Academic Form No.

19

KERALA VETERINARY AND ANIMAL SCIENCES UNIVERSITY

FACULTY OF VETERINARY AND ANIMAL SCIENCES
PROGRAMME OF RESEARCH WORK FOR THESIS FOR DOCTORATE DEGREE

1. Title of thesis 5. Objectives of the study

Diagnosis and management of cardiovascular-

renal axis disorder subtype H in dogs 1. Occurrence of cardiovascular-renal axis
disorder subtype H (CvRDH) in dogs

2(a). Title of the approved Department/

2. Estimation of urine microalbumin and
KVASU research project
serum inosine in early diagnosis of CvRDH
Not Applicable

3. Study the efficacy of ultrafiltration in

2(b). Code number, if any, and order by
CvRDH
which the Department / KVASU research
project is approved
Not Applicable 6. Practical/ Scientific utility

3(a). Name of the student Cardiovascular renal axis disorders

Rupalee Sunil Ghag (CvRD) are characterised by the cardiovascular
and renal disorders wherein failure of one
3(b). Admission number
organ leads to subsequent failure of the other.
16-DVM-003
There are three subtypes of cardiovascular
3(c). Name of the discipline renal axis disorders. The first subtype CvRDH

Veterinary Clinical Medicine, Ethics and describes renal damage due to primary
jurisprudence cardiovascular diseases and their management.
Although the prevalence of CvRDH is
4(a). Name of the major advisor (Guide)
unknown in dogs, there is strong evidence of
Dr. N. Madhavan Unny
worsening renal function due to progression of
4(b). Designation cardiovascular diseases and their management.
Assistant Professor,
Department of Veterinary Clinical
Medicine, Ethics and Jurisprudence,
College of Veterinary and Animal Sciences,
Mannuthy, Thrissur- 680 651
 Mechanisms involved in CvRDH are
decreased kidney perfusion secondary to
decreased cardiac output, activation
neurohormonal systems and generation of
reactive oxygen species. Cardiovascular renal
disorder subtype H is further divided into
animals with stable and unstable diseases.
Acute decompensation of cardiovascular
system leads to acute worsening of renal
function (unstable). Chronic cardiovascular
dysfunction and its management may lead to
CvRDH for better survival outcomes.
of 7. Important publications on which the
study is based
MacDonald et al. (1987) reported that
angiotensin converting enzyme inhibitors
(ACEI) were nephrotoxic at very high dosages
and were associated with volume contraction
and worsening of kidney function.
Nicolle et al. (2007) found that fifty

chronic kidney dysfunction (stable). Early percent of one hundred and twenty four dogs

detection of renal dysfunction due to with chronic valvular heart disease were

cardiovascular diseases and their management azotaemic.

is a great challenge. The assessment of serum

Atkins et al. (2009) suggested that
creatinine levels in CvRDH is not reliable as it diuretic-induced volume depletion could
detects renal dysfunction only after a increase the risk of angiotensin converting
considerable loss of nephrons. Biomarkers such enzyme inhibitors (ACEI) induced renal injury.
as urine microalbumin and serum inosine are
Echocardiography was useful to assess
useful for early detection of renal dysfunction
cardiac morphology and function. Doppler
and will in turn help in effective management
echocardiography provided information about
of the disorder.
velocity and direction of blood flow and
Ultrafiltration is a treatment modality myocardial motion (Chetboul and Tissier,
which has proved to be useful to treat 2012).
cardiorenal patients in human medicine.
Extensive studies in dogs to find the efficacy of Eatroff et al. (2012) opined that use of
this extracorporeal blood filtration technique in renal replacement therapy such as
ultrafiltration enabled management of
the CvRDH setting are scarce.
intravascular volume.
In this scenario, a study is proposed to
Pouchelon et al. (2015) defined urine
assess the potential of biomarkers in the
microalbumin as a marker for glomerular
diagnosis of CvRDH and to evaluate the
permselectivity.
efficacy of ultrafiltration in the management of
 Santos et al. (2015) opined that vascular structures and lung parenchyma.
ultrafiltration was an adjunct therapy for Electrocardiographic findings including
congestive cardiac failure as it resolved rhythm abnormalities and chamber
congestion, reduced right atrial and pulmonary enlargement will be recorded.
arterial wedge pressure, improved cardiac Echocardiography will be performed to
output, decreased neurohormonal levels, evaluate cardiac morphology, function and
corrected hyponatremia, restored diuresis and
relevant haemodynamic parameters.
reduced diuretic requirements.
Blood samples will be collected to

