Predictor Of Renal Function Decline Research Articles

Risk Prediction Models for Renal Function Decline After Cardiac Surgery Within Different Preoperative Glomerular Filtration Rate Strata.

Our goal was to create a simple risk-prediction model for renal function decline after cardiac surgery to help focus renal follow-up efforts on patients most likely to benefit. This single-center retrospective cohort study enrolled 24 904 patients who underwent cardiac surgery from 2012 to 2019 at Fuwai Hospital, Beijing, China. An estimated glomerular filtration rate (eGFR) reduction of ≥30% 3 months after surgery was considered evidence of renal function decline. Relative to patients with eGFR 60 to 89 mL/min per 1.73 m2 (4.5% [531/11733]), those with eGFR ≥90 mL/min per 1.73 m2 (10.9% [1200/11042]) had a higher risk of renal function decline, whereas those with eGFR ≤59 mL/min per 1.73 m2 (5.8% [124/2129]) did not. Each eGFR stratum had a different strongest contributor to renal function decline: increased baseline eGFR levels for patients with eGFR ≥90 mL/min per 1.73 m2, transfusion of any blood type for patients with eGFR 60 to 89 mL/min per 1.73 m2, and no recovery of renal function at discharge for patients with eGFR ≤59 mL/min per 1.73 m2. Different nomograms were established for the different eGFR strata, which yielded a corrected C-index value of 0.752 for eGFR ≥90 mL/min per 1.73 m2, 0.725 for eGFR 60-89 mL/min per 1.73 m2 and 0.791 for eGFR ≤59 mL/min per 1.73 m2. Predictors of renal function decline over the follow-up showed marked differences across the eGFR strata. The nomograms incorporated a small number of variables that are readily available in the routine cardiac surgical setting and can be used to predict renal function decline in patients stratified by baseline eGFR.

Morphologic and Molecular Features of Antibody-Mediated Transplant Rejection: Pivotal Role of Molecular Injury as an Independent Predictor of Renal Allograft Functional Decline.

Current knowledge about the factors correlating with functional decline and subsequent failure of kidney allografts in antibody-mediated rejection (ABMR) is limited. We conducted a cohort study involving 75 renal allograft recipients diagnosed with late ABMR occurring at least 6months after transplantation. The study aimed to examine the correlation of molecular and histologic features with estimated glomerular filtration rate (eGFR) trajectories and death-censored graft survival. We focused on sum scores reflecting histologic ABMR activity versus chronicity and molecular scores of ABMR probability (ABMRProb), injury-repair response (IRRAT) and fibrosis (ciprob). In multivariable Cox analysis, a Banff lesion-based chronicity index (ci+ct+cg[x2]; hazard ratio per interquartile range [IQR]: 1.97 [95% confidence interval: 0.97 to 3.99]) and IRRAT (1.93 [0.96 to 3.89]) showed the strongest associations with graft failure. Among biopsy variables, IRRAT exhibited the highest relative variable importance and emerged as the sole independent predictor of eGFR slope (change per IQR: -4.2 [-7.8 to -0.6] mL/min/1.73m2/year). In contrast, morphologic chronicity associated with baseline eGFR only. We conclude that the extent of molecular injury is a robust predictor of renal function decline. Transcriptome analysis has the potential to improve outcome prediction and possibly identify modifiable injury, guiding targeted therapeutic interventions.

PRIMARY ALDOSTERONISM: THE EFFECT OF SPECIFIC TREATMENT ON RENAL FUNCTION

Objective: The aim of the study was to evaluate the changes in eGFR in patients with idiopathic primary aldosteronism (IHA) and with aldosterone-secreting adenoma (APA) after specific therapy. Design and method: From January 2018 to March 2022, we consecutively enrolled 99 patients with PA distinguishing 75 with IHA (mean age 53.41±11.97 years) and 24 with PA (average age 48.79±8.96 years). We evaluated anthropometric, biochemicals and hemodynamic parameters at diagnosis and 12 months after pharmacological or surgical therapy. Results: Patients with IHA, pharmacologically treated with mineralocorticoid receptor antagonists (MRAs), showed a higher incidence of chronic renal failure and a faster progression of renal damage than in patients with APA who underwent unilateral adrenalectomy. The reduction of eGFR was significantly greater in patients with IHA than in APA (92.03±17.58 vs 86.63±18.89 mL/min/1.73m2, p <0.001). Systolic blood pressure (SBP) levels and increased aldosterone-to-renin ratio were found to be independent predictors of renal function decline (ß = 0.034; p = 0.045 and ß = 0.248; p = 0.032, respectively). Conclusions: Our results show that patients with PA undergoing surgical treatment have a better renal outcome than those receiving drug therapy. An early diagnosis of APA would allow intervention before renal damage occurs.

