23^rd European Nephrology Conference October 23-24, 2019 Rome, Italy

Biography:

Ghada A Ankawi is an Assistant Professor of internal medicine and nephrology at King Abdulaziz University, Jeddah, Saudi Arabia with special interest in glomerulonephritis, kidney disease in pregnancy, and critical care nephrology. She has completed her Bachelor degree of Medicine and Surgery at King Abdulaziz University, Jeddah, Saudi Arabia in 2007. She got Certification in 2009 for Medical Council of Canada Evaluating Examination Certification; American Board of Internal Medicine in 2014; Canadian Board of Internal Medicine in 2015; Canadian Board of Nephrology in 2016; American Board of Nephrology in 2016. She is the Head of the dialysis unit at King Abdulaziz University Hospital, Jeddah, Saudi Arabia since June 2019. She undergo research-based subspecialty training in critical care nephrology IRRIV, Vicenza, Italy from November 2017-June 2018; Subspecialty training in glomerulonephritis and kidney disease in pregnancy, University of Toronto, Toronto, Canada (July 2016- October 2017); Nephrology training, The University of Western Ontario, London Ontario, Canada (July 2014- June 2016); Internal Medicine training, The University of Western Ontario, London Ontario, Canada from July 2011 to June 2014. She published 14 papers in reputed journals and currently conducting studies in the field of pregnancy with kidney disease.

Abstract:

Biography:

Vinod C Tawar has completed his Graduate degree at Bombay University in 1964 with major in Chemistry and a minor in Botany with honours. He has completed his postgraduate program in Technology of Pharmaceuticals and Fine Chemicals at Bombay University in 1966. In 1967, he has completed his Master’s degree programme in pharmacology at University of Manitoba, Canada in 1969. In 1970, he has commenced his work as a toxicologist and had established a province wide analytical laboratory in the field till 1981. He has completed his MD degree from Medical School in 1985. He has also completed a 2 years residency, for a licensure as a physician. After a general practice of several years and pharmacology research he was awarded a family physician status in 2008. In the due course of his practise, he has continued with his interests in clinical research (diabetes, renal dysfunction, resistant dermatitis, peripheral vascular disease and leading into innovative treatment measures). Since 2016, he has published 5 articles in the international journals.

Abstract:

My prior presentation at the euro-nephrology conference in Rome in 2016 on “ renal dysfunction stage II to IV and the amelioration via novel ace inhibitors was my initial interest in nephrology since it was one of the most challenges in a family practice settings in the region. Consequently, patients with eGFR as low as 33 have shown a full recovery to normal function as been achieved while on perindopril 8mg/day dosage for 12 months. My current research interest has been on recognizing contributing factors and suggesting treatment measures based on current clinical data from literature. A literature data was reviewed from January 2004 to date. Earlier years study showed prevalence of renal disease to ethnic origin with greater incidence of obesity, diabetes, metabolic syndrome and hypertension. Subsequently, an effective management of blood pressure for prevention of kidney disease and a family history of ESRD became the primary focus, in as early as 2005 ACE or ARBs were recognized for the prevention and treatment of CKD. In 2015, an association of acute kidney injury with the parameters eg. EGFR, Albuminuria, Diabetes mellitus and hypertension was recognized. In my past presentation of 2016 (Rome) an effective management of diabetes and hypertension was identified as most essential tool in prevention of CKD. Studies on rats demonstrated Glyrrhic acid treatment for the prevention of Nephropathy. In addition, recent studies have shown Linaclotide  administration to rats  for the chronic kidney disease, amelioration. In my practise, treatment of Iron deficiency, event transiently showed relief from leg edema and likely cardio-vascular complications. An effective management of gout was seen as a further prevention of renal dysfunction. A role of newer Sartan analogues, medoximil and vitamin D supplementation deserves further studies in ESRD cases.

Biography:

Abstract:

Background Environmental factors contributing to diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) are incompletely understood. We investigated whether blood concentrations of cadmium (Cd) and lead (Pb) were associated with prevalent DKD, and to which extent diet and smoking contribute to blood Cd and Pb concentrations.

Methods We performed a cross-sectional analysis in 240 patients with T2DM included in the Diabetes and LifEstyle Cohort Twente (DIALECT-1). Blood Cd and Pb concentrations were determined from EDTA whole blood samples. Cd-Pb co-exposure was calculated by addition of Cd and Pb Z-scores. The association between Cd-Pb and DKD (CKD-epi <60ml/min/1.73m2 and/or albuminuria) was determined using multivariate logistic regression. The association between diet (derived from food frequency questionnaire), smoking and Cd and Pb was determined using multivariate linear regression.

