eGFR Preservation Research Articles

Efficacy and Safety of Nefecon in Patients with Immunoglobulin A Nephropathy from Mainland China: 2-Year NefIgArd Trial Results.

Immunoglobulin A nephropathy (IgAN), an immune-mediated kidney disease, is particularly prevalent among individuals of East Asian ancestry. Nefecon is a novel, oral, targeted-release budesonide formulation designed to inhibit galactose-deficient-IgA1 formation underlying IgAN pathophysiology. We present findings in patients with IgAN from mainland China participating in the 2-year, multicenter, randomized, double-blind, phase 3 NefIgArd trial of Nefecon. Patients (aged ≥18 years) with primary IgAN (estimated glomerular filtration rate [eGFR] 35-90 ml/min per 1.73 m2, persistent proteinuria [urine protein-creatinine ratio ≥0.8 g/g or proteinuria ≥1 g/24 h] despite optimized renin-angiotensin system blockade) received Nefecon or placebo over 9 months, followed by a 15-month follow-up phase on supportive care alone. The primary efficacy end point was time-weighted average of eGFR over 2 years. Sixty-two patients from mainland China were included in this prespecified analysis. The primary efficacy end point was 9.6 ml/min per 1.73 m2 (95% confidence interval [CI], 2.0 to 19.8) in favor of Nefecon versus placebo. This was consistent with (and numerically greater than) that of the global study population. Time to confirmed 30% eGFR reduction or kidney failure from baseline was substantially delayed with Nefecon (patients with an event: 9%) versus placebo (30%; hazard ratio, 0.21; 95% CI, 0.04 to 0.73]). No deaths were reported in the China cohort. In the Nefecon group, treatment-emergent serious adverse events were reported by one patient during treatment and two patients during follow-up (versus no patients and seven patients, respectively, in the placebo group). No severe infections requiring hospitalization were reported. Nefecon treatment for 9 months showed greater preservation of eGFR over 2 years compared with placebo. The efficacy outcomes were consistent with global study results, with a numerically greater treatment benefit observed in patients from China. Nefecon was well tolerated, with no unexpected safety signals.

Ultrasound-guided renal artery balloon catheter occluded hybrid partial nephrectomy (UBo-HPN) with branch renal artery occlusion: a single arm trial

BackgroundOne key focus of partial nephrectomy is preserving renal function. Segmental renal artery occlusion with microdissection at the renal hilum confines ischemia, effectively reducing warm ischemic injury. Ultrasound-Guided Renal Artery Balloon Catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN) can achieve branch occlusion without the need for dissecting the renal hilum.ObjectiveTo investigate the feasibility and safety of UBo-HPN of branch renal artery occlusion in the treatment of localized renal tumors.Subject and methodsA prospective single-arm analysis involving 20 patients with renal localized tumors underwent robot assisted UBo-HPN with branch renal artery occlusion from August 2021 to July 2023, with an average follow-up of 12 months.ResultsAll patient was successfully operated on without conversion to conventional arterial clamping or radical nephrectomy. One case (5%) of minor complication occurred in the whole cohort, which was bruising around the puncture site. The mean total operative time was 95.8 min, with a mean operative time of 21.25 min for vascular intervention. The mean warm ischemia time was 20.35 min, and the median estimated blood loss was 50 ml. The median eGFR preservation percentage at postoperative 48 h, 30 days, and the latest follow-up were 87.52%, 91.47%, and 92.2%, respectively. After a median follow-up of 10.2 (2.3–19.2) months, no patients had radiological tumor recurrence or died from tumor-related causes.ConclusionsUBo-HPN with renal artery branch occlusion emerges as an efficient alternative to partial nephrectomy (PN), which achieved branch artery occlusion without dissecting the renal hilum. Long-term follow-up is expected for functional outcomes.

