VALIDATION OF HOUSEKEEPER GENES FOR NORMALISATION FOR RT-qPCR GENE EXPRESSION STUDIES IN ISCHAEMIC AND TOXICOLOGICAL CONDITIONS IN RAT MODELS

S HERATH1, K TAYLOR1, A AU2, L SUCCAR1, Z  ENDRE2, J  ERLICH1
1University Of New South Wales , Kensington , Australia, 2Prince of Wales hospital, Randwick, Australia

Aim: To identify the most stably expressed housekeeper genes (HKG’s) under ischaemic and nephrotoxic conditions in various rat kidney models.
Background: Appropriate selection of housekeeper genes is pivotal to obtain accurate results in real time PCR. A number of studies have identified that the transcription levels of most commonly used HKG’s vary considerably under different experimental conditions.
Methods: Control and adenine fed Sprague Dawley (SD) rats were equally divided into 6 intervention groups each consisting of 8 biological replicates. The intervention groups were, subclinical CKD (sCKD), acute kidney injury (AKI) only, AKI on a background of sCKD, chronic kidney disease (CKD) and a control group. sCKD was induced with adenine and AKI was induced with cisplatin or ischaemia. 10 commonly used candidate HKG’s from different functional classes were selected. The cycle threshold (Ct) value for each gene was determined and data obtained were analyzed utilizing NormFinder, Genorm, BestKeeper and comparative delta Ct statistical algorithms.
Results: Polyadenylate-binding nuclear protein 1 (PABPN1) and hydroxymethylbilane synthase (HMBS) were determined to be the most stable by all 4 algorithms. Bestkeeper/Genorm and Normfinder/comparative delta Ct approach respectively ranked succinate dehydrogenase (SDHA) and tyrosine-3-monooxygenase/tryptophan 5-monooxygenase-activation protein zeta (YWHAZ) as the third most stable HKG. A normalisation factor constructed by calculating the geometric mean of the three most stable HKG’s showed the least variability across the experimental groups. In comparison, the commonly used GAPDH and 18S were the least stable of all 10 HKG’s studied.
Conclusions: Construction of a normalisation factor by utilizing two or three most stable HKG’s which includes HMBS and PABPN1 produces the least variability to control for experimental errors and adjust for inter-sample variations in rat kidney studies.


Biography:
Fellow of the Royal Australasian College of Physicians and curently doing a PhD under the supervision of Professor Zoltan Endre and Dr Jonathan Erlich. Focus of current research is on ischaemia reperfusion injury especially in  the area of transplantation. Actively engaged in teaching at University of New South Wales and at Prince of Wales hospital, Randwick.

 

VALIDATION OF A SCORED SALT QUESTIONNAIRE TO SCREEN FOR HIGH DIETARY SALT INTAKE IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

A WONG1,2, C MANNIX1,2, J ZHANG1,2, A RANGAN3, G RANGAN1,2
1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Australia, 2Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Sydney, Westmead, Australia, 3Nutrition and Dietetics, School of Life and Environmental Science, The University of Sydney, , Sydney, Australia

Aim: To test the hypothesis that the Scored Sodium Questionnaire (SSQ) is reliable for detecting HSI in adults with ADPKD.
Background: The restriction of dietary salt (≤100mmol/L) may reduce the growth of kidney cysts in autosomal dominant polycystic kidney disease (ADPKD). The SSQ is a validated tool to screen for high dietary salt intake (HSI) in elderly patients with Stage 3-5 Chronic Kidney Disease but its use in ADPKD is not known.
Methods: Patients with ADPKD (18 to 67 years old; eGFR≥30 mL/min/1.73m²) participating in the PREVENT-ADPKD study self-completed the SSQ at the Screening Visit. HSI was defined as 24-hour urine sodium excretion >100mmol/L. Receiver operating characteristic (ROC) analysis was used to determine the ideal cut-off for SSQ score in ADPKD population.
Results: The majority (78%) of the cohort (n=126; 43% male; 44±12 years old; 24-hour urine sodium 144±56mmol/d mean±SD) were HSI consumers. HSI positively correlated with younger age and male gender but not height-corrected total kidney volume. The SSQ score was higher in HSI (76.4±22.1 vs. 65.3±24.9; P=0.02) but correlation with 24-hour urine sodium was weak (Spearman rho r=0.184, P=0.040). By multivariate analysis, the combination of age, gender and the SSQ score predicted HSI (P<0.001). ROC analysis identified the ideal SSQ cut-off for was 74 to identify HSI (area under the curve, sensitivity and specificity was 0.644, 61% and 75%, respectively).
Conclusion: Consideration of demographic factors (age<40 years old; male gender) together with the SSQ score (>74) may assist in identifying ADPKD patients at risk for HSI who might benefit from formal dietetic consultation. Further refinement of the SSQ scoring system might help improve the performance of this approach in the ADPKD population.