Abstract 13448: Time Course and Predictors of Renal Function Decline After Pediatric Heart Transplantation: A PHTS Multi-Institutional Analysis

Introduction: Decline in renal function can impact both the management and outcomes of pediatric heart transplantation (HTx). Initial renal function decline may be subclinical and underappreciated. We sought to identify the time course and predictors of decline in renal function and the impact of these changes on HTx outcomes. Methods: The Pediatric Heart Transplant Society (PHTS) database was queried to identify HTx recipients at participating centers from 1996 to 2019 with at least 1 year of follow-up. Patients with simultaneous or previous kidney transplant were excluded. Renal function was measured by modified Schwartz formula eGFR on annual follow-up forms and stratified into eGFR groups by National Kidney Foundation chronic kidney disease staging guidelines. “Initial renal function decline” was defined as the initial drop by at least one eGFR group relative to stage at 1 year post transplant (“baseline”). Results: Of the 5,250 patients who met inclusion criteria, initial renal function decline occurred, relative to baseline, in 7.4%, 18.7%, and 55.7%, by 1, 5, and 10 years of follow up, respectively (Figure A). eGFR group distribution for the cohort progressively worsened over the follow up period (Figure B). On multivariate Cox modeling, risk factors for renal function decline were increased BSA at 1 year post-transplant (HR 1.24 [1.02, 1.52]), acute rejection with hemodynamic compromise (HR 1.24 [1.10, 1.39]), and Black race (HR 1.21 [1.08, 1.36]) with the use of tacrolimus (vs cyclosporine) being protective (HR 0.77 [0.69, 0.85]). Patients whose eGFR was < 30 mL/min at 1 year follow up had an increased risk of graft loss (P < 0.0001 compared to all other groups). Conclusions: Decline in renal function occurs progressively, affecting over 50% of HTx recipients in long term follow up, independent of renal condition at the time of HTx. Avoidance of potentially nephrotoxic events and medications must be considered at all times in the long term management of pediatric HTx.

Changes in renal function after nephroureterectomy for upper urinary tract carcinoma: analysis of a large multicenter cohort (Radical Nephroureterectomy Outcomes (RaNeO) Research Consortium)

PurposeTo investigate prevalence and predictors of renal function variation in a multicenter cohort treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).MethodsPatients from 17 tertiary centers were included. Renal function variation was evaluated at postoperative day (POD)—1, 6 and 12 months. Timepoints differences were Δ1 = POD-1 eGFR − baseline eGFR; Δ2 = 6 months eGFR − POD-1 eGFR; Δ3 = 12 months eGFR − 6 months eGFR. We defined POD-1 acute kidney injury (AKI) as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5 1.9-fold from baseline. Additionally, a cutoff of 60 ml/min in eGFR was considered to define renal function decline at 6 and 12 months. Logistic regression (LR) and linear mixed (LM) models were used to evaluate the association between clinical factors and eGFR decline and their interaction with follow-up.ResultsA total of 576 were included, of these 409(71.0%) and 403(70.0%) had an eGFR < 60 ml/min at 6 and 12 months, respectively, and 239(41.5%) developed POD-1 AKI. In multivariable LR analysis, age (Odds Ratio, OR 1.05, p < 0.001), male gender (OR 0.44, p = 0.003), POD-1 AKI (OR 2.88, p < 0.001) and preoperative eGFR < 60 ml/min (OR 7.58, p < 0.001) were predictors of renal function decline at 6 months. Age (OR 1.06, p < 0.001), coronary artery disease (OR 2.68, p = 0.007), POD-1 AKI (OR 1.83, p = 0.02), and preoperative eGFR < 60 ml/min (OR 7.80, p < 0.001) were predictors of renal function decline at 12 months. In LM models, age (p = 0.019), hydronephrosis (p < 0.001), POD-1 AKI (p < 0.001) and pT-stage (p = 0.001) influenced renal function variation (ß 9.2 ± 0.7, p < 0.001) during follow-up.ConclusionAge, preoperative eGFR and POD-1 AKI are independent predictors of 6 and 12 months renal function decline after RNU for UTUC.

MO457: Diffusion-MRI Predicts Decline of Renal Function in Chronic Kidney Diseases and Kidney Allograft Patients

Abstract BACKGROUND AND AIMS Kidney cortical interstitial fibrosis is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion-weighted magnetic resonance imaging is a promising non-invasive tool to evaluate kidney fibrosis. We recently adapted a diffusion-weighted imaging sequence, allowing for the discrimination between the kidney cortex and medulla. The cortico-medullary difference in apparent diffusion coefficient (ΔADC) correlated to histological interstitial fibrosis. The aim of this study was to assess whether ΔADC as measured with diffusion-weighted magnetic resonance imaging is predictive of renal function decline and dialysis in chronic kidney diseases (CKD) and kidney allograft patients. METHOD We performed a prospective study including 197 patients. We measured ΔADC in 43 CKD patients [estimated glomerular filtration rate (eGFR) 55 mL/min/1.73m2] and 154 kidney allograft patients (eGFR 53 ml/min/1.73m2). Patients underwent a renal biopsy and diffusion-weighted magnetic resonance imaging, within 1 week of biopsy. Follow-up was 2.2 years in median. During follow-up, laboratory parameters were measured. Primary outcome was defined as rapid decline of renal function (eGFR decline &amp;gt; 30% or dialysis initiation) during follow-up. RESULTS Patients with low ΔADC (&amp;lt;0 x10-6mm2/s) had 5.4 times more risk of rapid decline of renal function or dialysis [95% confidence interval (CI): 2.29–12.58; P &amp;lt; 0.001]. After correction for renal function at baseline and proteinuria, low ADC still predict renal function loss with a hazard ratio (HR) of 4.62 (P &amp;lt; 0.001, 95% CI 1.56–13.67). CONCLUSION We demonstrate in this study that low ΔADC is a predictor of renal function decline and dialysis initiation in CKD and kidney allograft patients, independent of baseline renal function and proteinuria.