C3 Nephrotic Factor at Diagnosis Is Associated with Better eGFR Preservation in Patients with C3 Glomerulopathy (C3G): Findings from the European Rare Kidney Disease Registry (ERKReg)

C3 Nephrotic Factor at Diagnosis Is Associated with Better eGFR Preservation in Patients with C3 Glomerulopathy (C3G): Findings from the European Rare Kidney Disease Registry (ERKReg)

Quantifying preserved renal volume and function in patients undergoing standard partial nephrectomy vs. tumor enucleation for localized renal tumors

IntroductionRenal parenchymal volume loss from standard partial nephrectomy (SPN) is a significant prognosticator for postoperative renal function. Tumor enucleation (TE) minimizes parenchymal loss compared to SPN. Little is known regarding discrete changes in renal function associated with volume loss. We sought to quantify the differences between SPN and TE in preserving parenchymal volume and estimated glomerular filtration rate (eGFR). MethodsWe identified 420 patients who underwent robotic partial nephrectomy (SPN or TE) at our tertiary care center from 2009 to 2022. Parenchymal volumes were calculated using TeraRecon 3D reconstruction software from axial imaging performed preoperatively and within 6 months postoperatively. Renal volume preserved and renal function were evaluated with multivariable linear and logistic regression models. ResultsAt 1 year, eGFR was 7% lower in patients undergoing SPN compared to TE (P < 0.01). Across both SPN and TE, only volume of preserved parenchyma was predictive of eGFR and chronic kidney disease (CKD) progression (both P < 0.01). TE preserved more healthy parenchymal volume compared to SPN (median percentage 97.6% vs 89.2%; P < 0.001). Each 1% of volumetric loss corresponded to a 0.35% decrease in eGFR at 1 year postoperatively (P < 0.01). ConclusionsVolume of preserved renal parenchyma was the strongest factor associated with preserved eGFR and reduced odds of CKD progression. TE preserved more parenchyma than SPN, which translated to higher eGFR preservation at 1 year postoperatively.

The association between the eGFR slope and cardiorenal prognosis in patients with renoprotective treatments: A systematic review and meta-analysis.

The associations between the estimated glomerular filtration rate (eGFR) slope and the cardiorenal prognosis in patients with renoprotective drugs have not been well characterized yet. PubMed, Medline, Embase, The Cochrane Library, CNKI, WanFang, Weipu databases and Clinicaltrial.gov were searched from inception to April 2023. Event-driven randomized controlled trials (RCTs) investigating renoprotective drugs and reporting eGFR slopes in patients with atherosclerotic cardiovascular disease, heart failure, type 2 diabetes, or chronic kidney disease were included. In all, 25 RCTs with 179,893 participants were included. The preservation of eGFR was observed in patients with renoprotective drugs, with a comparator-adjusted total eGFR slope of 0.51mL/min per 1.73 m2/year (95% CI, 0.31 to 0.70). It was indicated that the eGFR preservation reflected by the positive comparator-adjusted total eGFR slope was associated with a reduced risk of composite renal outcome (β=-0.097,95% CI, -0.178 to -0.016, p=0.022), but was not associated with the risks of major adverse cardiovascular events (MACE) or all-cause mortality. In patients with SGLT2i, MRA, or RAASi treatments, the placebo-adjusted acute eGFR slope was -0.59mL/min per 1.73 m2 per week (95% CI, -0.74 to -0.43), which was marginally associated with a reduced risk of composite renal outcome (β=0.290,95% CI, 0.000 to 0.581, p=0.050), but was not associated with the risks of MACE or all-cause mortality. The eGFR preservation reflected by the positive comparator-adjusted total eGFR slope was associated with a reduced risk of composite renal outcome in patients receiving renoprotective agents. Greater acute decline in eGFR during the initiation of the treatment might confer a trend of fewer renal events in patients receiving SGLT2i, MRA, or RAASi.

Functional outcomes in robot-assisted partial nephrectomy with three-dimensional images reconstructed from computed tomography: a propensity score-matched comparative analysis.

