree that until inulin is available again for studies of humans, it will be difficult to directly assess the comparable accuracy of iothalamate and iohexol in humans. Our study of 150 patients across a broad range of glomerular filtration rates (GFRs) showed a 15% difference in urinary clearance of iothalamate versus iohexol. Creatinine clearances were significantly greater than both iothalamate (by 24%) and iohexol (by 38%), suggesting that neither is likely to have a secretory component approaching creatinine. However, the dialyzability in vitro of iohexol versus iothalamate was less, which could have contributed to some of the observed clearance differences. We acknowledge the results cited in the letter of their own study3Sterner G. Frennby B. Mansson S. Nyman U. Van Westen D. Almen T. Determining ‘true’ glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.Scand J Urol Nephrol. 2008; 42: 278-285Crossref PubMed Scopus (75) Google Scholar comparing iohexol with inulin in 20 healthy individuals with normal GFRs. The dosing in their study was 1 to 2 orders of magnitude greater than in ours. Some of the published comparability discrepancy could be due to saturation or inhibition of mechanisms associated with different dosing. However, given the paucity of studies directly comparing renal clearance of iohexol with inulin, we believe it is premature to state with confidence whether one contrast agent is more accurate than the other. As mentioned in the editorial to our study,4Levey A.S. Inker L.A. GFR as the “gold standard”: estimated, measured, and true.Am J Kidney Dis. 2016; 67: 9-12Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar it is possible that the differences between iohexol and iothalamate renal clearances could reflect small, and opposite, biases with inulin. We also agree that explanations for the clearance differences would benefit from having inulin available for studies of humans. Financial Disclosure: The authors declare that they have no relevant financial interests. Peer Review: Evaluated by the Editor-in-Chief. Iohexol Versus Iothalamate for GFR MeasurementAmerican Journal of Kidney DiseasesVol. 67Issue 6PreviewWe read with great interest the article by Seegmiller et al1 demonstrating different urinary clearances of iothalamate and iohexol. The authors speculate that the difference reflects nonideal behavior of iohexol as a glomerular filtration rate marker. However, the study does not include a comparison with inulin; thus, it remains uncertain which marker is less accurate in this respect. Full-Text PDF

BACKGROUND Iothalamate and iohexol are contrast agents that have supplanted inulin for the measurement of glomerular filtration rate (GFR) in clinical practice. Previous studies have noted possible differences in renal handling of these 2 agents, but clarity about the differences has been lacking. STUDY DESIGN Study of diagnostic test accuracy. SETTING & PARTICIPANTS 150 participants with a wide range of GFRs were studied in an outpatient clinical laboratory facility. INDEX TESTS Simultaneous urinary clearances of iothalamate, iohexol, and creatinine. REFERENCE TEST None. OUTCOME Relative differences between the urinary clearances. Iohexol and iothalamate in plasma and urine were assayed concurrently by a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. RESULTS Mean iohexol, iothalamate, and creatinine clearances were 52±28 (SD), 60±34, and 74±40 mL/min/1.73 m(2), respectively. The proportional bias of iohexol to iothalamate urinary clearance was 0.85 (95% CI, 0.83-0.88) and was proportional across the GFR range. The mean proportional bias of iohexol clearance compared with creatinine clearance is 1.27 (95% CI, 1.20-1.34), whereas that of iothalamate clearance compared with creatinine clearance is 1.09 (95% CI, 1.03-1.15). LIMITATIONS Lack of reference standard. CONCLUSIONS This study reveals a significant and consistent difference between urinary clearances of iothalamate and iohexol. Comparison of studies reporting renal clearance measurements using iohexol versus iothalamate must account for this observed bias.

e15277 Background: NabP-Gem and FOLFIRINOX are standard mPC regimens.The optimal sequence is unknown.This phase II study evaluated the feasibility of NabP-Gem alternating with FOLFIRI as 1stline Rx for untreated mPC. Methods: Eligibility criteria included: 1) diagnosis untreated mPC, 2) ECOG PS 0-1 and 3) adequate organ function. Pts received Nab-P (125 mg/m2) and Gem (1000 mg/ m2) weekly x 3 every 4 weeks (wks) for 8 wks, alternating with FOLFIRI (irinotecan 180 mg/m2, folinic acid 400mg/m2, 5FU 2400 mg/m2over 46 hrs) x 4 for 8 wks. Rx continued in alternating fashion unless disease progression/toxicity for 48 wks, followed by Rx per investigator discretion, including “molecular guidance” as able. Primary study endpoint was overall survival (OS) with the goal to increase 1 year (yr) OS to > 70%, (n = 30, 95% CI +/- 20%). Results: The study accrued 27 pts. Median pt age 65 yrs. 1 pt withdrew consent prior to Rx. 14/26 (54%) pts experienced grade > 3 all cause adverse events during Rx including 15% grade ≥ 4 infections (1 grade 5) and 15% grade ≥ 4 neutropenia. 13/26 (50%) pts initiated FOLFIRI with stable/responding disease and acceptable Nab P-Gem toxicity after 8 weeks . The remaining 13 pts experienced disease progression (6 pts), NabP-Gem drug toxicity (3 pts), early death (2 pts) or other (2 pts). ORR by RECIST was 36% (8/22 evaluable pts). Of pts with elevated CA 19.9, median decline was 62%; 40% had > 90% decline. For all pts, current median follow up is 12.3 months (mo), median OS is 10.2 mo, 1-yr OS is 47%. For the 13 pts receiving FOLFIRI on protocol as defined above, med OS is currently 15.3 mo. Conclusions: 1) Alternating NabP-Gem and FOLFIRI can be feasible with toxicity comparable to either regimen alone. 2) Alternating Nab- P Gem and FOLFIRI yields ORR and OS that seem similar, but not superior, to Nab - P Gem, FOLFIRINOX, or, as reported by our group, Nab –P Gem followed by FOLFIRINOX (Ramanathan et.al. ASCO 2014). 3) The trial did not achieve 70% 1-yr OS, but pts able to receive both regimens may display superior OS. 4) Further study of Rx regimens that alternate/integrate both Gem and fluoropyrimidine-based treatments is warranted. (Supported by the Seena Magowitz foundation). Clinical trial information: NCT01488552.

BACKGROUNDTo determine the effect of statins on renal hemodynamics in normal volunteers and those with autosomal dominant polycystic kidney disease either with mild or moderate renal dysfunction.METHODSThirty-two study subjects were enrolled in this study: 11 normal volunteers, 11 study subjects with autosomal dominant polycystic kidney disease (ADPKD) and mild kidney disease and 10 study subjects with ADPKD and moderate kidney disease. Subjects in each group received simvastatin 40 mg once daily for a period of 4 weeks. Renal blood flow was measured based on para-amino-hippurate (PAH) clearance and with the use of a magnetic resonance (MR) scanner at the beginning and following 4 weeks of therapy with statins.RESULTSAt the end of the study, except for the lipid profile, which was significantly lower in all groups, other laboratory results showed no change. Four weeks of therapy with simvastatin resulted in no change in serum creatinine, 24-h urinary protein, sodium, iothalamate clearance, PAH clearance or renal blood flow as measured by MRI or based on PAH clearance.CONCLUSIONSFour weeks of therapy with simvastatin did not change renal blood flow in the study subjects with ADPKD with mild-to-moderate renal dysfunction or in healthy volunteers.CLINICAL TRIAL REGISTRATION NUMBERNCT02511418.