Biography:
Dr. Annette Wong is a postdoctoral research scientist in renal nutrition. She is interested in polycystic kidney disease and understanding the impact of diet and lifestyle on disease progression.

RANDOM DAYTIME SPOT URINE CORRELATES WITH TWENTY-FOUR HOUR URINE OSMOLALITY IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

C MANNIX1,2, AT WONG1,2, J ZHANG1,2, V LEE1,2, D HARRIS1,2, K SUD2,3, G RANGAN1,2
1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Australia, 2Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Sydney, Australia, 3Department of Renal Medicine, Nepean Hospital, Nepean Blue Mountains Local Health District, Sydney, Australia

Aim: To determine the relationship between random daytime spot urine osmolality (UOsm) and 24-hour (hr) UOsm in patients with autosomal dominant polycystic kidney disease (ADPKD).
Background: UOsm is a surrogate measure of hydration and dietary solute intake, regulated by levels of circulating arginine vasopressin (AVP). Monitoring UOsm may be useful to gauge adherence to fluid and diet prescriptions in ADPKD. Traditionally, UOsm is determined by 24-hr collection but patients find this method cumbersome, and hence we investigated if spot collection could be an alternative.
Methods: Spot urine was collected prospectively from ADPKD patients (18-65 years, eGFR ≥30 mL/min/1.73m²) during the Screening Visit of the PREVENT-ADPKD study (RCT investigating the efficacy of prescribed fluid intake on kidney cyst growth). Urine specific gravity (USG) and serum copeptin (a biomarker of AVP) were also analysed, followed by two 24-hr urine collections over the subsequent 12 weeks.
Results: Seventy-nine participants were included (age: 43±11 years; 54% male). The mean spot UOsm was 491±196 mosmol/L and correlated moderately with the mean 24-hr UOsm (424±173 mosmol/L; r=0.56; P<0.001). In contrast, the association between spot UOsm to urinary creatinine ratio and 24-hr UOsm was weak (r=0.16, P=0.03). As expected, spot UOsm also predicted the USG (P<0.001), which was correlated with 24-hr UOsm (r=049, P<0.001). Spot UOsm had a weak association with serum copeptin (median 4.2, range 0.9-28.1 ng/ml; r=0.26; P<0.001).
Conclusion: These data suggest that spot urine collected randomly during the day (either at a clinic visit for UOsm or by patient self-monitoring for USG) is an alternative method to estimate 24-hr UOsm in ADPKD. Further prospective studies and the outcome of the PREVENT-ADPKD trial are required to validate these findings.


Biography:
Carly Mannix is a Senior Research Dietitian and PhD candidate at the Westmead Institute for Medical Research (Westmead Hospital and University of Sydney). She is presently undertaking the PREVENT-ADPKD study which is a national multicentre randomised controlled trial that is investigating the role of hydration on slowing the progression of autosomal dominant polycystic kidney disease, and this is the subject of her PhD thesis. She is an Accredited Practising Dietitian with the Dietitians Association of Australia. She holds a Master of Nutrition and Dietetics (2016) and Bachelor of Applied Science (Exercise and Sport Science) (2014) from the University of Sydney.