Urinary mRNA Signatures as Predictors of Renal Function Decline in Patients With Biopsy-Proven Diabetic Kidney Disease.

The clinical manifestations of diabetic kidney disease (DKD) are more heterogeneous than those previously reported, and these observations mandate the need for the recruitment of patients with biopsy-proven DKD in biomarker research. In this study, using the public gene expression omnibus (GEO) repository, we aimed to identify urinary mRNA biomarkers that can predict histological severity and disease progression in patients with DKD in whom the diagnosis and histologic grade has been confirmed by kidney biopsy. We identified 30 DKD-specific mRNA candidates based on the analysis of the GEO datasets. Among these, there were significant alterations in the urinary levels of 17 mRNAs in patients with DKD, compared with healthy controls. Four urinary mRNAs—LYZ, C3, FKBP5, and G6PC—reflected tubulointerstitial inflammation and fibrosis in kidney biopsy and could predict rapid progression to end-stage kidney disease independently of the baseline eGFR (tertile 1 vs. tertile 3; adjusted hazard ratio of 9.68 and 95% confidence interval of 2.85–32.87, p < 0.001). In conclusion, we demonstrated that urinary mRNA signatures have a potential to indicate the pathologic status and predict adverse renal outcomes in patients with DKD.

Predictors of Decline in Renal Function 5 Years after EVAR.

While there exists copious short-term data regarding renal function following infra-renal endovascular abdominal aortic aneurysm repair (EVAR), long-term analysis is sparse. This is a single institution retrospective review of predictors of renal function decline 5 years after elective EVAR. All EVAR between 2007 and 2015 were queried. Patients in whom renal function was documented 5 years postoperatively were included in analysis. Exclusion criteria were ruptured aneurysm, mortality before 56 months, lack of follow-up, ESRD status, and concomitant renal intervention. The primary outcome investigated was a 20% or greater drop in glomerular filtration rate (GFR) 5 years postoperatively. The following variables at the time of surgery were investigated as potential predictors: age, gender, hypertension, hyperlipidemia, diabetes, CAD or prior MI, COPD, prior stroke, baseline eGFR under 60mL/min/1.73m2, supra-renal fixation, infra-renal fixation, neck diameter, neck length, and number of contrast CT. 354 EVAR were identified of which 143 met inclusion criteria (211 excluded). Univariate analysis revealed female gender (OR 2.7), hypertension (OR 9.4), baseline renal insufficiency (OR 3.8), larger neck diameter, and supra-renal fixation (OR 2.32) all predictive (P < .05) of GFR drop at 5 years. Multivariate binary logistic regression analysis found female gender (multivariate OR 3.9, P = .023) and baseline renal insufficiency (multivariate OR 3.0, P = .029) as significant predictors of greater than 20% GFR drop at 5 years. Only 2 patients of the 143 progressed to dialysis requirement at 5 years. Females and patients with baseline renal insufficiency are more vulnerable to significant decline in renal function 5 years following EVAR. Consistent with analogous literature, supra-renal fixation appears moderately deleterious toward renal function with no clinical significance in those with baseline normal renal function. The potential benefit of avoidance of supra-renal fixation in female patients with baseline renal insufficiency is worth further investigation in a more robust multi-center study.

797-P: Predictive Factors of Renal Function Decline in Patients with Type 2 Diabetes Treated with Canagliflozin in the Real-WECAN Study

The Real-WECAN study assessed in a real-world setting the efectiveness and safety of canagliflozin 100 mg (add-on therapy in SGLT-2i naive individuals) and canagliflozin 300 mg (switching from canagliflozin 100 mg or other SGLT-2i) in patients with T2DM. The aim of this analysis is to determine baseline predictors of renal function decline over the follow-up. A multiple linear regression analysis estimated the best predictive model of eGFR reduction using the Mallows criterion. 583 patients were included, mean age 60.4 years, A1C 7.76%, BMI 34.7 kg/m2, eGFR 85.6 ml/min, eGFR 30 mg/g 22.8%, median follow-up 13 months. There was a modest mean decrease in eGFR (-1.9 ml/min, p In summary, in the Real-WECAN study, patients with older age, combined hyperlipidemia, heart failure, higher baseline eGFR and macroalbuminuria showed greater reductions in eGFR after canagliflozin therapy. Disclosure J. J. Gorgojo-martinez: Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; Abbott, AstraZeneca, Lilly Diabetes, Mundipharma International, Novartis Pharmaceuticals Corporation, Novo Nordisk. J. E. M. Wong-cruz: None. M. Brito: Advisory Panel; Self; MSD Corporation, Novo Nordisk, Sanofi, Speaker’s Bureau; Self; Abbott Diabetes, Almirall, S. A., Amgen Inc., AstraZeneca, Eli Lilly and Company, Esteve, MSD Corporation, Mundipharma International, Novo Nordisk, Sanofi-Aventis. T. Anton-bravo: None. A. Galdon-sanzpastor: Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novo Nordisk Inc., Sanofi. M. A. Gargallo-fernandez: None.

