A. Bettiga

Alberto Briganti

Alessandra Cinque

Alessandro Larcher

Andrea Salonia

Esteban Porrini

F. Di Marco

F. Montorsi

Francesco Trevisani

G. Pizzagalli

M. Locatelli

U. Capitanio

English

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ISN WCN 2020, ABU DHABI, UAEMethods: This is a retrospective cohort study using the medical recordsof 300 patients attending the outpatient renal clinic department at InkosiAlbert Luthuli Central Hospital for the period January 2007 – December2009. The average patient agewas 43 years. The patientswere followedupfor 24 months following their first clinic visit. Socio-demographic (agesex, residence) and clinical characteristics including eGFR, blood pres-sure, BMI (body mass index), proteinuria, haemoglobin, cholesterolemia,uricaemia were recorded. Treatments received including ACE inhibitors,statins, non-dihydropyridine calcium channel blockers (NDCCB), Betablockers were also recorded. Patients were divided into 2 outcome cate-gories, according to changes in eGFR (estimated glomerular filtrationrate): patients with eGFR decline of 1ml/min/year or less and those withaccelerated eGFR decline(>1ml/min/year). Data analysis using SPSSversion 23 (IBM) comprised of descriptive tests and logistic regressionanalysis (expressed as OR (odd ratio) and confidence interval) for thestudy of the association of above characteristics with patients’ outcome.Receiver operator characteristics (ROC) analysis was performed todetermine cut off values associated with accelerate progression of CKD.Results: ACE inhibition was used by 92% of patients. Uricaemia and BMIwere associated with worsening of eGFR decline OR: 1.012[1.003-1.020]p¼0.007 and OR: 3.775[1.116-12.766], p¼0.033 respectively. The use ofcarvedilol and NDCCB was associated with a reduction of the decline ofeGFR with OR: 0.144[0.207-0.953] p¼0.037 and OR: 0.543[0.329-0.884],p¼0.016 respectively. No significant association was found between eGFRchange and daily proteinuria or cholesterolemia. The cut off value for uricacid was 4.15 micromol/l. The aetiology of the chronic kidney disease didnot affect rate of progression of eGFR. In addition, the rate of progressionwas not dependent on eGFR. Patients with high uric acid levels were moreprone to progression of chronic kidney disease irrespective of the aetiology.Conclusions: These results suggest that beyond ACE inhibition, thecontrol of uricaemia below the target of 4.15 micromol/l, BMI, and useof carvedilol and NDCCB may lead to a further delay in the progressionof chronic kidney disease in KwaZulu-Natal.SAT-091HISTONE DEACETYLASE 5 (HDAC5)-BMP-7AXIS REGULATES EPITHELIAL MESENCHYMALTRANSITION IN RENAL TUBULAR EPITHELIALCELLSSHARMA, P*1, Karnam, K1, Sedmaki, K1, Kulkarni, O21Bits pilani-hyderabad campus Pharmacy Hyderabad India, 2Bits pilanihyderabad campus pharmacy Hyderabad IndiaIntroduction: BMP-7 downregulation has been shown in both humanand mouse renal fibrosis. BMP-7 antagonises TGF-b mediated EMT inrenal tubular cells. HDAC5 negatively regulates BMP-7 but role ofHDAC5 in regulation of renal tubular EMT associated with renalfibrosis is yet be explored. Here we studied the role of HDAC5-BMP-7axis in regulation of EMT in renal tubular cells.Methods: NRK52E (tubular epithelial cells) were procured from NCCS(Pune India). NRK52E cells were stimulated with 10ng/ml of TGF-b for24Hrs and 48Hrs to either isolated cell lysate for RNA, protein analysisand for immunocytochemistry. Selective HDAC5 knock down wasinduced 24Hrs before stimulation with TGF-b.To determine the expression of HDAC5 in mouse model of renal fibrosis,C57/BL6 mice were procured from registered CPCSEA breeder (HyderabadIndia).Micewere then exposed to renalfibrosis byunilateral ischemic injurywith 45 min renal artery clamping (chronic IRI) and unilateral ureteralligation (UUO).Micewere then sacrificed on day 2,6 and 10 and on 15 and 21day for UUO and chronic IRI model respectively. Renal tissues were har-vested to study the markers of EMT and expression