Our objective was to investigate the long-term functional outcomes of robot-assisted partial nephrectomy (RAPN) combined with three-dimensional (3D) imaging. The 3D images, reconstructed using computed tomography, were introduced in RAPN procedures. The demographic, oncological, functional, and volumetric outcomes of 296 patients who underwent RAPN with and without 3D imaging between 2013 and 2021 were analyzed retrospectively. Propensity score matching (1:1) was performed to adjust for potential baseline confounders. After matching, 71 patients were allocated to each group. In the 3D RAPN (3DRPN) group, functional outcomes significantly improved: the number of patients with over 90% estimated glomerular filtration rate (eGFR) preservation rate (40 vs. 43, P = 0.044), eGFR preservation rate (88.0% vs. 91.6%, P = 0.006), the number of patients with chronic kidney disease (CKD) upstaging (26 vs. 13, P = 0.023), and split renal function preservation rate (operated kidney: 84.9% vs. 88.5%, P = 0.015). The 3DRPN group showed superiority in terms of >90% eGFR preservation (P = 0.010), CKD upstaging-free survival rates (P < 0.001), and volumetric outcomes (excess parenchymal volume: 27.9 vs. 17.7mL, P = 0.030; parenchyma volume preservation rate: 81.6% vs. 88.8%, P = 0.006). Three-dimensional imaging was positively associated with eGFR preservation (P = 0.023, odds ratio: 2.34) and prevention of CKD upstaging (P = 0.013, odds ratio: 2.90). In this study, RAPN combined with 3D imaging underscored the preservation of eGFR > 90% and the prevention of CKD upstaging by improving the preservation rate of renal parenchyma and split renal function.

Comparison of surgical outcomes of robot-assisted laparoscopic partial nephrectomy performed by a single experienced surgeon according to two reconstruction methods, including single-layer and double-layer renorrhaphy.

This study aimed to assess the surgical outcomes of single-layer versus double-layer renorrhaphy in robot-assisted laparoscopic partial nephrectomy (RAPN) performed by an experienced surgeon.We enrolled 655 patients who underwent RAPN between January 2019 and June 2023. After excluding those with multiple tumors or incomplete medical records, 554 patients were included in the final analysis. We compared surgical outcomes between single-layer renorrhaphy (outer cortical closure) and double-layer renorrhaphy (inner layer suture and outer cortical closure), adjusting for preoperative factors such as sex, age, body mass index, American Society of Anesthesiologists score, preoperative estimated glomerular filtration rate (eGFR), preoperative complications (diabetes or hypertension), surgical approach (transperitoneal or retroperitoneal), tumor size, and tumor complexity, using propensity score matching. Of the 554 patients analyzed, 59 were classified into the single-layer group and 495 into the double-layer group. Before matching, the double-layer group had more complex and larger tumors. After matching, 58 patients were included in each group. The single-layer group showed significantly shorter operative times (91min vs. 100min, p = 0.0361), lower estimated blood loss (EBL) (7.9ml vs. 27ml, p = 0.021), and better preservation of eGFR (-1.2% vs. -5.1%, p = 0.0313). Other outcomes, such as perioperative complications and postoperative hospital stay, were not significantly different between the groups. Single-layer renorrhaphy demonstrated better surgical outcomes, including shorter operative time, lower EBL, and better preservation of kidney function, compared to double-layer renorrhaphy. These findings suggest that single-layer reconstruction may optimize RAPN outcomes in selected patients.

#277 Update to the long-term safety and efficacy of iptacopan in C3G: 33-month extension study data from patients enrolled in a phase 2 study