RAPID TRANSLATION OF NOVEL NEPHROGENETIC AETIOLOGIES FROM FIRST REPORT TO ACCREDITED DIAGNOSTIC OUTCOME

A MALLETT1, C PATEL2,4, J CRAWFORD2,5, L HALE2,6,7, G HO2,8,9, K HOLMAN2,8, B BENNETTS2,8,9, M LITTLE2,6,7,  I SMYTH2,10, C SIMONS2,5,6
1Royal Brisbane And Women’s Hospital, Stafford, Australia, 2KidGen Collaborative, Australian Genomics Health Alliance, Parville, Australia, 3Faculty of Medicine, The University of Queensland, Herston, Australia, 4Genetic Health Queensland, Royal Brisbane And Women’s Hospital, Herston, Australia, 5Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia, 6Murdoch Children’s Research Institute, Parkville, Australia, 7Department of Paediatrics and Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Australia, 8Sydney Genome Diagnostics, Western Sydney Genetics Program, The Children’s Hospital at Westmead, Westmead, Australia, 9Discipline of Child & Adolescent Health; Discipline of Genetic Medicine, University of Sydney, Sydney, Australia, 10Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia

Aim: To describe the collaborative process involved in translating new genetic causes of monogenic kidney disease into diagnostic clinical outcomes.
Background: The rate of novel nephrogene discovery has been accelerated by genomic research applications. Translating these discoveries into clinical diagnostic testing for patients with rare heritable kidney disease has been less clear or accelerated.
Methods: After informed consent, families with genetically unexplained heritable kidney disease were offered research whole exome/genome sequencing (WES/WGS) (HREC/14/QRBW/34). Custom in-house bioinformatic analysis identified putatively causative variants, which were confirmed independently in an accredited diagnostic laboratory.
Results: Two families had a genetic finding identified in the setting of novel nephrogenes reported during 2017. Family 1 has autosomal dominant renal agenesis, varying between unilateral and bilateral. Despite recruitment in 2014, having 5 affected family members and being recurrently re-analysed, a clear genetic cause had not been identified. On 26/07/2017, GREB1L was reported in association with this phenotype. A heterozygous GREB1L variant (c.4964T>C;p.(Ile1655Thr), ACMG Class4) was identified in all affected family members, diagnostically confirmed and reported to the participants on 19/12/2017 (146days later). Family 2, recruited in 2016, has a phenotype approximating Bartter Syndrome Type3 with autosomal recessive hypokalemic metabolic alkalosis and variable normocalciuria. On 03/07/2017, CLDN10 was reported in association with a similar phenotype. A homozygous CLDN10 variant (c.494G>C;p.(Gly165Ala), ACMG Class3) was identified in the affected family member, diagnostically confirmed and reported to the participants on 19/01/2018 (200days later).
Conclusions: These two families demonstrate the diagnostic power afforded by WES/WGS in ultra-rare and unresolved heritable kidney disease. Furthermore, they suggest that the time taken to translate new gene discoveries into clinical practice is meaningfully shortening.

 

RAPID TRANSLATION OF NOVEL NEPHROGENETIC AETIOLOGIES FROM FIRST REPORT TO ACCREDITED DIAGNOSTIC OUTCOME

A MALLETT1, C PATEL2,4, J CRAWFORD2,5, L HALE2,6,7, G HO2,8,9, K HOLMAN2,8, B BENNETTS2,8,9, M LITTLE2,6,7,  I SMYTH2,10, C SIMONS2,5,6
1Royal Brisbane And Women’s Hospital, Stafford, Australia, 2KidGen Collaborative, Australian Genomics Health Alliance, Parville, Australia, 3Faculty of Medicine, The University of Queensland, Herston, Australia, 4Genetic Health Queensland, Royal Brisbane And Women’s Hospital, Herston, Australia, 5Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia, 6Murdoch Children’s Research Institute, Parkville, Australia, 7Department of Paediatrics and Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Australia, 8Sydney Genome Diagnostics, Western Sydney Genetics Program, The Children’s Hospital at Westmead, Westmead, Australia, 9Discipline of Child & Adolescent Health; Discipline of Genetic Medicine, University of Sydney, Sydney, Australia, 10Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia

Aim: To describe the collaborative process involved in translating new genetic causes of monogenic kidney disease into diagnostic clinical outcomes.
Background: The rate of novel nephrogene discovery has been accelerated by genomic research applications. Translating these discoveries into clinical diagnostic testing for patients with rare heritable kidney disease has been less clear or accelerated.
Methods: After informed consent, families with genetically unexplained heritable kidney disease were offered research whole exome/genome sequencing (WES/WGS) (HREC/14/QRBW/34). Custom in-house bioinformatic analysis identified putatively causative variants, which were confirmed independently in an accredited diagnostic laboratory.
Results: Two families had a genetic finding identified in the setting of novel nephrogenes reported during 2017.
Family 1 has autosomal dominant renal agenesis, varying between unilateral and bilateral. Despite recruitment in 2014, having 5 affected family members and being recurrently re-analysed, a clear genetic cause had not been identified. On 26/07/2017, GREB1L was reported in association with this phenotype. A heterozygous GREB1L variant (c.4964T>C;p.(Ile1655Thr), ACMG Class4) was identified in all affected family members, diagnostically confirmed and reported to the participants on 19/12/2017 (146days later).
Family 2, recruited in 2016, has a phenotype approximating Bartter Syndrome Type3 with autosomal recessive hypokalemic metabolic alkalosis and variable normocalciuria. On 03/07/2017, CLDN10 was reported in association with a similar phenotype. A homozygous CLDN10 variant (c.494G>C;p.(Gly165Ala), ACMG Class3) was identified in the affected family member, diagnostically confirmed and reported to the participants on 19/01/2018 (200days later).
Conclusions: These two families demonstrate the diagnostic power afforded by WES/WGS in ultra-rare and unresolved heritable kidney disease. Furthermore, they suggest that the time taken to translate new gene discoveries into clinical practice is meaningfully shortening.


Biography:
A/Prof Andrew Mallett is a Nephrologist with a special interest in inherited kidney disease and nephrogenetics. A/Prof Mallett has undertaken a Churchill Fellowship and been a recurrent Visiting Fellow at Addenbrooke’s Hospital (Cambridge, UK) and the Cambridge Institute for Medical Research. His PhD (2016, University of Queensland) in nephrogenetics involved extensive national and international collaboration. A/Prof Mallett is a Consultant Nephrologist at RBWH and co-lead of the statewide Queensland Conjoint Renal Genetics Service. He is the National Director of the KidGen Collaborative and the AGHA Renal Genetics Flagship.

ROLE OF CYCLIN-DEPENDENT KINASE 2 ON THE PROGRESSION OF JUVENILE CYSTIC KIDNEY DISEASE MICE

J ZHANG1,2, J BURGESS1,2, D STEPANOVA1,2, P KALDIS3, G RANGAN1,2
1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Australia, 2Department of Renal Medicine, Westmead Hospital, Westmead, Australia, 3Institute of Molecular and Cell Biology (IMCB), , Singapore