Results Almost half of all participants had DKD (49%). Median blood concentrations were 0.33 ug/l (IQR: 0.21-0.57 ug/l) for Cd and 1.45 ug/dl (IQR: 0.83-1.86 ug/dl) for Pb, all below the values known for acute toxicity. Higher Cd-Pb was associated with a 32% higher risk for DKD (OR: 1.317 (1.071-1.620), p=0.009). Smoking status was positively associated with Cd (β: 0.479, p<0.001) and alcohol intake with Pb (β: 0.299, p <0.001), while there was no association between dietary intake and Cd or Pb.

Conclusion The association between higher Cd-Pb and prevalent DKD might suggest Cd and Pb contribute to progressive DKD. The higher Cd-Pb associated with smoking and alcohol might provide another mechanism by which these intoxications adversely affect renal health in T2DM.

Biography:

S Setty is the Director of renal and transplant pathology at University of Illinois, Chicago.

Abstract:

Interstitial fibrosis (IF) is an indicator of chronic renal damage in transplanted kidneys. It results from an accumulation of insults namely drug toxicity, infection and rejection. Manual scoring (MS) using Banff criteria is a very reproducible means of establishing the IF score of a renal transplant biopsy and is distributed into four categories: <5%, 5-25%, 25-50% and 50%. But MS for smaller changes in IF between biopsies is neither accurate nor reproducible.  Thus the need for automation. Mason trichrome-stained whole slide images of renal transplant biopsies were scored using the Histolab program. Fibrosis scores were obtained of the cortex after excluding perivascular and periglomerular areas of collagen deposition/fibrosis. The method requires the creation of a 'mask' for the area of fibrosis and then adjustments of the settings to detect the areas of interest. Variability of staining between biopsies may occur due to differences in reagent lots, incubation times and variability of tissue processing. These can be accounted for by tweaking the settings. Staining artifacts such as staining of tubular epithelial cytoplasm and tissue-edge artifacts are overcome by manual inspection after creation of the mask. This adjustment facilitates selection of appropriate areas of interest. In conclusion, both man and machine working in concert, can obtain a more accurate fibrosis score than each working alone.

Biography:

Violina Minkova is the Head of Clinic of General and Clinical Pathology in Military Medical Academy in Sofia. She is a leading pathologist, specialized in the field of renal biopsy, with an extensive professional experience. She applies histological, histochemical immunohistochemical and electronmicroscopical methods in the diagnosis of immune nephropathies. In her everyday practice, she provides diagnostics for congenital and hereditary nephropathies with the use of electron microscopy and electronmicroscopical morphometry. She has contributed significantly to the development of diagnostic methods for C3- nephropathy, renal amyloidosis, the disease of thin membranes and Alport’s syndrome. She has participated in numerous symposia and has many publications in Bulgarian and international reviews. She provides expert consultations on matters of renal biopsies and gives professional training to younger physicians qualified in nephropathology. She is member of the Bulgarian society of pathology, the Bulgarian society of nephrology and ERAEDTA.

Abstract:

A 51 year-old woman with nephrotic syndrome since 6 months-proteinuria 8.1g/ 24 h, serum albumin 29, 25, 19.6 g/l, oedema, rapid depression of renal function-serum creatinin 159- 200-462 mmol/l; Hypertension since 2 years; Diabetes mellitus since May 2018; Anti-ds DNA-63.3; Sonography: the two kidneys are of normal size and location; echodencity- І degree; Renal biopsy: 21 glomeruli, 3-obsolescent; In some of the glomeruli a moderate mesangial hypercellularity is seen. In the mesangial regions of most glomeruli hyaline nodules with cellular borders, fibrin caps and hyaline thrombi are seen. In few glomeruli there is an extracapillar proliferation with forming of crescents. Many areas of atrophic tubules and mononuclear infiltrates in the interstitium are seen as well; Blood vessels-severe hyalinosis in the walls of the small arteria and arterioles; Immunofluorescence: light segmental subendothelial IgA deposition and 2-3+ IgM, 3+ C1q and 4+C3 with the same localization. The morphological diagnosis was combination of lupus nephritis and diabetic nephropathy, causing a rapid depression of renal function. A therapy with i.v. application of Metjylprednizolon 250 mg, Endoxan 500 mg, Klexan 2x 0.4 ml and symptomatical medicine was prescribed. Serum creatinin decreased to 395 mmol/l; oedema reduced and the cough disappeared.