Abstract Background and Aims Complement 3 glomerulopathy (C3G), due to dysregulation of the alternative complement pathway (AP), is an ultra-rare primary glomerulonephritis. Iptacopan (LNP023) is an oral, proximal complement inhibitor that specifically binds factor B and inhibits the AP. We previously reported the primary endpoint data from the Phase (Ph) 2 extension study (NCT03955445), showing proteinuria reduction (57% [p &amp;lt; 0.0001]) and estimated glomerular filtration rate (eGFR) improvement (by +6.83 mL/min/1.73 m2 [p = 0.0174]) from baseline, following 12 months (M) of treatment with iptacopan in patients with C3G. Here we present further long-term efficacy and safety data from patients with C3G and recurrent C3G (post-kidney transplantation), who completed 33M of treatment with iptacopan (NCT03955445). Method Adults with C3G disease (Cohort A) or C3G recurrence post-transplantation (Cohort B) received iptacopan 200 mg twice-daily (bid) for at least 12 weeks in the Ph2 study (NCT03832114) before entering the open label extension study (NCT03955445). Long-term efficacy was assessed by a number of renal endpoints, including a 2-component composite renal endpoint (eGFR stability [≤10% reduction] and ≥50% proteinuria reduction). Long-term safety and tolerability of iptacopan was continually monitored. Results Of 27 patients completing the Ph2 study (NCT03832114), 26 (16 Cohort A, 10 Cohort B) entered the extension study treatment with iptacopan 200 mg bid; 22 patients (14 Cohort A, 8 Cohort B) completed the 33M visit (i.e., 3M in the Ph2 study and 30M in the extension study). In Cohort A, 42.9% of patients met the 2-component composite renal endpoint criteria at 33M. Proteinuria (first morning void [FMV] urine protein–creatinine ratio [UPCR]) was reduced by 41% (p = 0.0097) compared to baseline. eGFR stabilized or improved in most patients (13/16) over time and change from baseline at the 33M time-point was −3.18 mL/min/1.73 m2 (p = 0.3512). C3 levels increased by 275% (p &amp;lt; 0.0001) from baseline. In Cohort B, eGFR change from baseline at the 33M time-point was −6.34 mL/min/1.73 m2 (p = 0.0571), and C3 levels increased by 102%. Baseline proteinuria values (FMV UPCR) were within the normal range for most participants in Cohort B and remained so during iptacopan treatment. Iptacopan was generally well-tolerated, and most adverse events were of mild severity in both cohorts. Biomarkers demonstrated substantial AP inhibition. Conclusion Long-term treatment with iptacopan was associated with sustained reduction in proteinuria in patients with C3G (Cohort A), and preservation of eGFR. These improvements in kidney function were associated with substantial inhibition of the AP leading to normalization of serum C3. Iptacopan was well-tolerated with no new safety findings in the long term, in patients with C3G, including those with recurrence post-transplantation on top of broad triple immunosuppression. The ongoing Ph3 APPEAR-C3G study (NCT04817618) is evaluating the efficacy and safety of iptacopan in patients with C3G.

Predictors of renal function deterioration at one year after off-clamp non-renorrhaphy partial nephrectomy.

Preservation of renal function is an important goal in renal cell carcinoma-related surgery. Although several case-dependent techniques for renal pedicle clamping and hemostasis have been used, their effects on long-term renal function are controversial. The clinical records of 114 patients who underwent off-clamp non-renorrhaphy open partial nephrectomy at our hospital were retrospectively reviewed. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors of eGFR decline 12 months post-surgery and overtime deterioration of renal function were identified using a multivariate regression analysis. The median patient age was 65 years, and the median tumor size was 27 mm. The mean eGFR preservation at 1, 3, and 12 months post-surgery were 90.1%, 89.0%, and 86.9%, respectively. eGFR decline at 1 and 3 months were associated with poor eGFR preservation at 12 months with the odds ratio (95% confidence interval (CI)) of 1.97 and 3.157, respectively. Multivariate regression analyses revealed that tumor size was an independent predictor of eGFR decline at 12 months. Among 65 patients with eGFR preservation over 90% at 1 month post-surgery, eGFR value of 28 patients deteriorated below 90% at 12 months post-surgery compared with preoperative eGFR. Tumor size and eGFR preservation at 1 month were independent predictors of long-term renal function deterioration. Tumor size predicted eGFR decline 12 months post-surgery. Only a mild decline in eGFR was observed between 3 and 12 months after open partial nephrectomy. Tumor size and eGFR preservation at 1 month predicted the deterioration of renal function over time.

Hydronephrosis severity as a predictor of postoperative renal function decline following laparoscopic radical nephroureterectomy.