MO073HISTOLOGICAL PREDICTORS OF PROTEINURIA AND RENAL OUTCOMES IN PRIMARY MEMBRANOUS NEPHROPATHY: IS INTERSTITIAL FIBROSIS THE MAIN CHARACTER?

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in older white adults, with an incidence of 12 cases per millions of people per year. Primary MN (PMN, 75%-80% of MNs) is an organ-specific autoimmune disease caused by antibodies anti-PLA2R and anti-THSD7A. Regardless of treatment one third of patients progresses to end-stage renal disease and two third develop non-progressive chronic kidney disease. Renal biopsy is the gold standard for MN diagnosis. Several clinical and biochemical markers have been associated with the risk of progressive loss of kidney function while contrasting results have been obtained by the few studies which have examined the prognostic value of histologic findings. In this study the clinical outcome of patients with PMN has been considered based on the prognostic value of histological findings. Method Forty-nine patients with PMN of our Nephrology Unit at Padova University Hospital from 2003 to 2018 were considered. 16 patients were excluded from the study due to missing data. Age, comorbidities, proteinuria (g/day) and renal function (eGFR, CKD-EPI) were collected. eGFR decline and decrease of proteinuria were used as clinical outcomes. The follow-up was considered from renal biopsy to the last visit (in absence of GFR decline or decrease in proteinuria). Histological grading (0-3) was assigned to parameters (glomerulosclerosis (GS), tubular atrophy (TA), interstitial fibrosis (IF), vascular hyalinosis (VH)) and were evaluated separately or in combination (as GSTIV score). Morphometric analysis was used to quantify IF and expressed in percentage as the mean of area covered by pixel. Statistical analysis was performed using Fisher’s exact test and Mann-Whitney U-test where appropriate. Cox regression analyses (univariate and multivariate) were performed to identify variables associated with both renal outcomes and p&amp;lt;0.05 was considered as significant. ROC curves were used to determine interstitial fibrosis cut-off values predictive for both outcomes. Area under the curve (AUC) between 0.8 and 1.0 was considered as significant. Diagnostic accuracy was assessed by Specificity (Sp), Sensibility (Se), positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR-) likelihood ratios. Results Patients with no decrease of proteinuria had a greater degree of IF vs those with a full response (p=0.006). Univariate Cox analyses identified age ≥65 years (HR 4.92), pre-existing CKD (HR 12.98) and IF (HR3.05) as significant predictors of renal function decline in all patients. Multivariate Cox analysis confirmed these variables (age ≥65 years HR 3.05, CKD HR 6.35, IF HR 3.03). In patients without CKD only IF was significantly associated with eGFR decline in both Cox univariate and multivariate analysis (HR 4.34 and 5.05 respectively). ROC analysis showed that IF threshold of 17.80% identified patients with eGFR reduction (AUC 0.65, Se 0.50, Sp 0.79, PPV 0.75, NPV 0.45, LR+ 2.38, LR-0.63) and IF threshold of 18.04% the lack of proteinuria reduction (AUC 0.78, Se 0.70, Sp 0.83, PPV 0.67, NPV 0.80, LR+ 4.12, LR- 0.36). Conclusion Our study shows that IF could be used as a histologic predictor of renal and proteinuria outcomes. Biopsy report should therefore also include quantitative IF data that could be helpful for the choice of a more appropriate therapeutic approach.

Blood pressure monitoring in kidney transplantation: a systematic review on hypertension and target organ damage.

Sparse studies show that ambulatory blood pressure monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population. Major medical databases were searched for studies enrolling adult KTRs undergoing 24h ABPM compared to office or home BP measurements. Main outcomes were: associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed. Twenty-two studies (2078 participants) were reviewed. Amongst 12 studies collecting data on renal endpoints, ten studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine (SCr) and/or creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR), than traditional office measurements. Twelve studies analyzed the relation between different BP recordings and CV target organ damages and reported robust correlations between echocardiographic abnormalities [i.e. left ventricular mass index (LVM/LVMI)] and 24h ABPM, but not with office BPs. Furthermore, 24h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness (IMT), diffuse thickening, and endothelial dysfunction. Additionally, abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities. In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, altered circadian BP profile associated with renal and CV target organ damages.