Aim: To determine if cyclin-dependent kinase (Cdk)-2 deficiency attenuates renal cyst growth in polycystic kidney disease (PKD) in vivo.
Background: Cdk2 is a key regulator of cell proliferation. In vitro, the loss of polycystin-1 promotes Cdk2 activity, and in vivo, the pan-Cdk inhibitor, roscovitine, reduced the progression of renal cystic disease in juvenile cystic kidney (jck) disease mice. However, the specific in vivo role of Cdk2 in PKD remains unclear.
Methods: Three studies were undertaken: (i) the time course of Cdk2 was examined in jck mice (which have a homozygous point mutation of Nek8) on day 28 (D28), D56, and D84 (n=6 per group); (ii) the progression of renal cystic disease was compared in compound jck mice with or without Cdk2 deficiency; and (iii) the effect of sirolimus on Cdk2 activity in jck mice.
Results: Renal disease in jck mice was characterised by diffuse tubular cyst growth, interstitial inflammation and fibrosis, and renal impairment peaking on D84. Renal epithelial cell proliferation peaked on D28, whereas whole-kidney expression of Cdk2-cyclin partners (A and E), as well as the kinase activity of Cdk2 and Cdk1, was only maximal on D84 in jck mice. However, renal disease progression was not attenuated by Cdk2 deficiency in jck mice, and was associated with persistent Cdk1 activity. In contrast, treatment of jck mice with sirolimus (D28-56) reduced both Cdk2 and Cdk1 activity, and decreased renal cyst growth.
Conclusions: Cdk2 kinase activity was maximal only in late-stage PKD, and the absence of Cdk2 did not reduce renal cyst growth, most likely due to compensation by Cdk1. These data suggest that specifically targeting Cdk2 is unlikely to attenuate cyst growth in PKD.


Biography:
Jennifer is currently a PhD student in the Polycystic Kidney Disease Group at the Westmead Institute for Medical Research, University of Sydney, under the supervision of Associate Professor Gopi Rangan. She previously completed a Bachelor of Science (Physiology and Nutrition & Metabolism), followed by a Master of Nutrition and Dietetics. Her PhD is focused on preclinical research into what triggers cyst formation in autosomal dominant polycystic kidney disease. She is also currently working as a research dietitian on the PREVENT-ADPKD study.

RELATIONSHIP BETWEEN DNA DAMAGE AND KIDNEY CYST FORMATION IN MURINE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

J ZHANG1, M LUCIUK1, P HARRIS3, Y WANG1,2, D HARRIS1,2, G RANGAN1,2
1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Australia, 2Department of Renal Medicine, Westmead Hospital, Westmead, Australia, 3Mayo Translational PKD Centre, Mayo Clinic, Rochester, USA

Aim: To determine if DNA damage is present in cyst-lining epithelial cells of Pkd1 mice.
Background: Kidney cyst formation in autosomal dominant polycystic kidney disease (ADPKD) is focal and random, coinciding with reduced PKD gene dosage. We hypothesised that DNA damage might be a trigger for this event, and that it might be detected in renal cysts.
Methods: Pkd1 (homozygous for hypomorphic Pkd1 allele R3277C; n=12 per timepoint), and wild-type (WT) mice (n=8 per timepoint), were examined at 1, 3 and 6 months of age. DNA damage was assessed by immunohistochemistry using H2AX and γ-H2AX (specific biomarkers of DNA damage).
Results: Focal and sporadic kidney cysts were evident throughout the cortex and outer medulla from 1 month of age. The two kidney to body weight ratio was 1.4, 1.6 and 1.6-fold higher in Pkd1 compared to WT mice at 1, 3 and 6 months respectively, and %cyst area increased from 6.9% at 1 month to 10.8% at 6 months. In WT kidneys, qualitative histological analysis demonstrated that H2AX was diffusely expressed in the majority of nuclei, whereas γ-H2AX was rare and present only in scattered nuclei. In Pkd1 mice, H2AX and γ-H2AX staining was similar to WT in non-cyst lining cells at all time points. However, H2AX and γ-H2AX staining was stronger in the majority of cyst-lining cells. In addition, γ-H2AX staining was stronger at 1 month compared to 3 and 6 months, and in smaller rather than larger cysts.
Conclusions: These data support the hypothesis that DNA damage is present in the early stages of cystic renal disease, and suggest that it may be a factor in triggering kidney cyst formation in ADPKD.


Biography:
Jennifer is currently a PhD student in the Polycystic Kidney Disease Group at the Westmead Institute for Medical Research, University of Sydney, under the supervision of Associate Professor Gopi Rangan. She previously completed a Bachelor of Science (Physiology and Nutrition & Metabolism), followed by a Master of Nutrition and Dietetics. Her PhD is focused on preclinical research into what triggers cyst formation in autosomal dominant polycystic kidney disease. She is also currently working as a research dietitian on the PREVENT-ADPKD study.