According to Orvalho and Cowgill estimate serum creatinine and blood urea

(2017), acute cardiorenal syndrome includes nitrogen, to rule out azotaemia.

acute decompensation of cardiovascular system Causes of renal failure associated with

leading to acute worsening of renal function haemoparasites will be ruled out by peripheral

(unstable) and chronic cardiorenal syndrome blood smear, buffy coat examination and PCR.

with chronic cardiovascular dysfunction and its Leptopsira will be ruled out using MAT.

management leading to chronic kidney A minimum of 30 non-azotemic (serum

dysfunction (stable). The authors suggested that creatinine <1.6 mg/dL) dogs with confirmed
serum inosine could be a potential marker to cardiovascular disorders will be utilised for this
detect renal tubular dysfunction. study.
The cases will be treated for
8. Outline of technical programme
cardiovascular diseases with drugs including
diuretics, angiotensin converting enzyme
Dogs presented to University Veterinary
inhibitors (ACEI), inodilators and beta blockers
Hospitals, Mannuthy and Kokkalai, with clinical
and other anti-arrhythmic agents as per
signs suggestive of cardiovascular disorders, i.e.
standard protocol.
nocturnal cough, syncope, exercise intolerance,
2. Renal Studies
etc, will be screened.
These dogs will be monitored for
1. Cardiac Studies
development of renal dysfunction based on
Cardiac function will be evaluated using
renal function tests, blood gas analysis,
thoracic radiography, electrocardiography and
urinalysis, urine protein creatinine ratio, urine
echocardiography.
microalbumin and serum inosine. Blood and
Thoracic radiography will be carried
urine samples will be collected on day of
out to detect changes in the cardiac silhouette,
presentation (day 0), day 45 and day 90.
Ultrasonographic evaluation of the kidneys will
4. Echocardiographic findings
be carried out.
Blood pressure evaluation will be done a. Ejection fraction (%)
with oscillometric method in all cases at the b. Fractional shortening (%)
intervals specified above.
c. E point septal separation (mm)
Doses of cardiac drugs will be titrated
depending on the changes in the renal function. d. Left atrium to Aorta Ratio
3. Ultrafiltration and intermittent 5. Radiographic observations
haemodialysis
6. Results of routine examination of urine
The dogs, with congestive heart failure,
refractory to medical management will be 7. Results of kidney function tests

subjected to ultrafiltration, with informed a. Blood urea nitrogen (mg/dL)

consent of owner (Santos et al., 2015).
b. Creatinine (mg/dL)
In cases of grade IV and V of acute
c. Phosphorous (mg/dL)
kidney injury, (International Renal Interest
Society, 2016) haemodialysis, in addition to d. Protein (g/dL)
ultrafiltration will be carried out, as and when e. Albumin (g/dL)
required. Renal replacement therapies such as
8. Urine protein creatinine ratio
intermittent haemodialysis and ultrafiltration
will be used for intravascular volume 9. Urine microalbumin (mg/dL)
management, alleviate life threatening 10. Serum inosine (mg/dL)
azotaemia, electrolyte and acid-base imbalances.
11. Findings of renal ultrasonography
Response to treatment will be evaluated.
Data recorded from the clinical study 12. Changes of blood electrolytes and acid
base
will be analysed statistically using SPSS version a. Sodium (Na+) (mEq/L)
24.
b. Potassium (K+) (mEq/L)