Biography:

Vinod C Tawar has completed his Graduate degree at Bombay University in 1964 with major in Chemistry and a minor in Botany with honours. He has completed his postgraduate program in Technology of Pharmaceuticals and Fine Chemicals at Bombay University in 1966. In 1967, he has completed his Master’s degree programme in pharmacology at University of Manitoba, Canada in 1969. In 1970, he has commenced his work as a toxicologist and had established a province wide analytical laboratory in the field till 1981. He has completed his MD degree from Medical School in 1985. He has also completed a 2 years residency, for a licensure as a physician. After a general practice of several years and pharmacology research he was awarded a family physician status in 2008. In the due course of his practise, he has continued with his interests in clinical research (diabetes, renal dysfunction, resistant dermatitis, peripheral vascular disease and leading into innovative treatment measures). Since 2016, he has published 5 articles in the international journals.

Abstract:

Benign prostatic hypertrophy is of common occurrence in a medical practice, seen in men of advanced age after 50 years. It also leads to obstructive voiding and cancer. Determination of PSA levels have been detection tool in the diagnosis. However, current studies have shown a lack of specificity. The relevance of hypertrophy or cancer in nephrology has been primarily, due to the presence of disease has to be ruled out in male kidney transplant donors. My primary interest in clinical research since 2016 on BPH and cancer has been on searching for safer treatment options e.g. topical formulations consisting 2 of PDE5 inhibitors (Papaverine and Sildenafil). The trials at pilot studies have shown relief from obstructive voiding symptoms, decrease in PSA levels, increased cavernous blood flow, and androgenic effects without a PSA rise. Current evidence has shown a decrease in pre-cancerous PC3 cells with Papaverine. My current research is targeting the assessment of this parameter at monthly intervals of the PDE5 inhibitors. The current literature review from 2015, to date has shown significant evidence supporting the benefit from Papaverine. Some authors have utilized injectable forms; however topical agents have been free of such complication.

Biography:

Olenovych Olha is an Associate Professor in the Department of Clinical Immunology, Allergology and Endocrinology in HSEEU, Bukovinian State Medical University,Chernivtsi, Ukraine). She has achieved the specialty certificate in Endocrinology in 2003 and completed her PhD degree in Endocrinology in 2005. She specializes in the study of kidney functions in case of endocrine pathology and her current field of scientific interest is diabetic kidney disease. She has published more than 49 papers in reputed journals and has been a speaker in national and international conferences.

Abstract:

Proteinuria was considered to be the evidence of a long existing kidney damage with already irreversible changes, confirming the degree of glomerular destruction in case of diabetes mellitus (DM). Recent scientific information demands reassessment of the micro/macroalbuminuria meaning in the context of the pathogenesis of diabetic kidney disease (DKD). Considering the multifactoriality of renal impairment mechanisms in case of DM and the importance of their identification at the initial stages of the disease, the objective of this research was to clarify the peculiarities of proteinuria in the early period of alloxan-induced experimental DM. On 11^th day after DM induction in white non-linear male rats urine samples of diabetic and control animals were collected under 2 hours-water diuresis condition for further study. As the results of the investigation demonstrated, the protein content in urine of diabetic animals markedly exceeded the control values. The significant augmentation of protein excretion was observed as well, including that standardized in 100 µL of glomerular filtrate. Developing against the background of marked renal hyperfiltration, the total protein loss resulted mainly from an increase of GFR with raised filtration loading of the nephron. Thereby, an overloading phenomenon develops for transport reabsorption systems in proximal tubules accompanied by their intactness. Thus, the character and dynamics of proteinuria evidences mainly the functional origin of renal disorders on the 11^th day of experimental diabetes in the absence of significant structural changes in the tubular apparatus of the kidneys.

Biography:

Katrin Brunner has studied biology for 6 years and subsequently started her research for a Doctoral degree in 2017 at the Institute for Molecular and Cellular Anatomy at the University of Regensburg. Her focus of research lies on structural analyses of Polycystin-1 and functional analyses of Polycystin-2 in association with ADPKD.

