Median GFR Research Articles

Gemcitabine-carboplatin (GCb) versus gemcitabine-oxaliplatin (GemOx) in cisplatin un-fit advanced urothelial carcinoma: Randomized phase II study (COACH Study).

355 Background: More than half of patients (pts) with advanced urothelial cell carcinoma (UCC) are ineligible for cisplatin because of renal dysfunction or poor performance status. We investigated the activity and safety of first-line gemcitabine-oxaliplatin (GemOx) compared with gemcitabine-carboplatin (GCb) in cisplatin-ineligible pts with advanced UCC. Methods: Treatment naïve, cisplatin-ineligible pts with advanced UCC were randomly assigned to GemOx (gemcitabine 1000 mg/m2, oxliplatin 100 mg/m2 on D1 Q2W) or GCb (gemcitabine 1000 mg/m2 on D1 and 8, carboplatin AUC 4.5 on D1 Q3W) stratified by ECOG performance status (PS) and visceral metastases. The primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Between May 2013 and Mar 2017, 80 pts were enrolled and 79 pts received at least one dose of chemotherapy (39 pts in GCb; 40 pts in GemOx). Median age was 73 years (47-86) and ECOG PS was 2 in 42% of pts and 60% had visceral metastases. Median GFR was 45 ml/min (range 22-108) in GCb and 47 ml/min (range 15-73) in GemOx arm. With median follow-up duration of 37.8 months, all pts were off study treatments. RR were 48.7% and 55.0% in GCb and GemOx, respectively (p = 0.742). Median PFS and OS in GCb and GemOx arm were 5.5 months (95% CI, 4.8-6.2) vs. 4.4 months (95% CI, 2.7-6.1) [HR GemOx/GCb 0.92; p = 0.756] and 9.1 months (95% CI, 5.2-13.0) vs. 11.0 months (95% CI, 6.9-15.0) [HR 0.72; p = 0.194], respectively. The median cycle was 6 (1-10) in GCb and 7 (1-12) in GemOx. Grade 3 leukopenia, neutropenia and fatigue were more common in GCb arm (25.6% vs. 2.5%, p = 0.003; 33.3% vs. 10.0%, p = 0.014; 15.4% vs. 0%, p = 0.012). Dose delay and reduction in GCb and GemOx group were needed in 46.2%, 50.0% and 53.8%, 32.5%, respectively. Salvage chemotherapy after study treatment was offered in 54.3% and 55.9% of patients who experienced PD in GCb and GemOx arm. Conclusions: GemOx has showed comparable efficacy with GCb and favorable hematologic toxicity profile. GemOx may be used as a new option for patients who are not suitable for cisplatin-containing chemotherapy. Clinical trial information: NCT01487915.

High Rate of Complete Response (CR) with Undetectable Bone Marrow Minimal Residual Disease (MRD) after Chemo-Sparing and MRD-Driven Strategy for Untreated Fit CLL Patients: Final Results of the Icll 07 Filo Trial

Achievement of CR with undetectable minimal residual disease (uMRD) may be associated with a longer survival in CLL, but BCR signaling inhibitors alone seldom allow reaching uMRD. We conducted a multicenter phase II trial aiming at exploring the efficacy of an induction treatment associating obinutuzumab and ibrutinib, followed by immunochemotherapy for patients who do not reach CR with uMRD. Previously untreated fit patients with active Binet stage A and B or stage C CLL, no TP53 mutation/deletion, CIRS score Between November 2015 and May 2017, 135 patients (89 males/46 females) were enrolled; 7% were Binet stage A, 67% stage B and 26% stage C. Median age was 62 years (range, 35-80). Genetic alterations included 26% del(11q), 19% trisomy 12 and 56% del(13q); 15% had a complex karyotype and 56% patients had unmutated IGHV status. Median Beta 2 microglobulin was 3.6 mg/L (1.5-7.5) and median GFR (Cockroft) was 81 mL/min (42-173). At Month 9, 92% patients had received the 8 planned infusions of obinutuzumab. Ibrutinib dosage was reduced in 4 patients and definitively discontinued in 3 of them (3.9%) due to AE (atrial fibrillation, atrial flutter and neutropenia). Fifty seven percent of the patients presented at least a grade (G) 3 toxicity during the first 9 months of treatment (neutropenia 24%, anemia 6% and thrombocytopenia 31%). One hundred and thirty patients were evaluable for response at M9 and 5 not evaluable (2 deaths: one sudden at M7 and one accidental at M8; one acute coronary syndrome; one listeria meningitidis and one acute pulmonary edema at day 1 cycle 1). In intention to treat (ITT), ORR was 100% with 41% of patients reaching CR (42% for evaluable patients) but only 12% had BM MRD At month 16, 115 patients were evaluable for response. In ITT, the CR rate was 69% (78% for evaluable patients) and 79% of patients had BM MRD During the trial second period (M9 to M16), 38% patients presented at least a G3 toxicity: neutropenia 24%, thrombocytopenia 15%, anemia 1.5%, febrile neutropenia 3%, gastrointestinal disorders 9.5% and cardiac events 2.4%. A total of 41 serious AEs were observed throughout the entire treatment duration: 9 cardiac events including 1 atrial flutter and 3 atrial fibrillations, 4 hemorrhagic events, 7 infections, 3 second cancers (2 basocellular carcinoma, 1 renal adenocarcinoma) and 2 deaths. In conclusion, this MRD-driven strategy given for a definite period of time leads to a very high rate of uMRD CR in previously untreated CLL fit patients without TP53 aberration and displays an acceptable security profile. To our knowledge, these results are superior to standard FC + rituximab (FCR) or any chemo-free regimen. We hypothesize that this very high rate of bone marrow undetectable MRD will translate in a prolonged PFS while discontinuing treatment. Disclosures Laribi:Novartis: Other: Grant and personal fees; Takeda: Other: Grant and personal fees; Teva: Other: Grant; Gilead: Other: Personal fees; Sandoz: Other: Grant; Roche: Other: Grant; Amgen: Other: Personal fees; Hospira: Other: Grant. Salles:Novartis: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Abbvie: Honoraria; Acerta: Honoraria; Amgen: Honoraria; Epizyme: Honoraria; Gilead Sciences: Honoraria; Janssen: Honoraria; Merck: Honoraria; Morphosys: Honoraria; Pfizer: Honoraria; Servier: Honoraria; Takeda: Honoraria. Leblond:Gilead: Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Sandoz: Honoraria; Amgen: Honoraria. Cartron:Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Sanofi: Honoraria; Gilead Sciences: Honoraria; Janssen: Honoraria. Ysebaert:Roche: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Cymbalista:Gilead: Honoraria; AbbVie, Inc: Honoraria; Janssen: Honoraria; Sunesis: Research Funding. Feugier:Gilead: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding.

