From, Dr.V.S.Deepa, Ist Year,M.D.Biochemistry, Sree Mookambika Institute of Medical Science, Kulasekaram.

To, The Chairman, IAEC/IHEC, Sree Mookambika Institute of Medical Science, Kulasekaram.

Respected Sir, Subject: Submission of Protocol Reg. I am hereby submitting the protocol of my thesis work A STUDY ABOUT THE CHANGES IN LEVELS OF PANCREATIC ENZYMES IN CASES OF CHRONIC RENAL FAILURE. Kindly give permission to carry out the above research study. Place:Kulasekaram Yours Sincerely,

Date: 29-02-2012

(Signature)

PROTOCOL FOR ETHICAL CLEARANCE

1) Name of the candidate 2) Name of the course studying 3) Year of admission 4) Month and year of appearing for final examination 5) Month and year of submitting dissertation 6) Name of the guide and designation

: Dr.V.S.Deepa : M.D.Biochemistry : 2011 : April 2014 : December 2013 : Dr.S.Jaya, Professor, Department of Biochemistry, Sree
Mookambika Institute of Medical Science,Kulasekaram

7) Name of the co-guide and designation

: Dr.J.K.Sathya Sudha Devi, Professor & HOD,

Department of Biochemistry, Sree Mookambika Institute of Medical Science, Kulasekaram

8) Title of the study

:A STUDY ABOUT THE CHANGES IN LEVELS OF

PANCREATIC ENZYMES IN CASES OF CHRONIC RENAL FAILURE

Introduction Chronic renal failure (CRF) encompasses a spectrum of different pathophysiologic process associated with abnormal kidney function and a progressive decline in glomerular filtration rate [1].CRF is caused due to many diseases out of which the most common is glomerulo nephritis. Increase in blood levels of NPN(Urea creatinine and uric acid) is referred to as azotemia [2], which is the hallmark of kidney failure. Uraemic syndrome is the terminal manifestation of renal failure, which is characterised by azotemia, electrolytes imbalance, anaemia, atherosclerosis, hypertension, decreased immunity due to impaired WBC function which causes susceptibility to many infections, altered calcium metabolism causing renal osteodystrophy, gastro intestinal(GI) symptoms like loss of appetite, nausea, vomiting and rarely GI bleeding and very rarely acute pancreatitis. Diagonising these complications may prevent further worstening of the condition of CRF patients. Since CRF patients suffer from pain abdomen and vomiting already, it is difficult to differentiate these symptoms from that of acute pancreatisis. Quantitative estimation of serum amylase and serum lipase will show a marked increase in level when we compare the levels of these enzymes in CRF patients without acute pancreatitis. The present study focuses on the level of pancreatic enzymes in CRF patients without known pancreatitis and to find out the incidence of acute pancreatitis in these patients. Aims and Objectives: The main aim of the study is to investigate about the changes in levels of pancreatic enzymes in
cases of chronic renal failure.The objectives of the study includes the following

a)

To detect the incidence prevelance of acute pancreatitis in known CRF patients with or without

dialysis.
b) To find out the diagnostic value of serum amylase by measuring the rate of serum amylase

clearance to the rate of creatinine clearance in relation to the stages of chronic renal failure (i.e.) mild moderate and severe
c)

To evaluate if serum creatinine, serum amylase and serum lipase have any correlation with the severity of CRF (i.e.) mild moderate and severe

REVIEW OF LITERATURE A study by Royse VL,Jensen DM, Corwin HL in1987 suggested by serum amylase activity greater than threefold elevation suggest coexistence of pancreatitis in CRF patients[3]. Another study by Lin XZ,Chen TW, in the year 1988 concluded that elevation of pancreatic enzymes in CRF patients is more frequent and more extensive and the extent of increase is related to renal function and not to the dialysis status[4]. Collen MJ and Ansher AF in the year 1990 suggested that elevation of serum amylase is not evident until creatinine clearance falls below 50 ml/min[5]. 1n1976 E.B.Pederson and A.Brock as a result of their work suggested that the ratio of Cam/Ccr was significantly increased in patients with severe renal impairment when compared to patients treated with renal allotransplantation. The elevation of serum amylase activity in patients with CRF is primarily due to decreased glomerular filtration rate. So the value of Cam/Ccr for for diagonising acute pancreatitis is doubtful in patients with severe renal disease[6]. Micheal D and Levitt M.D, in 1969 suggested that in renal insufficiency C am was in proportion with Ccr. The clearance of amylase makes urinary amylase and more more sensitive indicator of pancreatitis than in the serum. The diagonistic value of amylase is enhanced if amylase excretion is related to creatinine cxcreation[7]. Giuseppe Montalto, Antonio Carroccio, suggested that increase in pancreatic enzymes during chronic renal pathology is slight but frequent[8].

