POTENTIALLY INAPPROPRIATE MEDICATION USE IN ADULTS WITH ADVANCED CHRONIC KIDNEY DISEASE

W TESFAYE1, RL CASTELINO2, BC WIMMER1, C MCKERCHER3, MD JOSE1,3,4, GM PETERSON1, ST ZAIDI1
1School of Medicine, University of Tasmania, Hobart, Australia, 2The University of Sydney, Sydney, Australia, 3Menzies Institute for Medical Research, Hobart, Australia, 4Renal Unit, Royal Hobart Hospital, Hobart, Australia

Aim: To estimate the prevalence of potentially inappropriate medications (PIMs) use and identify the medications involved, in community-dwelling adults with advanced chronic kidney disease (CKD).
Background: Inappropriate medication use is associated with detrimental clinical outcomes in CKD. However, limited data are available on the level and type of PIMs use in non-institutionalised CKD patients.
Methods: Ninety-three people (67% men) with advanced CKD (estimated glomerular filtration <30ml/min/1.73m2) not receiving dialysis were recruited via treating physicians (general practitioners & nephrologists). PIMs use was evaluated in two ways – (i) Beers criteria and (ii) the Australian Medicines Handbook (AMH) for renally-cleared medications that needed adjustment based on creatinine clearance (CLcr).
Results: The median (interquartile range (IQR)) age of participants was 73 (65-80) years and the majority (76%) were aged (≥65 years). A total of 737 medications, predominantly cardiovascular agents (34%), were prescribed and the mean (SD) number of medications per participant was 8 (3.4). Based on Beers criteria, 17 (24%) of the older participants were exposed to at least one PIM, and clinically important drug interactions were identified in another 10% of them. In contrast, 28 (30%) patients had at least one PIM based on their CLcr (AMH). Prazosin (26%) and benzodiazepines (19%) were the most common PIMs identified using Beers criteria. On the other hand, atenolol (27%) and spironolactone (12%) were frequently identified PIMs per AMH’s dosage recommendations.
Conclusions: The use of PIMs in these patients with advanced CKD is common. While more data are required from large studies on the clinical consequences of PIMs use in these patients, regular medication review using criteria applicable to older adults together with renal dosage adjustment guidelines appears warranted.


Biography:
To come.

THE EFFECT OF SPIRONOLACTONE ON RENAL INJURY (FIBROSIS) IN A HYPERTENSIVE TRANSGENIC CYP1A1REN2 RAT MODEL.

C LEADER1, M MOHARRAM1, I SAMMUT1,  S COFFEY1, G WILKINS1, R WALKER1
1University Of Otago, Dunedin, New Zealand

Aim:  To investigate the impact of chronic hypertension with and without daily spironolactone (SP) on heart and kidney function and injury in a rat model of hypertension.
Background:  Hypertension is one of the leading contributors to cardiovascular and renal disease.   Spironolactone (SP) improves cardiac outcomes following injury, but its impact on hypertension-induced kidney fibrosis is uncertain.
Methods:  Male Cyp1a1Ren2 rats were randomised to normal chow or chow with addition of 0.167% indol-3-carbinol to induce hypertension (>150mmHg).  Hypertensive rats were further divided into those receiving spironolactone 50mg daily or not.  Systolic blood pressure (SBP), urine collection and echocardiograms were performed before termination (after three months) and tissue collected for analyses. The extent of fibrosis was determined on Masson’s trichrome stained sections using pixel counts (ImageJ). Glomerulosclerosis was scored semi-quantitatively on PAS sections.
Results: Chronic hypertension resulted in elevated SBP (196±19 vs 91±12 mmHg (controls)), proteinuria (60±19 vs 14±3 ml.kg-1.hr-1), cortical fibrosis (7±0.4% vs 0.2±0.1%) and glomerulosclerosis index scores (GSI: 2.6±0.3 vs 0.2±0.06) [all variables were significant at p<0.001]. Hypertension also reduced cardiac ejection fraction (EF, 67±7 vs 80±3%, p<0.001) and endocardial global longitudinal strain (endoGLS, -19±3 vs -28±3%, p<0.001) compared to normotensive animals.
SP had no impact on SBP, proteinuria, EF or endoGLS, but did result in significant reductions to cortical fibrosis (3±1.3%, p<0.05) and GSI (2±0.1, p<0.05) when compared to hypertensive alone animals.
Conclusions: Chronic elevation of SBP caused significant renal damage over three months.  The addition of spironolactone did not improve physiological measurements but did reduce fibrotic and sclerotic damage in the kidney.  Further work will aim to analyse the relationship between hypertension and renal deterioration.