Néphrectomie partielle pour tumeur de plus de 7 cm : morbidité, résultats oncologiques et fonctionnels (UroCCR-7 study)

To describe the morbidity, mortality, oncological and functional results of Partial nephrectomy (PN) for the treatment of renal tumors of more than 7cm. Thirty-seven partial nephrectomies for tumors larger than 7cm operated in a single center between 1987 and 2016 were analyzed retrospectively. The pre, per and postoperative clinico-biological data were collected within the UroCCR database. The GFR was assessed at day 5, 1 month and last follow-up. Intraoperative and postoperative surgical complications, the recurrence rate and the overall and specific mortality were collected. The mean age of the patients was 57 years (44-68). The preoperative GFR and the median tumor size were 80mL/min and 8cm, respectively. The indication for surgery was elective in 21 cases (60%) and 19 tumors (54%) were malignant. Postoperative complications occurred in 24,3 cases (24.3%). The median post-operative GFR was respectively 77mL/min, 80mL/min and 77mL/min at day 5, 1month and at last follow-up. With a median follow up of 31 months [1-168], 5 patients (26,3%) had metastatic progression of whom 1 (5.3%) had a concomitant local recurrence and 3 (15.8%) had died from cancer. This study confirms the feasibility of PN for large tumors with acceptable morbidity, limited risk of local recurrence and excellent functional results. 4.

A 3-year longitudinal study of skeletal effects and growth in children after kidney transplantation.

This prospective study investigated growth and skeletal development for 3years after kidney transplantation in pediatric patients, 3.4-15.0years of age. Growth, BMD, bone resorption markers (CTX and TRACP5b), bone formation markers (PINP, ALP, and osteocalcin), PTH, and vitamin D were assessed at start, 3, 12, and 36months after transplantation. Median GFR was 63 (range 37-96) mL/min/1.73m2 after 3years. The median height SDS increased from -1.7 to -1.1, and median BMI SDS increased from -0.1 to 0.6 over 3years, which shows that transplantation had a favorable outcome on growth. Fat mass increased after transplantation at all time points, whereas lean mass increased after 1year and 3years. Total BMC increased at all time points. No changes were observed for total BMD. Bone resorption markers decreased initially after 3months and remained stable throughout the study, whereas the bone formation markers decreased initially, but successively increased over the study period. In conclusion, this study demonstrates that height SDS and BMI SDS increased, along with the increased formation markers that reveal a positive bone acquisition after kidney transplantation, which was reflected by the significant increase in total body BMC.

Impact of comorbidities on functional recovery from partial nephrectomy.