Pitchumoni, C.S, Arguello.P concluded that acute pancreatitis in CRF is frequently of unknown cause suggesting the role of either CRF or other factors irrespective of cause acute pancreatitis in CRF is a serious disease associated with a high morbidity and mortality[9] WORK ALREADY DONE: No MATERIALS AND METHODS: a) Whether the study involves animals humans or both: Humans b) Type of study: Cross sectional study.

INCLUSION CRITERIA :
c) 50 patients with CRF.from Nephrology Department of Sree Mookambika Institute of Medical Sciences between the age group from 30 to 80 years

EXCLUSION CRITERIA:1) Chronic alcoholics with portal hypertension 2) Known cases of previous pancreatitis Parameters to be studied: Blood Urea, Serum creatinine, Serum Amylase, Urinary Amylase, Serum Lipase, Serum Calcium and Serum Phosphorous. Procedure: The protocol is to be submitted to the human ethical committee for its approval. After getting approval from the HEC written onformed consent is to be obtained fronm all the volunteers before enrolling them in to study. The study is to be conducted in collaboration with the nephrology department of SMIMS.50 volunteers are to be recruited from nephrologic clinic of medicine department of SMIMS after considering the inclusion and exclusion criteria. 50 patients with CRF and other matching parameters are to be recruited in to the study. Before the study the volunteers are to informed about the procedure of the study.

Detailed history of whether the patient is under dialysis will be recorded on a case record form.A sample of 2 hours timed urine is to be collected during whichperiod about 10 cc of blood is to

be collected in a dry syringe.Whole blood will be used for blood urea estimation.Amylase,lipase,calcium and phosphorus will be estimated using the serum. Determination of serum lipase will be done byCNPG3 (ChloroNitroPhenol) method using alpha amylase kit.Determination of serum creatinine is done by Modified Jaffes method using Biosystem kit.Determination of blood urea is done by Urease-GLDH(Glutamate Dehydrogenase )method,using Biosystem kit.Determination of serum calcium is done by modified OCPC(OrthoCresolPhtaleinComplex) method using Biosystem kit.Determination of serum Phosphorus is done by UV End point method using Bayers kit. Methods of Analysis: Data is to entered in excel spread sheet and is to be analysed using statistical software Epi Info Version 3.5.3. Analysis is to be done by simple proportion, mean SD and Chisquare test. Hypothesis There is appositive correlation and association between serum amllase and serum lipase and the severity of CRF References

1) Harrisons principles of internal medicine 18e,Chapter 280. 2) Vasudevan Text Book of Biochemistry, 6e,Chapter 27. 3) Robitaille R, Lafrance JP, Leblanc M, Altered laboratory findings associated with end-stage renal disease., Semin Dial. 2006;19(5):373. 4) Lin XZ, Chen TW, Wang SS, Shiesh SC, Tsai YT, Huang TP, Lee SD, Ting SW, Pancreatic enzymes in uremic patients with or without dialysis., Clin Biochem. 1988;21(3):189. 5) Collen MJ, Ansher AF, Chapman AB, Mackow RC, Lewis JH, Serum amylase in patients with renal insufficiency and renal failure., Am J Gastroenterol. 1990;85(10):1377. 6) E. B. Pedersen, A. Brock and H. J. Kornerup, Serum Amylase Activity and Renal Amylase Activity Clearance in Patients with Severely Impaired Renal Function and in Patients Treated with Renal Allotransplantation, Scandinavian Journal of Clinical & Laboratory Investigation,1976, Vol. 36, No. 2 , Pages 137-140. 7) Michael D. Levitt, M.D.; Mark Rapoport; And Sidney R. Cooperband, M.D., The Renal Clearance of Amylase in Renal Insufficiency, Acute Pancreatitis, and