Abstract:

With an incidence of about 1:1000, autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. In 15% of the patients, mutations in the PKD2 gene have been identified. PKD2 encodes polycystin-2, an integral membrane protein that acts as a non-selective cation channel. Up to now, however, the underlying mechanism of cyst formation in patients is unknown. An exchange of 11 amino acids in the polycystin-2 channel with that of the related protein polycystin-2L1 results in the selective replacement of the pore region so that the mutant protein is still located in primary cilia and the endoplasmic reticulum. The resulting polycystin-2^poreL1 protein leads to dilations of collecting ducts, cyst formation and elongated cilia in homozygous knock-in mice. Furthermore, in calcium imaging assays of these mice increased intracellular calcium levels could be detected after stimulation with vasopressin. Electrophysiological experiments in Xenopus oocytes showed increased calcium currents in oocytes injected with cRNA for polycystin-2^poreL1 compared to cRNA for wild-type polycystin-2.

In silico homology modeling revealed a wider selectivity filter in our mutant protein compared to the wild-type protein, which supports the higher conductance of calcium in the mutant. From this, it can be concluded that a pore exchange leads to an intracellular dysbalance of calcium levels and subsequent cyst formation in mice, thus emphasizing the importance of the pore region in maintaining tubular geometry in the kidney.

Biography:

Abstract:

Nail-patella syndrome (NPS) is an autosomal-dominant genetic disorder characterized by malformed fingernails and hypoplastic kneecaps. Approximately 40% of NPS patients develop a nephropathy caused by malfunctioning podocytes. Mutations in the gene LMX1B which encodes a transcription factor of the LIM-homeodomain family are known to be the cause of NPS. The pathomechanism underlying NPS is still unknown. Notably, only homozygous Lmx1b knock-out mice develop symptoms resembling those in NPS patients. We therefore hypothesized that patients suffer from missense mutations which confer a gain-of-function or a dominant-negative effect. To identify possible molecular pathomechanisms of NPS, knock-in mice were established with point mutations either in the first (H54L) or the second (C95F) LIM domain such as those described in patients. Heterozygous Lmx1b knock-in mice showed no NPS phenotype whereas homozygous knock-in mice displayed a reduced number of filtration slits in podocytes, similar to that of conventional Lmx1b knock-out animals. The presence of the mutated Lmx1b mRNA was confirmed but the protein was not detectable in podocytes. Detailed analyses of LMX1B mutants showed a reduced half-life of the mutant proteins in comparison to wild-type LMX1B. Another mutant LMX1B protein with a mutation in the homeodomain, V265D, showed a prolonged half-life compared to the wild-type protein. Due to protein instability, the knock-in mutations H54L and C95F lead to a loss of function in knock-in mice. As previously described, the mutation V265D within the homeodomain causes a dominant-negative effect. This suggests that different NPS mutations can lead to different pathomechanisms requiring distinct therapeutical approaches.

Biography:

Sandra Elisabeth Meisinger completed her Master of Science in Biology at the University of Salzburg in 2016. Since 2017, she is pursuing her PhD at the University of Regensburg in analysing the role of miRNAs in the kidney.

Abstract:

miRNAs are short non-coding RNAs which posttranscriptionally regulate the intracellular level of mRNAs. It is known since 2008 that miRNAs are important for the development and maintenance of podocyte structure. Deletion of the two key enzymes of miRNA biogenesis, Drosha or Dicer, leads to proteinuria and glomerular injury in podocytes, e.g. podocyte foot process effacement, in mice. Although many podocyte miRNAs are meanwhile known, their potential target mRNAs are still mostly unknown. In the present work a mouse model with inducible podocyte-specific deletion of Dicer was generated. Using SDS-Page and protein-creatinine-ratio, proteinuria was determined. In addition, H&E and PAS staining as well as electron microscopy were used to investigate histological and ultrastructural abnormalities. We were able show that the inducible deletion of Dicer leads to an onset of proteinuria after 3 weeks with further progression. Proteinuria was accompanied by podocyte foot process effacement and endothelial changes. We also observed mesangial matrix expansion and protein casts in the tubule system. Using freshly isolated podocytes of double-fluorescent Cre reporter mice, we identified miRNAs and putative target mRNAs by different approaches. Through in silico predictions putative miRNA-mRNA pairs were generated and validated using a luciferase reporter assay. We were able to identify specific miRNA-mRNA interactions which are currently investigated using the Dicer knock-out mouse model.

Biography:

Tayse Tamara da Paixao Duarte completed her Master's degree in Health Sciences from the University of Brasília (UnB). Since 2013, she is a Professor at the University of Brasília, Brazil.  She is the member of the Group of Integrated Studies and Groups of Research in Technology of Care. Since then, she has presented poster at the international and national congress of cardiology and nephology and has been involved in various teaching projects.

Abstract:

Objective: To verify if creatinine clearance variations interfere with the outcome of the patient  with acute kidney injury (AKI).