612 Background: Preservation of parenchymal mass and ischemia type/duration can influence functional recovery after partial nephrectomy (PN). Some have hypothesized that relevant comorbidities may also impact functional recovery, but this has not been adequately investigated. Methods: 405 patients with PN at our center (2007-2015) had necessary data to determine function/parenchymal mass preserved within the ipsilateral kidney. All comorbidities potentially associated with renal functional status were reviewed. Multivariable linear regression assessed factors associated with functional recovery, defined as percent ipsilateral GFR preserved. Results: Median tumor size and R.E.N.A.L. score were 3.5cm and 8, respectively. Overall, 264 (65%) patients had warm ischemia and 141cold ischemia (median durations = 21/27 minutes, respectively). The median ipsilateral GFR preserved was 79%. Age, comorbidity index, hypertension, and proteinuria all associated with preoperative GFR (all p < 0.01). Parenchymal mass preserved and ischemia characteristics significantly associated with functional recovery (all p < 0.001). On univariable analysis of comorbidities, only hypertension associated significantly with functional recovery. However, on multivariate analysis, none of the analyzed comorbidities associated with functional recovery. Conclusions: Recovery of function after PN depends primarily on parenchymal mass preservation and ischemia characteristics, while comorbidities failed to associate with functional outcomes. Comorbidities can impact function leading into surgery and may influence long-term functional stability, yet our data suggest that they do not influence short-term recovery after PN. [Table: see text]

Robotic cold ischemia achieves comparable functional outcomes to open cold ischemia during partial nephrectomy for complex kidney tumors.

Objectives:To compare the perioperative and functional outcomes after open and robotic partial nephrectomy performed with cold ischemia.Methods:A retrospective chart review was completed of consecutive patients who underwent partial nephrectomy with renal hypothermia between January 2011 and September 2016. The study cohort included both open (Open Cold Ischemia, OCI; n=170) and robotic (Robotic Cold Ischemia, RCI; n=31) patients with complex renal masses (R.E.N.A.L. score >7) who did not meet exclusion criteria. A modified intracorporeal technique 1 was utilized for the introduction of ice slush at the time of hilar clamping in the RCI group. Statistical testing was performed to compare key perioperative and functional outcomes after ensuring equilibration of both groups by clinicodemographic criteria.Results:Both groups were statistically equivalent with respect to baseline characteristics. Median GFR preservation postoperatively was 86.7% for the open group and 86.6% in the robotic group (p=0.49). Cold ischemia time (CIT) in the open group was 35 minutes compared to 28 minutes (p = 0.03) in the robotic group. LOS was significantly shorter by 2 days (p < 0.01) in the robotic group. Positive margins was noted to be 17 (10%) in the open group and 2 (6.5%) patients in the robotic group (p=0.48).Conclusions:We demonstrate an effective and simplified method of intracorporeal ice cooling during robotic partial nephrectomy. Our data suggests that results with this approach compare favorably to open cold ischemia technique. Intracorporeal ice cooling can be considered when performing complex partial nephrectomies with ischemia times expected to exceed 25 minutes.

Clinical benefit and residual kidney function of en bloc nephrectomy for perirenal retroperitoneal sarcoma.

The purpose of this study was to evaluate the efficacy of en bloc nephrectomy for perirenal retroperitoneal sarcoma (RPS) with respect to postoperative kidney function and oncological benefits. We performed a comparative study of 114 patients undergoing surgery for primary RPS, classifying cases as nephrectomy (NPX, n=65) versus no nephrectomy (no-NPX, n=49). The Δ and % change between preoperative and postoperative estimated glomerulus filtration rate (eGFR) were analyzed to compare renal function changes after surgery. Kaplan-Meier analysis was performed to verify the incidence of local relapse between the two groups. During a median follow-up of 29 months, median postoperative GFR of 65 patients in the NPX group decreased to 73.5% of preoperative eGFR. Although 38 patients (58%) in the NPX group experienced a progression in chronic kidney disease stage after nephrectomy, no patients progressed to end-stage renal disease (ESRD). In French Federation of Cancer Centers Sarcoma grade 2, the NPX group had statistically significant local control benefits, compared with the no-NPX group (P=0.048). Residual renal function after en bloc nephrectomy was stabilized without progression to ESRD. Moreover, en bloc nephrectomy for perirenal RPS might secure a complete resection margin for local tumor control.

Tissue expression of tubular injury markers is associated with renal function decline in diabetic nephropathy

AimsThe pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial; increasing evidence suggests that tubular injury and inflammatory process are involved in disease progression. We investigated the potential association of renal expression of tubular injury markers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and inflammatory markers, tumor necrosis factor receptor (TNFR) 1 and 2 with renal progression in pathologically proven diabetic nephropathy (DN). MethodsWe identified 122 patients with confirmed DN. After excluding patients with other coexisting renal disease or estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2, 35 patients were included. Annual decline of (GFR decline slope) was calculated using linear regression analysis. Tissue tubular and glomerular expressions of NGAL, KIM-1, TNFR1, and TNFR2 were assessed using immunohistochemistry. ResultsMedian baseline urinary protein to creatinine ratio (uPCR) was 6.76 (2.18–7.61) mg/mg Cr, median baseline eGFR was 50 (43–66) mL/min per 1.73m2, and median GFR decline slope was 15.6 (4.4–35.1) mL/min per 1.73m2 per year. Positive correlations were observed between tubular expressions of NGAL and KIM-1, and GFR decline slopes (r=0.601, p<0.001; r=0.516, p=0.001, respectively), and between tubular expressions of KIM-1 and uPCR (r=0.596, p<0.001), and between NGAL and interstitial fibrosis and tubular atrophy (IFTA) score (r=0.391, p=0.024). No correlations were found between glomerular or tubular expressions of TNFRs, and clinical parameters including GFR decline slopes. On multivariate analysis, the association between tubular expressions of KIM-1 and GFR decline slopes was dependent on uPCR. Tubular expressions of NGAL were independently associated with GFR decline slopes, with an adjusted coefficient factor of 0.290 (95% confidence interval, 0.009–0.202, p=0.038). ConclusionsThese findings suggest that tubular injury plays a key role in the pathogenesis of DKD in high-risk patients. Further studies are warranted to determine whether tubular injury could be a therapeutic target in DKD.