Macroamylasemia, Annals of Internal Medicine, November 1, 1969 vol. 71 no. 5 919-925. 8) Giuseppe Montalto, Antonio Carroccio, Pancreatic enzymes in chronic renal failure and transplant patients,International Journal of Gastrointestinal Cancer Volume 12, Number 3, 211-217, DOI: 10.1007/BF02924359 9) Pitchumoni C. S. , Arguello P. ,Agarwal N. ,Yoo J. ; Acute pancreatitis in chronic renal failure, The American journal of gastroenterology, 1996, vol. 91, no12, pp. 2477-2482 (38 ref)

A. Whether study is intradepartmental or interdepartmental: interdepartmental. B. If in interdepartmental whether consent obtained from the department consent: yes

C. Any extra material or finance required or obtained to carry out the study: No D. Whether Ethical problems or involved: No

CONSENT FORM Part I Information for participants of the study Dear Sir / Madam, I welcome you for the research work entitled A STUDY ABOUT THE CHANGES IN LEVELS OF PANCREATIC ENZYMES IN CASES OF CHRONIC RENAL FAILURE. This form will explain about the purpose, Procedure, benefits and risks of the study. You are free to ask any doubts before you give consent and also at any time during the course of the research work.

Name of the investigator

Dr. Deepa V.S, Post Graduate student, Department of Biochemistry SMIMS, Kulasekharam.

Name of the guide

Dr. S.Jaya M.D, Professor, Department of Biochemistry SMIMS, Kulasekharam.

Name of the Co-guide

Dr. J.K. Sathya Sudha Devi, M.D, Professor and Head, Department of Biochemistry SMIMS, Kulasekharam.

OBJECTIVES :-

Chronic renal failure (CRF) is a condition associated with abnormal kidney function and a progressive decline in glomerular filtration rate. Increase in blood levels of urea, creatinine and uric acid is the hallmark of kidney failure. Diagnosing the complications may prevent further worsening of the condition in CRF patients

Since CRF patients suffer from pain abdomen and vomiting already it is difficult to differentiate these symptoms from that of acute pancreatitis. Estimation of serum amylase and serum lipase will show a marked increase in level of these enzymes in CRF patients without known acute pancreatitis. The present study is done to study the level of pancreatic enzymes in CRF patients without known pancreatitis & to find out the incidence of acute pancreatitis in these patients.

PROCEDURE :-

50 volunteers with CRF will be recruited from the nephrology department of SMIMS, who are of the age group between 30 to 80 years for the study.

The study will be done by drawing 10ml of blood from the volunteers & will be tested for serum amylase & Serum lipase. Prior to the test the procedure will be explained thoroughly to you. Value of all pancreatic enzymes level obtained from you will be saved in the computer. Hard copy of all the parameters will be maintained in a separate file and the values will be taken for analysis.

1. Expected risks for the participants : Nil 2. Expected benefits of research for the participants : Early detection of complications may prevent further worsening of the condition of CRF patients. 3. Whether confidentiality will be maintained : Yes 4. Can I withdraw from the study at any time during the study period ? Yes 5. If there is any new finding would I be informed ? Yes

For any study related queries please contact

Dr.Deepa V.S, Post graduate student, Department of Biochemistry, SMIMS Kulasekharam.

Place :

Signature

Date : (investigator)

CONSENT FORM Part II I have been fully informed about the nature of the study entitied A STUDY ABOUT THE CHANGES IN LEVELS OF PANCREATIC ENZYMES IN CASES OF CHRONIC RENAL FAILURE. This test for pancreatic enzymes will be done in me when ever needed.

Though the result of the study may not be beneficial to me directly it will be of great help in the advancement of medical sciences. I have understood the study properly & have been given the opportunity to refuse the study if I am not willing.

I have been given an information sheet giving details of the study. My participation is voluntary & I fully consent to the above study.

Name

Address

Signatue of the participant

Place : Date :

CASE RECORD FORM

Name

Age

Sex

Address

Height (cm)

Weight (kg)

Duration of illness

Type of treatment

If treated with haemodialysis / not

Any h/o Chronic alcoholism Any Previous h/o pancreatitis

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