This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. The median preoperative and postoperative eGFR were 61.1 and 46.4ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.

An open-label study evaluating the safety and efficacy of budesonide in patients with IgA nephropathy at high risk of progression

We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m2 and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI − 53.6 to − 12.2), − 49.7% (95% CI − 70.1 to − 29.4) and − 68.1% (95% CI − 80.6 to − 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI − 4.7 to 20.1), + 7.42% (95% CI − 7.23 to 22.1) and + 4.74% (95%CI − 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI − 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy.

Renin Inhibition and the Long-Term Renal Function in Patients With Hypertensive Emergency: A Retrospective Cohort Study.

The rehospitalization rate in a hypertensive emergency is high, indicating the necessity for optimizing its long-term management. The role of the renin-angiotensin system (RAS) blockade in this disorder remains uncertain. We conducted a retrospective analysis involving 20 admitted patients who received aliskiren, a direct renin inhibitor (DRI), for the management of hypertensive emergency associated with elevated plasma renin activity (PRA). We analyzed the changes in blood pressure (BP), kidney function, and RAS activity in the subacute and chronic phases. The use of DRI was associated with a marked reduction in PRA (median, from 25.0 to 1.2 ng/ml/h) and serum aldosterone levels (from 404 to 130 pg/ml) during the index admission. BP also decreased from 226/143 to 142/80 mm Hg. A comparison of clinical characteristics according to the renal function indicated that dialysis-dependent patients had higher aldosterone levels than non-dialysis-dependent patients at admission, despite comparable BP levels. After a median follow-up of 567 days in non-dialysis-dependent patients with DRI, eGFR levels were significantly increased from 14.3 to 23.1 ml/min/1.73 m2. PRA levels were consistently suppressed at 0.8 ng/ml/h. We found a significant correlation between the degree of PRA suppression and changes in eGFR (r = -0.58), indicating that the effective blockade of RAS is associated with the preservation of eGFR in the study subjects. DRI can successfully suppress PRA in patients with high-renin hypertensive emergency in both subacute and chronic phases. An efficient RAS blockade is associated with preserved renal function in these patients.

SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study

Aims/hypothesisInsulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium–glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes.MethodsWe performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy.ResultsWe identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA1c (−2.6 mmol/mol [−0.2%] with SGLT2i and −5.4 mmol/mol [−0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m2 vs −7.2 ml/min per 1.73 m2, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort.Conclusions/interpretationBoth SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.Graphical

One-year reductions in cisplatin-related chronic kidney disease (CKD) in patients with head and neck (HNC) cancer treated with avasopasem manganese: A prespecified analysis from the phase 3 ROMAN trial.