 

DIETARY SODIUM INTAKE IS CORRELATED WITH SERUM COPEPTIN IN EARLY-STAGE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

J ZHANG1,2, C MANNIX2,  A RANGAN1, AT WONG2, G RANGAN2,3
1Discipline of Nutrition and Dietetics, School of Life and Environmental Sciences, University of Sydney, Camperdown, Australia, 2Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Australia, 3Department of Renal Medicine, Westmead Hospital, Westmead, Australia

Aim: To determine the association between dietary sodium and protein intakes with serum copeptin (a marker of arginine vasopressin (AVP)) in patients with autosomal dominant polycystic kidney disease (ADPKD).
Background: Elevated levels of AVP are hypothesised to worsen renal cyst growth in ADPKD. Apart from low fluid intake, the dietary intake of sodium and protein also influence AVP levels, but this has not been specifically investigated in ADPKD.
Methods: Patients with ADPKD (18-65 years, eGFR≥30 mL/min/1.73m²) underwent a structured diet history interview to assess usual intake over the past 3 months, as part of the PREVENT-ADPKD study. Twenty-four-hour urinary sodium and urea excretion were measured to validate the diet history-reported sodium and protein intakes, respectively. Serum copeptin was measured by a sandwich immunoassay (B.R.A.H.M.S).
Results: Twenty-nine participants (age 42±12 yrs; BMI 26±5 kg/m²; mean±SD) were analysed. The diet history was a valid method for estimating dietary protein, as reported intakes demonstrated a strong correlation with 24-h urine-derived estimates (r=0.658; P<0.001), and there was no evidence of systematic bias by the Bland-Altman method. Median±IQR serum copeptin concentration was 4.09±8.55 pmol/L. Multivariate analyses (adjusted for age, gender, 24-h urine volume and serum creatinine) revealed that higher serum copeptin was strongly associated with higher 24-h urine sodium (B=0.695; P=0.017) (the gold-standard for dietary sodium intake), but not with diet history-reported sodium or protein intake, 24-h urine urea, urine osmolality or dietary solute intake.
Conclusions: These cross-sectional, observational data support the hypothesis that dietary sodium intake stimulates AVP release in ADPKD. An ongoing randomised clinical trial will determine the combined long-term effects of adequate hydration and lowering dietary sodium intake on serum copeptin and the renal progression of ADPKD.


Biography:
Jennifer is currently a PhD student in the Polycystic Kidney Disease Group at the Westmead Institute for Medical Research, University of Sydney, under the supervision of Associate Professor Gopi Rangan. She previously completed a Bachelor of Science (Physiology and Nutrition & Metabolism), followed by a Master of Nutrition and Dietetics. Her PhD is focused on preclinical research into what triggers cyst formation in autosomal dominant polycystic kidney disease. She is also currently working as a research dietitian on the PREVENT-ADPKD study.

SEASONAL CHANGES IN FLUID INTAKE IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

C MANNIX1,2, A RANGAN3, J ZHANG1,2,G RANGAN1,2, AT WONG1,2
1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, Australia, 2Department of Renal Medicine, Westmead Hospital, Westmead, Australia, 3Nutrition and Dietetics, School of Life and Environmental Science, University of Sydney, Sydney, Australia