of HDAC5 and BMP-7.Results:HDAC5 was upregulated in NRK52E cells stimulated with TGF-b along with EMT markers like (Vimentin, a-SMA) at 48hrs. HDAC5siRNA mediated knock-down of HDAC5 reduced the up regulation ofboth Vimentin and a-SMA, while the E-cadherin expression was un-affected with retention of epithelial phenotype in renal epithelial cellsstimulated with TGF-b. The expression of BMP-7 was upregulated inHDAC5 depleted NRK52E cells stimulated with TGF-b at 48hrs.HDAC5 was upregulated while BMP-7 was downregulated in har-vested renal fibrotic tissues harvested at day 10 in UUO and day 15, day21 in Chronic IRI mouse model of renal fibrosis.Conclusions: Here we show HDAC5 upregulation in chronic renal injurymodels as well as in tubular epithelial cells stimulated with TGF-b. Thefactors regulated by HDAC5 are expressed differentially in these mousemodels (like BMP-7, KLF2 and Foxc2). The HDAC5 depleted tubularepithelial cells preserved their epithelial phenotype in the presence of TGF-Kidney International Reports (2020) 5, S1–S392b due up-regulation of BMP-7. We propose HDAC5 as one of the potentialtherapeutic target to reduce progression of EMT and renal fibrosis.SAT-092THE DUEL OF DAVID AND GOLIATH: HOWSHOULD MGFR BEAT THE ESTIMATED GFR?TREVISANI, F*1, Di Marco, F1, Locatelli, M2, Pizzagalli, G2,Larcher, A1, Capitanio, U1, Bettiga, A1, Cinque, A1, Porrini, E3,Briganti, A1, Salonia, A1, Montorsi, F11IRCCS San Raffaele Scientific Institute Urological Research Institute MilanItaly, 2IRCCS San Raffaele Scientific Institute Laboratory Medicine ServiceMilan Italy, 3University Hospital of the Canary Island Dept. of nephrology LaLaguna SpainIntroduction:An accurate assessment of renal function in urological andoncological patients should be mandatory to define the most appro-priate urological surgery technique (nephron sparing vs radical ne-phrectomy) and to decide the correct dose for each type of chemo-immuno therapy for metastatic pts. Unfortunately, the most usedmethod to measure GFR in day to day clinical practice is represented bythe estimated glomerular filtration rate (eGFR) which harbours a sig-nificant error in comparison to gold standards methods (mGFR). Theobjective of this study is to determine the extent of the error of eGFRcompared to the mGFR in the oncological and urological pts category.Methods: A prospectively consecutive cohort of 129 pts affected by uro-oncological neoplasmwas collected comparing eGFR formulaswithmGFRusing iohexol renal measurement (gold standard). The iohexol plasmaclearance protocol involves the administration of an endogenous marker(Iohexol) and the measurement of the disposal time curve for renal ac-tivity from the body. Four estimated GFR formulas were used for thisstudy: CKD-EPI, MDRD, MCQ, FAS. The agreement between eGFR andmGFR was evaluated taking in account Bias, expressed as median ofpercent difference between mGFR and eGFR and overall accuracy as P30representing the percent of estimates within 30% of measured GFR.Results: Mean age of our cohort was 65 ys (s.d. 14), with a male:femaleratio of 3.6. The agreement between formulas and mGFR was poor. TheBias for MDRD, CKD-EPI and FAS was 2% and for MCQ was -11%indicating that, except for MCQ formula, the considered formulas don’tharbour huge systematic errors. Different information was provided bythe accuracy parameter: P30. The P30 observed for the four formulas were82% for CKD-EPI, 78% for MDRD, 84% for FAS and 61% for MCQ. Thecomparisons between the eGFR formulas and mGFR show that there is aloss of accuracy at lower values of GFR (# 60 mL/min/1.73 m2) where themetrics P30 for all the formulas is lower than 85%. In particular, a notnegligible percentage of patient with mGFR lower than 60 mL/min/1.73m2, tends to be wrongly over or underestimated with a discrepancygreater than 20 mL/min/1.73 m2 (especially the MCQ formulas).Conclusions: Direct measurement of GFR using a gold standard techniquemust be considered in selected pts before clinical decision. Assuming