Acute kidney injury strongly influences renal function after radical nephroureterectomy for upper tract urothelial carcinoma: A single-centre experience

The aim of our study was to investigate frequency and predictors both of postoperative acute kidney injury (AKI) and renal function decline in a population of consecutive upper tract urothelial carcinoma (UTUC) patients who underwent radical nephroureterectomy (RNU). Between October 2014 and February 2020, 93 patients underwent RNU at our Institution. After considered exclusion criteria, 89 patients were selected. Perioperative clinical factors were retrospectively collected. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation. We defined AKI as an increase in serum creatinine by ≥ 0.3 mg/dl or a 1.5-1.9-fold increase in serum creatinine from baseline to I post-operative day (POD). A significant renal function reduction was defined as an eGFR reduction of 40% from baseline at discharge and at last clinical evaluation. Frequency of AKI and eGFR decline was investigated. Association between perioperative clinical factors and AKI and eGFR reduction at discharged and last follow-up was studied using univariate and multivariate models. AKI was detected at I POD in 45 patients. On multivariate analysis, pre-operative eGFR was an independent predictor of AKI (OR 1.03; p = 0.042). Further, AKI was found to be a significant predictor of eGFR reduction ≥ 40% at discharge at univariate analysis (OR 19.42; p = 0.005) and at multivariate analysis (OR 12.49; p = 0.02). In a multivariate logistic regression model post-operative AKI (OR 5.18; p = 0.033), lack of ipsilateral preoperative hydronephrosis (OR 0.17; p = 0.016), preoperative eGFR (OR 1.04; p = 0.047) and antiplatelet therapy (OR 5.14; p = 0.018) were found to be independent predictors of an eGFR reduction higher than 40% at last clinical evaluation made at a median of 15 (IQR 5-30) months. In our cohort, AKI was present in almost 50% of patients after RNU and it was a strong predictor of renal function decline after RNU.

Plasma Homocysteine Is a Predictive Factor for Accelerated Renal Function Decline and Chronic Kidney Disease in a Community-Dwelling Population

Background: Whether elevated plasma total homocysteine (tHcy) is a risk factor for the progression of kidney disease in general population has not been well established. The purpose of this study was to investigate the prognostic properties of plasma tHcy for renal function decrement and early chronic kidney disease (CKD) in community-dwelling populations with normal renal function at baseline. Methods: A total of 1,426 participants were enrolled and followed for a median of 4.8 years (interquartile range, 4.5–5.2), and estimated glomerular filtration rate (eGFR) was evaluated. One main outcome was the rapid eGFR decline defined as a decline in eGFR of >3 mL/min per 1.73 m² per year; the other was the new incidence of CKD. Results: At the end of follow-up, the incidence of rapid eGFR decline and new-onset CKD was 20.7 and 5.6%, respectively. In multivariate linear regression analysis, age, central pulse pressure, fasting blood glucose, and concentration of tHcy were independent determinants of the change in eGFR. There was a graded association between tHcy quartiles and eGFR decline. Compared with participants with the lowest quartile of tHcy levels, those with the highest quartile had significantly increased risk for rapid eGFR decline (adjusted odds ratio [aOR] = 1.81; 95% confidence interval [CI]: 1.25–2.94) and new onset of CKD (adjusted hazard ratio = 4.29; 95% CI: 1.42–12.99) after adjusting for various confounders. Similarly, significant associations were also found when baseline tHcy was classified as hyperhomocysteinemia (>15 μmol/L) versus normal tHcy level (≤15 μmol/L). However, there was only association between the change in tHcy levels and new occurrence of CKD but not with rapid eGFR decline (aOR = 0.99, p = 0.613). Conclusions: In this prospective cohort of individuals from community-based population, elevated plasma tHcy emerged as an independent predictor of renal function decline and incident CKD, which might support selection of at-risk individuals.

Risk of Renal Function Decline in Patients with Ketamine-Associated Uropathy.

Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-associated uropathy is one of the most common complications. We investigated the effects of ketamine-associated uropathy on renal health and determined predictors of renal function decline in chronic ketamine abusers. This retrospective cohort study analyzed 51 patients (22 with ketamine-associated hydronephrosis and 29 with ketamine cystitis) from Kaohsiung Veterans General Hospital in Taiwan. Primary renal outcome was end-stage renal disease or estimated glomerular filtration rate decline >30% from baseline. Compared with the ketamine cystitis group, the hydronephrosis group had lower initial and final estimated glomerular filtration rates and higher alkaline phosphatase and gamma-glutamyl transferase levels (p < 0.05). Elevated cholestatic liver enzyme levels correlated with renal dysfunction in ketamine-associated uropathy. The hydronephrosis group had a higher proportion of patients reaching endpoints than the ketamine cystitis group (50% and 7%, respectively, p < 0.001). After adjusting for age, sex, and initial serum creatinine level, hydronephrosis remained an independent risk factor for renal function deterioration. Ketamine-associated hydronephrosis was a poor renal outcome and strong predictor of renal function decline in chronic ketamine abusers. Elevated cholestatic liver enzyme levels correlated with the severity of ketamine-associated uropathy. Ultrasonography screening of these high-risk groups and regular renal function follow-ups are necessary.