9. Main items of observations to be made c. Chloride (Cl-) (mEq/L)

1. Clinical findings d. Ionised calcium (iCa+2) (mg/dL)

2. Complete blood count e. Bicarbonate (cHCO3-) (mEq/L)

3. Electrocardiographic findings f. Base excess (mEq/L)


g. pH
13. Blood pressure (mm of Hg)
14. Ultrafiltration parameters
a. Body weight (kg) – pre and post
session
b. Ultrafiltration rate (ml/kg/hr)
c. Ultrafiltration coefficient (KUF)
d. Duration of session (hours)
e. Ultrafiltration volume (litres)
f. Number of sessions needed
15. Response to treatment
10. Facilities
a) Existing: Facilities in the Department of
Veterinary Clinical Medicine, Ethics
Jurisprudence, Teaching Veterinary Clinical
Complex, Central Instrument Laboratory at the
College of Veterinary and Animal Sciences,
Mannuthy will be utilized for the study.
11. Duration of the study
Six semesters
12. Financial estimate
a. Chemicals and biologicals : Rs. 45000/-
b. Contingencies : Rs. 5000/-
Total : Rs. 50000/-
13. Signature of the student
14. Signature of the Major Advisor
Place: Mannuthy
Date: 18/05/2018
Name and signature of the members of the
advisory committee
Chair person
Dr. N. Madhavan Unny
Assistant Professor,
Department of Veterinary Clinical Medicine,
Ethics and Jurisprudence, College of
Veterinary and Animal Sciences,
Mannuthy, Thrissur- 680 651.
Members
Dr.Usha Narayana Pillai
and
Professor and Head,
Department of Veterinary Clinical Medicine,
Ethics and Jurisprudence, College of
Veterinary and Animal Sciences,
Mannuthy, Thrissur- 680 651.
2. Dr. S. Ajithkumar
Professor and Head,
University Veterinary Hospital and Teaching
Veterinary Clinical Complex, College of
Veterinary and Animal Sciences, Mannuthy,
Thrissur- 680 651.
3. Dr. M. Shynu
Assistant Professor,
Department of Veterinary Biochemistry,
College of Veterinary and Animal Sciences,
Mannuthy,
Thrissur- 680 651.
MacDonald, J. S., Bagdon, W.J., Peter, C.P.,
4. Dr. S. Anoop
Assistant Professor, Sina, J.F., Robertson, R.T., Ulm, E.H. and
Department of Veterinary Surgery and Bokelman, D.L. 1987. Renal effects of
Radiology,
College of Veterinary and Animal Sciences, enalapril in the dog. Kidney Int. 31:148-53.
Mannuthy,
Thrissur- 680 651.
Nicolle, A.P., Chetboul, V., Allerheiligen, T.,
Pouchelon, J.L., Gouni, V., Tessier-Vetzel, D.,
APPENDIX-I
Sampredrano, C.C. and Lefebvre, H.P.
REFERENCES
2007.Azotaemia and glomerular filtration rate
in dogs with chronic valvular disease. J. Vet.
Atkins, C., Bonagura, J., Ettinger, S., Fox, P.,
Intern. Med. 21:943-949.
Gordon, S., Haggstrom, J., Hamlin, R., Keene,
B., Luis-Fuentes, V. and Stepien, R.
Orvalho, J.S. and Cowgill, L.D. 2017.
2009.Guidelines for the diagnosis and treatment
Cardiorenal syndrome. Vet. Clin. North Am.
of canine chronic valvular heart disease. J. Vet.
Small Anim. Pract. 47:1083-1102.
Intern. Med. 23:1142-1150.

Pouchelon, J.L., Atkins, C.E., Bussadori, C.,

Chetboul, V. and Tissier, R. 2012
Oyama, M.A., Vaden, S.L., Bongura, J.D.,
Echocardiography assessment of canine
Chetboul, V., Cowgill, L.D., Elliot, J., Francey,
degenerative mitral valve disease. J. Vet.
T., Grauer, G.F., Luis Fuentess, V., Sydney
Cardiol. 14:127-148.
Moise, Polzin, D.J., Van dongen, A.M. and

Eatroff, A.E., Langston, C.E., Chalhoub, S., Van Israel, N. 2015. Cardiovascular-renal axis

Poeppel, K. and Mitelberg, E. 2012. Long term disorders in the domestic dog and cat: a

outcome of cats and dogs with acute kidney veterinary consensus statement. J. Small Anim.

injury treated with intermittent haemodialysis: Pract. 56:537-52.

135 cases (1997-2010). J. Am. Vet. Med. Assoc. Santos, F., Bandt, C. and Bolfer, L.
241:1471-1478. 2015.Extracorporeal blood ultrafiltration in
decompensated congestive heart failure and
International renal interest society,
cardiorenal syndrome. Anclivepa. 2:6-17.
2016.Available:http://www.iriskidney.com/guid
elines/grading.html.
APPENDIX-II

Time frame of work

Semester -1 Semester – 5
1. Collection of literature 1. Recruitment of patients
2. Review of literature
2. Categorising into stable and unstable
3. Preparation of project proposal groups
3. Sample collection and analysis
Semester-2
4. Monitoring cases
1. Collection of literature
Semester – 6
2. Review of literature
1. Compilation of data
Semester -3 2. Interpretation of results
1. Recruitment of patients 3. Thesis writing
2. Categorising into stable and unstable 4. Submission of thesis
groups
3. Sample collection and analysis
4. Monitoring cases

Semester -4
1. Recruitment of patients
2. Categorising into stable and unstable
groups
3. Sample collection and analysis
4. Monitoring cases
 CERTIFICATE

Certified that the research project has been formulated observing the stipulations laid down under the
Prevention of Cruelty to Animal (Amendment) Act, 1998.

Mannuthy, Dr. N. MadhavanUnny

18/05/2018 (Major Advisor)