Methods: This was a prospective, quantitative, cohort study conducted at the medical clinic of a public hospital in the Federal District. The questionnaire was used to collect clinical and laboratory data. The AKI was defined as an increase of serum creatinine (sCr) ≥ 0.3 mg/dL increase in 48 hours or increase of 1.5 to 1.9 times of your initial/baseline value within seven days, according the Kidney Disease Improving Glogal Guidelines (KDIGO). It's considered significant p≤0.05.

Results: In 294 patients evaluated, 85 were identified with AKI, the most part of males (51.8%), with a mean age of 66 ± 14 years, of brown race (56.5%). Individuals with worse renal function (CrCl <60 mL/min) were predominantly male (57.9%), elderly (median age 74 years), black (73.7%) and bedridden (57.9%). Elderly patients presented greater renal impairment (CrCl <60 mL/min, p = 0.05). Individuals with worse renal function (CrCl <30 mL /min) evolved more frequently at death (p = 0.007).

Conclusion: Fluctuations in the clearance of creatinine are common during hospitalization, however in this study it was found that the individuals with lower value of CrCl (<30 mL/ min) evolved more often to the death against those with CrCl ≥30 mL/min. The data can support an adequate management of patients with AKI, providing subsidies for additional measures and individualized intervention strategies, in order to avoid progression, chronicity of kidney disease and mortality of these patients.

Biography:

Wellington Luiz de Lima is a specialist in intensive care unit. He is pursuing his Post Graduate Program in Nursing at the University of Brasilia, with a study on acute kidney injury. He has published in the last years several works in the area of acute kidney injury.

Abstract:

Objective: To identify and staging of acute kidney injury (AKI) in the post-operative period of coronary artery bypass surgery.

Methodology: Prospective, longitudinal, quantitative study developed in an intensive care unit (ICU). The Kidney Disease: Improving Global Outcomes (KDIGO) classification was used. The results were expressed in absolute and relative frequency. The analysis of categorical variables was performed using Fisher's exact test and chi-square test. P-values ​​<0.05 were considered significant.

Results: Among the 57 patients, the age was 63 ± 9 years, with 54.4% female, a body mass index (BMI) of 29.7 ± 5.23 kg/m². 98.2% of the patients evolved with hospital discharge with a time of 4.9 ± 8.8 days of ICU stay. The use of extracorporeal circulation was predominant (96.5%) with extracorporeal circulation time of  93 ± 29 minutes. According to the KDIGO classification, 78.9% presented kidney dysfunction. In the urinary flow criterion, 38.6% focused on the risk stage, 17.6% were stratified at the stage of kidney injury and only 1.8% fit into the stage of kidney failure. According to the serum creatinine criterion, 49.1% were identified in the risk stage, 5.3% in the lesion and 1.8% in kidney failure. There was a significant relationship between age (p = 0.05), BMI (p = 0.02), extracorporeal circulation time (p = 0.05) and AKI development.

Conclusion: Most patients focused on stage 1 of renal impairment. Age, BMI and CPB time was association to AKI.

Biography:

Gabrielle Goldet has completed her DPhil at the age of 28 years from Oxford University in chemsitry and then continued onto to study medicine at Oxford University as a graduate student, graduating in 2013. She has since been training as a doctor, specializing in nephrology in London at the Royal Free Hospital and the Hammersmith Hospital.

Abstract:

Pregnancy presents a number of challenges for women with renal disease.  Early intervention and specialist care are fundamental to ensuring the best care for such patients.  We performed an audit utilising our database of female patients under the age of 40 with renal disease in a tertiary renal centre (the Royal Free Hospital, London) to investigate whether certain features of their care, which were key to improving their renal and pregnancy outcomes, were being examined in clinic.  These included:- contraception mode if not trying to conceive; whether the patient was taking folate if they were planning a pregnancy; whether they were taking any teratogens, and if so whether a plan was in place for pregnancy; documentation of their last smear; what their virology status was; whether they are taking aspirin if pregnant; whether they were vitamin D replete; whether their periods were irregular, and if so whether they were referred to fertility services; for patient with lupus nephritis, if Ro+ in pregnancy, whether they were referred for foetal echocardiography.We found that, of the 92 patients audited, all points were covered in very few cases.  These fortunate few had all been seen in the renal obstetric clinic which ran briefly at the Royal Free Hospital but is due to restart soon.  Informed by the lack of consistent discussions of points of import to these patients in our clinics, we have embarked on a Quality Improvement Project to improve these outcomes.