6066 Background: Cisplatin-induced acute kidney injury (AKI), acute kidney disease (AKD), and chronic kidney disease (CKD) are associated with increased production of reactive oxygen species, notably superoxide, in conjunction with alterations in mitochondrial electron transport chain complex activities in tubular epithelial cells (Mapuskar et al. Antioxidants 2021;10:1329). These pathologies can be targeted and thereby inhibited by increasing superoxide dismutase activity, which converts superoxide to hydrogen peroxide. The investigational new drug avasopasem manganese (AVA), a selective dismutase mimetic, ameliorated cisplatin-induced kidney injury in mice (Mapuskar et al. Redox Biol 2019;20:98). Preclinical results also demonstrate that AVA does not interfere with cisplatin anticancer activity (Mohanty et al. Cancer Res 2018;78[13_suppl]:Abstract 2929). Consistent with this, a retrospective analysis of 1- and 2-year kidney function of a limited subset of patients treated in a randomized, placebo (PBO)-controlled phase 2b trial of AVA to reduce severe oral mucositis (SOM) from radiotherapy and cisplatin (CRT) suggested that AVA prevented or reduced cisplatin-related CKD compared to PBO (Steinbach et al. J Clin Oncol 2020;38[15_suppl]:Abstract 12071). Methods: The ROMAN phase 3 trial (NCT03689712; ITT n = 407) of CRT in combination with AVA or PBO demonstrated improved incidence, duration, and onset of SOM by AVA (n = 241) vs PBO (n = 166) (Anderson et al. J Clin Oncol 2022;40[16_suppl]:Abstract 6005). In ROMAN, prospectively defined follow-up of serum creatinine (sCr) and estimated glomerular filtration rates (eGFR) were assessed every 3 months for 1 year following 7 weeks of CRT. Results: At 1-year follow-up, AVA was associated with significant improvements in preservation of eGFR ( P= 0.0008) and sCr ( P= 0.006) levels vs PBO. Grade 3+ CKD (eGFR &lt; 60 mL/min) results through 12 months show 10% AVA vs 20% PBO (relative risk 0.55, P= 0.0043). Regarding cisplatin schedule, patients receiving Q3W therapy show grade 3+ CKD of 12% AVA vs 22% PBO; patients receiving QW therapy show AVA 9% vs PBO 19%. During treatment, nominal reduction of the incidence of AKI adverse events (0.8% AVA vs 3.6% PBO) was also observed. Conclusions: At 1-year follow-up, AVA appears to reduce cisplatin-related CKD in the study population and may also reduce cisplatin-related AKI during treatment. These results carry significance beyond CRT for HNC, potentially impacting platinum-containing regimens in other cancers. Clinical trial information: NCT03689712 .

Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy

The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m2 difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN study.

Effects of empagliflozin in patients with heart failure and preserved ejection fraction according to baseline diuretic use: results from the EMPEROR-Preserved trial

Abstract Background In the EMPEROR-Preserved trial, empagliflozin reduced the risk of hospitalizations for heart failure (HHF) or cardiovascular (CV) death in patients with heart failure and preserved ejection fraction (HFpEF). Almost one in five patients in the trial were not on baseline diuretic therapy. Purpose To evaluate the efficacy and safety of empagliflozin according to baseline diuretic treatment, as well as change in diuretic therapy after initiation of empagliflozin. Methods Patients were categorized into subgroups as no diuretic and furosemide-equivalent diuretic dose of &amp;lt;40, 40 and &amp;gt;40mg and were compared for first HHF or CV death, HHF, CV death, total HHF, change in eGFR slope, and change in Kansas City Cardiomyopathy Questionnaire – Clinical Summary Scores (KCCQ-CSS) between patients on empagliflozin vs. placebo. Changes in diuretic therapy in the two treatment groups were also compared. Results Amongst 5815 patients with data on diuretic dose, 1179 (20%) were on no diuretic, 2039 (35%) were on &amp;lt;40mg, 1700 (29%) were on 40mg, and 897 (15%) were on &amp;gt;40mg at baseline. Patients on higher diuretic doses at baseline were more likely to be diabetic, had a higher body weight and NT-proBNP, and lower estimated glomerular filtration rate (eGFR) on average. Patients on higher diuretic doses also had worse health status based on NYHA class and KCCQ-CSS estimates. The reduction of the risk of CVD or HHF, total HHF, preservation of eGFR, and KCCQ-CSS improvement with empagliflozin were consistent across all doses of diuretics (Table 1). The findings for all outcomes were consistent in patients on diuretics (any dose) vs. not on diuretics. Treatment with empagliflozin was associated with decreased rates of initiation (HR: 0.73 [0.59,0.90; p=0.004) or intensification (HR: 0.74; [0.65, 0.84]; p&amp;lt;0.001) of diuretics, while there were increased rates in permanent discontinuation of diuretics (HR: 1.46 [1.17, 1.82]; p&amp;lt;0.001) or diuretic dose reduction (HR: 1.22 [1.06, 1.42]; p=0.007). The incidence of adverse events were similar between treatment arms, irrespective of baseline use of diuretics. Volume depletion events were more common with empagliflozin amongst patients treated with diuretics (7.4 vs 5.7 events per 100 patient-years for empagliflozin vs placebo). Conclusion Empagliflozin improved clinical outcomes and health status in patients with HFpEF irrespective of baseline use of diuretics. Additionally, empagliflozin was associated with increased de-escalation or discontinuation of diuretics and decreased chances of initiation or intensification. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim &amp; Eli Lilly and Company Diabetes Alliance

Predictive factors for postoperative renal function after off-clamp, non-renorrhaphy partial nephrectomy.