Biography:
Catherine completed a Master’s degree in Biological Science, exploring the bat-moth arms race, studying the neuroethology of two endemic New Zealand moth species to endemic New Zealand bat calls.  Following this, Catherine developed a keen interest in the medical research field, with specific interest in cardiology, circulation and nephrology. More recently, she completed her PhD (under the supervision of Professor R. Walker) at the University of Otago (New Zealand), investigating the effect of a mineralocorticoid receptor antagonist (Spironolactone) on renal fibrosis following a myocardial infarction in a transgenic hypertensive rat model.

DOES THE TYPE OF INTERVENTION FOR ISCHAEMIC HEART DISEASE IMPACT ON MORTALITY AND MORBIDITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE

A JEYARUBAN1,2,3, WE HOY1,2, A CAMERON1,2, HG HEALY1,2,3, J ZHANG1,2,  A MALLETT1,2,3
1CKD.QLD and NHMRC CKD.CRE, Brisbane, Australia, 2Faculty of Medicine, The University of Queensland, Herston, Australia, 3Kidney Health Service, Royal Brisbane and Women’s Hospital, Herston, Australia

Aim: To identify whether the type of intervention for ischaemic heart disease (IHD) impacts on mortality or further renal deterioration.
Background: The associations of chronic kidney disease (CKD) and IHD are well known. Clinically, because of the use of intra-arterial contrast media, coronary angiograms are sometimes not performed to avoid further deterioration in kidney function amongst CKD patients.
Method: A retrospective cohort study involved 144 RBWH patients with a diagnosis of IHD enrolled in the CKD.QLD registry from January 2011 to August 2017 with a minimum of 2 years follow up. 59 patients had medical management (MED) and 85 patients had interventions (INT i.e. PCI or CABG) for IHD. Comorbidities, mortality and delta eGFR (CKD-EPI) were analysed.
Results: Patients in the MED group were older (77.5 vs 67.4years; p<0.05) with worse baseline renal function (eGFR:33mL/min/1.73m² vs 40mL/min/1.73m²; p=0.02) and higher serum urate level (0.48 vs 0.45mmol/L; p=0.23). The INT group had lower prevalence of gout (44% vs 56%; p=0.69), diabetes (42% vs 58%; p=0.719), dyslipidaemia (38% vs 62%; p=0.29), cerebrovascular disease (48% vs 52%; p=0.63), peripheral vascular disease (45% vs 55%; p=0.34) and hypertension (44% vs 56%; p=0.06).Kaplan-Meier analysis revealed a significant decrease in mean survival of MED compared to INT patients (1,742.3 days (90.7) vs 2,362.3(80.3); p<0.05). Post adjustment for age and above comorbidities, MED and higher age were associated with significantly higher mortality (p<0.05).  However, the patients in the MED and INT groups had no significant difference in delta eGFR (CKD-EPI; p=0.4).
Conclusion: In this small cohort study, intervention for IHD was associated with increased survival with no change in renal disease progression in comparison to medically managed patients.


Biography:
Andrew Jeyaruban is currently a medical registrar with a keen interest in renal medicine. He graduated from James Cook University with Honours in 2014.  Andrew then completed his residency at the Royal Brisbane and Women’s Hospital Brisbane, Australia. He is currently a basic physician trainee at the Liverpool Hospital, Sydney.

CARDIOVASCULAR EVENTS DO NOT ACCELERATE DECLINE OF RENAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

A JEYARUBAN1,2,3, WE HOY1,2, A CAMERON1,2,  HG HEALY1,2,3, J ZHANG1,2, A MALLETT1,2,3
1CKD.QLD and NHMRC CKD.CRE, Brisbane, Australia, 2Faculty of Medicine, The University of Queensland, Herston, Australia, 3Kidney Health Service, Royal Brisbane and Women’s Hospital, Herston, Australia

Aim: To investigate the association of cardiovascular events (CVE) on deterioration of renal function in patients with chronic kidney disease (CKD).
Background: The association of CKD and CVE is well publicised. How CVE modify the pattern and rate of subsequent deterioration of renal function is not well described.
Method: A retrospective cohort study of 1,123 RBWH patients enrolled in the CKD.QLD registry from January 2011 to August 2017 with a minimum of 2 years follow up time. Patients’ CVE data and renal function (eGFR CKD-EPI) were extracted from the clinical records. Patients on renal replacement therapy (RRT) were imputed an eGFR 8mL/min/1.73m² at the date of the first treatment. Delta eGFR(mL/min/1.73m²/year, CKD-EPI) was calculated (difference between latest eGFR compared to eGFR at time of  CVE incident) and stratified by quartiles.
Results: 222 patients experienced at least one CVE with ischaemic heart disease in 144, stroke in 51 and peripheral vascular disease in 40. There was no significant change in the absolute mean delta eGFR between patients with CVE and without CVE  (-2.6mL/min/1.73m²/year (SE=0.4)   vs -1.7mL/min/1.73 m²/year (SE=0.2); p=0.2), after adjustment for age. There was also no significant association of CVE to either first or fourth quartile of delta eGFR (48.9% vs 51.1%; p=0.4). Furthermore, when adjusting for age, gender and previous cardiovascular events there was no significant difference in the progression of RRT in patients with CVE compared to patients without CVE (11.5% vs 10.4%; p=0.6).
Conclusion: Incident CVE do not seem to have a significant association with progression i.e. differential rate of decline of renal dysfunction in CKD patients.