thatperformingmGFR for routine practice or in epidemiological studies could benot always feasible, the current findings emphasize the absolute need toS41ISN WCN 2020, ABU DHABI, UAEdetermine anmGFRwith gold standardmethod at least for those pts at eGFRlower than 60 mL/min/1.73 m2 who deserve surgical operations, anti-coag-ulant therapies, nephrotoxic drugs, oncological medical therapies (includedexperimental protocols) and radiological contrast medium agents injections.SAT-093THE STRANGE CASE OF RENAL FUNCTIONAFTER RADICAL NEPHRECTOMY: A FOGGYFORECASTTREVISANI, F*1, Di Marco, F1, Dell'Antonio, G2, Pani, A3,Larcher, A1, Capitanio, U1, Bettiga, A1, Porrini, E4, Briganti, A1,Salonia, A1, Montorsi, F11IRCCS San Raffaele Scientific Institute Urological Research Institute MilanItaly, 2IRCCS San Raffaele Scientific Institute Dept. of Pathology Milan Italy,3Azienda Ospedaliera G. Brotzu Dept. of Nephrology Cagliari Italy, 4Uni-versity Hospital of the Canary Island Dept. of Nephrology La Laguna SpainIntroduction: The risk of developing a mild to severe chronic kidneydisease stage after radical nephrectomy represents one the major night-mare for oncological patients who require surgery for kidney cancer. Thefear of a renal replacement therapy which may occur after the operationin patients with a baseline compromised renal function drives the choiceof the surgical approach for clinicians. But are we really sure thatremoving a kidney means the halving of the baseline eGFR? Are we ableto select at baseline which patient will develop acute kidney injury andwhich one no? And finally, do we exactly know if a mild to severe CKDstage at baseline represents a risk factor to decrease eGFR in comparisonto normal renal function pts? Aim of our work is to better understandthis pathological-physiological mechanism of compensation.Methods: We collected retrospectively clinical data of a group of 114 pa-tients who underwent RN for the presence of a benign or malignant renalmass.To evaluate the risk todevelop acutekidney injury (AKI) after surgery,serum-creatinine (sCr) values were collected before surgery and after 1 yearthe surgery. We estimated Glomerular Filtration Rate (eGFR) with CKD-EPIformula.According toRIFLEcriteria,wedefined theAKIonsetwith a ratio ofsCr/sCr(t0) higher than 1.5 during hospitalization.Moreover, to investigate apossible correlation between renal basal histology and renal functionaldecay, two renal biopsies (> 20 glomerula for each section) were performedon each renal tissues [from the healthy part of the removed kidney> 3cm farfrom tumor]. A pathological evaluation using a chronicity score (RemuzziScore) was subsequently carried out evaluating damage on four parameters:(a) glomerular global sclerosis, (b) tubular atrophy, (c) interstitialfibrosis and(d) arterial narrowing. Statistical analysis were performed using generalizedlinear model (GLM), Kruskal-Wallis test and chi-square test. Statisticallysignificant correlations were considered for p-value<0.05.Results: At t0, 21% of the patients had an eGFR>90ml/min/1.73m2, 45%between 60 and 90, 23% between 30 and 45, and 11% under 45. Taking inaccount thepercentageof decay therewas a strongnegativecorrelationwithAKI onset (p<0.0001), a positive correlation with Diabetes (p<0.05) whileno correlation with CKD Stage at t0 (p¼0.051). No significative correlationswere found between the decay of eGFR and other variables such as age,gender or comorbidities. Considering a subgroup of 98 patients the analysisenlighteneda significativenegative correlationbetween theeGFRdecayandthe presence of arterial narrowing (p<0.01) and tubular atrophy (p<0.05)but no correlation was found with the whole chronicity score.S42Conclusions: Renal function after RN shows for each class ofCKD stage after 1 year from surgery a diverse decay related tothe baseline eGFR. Healthy patients display a huge decrease ofeGFR in comparison to CKD stages III-IV which remain stable at1 year. One possible explanation is that the healthy kidney ofthe