P0666BRILLOUIN AND RAMAN SPECTROSCOPIES FOR NON-CONTACT ASSESSMENT OF MECHANO-CHEMICAL PROPORTIES OF URINARY PROTEINS: A PROOF OF CONCEPT STUDY

Abstract Background and Aims Proteinuria is a major marker of chronic kidney disease (CKD) severity, the predictor of renal function decline and cardiovascular mortality. The main pathway of CKD progressive is caused by tubular toxicity of filtering proteins, so more, the rapid development of renal failure is expected in those patients who have higher level of proteinuria. However, despite high level of proteinuria, paradoxically, some patients may have slow decline of renal function compared to those patients with lower level of urinary protein excretion. This may possibly due to their different mechanical (visco-elastic) and chemical properties, as well as the proteomics of excreting urinary proteins. Brillouin light scattering (BLS) and surface enhanced Raman scattering (SERS) spectroscopies are non-contact (laser optical-based) techniques providing visco-elastic and chemical property information of probed human biofluids. We aimed to study and compare the visco-elastic and chemical properties of urinary proteins using BLS and SERS spectroscopies in nephrotic patient with high protein excretion and healthy subject. Method Two urine samples from nephrotic patient (proteinuria&amp;gt;3.5 g/24h) and healthy subject (undetectable proteinuria) investigated using BLS and SERS spectroscopies. Brillouin spectroscopy performed using Torus single longitudinal mode laser in conjunction with high contrast JRS Instruments 6-pass tandem Fabry-Perot interferometer coupled with confocal microscope. Using Horiba LabRAM HR Raman microscope with 785 nm laser excitation andx100 microscope objective the SERS spectroscopy was performed on urine samples in contact 60 nm gold nanoparticles placed on gold film. Additionally, reversed-phase liquid chromatography-mass spectrometry (LC-MS) was conducted for profiling of urinary proteins LC-MS data was analysed by Mascot software using the SwissProt protein database. Results We found that elevated protein levels in urine alter the urine fluid elasticity sufficiently to be measurable by BLS spectroscopy, with urine from healthy and proteinuric subjects distinguishable to marked significance, which increases with sample concentration. BLS spectroscopy demonstrated that patients with High Protein Loss, characterized by stiffer urine (i.e. higher Brillouin shift and elastic modulus) and less viscous (i.e. less hypersound attenuation) compared to healthy subject. (Figure 1A). SERS measurements of two urine samples taken from patient with high protein loss in healthy subject (Figure 1B) showed the integrated Raman intensity ratio of 1338 cm-1 and 1002 cm-1 peaks is many times higher for the sample with high protein concentration vs sample with low protein concentration. Urinary protein sequencing and Mascot analysis (Table 1) demonstrated that proteinuric patient had different type of proteins with up to 187k Daltons of molecular weight. Conclusion In this proof of concept study, we demonstrated that laser-optical BLS and SERS techniques combined with LC-MS measurements revealed that human urine fluids of healthy and proteinuric subjects had strong variation in the visco-elastic and chemical properties coupled with various level of protein content.

PD51-08 RADICAL CYSTECTOMY AND ORTHOTOPIC NEOBLADDER IN WOMEN

INTRODUCTION AND OBJECTIVE: Available data regarding long-term survival and functional outcomes after surgery are limited. Herein, we report on the long-term survival and functional outcome, 10 years or more after RC. METHODS: We retrieved all electronic data of the prospectively evaluated women who underwent RC and ONB in our institute between 1995 and 2009. Patients’ demographics including early and late complications were retrieved. Cancer-specific survival and overall survival were assessed. Patients completed ≥10 years of follow-up were evaluated for continence, voiding status and renal function. Renal function was estimated using serum creatinine (Sr.Cr) and eGFR (measured by Modification of Diet in Kidney Disease Equation) and compared to preoperative values using Wilcoxon matched-pair signed-rank test. Significant renal function changes (improvement or deterioration) were considered when > 20% changes in eGFR occurred in comparison to preoperative value. Univariate and multivariate analysis were performed to determine predictors of renal function deterioration. RESULTS: The study included 297 patients with mean± SD age of 51.3±9.1 years. Patients’ demographic criteria were illustrated in table 1. At a median (range) follow up of 78 (0-247) months, CSS and OS were 78.1% and 62%, respectively (Figure 1). Among 184 disease-free living patients, 95 were lost follow-up after 67.5 (12-109) months of follow up. Eighty nine completed more than 10 years (164.5±34.7 months) of follow up. At last follow-up, 80 patients (90%) were totally continent at daytime; 3 of them achieved continence after treatment of chronic urinary retention (CUR) by clean intermittent catheterization (CIC). The remaining 9 patients had total (3) or varying degrees of stress (6) urinary incontinence. Night time continence was achieved in 56 patients (63%); 8 of them were having CUR and cured by CIC and anticholinergics. CUR was noted in 29 (32.6%) patients. Compared to preoperative values, there were statistically significant increase in serum creatinine [0.8 (0.5-1.5) to 1 (0.5-5.3), P<0.001] and decrease in eGFR [84.4 (46-134) to 65.3 (11-125), P< 0.001]. Six (6.7%) and three (3.4%) patients developed grade IV and grade V CKD, respectively. Forty six (51.7%) and 43 (48.3%) patients showed significant decline and static renal function, respectively. In univariate analysis, young patients’ age, higher serum Cr, lower eGFR and DM were the predictors of renal function decline (P<0.05). In multivariate analysis, only DM was the independent predictor of renal function decline [OR (95%CI)= 12.7 (1.15-41.38), p=0.03]. CONCLUSIONS: Ten years after RC and ONB in women, 30% are disease-free and have acceptable continence status. Although a decline in kidney function is noted in 50% of the cases, only 10% develop ESRD. Diabetes mellitus has been proved to be an independent predictor of renal function decline.IDyGZAAAAAElFTkSuQmCC"> Source of Funding: no funding