A 3-year longitudinal study of skeletal effects and growth in children after kidney transplantation

This prospective study investigated growth and skeletal development for 3 years after kidney transplantation in pediatric patients, 3.4-15.0 years of age. Growth, BMD, bone resorption markers (CTX and TRACP5b), bone formation markers (PINP, ALP, and osteocalcin), PTH, and vitamin D were assessed at start, 3, 12, and 36 months after transplantation. Median GFR was 63 (range 37-96) mL/min/1.73 m2 after 3 years. The median height SDS increased from -1.7 to -1.1, and median BMI SDS increased from -0.1 to 0.6 over 3 years, which shows that transplantation had a favorable outcome on growth. Fat mass increased after transplantation at all time points, whereas lean mass increased after 1 year and 3 years. Total BMC increased at all time points. No changes were observed for total BMD. Bone resorption markers decreased initially after 3 months and remained stable throughout the study, whereas the bone formation markers decreased initially, but successively increased over the study period. In conclusion, this study demonstrates that height SDS and BMI SDS increased, along with the increased formation markers that reveal a positive bone acquisition after kidney transplantation, which was reflected by the significant increase in total body BMC.

Association of Circulating Biomarkers (Adrenomedullin, TNFR1, and NT-proBNP) With Renal Function Decline in Patients With Type 2 Diabetes: A French Prospective Cohort.

We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes. Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA1c, blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors. Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89], P < 0.0001; 1.33 [1.14-1.55], P = 0.0003; and 1.22 [1.07-1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], P = 0.003; 1.72 [1.33-2.22], P < 0.0001; and 1.28 [1.03-1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD). In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes.

Disparities in Renal Recovery Between African Americans Vs. Non African Americans Following Initial Treatment of Newly Diagnosed Multiple Myeloma: A Retrospective Chart Review

Introduction:Renal insufficiency (RI) in newly diagnosed multiple myeloma (NDMM) represents a poor prognostic factor (Knudsen, Hjorth, and Hippe 2000). Recent clinical trials have demonstrated that patients treated with novel agents, particularly proteasome inhibitors, may experience renal recovery with improvement in overall survival (Dimopoulos et al. 2013; Gonsalves et al. 2015). The majority of patients in these trials were Caucasians, although multiple myeloma is twice as common in African Americans (AA) as it is in Caucasians. Moreover, AA have a 5 times higher rate of stage 4 chronic kidney disease (CKD) and end-stage-renal-disease (ESRD) in the United States compared to Caucasians. The cause for this disparity is thought to be multifactorial, including a higher incidence of comorbidities such as diabetes and hypertension among AAs (Williams and Pollak 2013; Grams et al. 2013). There is currently a dearth of evidence regarding renal recovery in AA receiving therapy for MM. The goal of this study is to compare renal recovery between AA and non AA patients following initial treatment for NDMM.Methods:We performed a retrospective chart review of patients with NDMM at Rush University Medical Center from January 1, 2005 to August 1, 2016. 690 charts were selected and reviewed; patients who were on hemodialysis for alternative reasons prior to diagnosis, had a GFR > 90, or for whom records were incomplete were excluded. 118 patients with NDMM and a GFR < 90 (corresponding to National Kidney Foundation’s chronic kidney disease stage 2 or worse) at the time of diagnosis were identified. Continuous variables were compared between the two groups using the Mann-Whitney U test, and binary variables were compared using Fisher’s exact test.Results:We compared 59 AA and 59 non AA patients with RI at the time of diagnosis of MM. Both groups were comparable by age, gender, ISS and high risk cytogenetics. The degree of RI at the time of diagnosis was similar: median GFR at diagnosis was 47.89 in the AA group and 51.95 in the non AA group (p=0.56). Hypertension was more common in the AA group (78% vs. 52.5%, p=0.0064), while other comorbidities were statistically comparable.The majority of patients were treated with a bortezomib-based regimen (86.4% for the AA group and 84.7% for the non AA group, p=1). MM response rates to induction therapy were similar: very good partial response (VGPR) or better was achieved in 39% of AA and 25.4% of non AA (p=0.17). 45.8% of AA patients underwent autologous stem cell transplant (ASCT) compared to 64.4% of non-AA (p=0.0637, see table 3). 80% of AA and 88% of non AA patients received bisphosphonates (see table 1).Although median GFR at the time of diagnosis of MM was similar between the AA and non AA groups (47.89 vs. 51.95, p=0.56), the median absolute change in estimated GFR after initial therapy was significantly higher in the AA group (+33.64) vs. the non-AA group (+21.07, p=0.00183). This difference remained whether the baseline GFR at diagnosis was <90 or <60 (see table 2). The median time to best renal response was 91 days in AA and 79 days in non-AA (p=0.383).Conclusions:This is the first study to analyze disparities in renal dysfunction and recovery between AA and non-AA patients with NDMM. We demonstrate that in our institution AA patients with NDMM treated in the era of novel agents have greater improvement in renal function in comparison to non AA patients. Given that renal recovery in NDMM impacts overall survival, this finding suggests that further studies should be done to explore differences in the epidemiology and disease biology that could account for the racial disparities in renal dysfunction and recovery. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Feasibility of Omitting Cortical Renorrhaphy During Robot-Assisted Partial Nephrectomy