Biography:
Andrew Jeyaruban is currently a medical registrar with a keen interest in renal medicine. He graduated from James Cook University with Honours in 2014.  Andrew then completed his residency at the Royal Brisbane and Women’s Hospital Brisbane, Australia. He is currently a basic physician trainee at the Liverpool Hospital, Sydney

HIGH-SENSITIVITY CARDIAC TROPONIN T AND C-REACTIVE PROTEIN HAVE DIFFERENT PROGNOSTIC VALUES IN HAEMO- AND PERITONEAL DIALYSIS POPULATION: A COHORT STUDY

T CHEN1, 5, H HASSAN2, 7, M VU4, 5, P Rao1, 5, A MAKRIS3, 6

1The Westmead Institute for Medical Research, Westmead, NSW; 2Wollongong Hospital, Wollongong, NSW; 3Liverpool Hospital, Liverpool, NSW; 4Royal Prince Alfred Hospital, Camperdown, NSW; 5University of Sydney, Camperdown, NSW; 6University of New South Wales, Kensington, NSW; 7University of Wollongong, Wollongong, NSW

Aim: To evaluate the prognostic value of high sensitivity cardiac troponin T (hs-cTnT) and C-reactive protein (CRP) in stable haemodialysis (HD) and peritoneal dialysis (PD) patients.

Background: In dialysis population, clinical assessment based on traditional risk factors is inadequate in identifying patients at high risk of adverse outcome. Serum biomarkers can be a useful tool in risk stratification of this population.

Methods: A 3.5-year retrospective observational study of a cohort of 574 HD (n=347) and PD (n=227) patients. All-cause mortality and major adverse cardiovascular events (MACE) were assessed. SPSSv23 was used, P<0.05 was significant.

Results: No patient was lost to follow up. For HD patients, hs-cTnT remained relatively stable for the follow up period. For PD patients, hs-cTnT increased significantly every year (P<0.001).

High-sensitivity cardiac troponin T was an independent predictor of both outcomes in HD and PD patients. C-reactive protein was an independent predictor of both outcomes in PD patients only. Performing CRP in addition to hs-cTnT further improved risk prediction. The area under the receiver operating curves (AUC) for hs-cTnT (mortality AUC=0.706, MACE AUC=0.62) and traditional clinical parameters (mortality AUC=0.703, MACE AUC=0.634) were similar and they were larger than CRP (mortality AUC=0.591, MACE AUC=0.523). Adding hs-cTnT to traditional clinical parameters significantly increased its AUC (P=0.018).

Conclusions:

  1. Both hs-cTnT and CRP have a useful role in predicting adverse outcomes in dialysis patients at 3.5 years. Their prognostic performance is different in HD and PD patients.
  2. Adding hs-cTnT to traditional clinical parameters significantly improves the its prognostic performance.
  3. The frequency of hs-cTnT measurement should be at least yearly for PD. For HD patients, a less frequent measurement may be acceptable.

FIRST CARDIOVASCULAR EVENT POST ENROLMENT IN CKD.QLD REGISTRY PATIENTS WITH DIABETES WHO HAVE UNDERGONE RENAL BIOPSY

KS TAN1,2,3, S NG3, J ZHANG1,2, Z WANG1,2, A CAMERON1,2, WE HOY1,2

1NHMRC CKD.CRE and CKD.QLD, Brisbane, Queensland; 2Faculty of Medicine, University of Queensland, Brisbane, Queensland; 3Renal unit, Logan Hospital & Metro South Health Service, Brisbane, Queensland.

AIMS: Determine the type of first Cardiovascular (CVS) event in patients with diabetes mellitus (DM) enrolled in the CKD.QLD registry who had undergone renal biopsy.

BACKGROUND: The CKD.QLD registry is a Queensland-wide registry of patients with chronic kidney disease (CKD) who are followed up in the state’s public hospital renal units and have provided informed consent. Enrolment commenced in 2011.

METHODS: Patients with DM enrolled in the registry between 22/01/2011 and 15/11/2016 inclusive with previous renal biopsy were included. Baseline characteristics, incidence and nature of the first CVS event post enrolment were determined. Censor date was 1/03/2017.