MP21-20 THE IMPACT OF ISCHEMIA ON CHRONIC KIDNEY DISEASE PROGRESSION AFTER ROBOTIC PARTIAL NEPHRECTOMY IN PATIENTS OVER 75 YEARS OLD: RESULTS OF A MULTI-INSTITUTIONAL COLLABORATIVE SERIES (ROSULA)

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy III (MP21)1 Apr 2020MP21-20 THE IMPACT OF ISCHEMIA ON CHRONIC KIDNEY DISEASE PROGRESSION AFTER ROBOTIC PARTIAL NEPHRECTOMY IN PATIENTS OVER 75 YEARS OLD: RESULTS OF A MULTI-INSTITUTIONAL COLLABORATIVE SERIES (ROSULA) Umberto Anceschi*, Aldo Brassetti, Gabriele Tuderti, Andrea Minervini, Andrea Mari, Antonio Andrea Grasso, Marco Carini, Umberto Capitanio, Alessandro Larcher, Francesco Montorsi, Riccardo Autorino, Alessandro Veccia Richmond, VA, Daniele Amparore, Francesco Porpiglia, Ithar Deerwesh, Daniel Eun, Jennifer Lee, Philadelphia, PA Michele Gallucci, and Giuseppe Simone Umberto Anceschi*Umberto Anceschi* More articles by this author , Aldo BrassettiAldo Brassetti More articles by this author , Gabriele TudertiGabriele Tuderti More articles by this author , Andrea MinerviniAndrea Minervini More articles by this author , Andrea MariAndrea Mari More articles by this author , Antonio Andrea GrassoAntonio Andrea Grasso More articles by this author , Marco CariniMarco Carini More articles by this author , Umberto CapitanioUmberto Capitanio More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Riccardo AutorinoRiccardo Autorino More articles by this author , Alessandro Veccia Richmond, VAAlessandro Veccia Richmond, VA More articles by this author , Daniele AmparoreDaniele Amparore More articles by this author , Francesco PorpigliaFrancesco Porpiglia More articles by this author , Ithar DeerweshIthar Deerwesh More articles by this author , Daniel EunDaniel Eun More articles by this author , Jennifer Lee, PhiladelphiaJennifer Lee, Philadelphia More articles by this author , Michele GallucciMichele Gallucci More articles by this author , and Giuseppe SimoneGiuseppe Simone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000854.020AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial nephrectomy (PN) in elderly patients (over 75 years) is certainly underused with concerns regarding risk of major complications and a negligible impact on renal function. The aim of this study was to compare the progression to chronic kidney disease (CKD) of purely off-clamp vs on-clamp robotic partial nephrectomy in patients ≥ 75 years in a multinstitutional series. METHODS: A collaborative multicentric renal surgery dataset (ROSULA) was queried for “partial nephrectomy” and “age≥75 years”. Between May 2008 and October 2019, a total of 207 patients who underwent robotic partial nephrectomy (RAPN) matched the inclusion criteria. Newly onset of any CKD stage (3a,3b,4,5) after surgery was computed by Kaplan-Meier curve and compared for surgical approach (purely-off clamp vs on-clamp) with the log-rank test. Univariable and multivariable Cox regression analyses were performed to identify predictors of CKD progression. For all statistical analyses, a two-sided p < 0.05 was considered significant. RESULTS: Mean age of the cohort considered was 77 years (IQR 76-81). At a median follow-up of 25 months (IQR 12-42.2) newly onset of CKD-3a and CKD-3b stages were observed in 7.2% and 8.7% of patients, respectively. At Kaplan-Meier analysis, on-clamp approach was associated with a significantly higher risk of developing a CKD progression, while a purely-off clamp approach was associated with a significantly lower risk of renal decline in patients ≥ 80 years old. (Figure 1; p=0.04 - Figure 2; p=0.03). On univariable analysis surgical approach (HR 4.22 – 95% CI 1.52-11.6; p=0.006) warm ischemia time (HR 1.05 – 95% CI 1.02-1.08; p=0.01) and tumor size (HR 1.05 -95% CI 1.01-1.09) were all significant predictors of renal function decline. On multivariable analysis warm ischemia time (HR 1.04 – 95% CI 1.01-1.08; p=0.006) was the only independent predictor of any CKD stage progression. CONCLUSIONS: Robotic partial nephrectomy in the elderly population may achieve acceptable mid-term functional outcomes. Ischemia time during robotic partial nephrectomy remains the only modifiable surgical factor to avoid a significant progression of CKD even at the oldest age. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e325-e326 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Umberto Anceschi* More articles by this author Aldo Brassetti More articles by this author Gabriele Tuderti More articles by this author Andrea Minervini More articles by this author Andrea Mari More articles by this author Antonio Andrea Grasso More articles by this author Marco Carini More articles by this author Umberto Capitanio More articles by this author Alessandro Larcher More articles by this author Francesco Montorsi More articles by this author Riccardo Autorino More articles by this author Alessandro Veccia Richmond, VA More articles by this author Daniele Amparore More articles by this author Francesco Porpiglia More articles by this author Ithar Deerwesh More articles by this author Daniel Eun More articles by this author Jennifer Lee, Philadelphia More articles by this author Michele Gallucci More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement PDF downloadLoading ...