Introduction: Use of robot-assisted partial nephrectomy is increasing rapidly for the treatment of patients with small renal masses. The use of cortical renorrhaphy has traditionally been used in partial nephrectomy to prevent urine leaks and postoperative bleeding; however, the efficacy of this technique in preserving renal function has never been questioned. In this video, we demonstrate the different techniques of robot-assisted partial nephrectomy (i.e., omission of cortical renorrhaphy vs. a standard two-layer renorrhaphy), assess the safety of this base-only layer technique, and measure preliminary functional outcomes. Materials and Methods: Fifteen robot-assisted partial nephrectomies were performed with a running, base-layer suture for the collecting system and vessel hemostasis, but without cortical renorrhaphy. The nonrenorrhaphy group was retrospectively matched 1:2 by R.E.N.A.L. nephrometry score to a running, sliding-clip cortical renorrhaphy group. Intraoperative blood loss, postoperative urine leaks, postoperative hemorrhage, and functional outcomes were evaluated. Predictors of percentage volume loss were evaluated using multivariable regression. Results: No differences were seen between renorrhaphy and nonrenorrhaphy in sex (p = 0.53), age (p = 0.14), body mass index (p = 0.08), Charlson score (p = 0.44), tumor diameter (p = 0.55), nephrometry score (p = 0.77), preoperative glomerular filtration rate (GFR, p = 0.63), or the amount of resected healthy kidney margin (p = 0.21). Warm ischemia time was less for the nonrenorrhaphy group (p < 0.002). One pseudoaneurysm necessitating embolization (1/30 = 3%) was seen in the renorrhaphy group compared with none in the nonrenorrhaphy group. No urine leaks occurred in either group. The median percentage GFR loss was 8.8% for renorrhaphy and 4.4% for nonrenorrhaphy (p = 0.14) at a median follow-up of 4.1 months. The median percentage volume loss was 17 cm3 for renorrhaphy and 9 cm3 for nonrenorrhaphy (p = 0.003). In a multivariable model, both cortical renorrhaphy (p = 0.004) and tumor diameter (p = 0.004) were predictors of percentage volume loss. Conclusion: Omission of cortical renorrhaphy appears feasible with no urine leaks or bleeding complications observed. The percentage renal volume loss was improved by omission of cortical renorrhaphy. Reconstruction technique is important to control for when studying renal function after partial nephrectomy. No competing financial interests exist. Runtime of video: 7 mins 56 secs

An institutional experience of pre-emptive liver transplantation for pediatric primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre-emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30-46) mL/min/1.73 m(2) and five underwent sequential combined liver-kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used "early" or "late." Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m(2) ), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.

The effects of cytotoxic therapy in progressive IgA nephropathy

Background: IgA nephropathy (IgAN) is not always benign, and some patients at high risk of end-stage renal disease (ESRD) experience a rapid decline in renal function. This study retrospectively examined the beneficial effects of cytotoxic therapy. Methods: We identified 102 patients with progressive IgAN despite optimal conservative management. Of these, 31 who received cytotoxic therapy and 55 who were managed conservatively were included. Results: Median eGFR and urinary protein-to-creatinine ratio (uPCR) at baseline did not differ between the groups (p = 0.475 and 0.259, respectively). Median GFR slope was also similar (p = 0.896). Cumulative renal survival was better in the cytotoxic therapy group than in the control group (p = 0.009). Cytotoxic therapy was associated with lower risk of progression to ESRD, independent of eGFR, uPCR, GFR slope and kidney histologic findings (HR 0.13, 95% CI 0.03–0.66). In the cytotoxic therapy group, the median GFR slope decreased from −7.8 (−10.5, −5.0) mL/min/1.73 m2 per year to −3.4 (−5.1, −1.8) mL/min/1.73 m2 per year after treatment (p < 0.001). Mortality was not observed, but infection requiring hospitalization occurred at similar rates in both groups (p = 0.886). Conclusions: Cytotoxic therapy attenuated the rate of GFR decline and was associated with a favorable renal outcome in patients with progressive IgAN.Key messagesCytotoxic therapy was associated with a favorable renal outcome in IgA nephropathy patients whose glomerular filtration rate progressively declined despite optimal conservative management.Cytotoxic therapy significantly attenuated the rate of glomerular filtration rate decline as well as the amount of proteinuria in patients with progressive IgA nephropathy.Adverse events following cytotoxic therapy were comparable to conservative management.