Aim: To determine the influence of season on fluid intake in patients with autosomal dominant polycystic kidney disease (ADPKD).
Background: Adequate hydration has been hypothesised to reduce the progression of ADPKD. Multiple factors influence fluid intake behaviour and specifically the role of seasonal variations in patients with ADPKD are not known.
Methods: The mean baseline daily fluid intake was assessed in patients with ADPKD (18-65 years old; eGFR≥30ml/min/1.73m²; n=100 and living primarily in Sydney and Perth) who were screened for the PREVENT-ADPKD study (a randomised controlled trial to determine if adequate hydration will slow kidney growth in ADPKD). Fluid intake was assessed using a beverage frequency questionnaire (BFQ) (previously validated for this purpose in this population), 24-hour urine volume, osmolality and other serum markers of hydration. One-way ANOVA was used to analyse inter-group differences.
Results: Fifty-three percent of the cohort were male with a mean age of 43±11 years old and BMI 27±5kg/m². The mean daily fluid intake in summer (n=20, 3040±930ml), autumn (n=28, 2843±1076ml), winter (n=18, 2822±1138ml) and spring (n=34, 2715±1027ml) were similar and the inter-seasonal differences were not significant (P=0.748). Similarly, 24-hour urine volume did not vary by season (P=0.221), nor did 24-hour urinary osmolality and sodium, or serum sodium and osmolality.
Conclusion: Fluid intake was stable through the year with no increase during the warmer months. These baseline data suggest that additional coaching during summer may be warranted in patients who are randomised to the prescribed fluid intake group (the intervention) in the PREVENT-ADPKD study. The limitations of this data are the sample size and that further studies are needed to determine if seasonal variations in intra-individual fluid intake exist.


Biography:
Carly Mannix is a Senior Research Dietitian and PhD candidate at the Westmead Institute for Medical Research (Westmead Hospital and University of Sydney). She is presently undertaking the PREVENT-ADPKD study which is a national multicentre randomised controlled trial that is investigating the role of hydration on slowing the progression of autosomal dominant polycystic kidney disease, and this is the subject of her PhD thesis. She is an Accredited Practising Dietitian with the Dietitians Association of Australia. She holds a Master of Nutrition and Dietetics (2016) and Bachelor of Applied Science (Exercise and Sport Science) (2014) from the University of Sydney.

FROM A MISDIAGNOSIS TO DIAGNOSIS OF MYOSIN HEAVY CHAIN 9 RELATED PLATELET DISORDER

S BEK1,  N EREN1
1Kocaeli University Hospital, Kocaeli, Turkey

Background: Myosin Heavy Chain 9 (MYH9) missense mutations have been characterized by large platelets, leukocyte Döhle bodies, in variable extent sensorineural deafness, cataracts, and glomerulopathy. We report the clinical manifestations and treatment of a case with heterozygous MYH9 R702 mutation.
Case Report: A 25-year old female with triad of thrombocytopenia, sensorineural hearing loss and end stage renal disease (ESRD) presented with uremic symptoms with a history of chronic thrombocytopenia with recurrent epistaxis, gum bleeding and anemia  since childhood. She was misdiagnosed with ITP, Bernard -Soulier and Alport’s syndrome chronologically. First misdiagnosis of idiopathic thrombocytopenia was treated oral methylprednisolone, then pulses of  intravenous immunoglobulin (IVIG) and azathioprine 300 mg/day were tried  respectively with no response. The diagnosis was re-evaluated; bone marrow biopsy was done relieving increased number of megakaryocytes with moderately decreased platelet budding and increased reticulin build-up. Large platelets and Döhle bodies on peripheral blood smear were noted.  The audiogram done at the age of 22 revealed a profound  high-frequency sensorineural hearing deficit bilaterally and the renal biopsy was done with 3 gr/day proteinuria. Renal biopsy revealed features consistent with chronic glomerulosclerosis. Genetic analysis was performed at the age of 23  revealing MYH9 gen: NM_002473.5 p.R702C (c.2104C>T) heterozygous mutation. She has no findings of cataract on examination. She has been diagnosed with MHY9 Related Disease (MHY9RD) and treated with eltrombopag 75 mg/day. After a successful increase to 17 000/mm3 in platelet count, the peritoneal catheter was  implanted successfully without complications.
Conclusions: MHY9RD is a rare syndrome that can end with ESRD and severe hearing loss. This rare diagnosis should be kept in mind and treatment modalities like renal biopsy should be done with eltrombopag.


Biography:
I am an assistant professor in Kocaeli University Hospital and will be working for one-year in Sydney University, Nephrology Department as an ISN-fellow between 1st June- 2018/ 2019.

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