BackgroundThere is limited information on perioperative renal function during off-clamp, non-renorrhaphy open partial nephrectomy. Therefore, this retrospective study aimed to identify predictive factors of perioperative decline in renal function after off-clamp, non-renorrhaphy open partial nephrectomy.MethodsClinical records of 138 patients with renal tumors who underwent off-clamp, non-renorrhaphy open partial nephrectomy at our institution were reviewed. Off-clamp, non-renorrhaphy partial nephrectomy was performed using a soft coagulation system. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors were identified using multivariate regression analysis at 5 days, 1 month, and 3 months after surgery.ResultsThe median operation time was 122 minutes, and the median volume of estimated blood loss was 155 mL. The mean eGFR preservation at 5 days, 1 month, and 3 months after surgery was 95.3%, 91.0%, and 90.7%, respectively. Estimated blood loss was an independent predictor of perioperative decline in eGFR 5 days after surgery [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.96, 0.98; P<0.001]. Preoperative eGFR and estimated blood loss were independent predictors of perioperative decline in eGFR 1 month after surgery (OR: 0.86; 95% CI: 0.77, 0.95; P=0.007 and OR: 0.98; 95% CI: 0.97, 0.99; P<0.001, respectively). Age, preoperative eGFR, and estimated blood loss were independent predictors of perioperative decline in eGFR 3 months after surgery (OR: 0.64; 95% CI: 0.54, 0.81; P<0.001, OR: 0.72; 95% CI: 0.61, 0.85; P<0.001; and OR: 0.98; 95% CI: 0.97, 0.99; P=0.004, respectively).ConclusionsEstimated blood loss during surgery was a predictor of perioperative decline in eGFR within 3 months after off-clamp, non-renorrhaphy open partial nephrectomy. Age was a predictor of perioperative decline in eGFR 3 months after surgery.

Partial Nephrectomy Versus Radical Nephrectomy for Endophytic Renal Tumors: Comparison of Operative, Functional, and Oncological Outcomes by Propensity Score Matching Analysis

PurposeThe study aimed to compare operative, functional, and oncological outcomes between partial nephrectomy (PN) and radical nephrectomy (RN) for entophytic renal tumors (ERTs) by propensity score matching (PSM) analysis.MethodsA total of 228 patients with ERTs who underwent PN or RN between August 2014 and December 2021 were assessed. A PSM in a 1:1 ratio was conducted to balance the differences between groups. Perioperative characteristics, renal functional, and oncological outcomes were compared between groups. Univariate and multivariate logistic and Cox proportional hazard regression analyses were used to determine the predictors of functional and survival outcomes.ResultsAfter PSM, 136 cases were matched to the PN group (n = 68) and the RN group (n = 68). Patients who underwent RN had shorter OT, less EBL, and lower high-grade complications (all p <0.05) relative to those who underwent PN. However, better perseveration of renal function was observed in the PN group, which was reflected in 48-h postoperative AKI (44.1% vs. 70.6%, p = 0.002), 1-year postoperative 90% eGFR preservation (45.6% vs. 22.1%, p = 0.004), and new-onset CKD Stage ≥III at last follow-up (2.9% vs. 29.4%, p <0.001). RN was the independent factor of short-term (OR, 2.812; 95% CI, 1.369–5.778; p = 0.005) and long-term renal function decline (OR, 10.242; 95% CI, 2.175–48.240; p = 0.003). Furthermore, PN resulted in a better OS and similar PFS and CSS as compared to RN (p = 0.042, 0.15, and 0.21, respectively). RN (OR, 7.361; 95% CI, 1.143–47.423; p = 0.036) and pT3 stage (OR, 4.241; 95% CI, 1.079–16.664; p = 0.039) were independent predictors of overall mortality.ConclusionAmong patients with ERTs, although the PN group showed a higher incidence of high-grade complications than RN, when technically feasible and with experienced surgeons, PN is recommended for better preservation of renal function, longer OS, and similar oncological outcomes.