Baseline GFR and cisplatin-induced renal toxicity in urothelial cancer patients.

380 Background: Cisplatin eligibility for clinical trials has been defined as calculated GFR &gt; 60 mL/min due to risk of nephrotoxicity in patients (pts) with renal impairment. For urothelial cancer (UCa), substitution of cisplatin compromises outcomes. We evaluated change in GFR in pts treated with cisplatin despite baseline GFR &lt; 60 to determine risk of nephrotoxicity. Methods: 150 USC pts were identified who received systemic therapy for UCa from 2009 to 2014. Creatinine and weight values closest to treatment start and finish were used for calculation of GFR using the Cockcroft-Gault formula. Wilcoxon rank-sum tests and analyses of variance (ANOVA) were used to compare GFR percent change by age ( &lt; 75 vs &gt; 75 years), pre-treatment GFR ( &lt; 60 vs &gt; 60), therapy setting (neoadjuvant, adjuvant, or metastatic), primary disease site, and comorbidities (diabetes, hypertension, hyperlipidemia). Log-rank tests and Cox regression models were used to examine the association between overall survival (OS) and age or GFR. Results: 114 received cisplatin-based therapy at least once; 26 in the neo-adjuvant setting, 27 adjuvant, and 61 for metastatic disease. GFR could be calculated pre- and post-treatment for 81 pts; lowest GFR in pt receiving cisplatin was 25.5 mL/min. Median GFR change was -1.6% (range: -50% ~ 49%) for pts with pre-treatment GFR &lt; 60 compared to -10.9% (range -72%, 135%) for pts with pre-treatment GFR &gt; 60 (p = 0.17). Treatment setting (neo-adjuvant, adjuvant, or metastatic) had significant association with GFR change (p = 0.027). Median (range) of GFR change for the neo-adjuvant setting, adjuvant setting and metastatic setting was 4.6% (95% CI -32%, 90%), -5.8% (95% CI-39%, 20%), -11.9% (95% CI -72%, 135%), respectively. Age, primary disease site, diabetes, hypertension and hyperlipidemia were not associated with GFR change. Univariate analysis showed an association between GFR &gt; 60 at stop of treatment with worse OS (p = 0.087) in metastatic pts. Conclusions: Our data support the hypothesis that UCa pts with GFR &lt; 60 do not experience a greater decline in renal function after cisplatin treatment compared to patients with GFR &gt; 60. If validated, this may extend the option of cisplatin-based therapy to previously ineligible pts.

Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes.

Elevated serum tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) concentrations are strongly associated with increased risk of end-stage renal disease in type 2 diabetes. However, little is known about the early glomerular structural lesions that develop in patients when these markers are elevated. Here we examined the relationships between TNFRs and glomerular structure in 83 American Indians with type 2 diabetes. Serum TNFRs and glomerular filtration rates (GFR, iothalamate) were measured during a research exam performed within a median of 0.9 months from a percutaneous kidney biopsy. Associations of TNFRs with glomerular structural variables were quantified by Spearman's correlations and by multivariable linear regression after adjustment for age, gender, diabetes duration, hemoglobin A1c, body mass index, and mean arterial pressure. The baseline mean age was 46 years, median GFR 130 ml/min, median albumin/creatinine ratio 26 mg/g, median TNFR1 1500 pg/ml, and median TNFR2 3284 pg/ml. After multivariable adjustment, TNFR1 and TNFR2 significantly correlated inversely with the percentage of endothelial cell fenestration and the total filtration surface per glomerulus. There were significant positive correlations with mesangial fractional volume glomerular basement membrane width, podocyte foot process width, and percent of global glomerular sclerosis. Thus, TNFRs may be involved in the pathogenesis of early glomerular lesions in diabetic nephropathy.

Carfilzomib, Cyclophosphamide and Dexamethasone Is Well Tolerated in Patients with Relapsed/Refractory Multiple Myeloma Who Have Received One Prior Regimen