RESULTS: Among 2665 CKD patients with DM, 189 patients (84 women) had undergone renal biopsy. Mean follow up at censor date was 3.1 years. Mean age at enrolment was 60.2y (SD 12.5).  57 patients (30%) had known CVS disease at enrolment.

At censor date, 52 patients had experienced at least one CVS event. The commonest first CVS event which occurred in 35 patients (67%) was cardiac (acute coronary syndrome/coronary revascularization procedure/admission for acute heart failure). 37% of those who suffered a CVS event had at least one prior CVS event at time of enrolment compared to 28% of those who did not suffer a CVS event although this difference was not statistically significant (p= 0.24).

At censor date, 14 of these 52 patients (27%) had died without commencing renal replacement therapy (RRT) although three (6%) were already committed to supportive care. Eight patients (15%) had commenced RRT.

CONCLUSIONS: In this group of patients at high risk of CVS events, the commonest type of CVS event was cardiac. Known underlying CVS disease did not obviously increase risk.

RENAL ARTERY STENOSIS AS A CAUSE OF TAKOTSUBO CARDIOMYOPATHY

V SASONGKO1, R QASABIAN1,2, S MAY1

1Tamworth Rural Referral Hospital, Tamworth, NSW;  2Royal Prince Alfred, Sydney, NSW

Background: Takotsubo cardiomyopathy, a transient cardiac syndrome that mimics acute coronary syndrome, is thought to be precipitated by sympathetic nervous system activation. Renal artery stenosis (RAS) induces hypertension by several mechanisms, including the rise in serum cathecolamines. We describe a case of Takotsubo cardiomyopathy in a patient with RAS and propose a causal association between the two phenomenon.

Case report: A 78-year-old female haemodialysis patient with background history of hypertension and anxiety presented with acute dyspnoea, elevated troponin and anterior ST-segment changes on electrocardiogram. An echocardiogram performed three months earlier showed normal left ventricular systolic function with Ejection Fraction (EF) of 67%.

Our patient had recently commenced haemodialysis six weeks earlier following a presentation with acute kidney impairment (creatinine of 734mmol/l). She was noted to have small left kidney and a 11.6cm non-obstructed right kidney. Renal biopsy showed viable kidney with mild mesangial matrix expansion.

A repeat echocardiogram showed a severe left ventricular systolic dysfunction (EF of 32%) and coronary angiography was suggestive of Takotsubo cardiomyopathy with minimal coronary artery disease. A renal angiogram was performed at the same time due to our suspicion of RAS and this confirmed no identifiable flow to the right kidney.

Given the apparent viability of the right kidney, angioplasty and stenting of right renal artery was performed, resulting in dramatic improvement of dyspnoea, a return to normal cardiac function and a gradual recovery of renal function. Our patient is currently off dialysis with creatinine of 129mmol/l.

Conclusion: Renal artery stenosis can be suspected as a rare cause of Takotsubo Cardiomyopathy. Stenting of the stenosed renal artery may result in the recovery of renal function and cardiac function.

SUDDEN SEVERE HYPERTENSION: AN ATYPICAL MANIFESTATION OF PRIMARY HYERPARATHYROIDISM. A CASE REPORT

FERRIER C 1, CATTANEO F1, SOLCA C1, BRUNO V2

1Clinica Moncucco, Lugano Switzerland; 2University Hospital, Berne, Switzerland

Background: Calcium plays an important role in blood pressure (BP) regulation, probably through a direct effect on cardiovascular contractility. Hypercalcemia may rise BP by increasing adrenergic activity and vascular reactivity. Primary hyperparathyroidism(PHPT)-associated hypercalcemia is often asymptomatic and detected by routine blood tests. Although hypertension is common in PHPT, the clinical manifestation of PHPT may be atypical.

Case Report: We report a case of a 56 year old Caucasian woman with no H/O hypertension presenting sudden onset of vertigo with severe hypertension. Medical history was otherwise unremarkable, and clinical examination showed a BP of 215/150mmHg and a BMI of 32.2 kg/m2. Initial laboratory data revealed an elevated total serum calcium (2.79 mmol/l), low phosphate (0.83 mmol/L) and normal 24hr urinary calcium excretion (3.4 mmol/day). Other laboratory and radiological examinations excluded a vascular, renal (PCr 73mcmol/L, no proteinuria, normal urinary sediment), thyroid and adrenal disease and/or a pheochromocytoma. Further evaluation for suspected PHPT showed an elevated iPTH level of 182 ng/L (Normal range: 22.5-105) and a left parathyroid adenoma on ultrasound.

Conclusions: In the presence of chronic or acute hypertension PHPT should be excluded. The determination of serum calcium should be mandatory in any patient with suspected secondary form of hypertension.

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