Clinical Benefits of Indocyanine Green Fluorescence in Robot-Assisted Partial Nephrectomy.

Simple SummaryIndocyanine green (ICG) administration in robot-assisted partial nephrectomy (RAPN) can minimize warm ischemia time and preserve more parenchyma resulting in exceptional preservation of renal function and reduced incidence of postoperative complications. However, previous studies have seldom compared how ICG-RAPN use differs when used to treat benign versus malignant renal tumors because the baseline patient and tumor characteristics as well as treatment goals are completely different. The aim of our retrospective study was to compare the intraoperative and postoperative outcomes and the differences in the results of ICG administration between patients with benign and malignant tumors. We have demonstrated that ICG-RAPN yielded superior preservation of short-term renal function. Of the patients with malignant renal tumors, it had less operative blood loss without a more positive margin rate than standard RAPN.Background: To compare the intraoperative and postoperative outcomes of indocyanine green (ICG) administration in robot-assisted partial nephrectomy (RAPN) and report the differences in the results between patients with benign and malignant renal tumors. Methods: From 2017 to 2020, 132 patients underwent RAPN at our institution, including 21 patients with ICG administration. Clinical data obtained from our institution’s RAPN database were retrospectively reviewed. Intraoperative, postoperative, pathological, and functional outcomes of RAPN were assessed. Results: The pathological results indicated that among the 127 patients, 38 and 89 had received diagnoses of benign and malignant tumors, respectively. A longer operative time (311 vs. 271 min; p = 0.006) but superior preservation of estimated glomerular filtration rate (eGFR) at 3-month follow-up (90% vs. 85%; p = 0.031) were observed in the ICG-RAPN group. Less estimated blood loss, shorter warm ischemia time, and superior preservation of eGFR at postoperative day 1 and 6-month follow-up were also noted, despite no significant differences. Among the patients with malignant tumors, less estimated blood loss (30 vs. 100 mL; p < 0.001) was reported in the ICG-RAPN subgroup. Conclusions: Patients with ICG-RAPN exhibited superior short-term renal function outcomes compared with the standard RAPN group. Of the patients with malignant tumors, ICG-RAPN was associated with less blood loss than standard RAPN without a more positive margin rate. Further studies with larger cohorts and prospective designs are necessary to verify the intraoperative and functional advantages of the green dye.

Preservation of Split Renal Function After Laparoscopic and Robot-assisted Partial Nephrectomy.

To analyze the effects of laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) for the treatment of renal cell carcinoma (RCC) on subsequent split renal function using renal scintigraphy. We retrospectively analyzed data from 174 patients who underwent LPN or RAPN by a single surgeon, and assessed their total and split renal function before and 6 months after each procedure. Split renal function was analyzed using 99mTc-2,3 dimercaptosuccinic acid renal imaging and calculated as the total estimated glomerular filtration rate (eGFR) × uptake ratio on the surgical side/uptake ratio on the contralateral side. LPN or RAPN were performed in 51 (29.3%) and 123 (70.7%) participants, respectively. Their median eGFRs before and after surgery were 32.76 and 27.74 ml/min/1.73 m2, respectively, and 70 of them (40.2%) showed a preservation of split eGFR of >90%, which was used to define a successful procedure. Participants who underwent a successful procedure had significantly lower RENAL nephrometry scoring system (RNS) scores and fewer of them had external tumors. Successful procedures were associated with shorter warm ischemia time, were more likely to be RAPN, and less likely to involve parenchymal suturing. Multivariate analysis showed that a low RNS score and parenchymal suturing were significant independent predictors of split renal function following partial nephrectomy (PN). Preoperative RNS score and the use of parenchymal suturing are significantly associated with a preservation of split renal function of >90% in patients who undergo PN for the treatment of RCC.