Introduction. Carfilzomib-containing doublet and triplet regimens demonstrate high response rates both in the relapsed and frontline settings and will soon enter the treatment pathways for multiple myeloma (MM). While the phase 3 studies, ENDEAVOUR and ASPIRE provide information on combinations with dexamethasone with or without lenalidomide, there are limited data on other combinations, especially with alkylating agents.Aim. To describe the safety and toxicity of Carfilzomib, cyclophosphamide and dexamethasone in patients at first relapse of MM, based on an interim assessment of the MyelomaUKfive (MUKfive) study.Methods. MUKfive is a randomised phase 2 study comparing carfilzomib with bortezomib, in triplet combination with cyclophosphamide and dexamethasone for patients who require treatment after one prior regimen, in a 2:1 randomisation, target 300 patients. Patients receive 6 months of induction treatment with six 28-day cycles of carfilzomib (20/36 mg/m2 in stepped up dosing d1, 2, 8, 9, 15, 16 by IV infusion over 30 minutes), oral cyclophosphamide (500 mg d1, 8, 15) and oral dexamethasone (40mg d1, 8, 15, 22) or eight 21-day cycles of bortezomib (1.3mg/m2 SC d1, 4, 8, 11) by SC or IV, cyclophosphamide (500 mg d1, 8, 15) and dexamethasone (40mg d1, 8, 15). The primary endpoint for this part of the study is ≥VGPR rate. The study opened in 2013, and we have carried out an interim assessment of safety data on the first 69 patients randomised to the Carfilzomib arm, with toxicities graded by CTCAE V4.0.Results. Median age was 67.6 years (range 35-85), 62.3% were male, and ISS stage as follows: 32 patients ISS 1, 22 patients ISS 2, 15 patients ISS 3. Median GFR was 78ml/min (range 30-243) and ECOG performance status as follows: 43 patients PS 0, 20 patients PS 1, 5 patients PS 2, 1 patient missing PS. Sixty-seven patients received at least one dose of trial treatment and are evaluable for safety.In cycle 1, the commonest treatment-related toxicities of any grade (adverse reactions, ARs) were anaemia (89.6%), thrombocytopenia (67.2%) neutropenia (29.9%), nausea (14.9%), diarrhoea (11.9%), vomiting (10.6%), constipation (9%), infections (4.5%) and infusion reactions (4.5%). During induction treatment (all cycles), the most common ARs of all grades were anaemia (97%), thrombocytopenia (83.6%) neutropenia (58.2%), nausea (47.8%), diarrhoea (37.3%), infections (29.9%) vomiting (22.4%), constipation (22.4%), hypotension (4.5%) and infusion reactions (4.5%). Haematologic grade ≥3 ARs included anaemia (19.4%), neutropenia (12%), and thrombocytopenia (10.5%), while non-haematological grade ≥3 ARs were infections (20.9%), vomiting (4.5%), nausea (3%), diarrhoea (3%), infusion reactions (3%). Treatment emergent neuropathy was reported by 18 patients (26.9%), all G1 except for 1 patient (G2). Three patients had thromboembolic ARs: one each of pulmonary embolism (G3), thrombophlebitis (G2) and brachial vein thrombosis (G1).Serious AEs were reported in 29 patients (43.3%). A total of 47 SAEs were reported, of which 31 (66%) were treatment related (28 related to carfilzomib). Treatment related SAEs included 22 infections (noted above, of which 15 were respiratory infections), 2 gastrointestinal, 1 acute kidney injury (G2) and 1 worsening of renal function (G1), 2 endocrine (1 each of hypo- and hyperglycemia), and 1 hepatobiliary. Two G3 SUSARs were reported, one cardiomyopathy, one extensive pulmonary embolism. In 87.2% of SAEs, patients had recovered or were improving.In cycle 1, 19 patients (28.4%) had at least one dose modification; carfilzomib dose was modified in 14, cyclophosphamide in 7 and dexamethasone in 11. The majority of these were dose omissions. Across all cycles, 54 patients (80.6%) had dose modification/s, 47 to carfilzomib, 32 to cyclophosphamide and 40 to dexamethasone. Of carfilzomib modifications, 53.3% were omissions, while the rest were reductions (24.6%) or delays (22.1%). Of carfilzomib dose reductions, the majority (72.9%) were due to haematological toxicity. Five patients (7.2%) stopped treatment due to toxicity after a median of 3 (range 1-4) cycles. There were no treatment related deaths.Conclusion. The triplet regimen carfilzomib, cyclophosphamide and dexamethasone is well tolerated in this patient group, with toxicity profile that is as expected from published data on carfilzomib.Acknowledgments: This trial a Myeloma UK Clinical Trial Network study DisclosuresYong:Autolous: Consultancy; Novartis: Consultancy; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS: Honoraria. Off Label Use: Carfilzomib with cyclophosphamide and dexamethasone as therapy in relapsed myeloma. Ramasamy:Celgene: Honoraria; Amgen: Honoraria; Takeda Millenium: Honoraria. Cavenagh:Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Owen:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Kaiser:Chugai: Consultancy; Janssen: Honoraria; BristolMyerSquibb: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Williams:Amgen: Honoraria; Janssen: Honoraria.

Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression.

Common apolipoprotein L1 (APOL1) variants are associated with increased risk of progressive CKD; however, not all individuals with high-risk APOL1 variants experience CKD progression. Identification of factors contributing to heterogeneity has important scientific and clinical implications. Using multivariable Cox models, we analyzed data from 693 participants in the African American Study of Kidney Disease and Hypertension to identify factors that modify the association between APOL1 genotypes and CKD progression (doubling of serum creatinine or incident ESRD). Participant mean age was 54 years old, median GFR was 49 ml/min per 1.73 m(2), and 23% had the APOL1 high-risk genotype (two copies of the high-risk allele). Over a mean follow-up of 7.8 years, 288 (42%) participants experienced CKD progression. As previously reported, the high-risk genotype was associated with higher risk of CKD progression compared with the low-risk genotype (hazard ratio [HR], 1.88; 95% confidence interval [95% CI], 1.46 to 2.41). Although we found some suggestion that obesity (HR, 1.48; 95% CI, 1.05 to 2.08 and HR, 2.44; 95% CI, 1.66 to 3.57 for body mass index ≥ 30 versus <30 kg/m(2); P interaction =0.04) and increased urinary excretion of urea nitrogen (HR, 1.43; 95% CI, 0.98 to 2.09 versus HR, 2.33; 95% CI, 1.65 to 3.30 for urine urea nitrogen ≥ 8 versus <8 g/d; P interaction =0.04) were associated with lower APOL1-associated risk for CKD progression, these findings were not robust in sensitivity analyses with alternative cut points. No other sociodemographic (e.g., education and income), clinical (e.g., systolic BP and smoking), or laboratory (e.g., net endogenous acid production, urinary sodium and potassium excretions, 25-hydroxy vitamin D, intact parathyroid hormone, or fibroblast growth factor 23) variables modified the association between APOL1 and CKD progression (P interaction >0.05 for each). Sociodemographic factors and common risk factors for CKD progression do not seem to alter APOL1-related CKD progression. Additional investigation is needed to identify nontraditional factors that may affect the association between APOL1 and progressive CKD.

Safety of percutaneous coronary intervention in patients with acute coronary syndromes complicating chronic kidney disease

To evaluate the safety of percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) complicating chronic kidney disease (CKD). We retrospectively evaluated the medical data of 335 patients hospitalized in our hospital with a diagnosis of ACS and CKD between 1 January 2011 and 30 May 2014. Patients were divided into two groups: PCI group who received PCI treatment during hospitalization (n = 135) and non-PCI group who did not receive PCI treatment (n = 200). Multivariable logistic regression analysis was performed to evaluate the connection between PCI and in-hospital death and acute renal insufficiency. The median GFR level of 335 patients was 36.26 (25.09-47.65) ml · min⁻¹ · 1.73 m⁻². GFR level was similar between the two groups (P = 0.205). Multivariable logistic regression analysis showed that PCI did not increase the risk of in-hospital death (OR = 0.465, 95% CI: 0.190-1.136, P = 0.093) and in-hospital acute renal insufficiency (OR = 0.830, 95% CI: 0.375-1.836, P = 0.669). In patients of 45 ml · min⁻¹ · 1.73 m⁻² ≤ GFR < 60 ml · min⁻¹ · 1.73 m⁻², 30 ml · min⁻¹ · 1.73 m⁻² ≤ GFR < 45 ml · min⁻¹ · 1.73 m⁻² and GFR < 30 ml · min⁻¹ · 1.73 m⁻², the OR of in-hospital death in PCI group were 0.235 (95% CI: 0.024-2.301, P = 0.213), 0.640 (95% CI: 0.112-3.649, P = 0.616) and 0.919 (95% CI: 0.159-5.307, P = 0.925), and the OR of in-hospital acute renal insufficiency were 0.436 (95% CI: 0.120-1.587, P = 0.208), 2.209 (95% CI: 0.394-12.391, P = 0.368) and 0.724 (95% CI: 0.127-4.117, P = 0.716) indicating that PCI did not increase above events in ACS patients complicating CKD. PCI does not increase the risk of in-hospital death and in-hospital acute renal insufficiency in ACS patients complicating CKD.

Shear wave elastography in chronic kidney disease: a pilot experience in native kidneys.

BackgroundThere currently is a need for a non-invasive measure of renal fibrosis. We aim to explore whether shear wave elastography (SWE)-derived estimates of tissue stiffness may serve as a non-invasive biomarker that can distinguish normal and abnormal renal parenchymal tissue.MethodsParticipants with CKD (by estimated GFR) and healthy volunteers underwent SWE. Renal elasticity was estimated as Young’s modulus (YM) in kilopascals (kPa). Univariate Wilcoxon rank-sum tests were used.ResultsTwenty-five participants with CKD (median GFR 38 mL/min; quartile 1, quartile 3 28, 42) and 20 healthy controls without CKD underwent SWE performed by a single radiologist. CKD was associated with increased median YM (9.40 [5.55, 22.35] vs. 4.40 [3.68, 5.70] kPa; p = 0.002) and higher median intra-subject inter-measurement estimated YM’s variability (4.27 [2.89, 9.90] vs. 1.51 [1.21, 2.05] kPa; p < 0.001).ConclusionsSWE-derived estimates of renal stiffness and intra-subject estimated stiffness variability are higher in patients with CKD than in healthy controls. Renal fibrosis is a plausible explanation for the observed difference in YM. Further studies are required to determine the relationship between YM, estimated renal stiffness, and renal fibrosis severity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0120-7) contains supplementary material, which is available to authorized users.