patients affected by moderate and severe CKD starts work-ing with a compensatory mechanism before the entire removalof the kidney with cancer so that the surgical acute nephronloss does not represent a shock in comparison to healthypatients. The second hypothesis is that CKD patients are treatedin a more precise and specialistic way in comparison to theother.SAT-094HEMODIALYSIS EMERGENCIES IN ANEPHROLOGY DEPARTMENT: ABOUT 117CASESTRIQUI, C*1, Najjar, M2, Ben Amor, S2, Hlioui, F2, Agerbi, S2,Barbouch, S2, Ben Hmida, F2, Ben Abdallah, T21Charles Nicolle Hospital Medecine A ben arous Tunisia, 2Charles NicolleHospital Medecine A Tunis TunisiaIntroduction: Hemodialysis (HD) emergencies in nephrology arevery common. Prompt diagnosis and management are needed as itcan be life-threatening. We aim to determine epidemiological,clinical, biological aspects as well as the etiological profile of ourpopulation.Methods: We conducted a cross-sectional study during 3 months(February, March and April 2019) collecting patients who underwent atleast one session of HD at our nephrology department. Were includedpatients aged over 18 years old. Were excluded chronic dialysis pa-tients presenting for their usual session. Data collection was conductedfrom HD registers. We collected the following parameters: age, gender,comorbidities, initial nephropathy, clinical data(blood pressure, pul-monary auscultation, diuresis, oxygen saturation), the current treat-ment and biological data( creatinin, kalemia, hemoglobin, andgasometry).Data were entered and analyzed using SPSS software. Chi-squaredtest with a level of significance of 0.05 was used for the qualitativevariables.Results: A total of 117 patients were included, mean aged 60.71years old (range:28-90) with a sex ratio M/F at 1.3. Our popu-lation consists in 42 chronic HD patients(37.9%), 34 Patientswith moderate to severe renal failure(RF) (29.9%) and 41 patientswith acute kidney injury (AKI) (35%). Initial nephropathy causeswere vascular in (40%), glomerular in(25%) and undeterminedin(35%) of cases. Our patients had hypertension, diabetes, dys-lipidemia in respectively (58%),(45%) and (7.6%). Twenty twochronic HD patients were anuric (48.8%). Seventy-nine patientswere admitted from the emergency department(68%), 21 patientsfrom the surgical and urology departments(18.4%),8 patientsfrom the intensive care unit (7.6%) and 4 patients from otherdepartments(4.2%). HD indications were acute pulmonary edemain (41.8%), metabolic acidosis in (41.8%), hyperkalemia in(37.6%), Uremic signs in (22.2%). Inadequate hyperkalaemictreatment was noted in( 22.7% )of cases. Conventional HD wasperformed with mean session duration of 3 hours. Ultrafiltrationwas required in 46 cases (36.8%) with an average of1860ml(range:500-4000). Perdialytic complications were observedin(12.5%)of cases. Hypotension was the most common compli-cation which leads to the interruption of the session in(5.9%)ofcases. Disequilibrium syndrome was observed in 2 patients.Arrhythmia and acute cardiac failure were noted in 2 patients.Death occurred in 1 case caused by arrhythmia. Advanced age,anuria and underlying RF were independent risk factors ofemergency dialysis with respectively (p¼0.02, p¼0.01 andp¼0.05).Conclusions: Dialysis emergencies remain frequent in our country.Acute Pulmonary edema and metabolic acidosis were the main in-dications followed by hyperkalemia and anuria. Poor and delayedchronic renal failure management could explain the frequent use ofemergency HD. The analysis of the causes and dialysis modalities inemergency situations, contributes to adopt a preventive strategy inorder to identify high-risk patients and to optimize treatment pro-tocols.Kidney International Reports (2020) 5, S1–S392

SAT-092 THE DUEL OF DAVID AND GOLIATH: HOW SHOULD MGFR BEAT THE ESTIMATED GFR?

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SAT-092 THE DUEL OF DAVID AND GOLIATH: HOW SHOULD MGFR BEAT THE ESTIMATED GFR?

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