Visit-to-Visit Variability in Total Cholesterol Correlates with the Progression of Renal Function Decline in a Chinese Community-Based Hypertensive Population

Background: Studies have demonstrated that cholesterol variability is an independent predictor of cerebrovascular and cardiovascular events. Objective: This study aimed to investigate the association of visit-to-visit variability in total cholesterol (TC) with kidney decline in a Chinese community-based population. Methods: We assessed intraindividual variability in TC among 6,465 hypertensive participants and correlated the results with endpoints. TC variability was measured using standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variability independent of the mean (VIM). The endpoint of this study was progression of renal function decline defined as a decrease in estimated glomerular filtration rate (eGFR) ≥30% and to a level <60 mL/min/1.73 m² during follow-up if the baseline eGFR was ≥60 mL/min/1.73 m², or a decrease in eGFR ≥50% during follow up if the baseline eGFR was <60 mL/min/1.73 m². Results: After a median follow-up of 27 months, 13.5% (n = 877) of the participants experienced progression of renal function decline. In the multivariable-adjusted Cox model, each 1-SD increase in TC variability (by SD) increased the risk of renal function decline by 11% (HR = 1.11; 95% CI 1.034–1.197; p = 0.004); this was independent of the baseline eGFR, mean follow-up TC levels, and the lipid-lowering therapy. Similar results were found for the 3 other measures of variability, i.e., ASV, CV, and VIM. Conclusion: In subjects with hypertension, visit-to-visit variability in TC is an independent predictor of renal function decline.

Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease

Sickle cell disease (SCD) nephropathy and lower estimated glomerular filtration rate (eGFR) are risk factors for early mortality. Furthermore, rate of eGFR decline predicts progression to end-stage renal disease in many clinical settings. However, factors predicting renal function decline in SCD are poorly documented. Using clinical, laboratory, genetic, and metabolomic data, we evaluated predictors of renal function decline in a longitudinal cohort of 288 adults (mean age 33.0 years). In 193 subjects with 5-year follow-up data, mean rate of eGFR decline was 2.35 mL/min/1.73 m2 /year, nearly twice that of African American adults overall. Hyperfiltration was prevalent at baseline (61.1%), and 36.8% of subjects experienced rapid eGFR decline (≥3 mL/min/1.73 m2 /year). Severe Hb genotype; proteinuria; higher platelet and reticulocyte counts, and systolic BP; and lower Hb level and BMI were associated with rapid decline. A risk scoring system was created using these 7 variables and was highly predictive of rapid eGFR decline, with odds of rapid decline increasing 1.635-fold for every point increment (P < 0.0001). Rapid eGFR decline was also associated with higher organ system severity score and peak creatinine. Additionally, two metabolites (asymmetric dimethylarginine and quinolinic acid) were associated with rapid decline. Further investigation into longitudinal SCD nephropathy (SCDN) trajectory, early markers of SCDN, and tools for risk stratification should inform interventional studies targeted to slowing GFR decline and improving SCD outcomes.

Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease

Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease (CKD), but whether renal oxygenation predicts renal function decline in humans has not been proven. Therefore, we performed a prospective study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in 112 patients with CKD, 47 with hypertension without CKD, and 24 healthy control individuals. Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2* value of each layer (a high R2* corresponds to low oxygenation), along with the change in R2* between layers called the R2* slope. Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate (MDRD eGFR). Follow up was three years. The change in eGFR in CKD, hypertensive and control individuals was -2.0, 0.5 and -0.2 ml/min/1.73m2/year, respectively. In multivariable regression analysis adjusted for age, sex, diabetes, RAS-blockers, eGFR, and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2* value of the cortical layers, and positively with the R2* slope, but not with the other covariates. Patients with CKD and high outer R2* or a flat R2* slope were three times more likely to develop an adverse renal outcome (renal replacement therapy or over a 30% increase in serum creatinine). Thus, low cortical oxygenation is an independent predictor of renal function decline. This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression.