1. How to properly plan and conduct research projects? Farahnak Assadi, MD Emeritus Professor Pediatric Nephrology

2. ©2007 RUSH University Medical Center 1.Turn your ideas into research questions 2. Review the literature 3. Design the study and develop your methods 4. Writing your research proposal 5. Obtain ethical and trust approval 6. Collect and collate the data 7. Analyze the data and interpret the findings 8. Report on the study and the findings Decide on an area of research What is your aim and hypothesis? Where do I start? Libraries Links to useful websites Participant involvement Statistic issues Collaboration Peer review Sponsor issues Why ethics are so important? Prepare consent forms Contact your RD office Issues to consider Data protection and confidentiality Data analysis Interpreting data Publishing your research Future direction Research Process Flowchart

3. Turning your ideas into research Stay up to date on the area of specific research Keep up with the current literature on the area of your research proposal Avoid duplicating what is already known Be creative and develop a new idea ©2007 RUSH University Medical Center

4. Review the literature Where do I start? - Discuss with your mentor - Start reading - Identify the most important gaps in knowledge and prioritize the unanswered questions about your research Libraries Links to useful websites - PubMed, MEDLINE, etc ©2007 RUSH University Medical Center

5. Review literature (cont’d) Isolated persistent asymptomatic hematuria occurs in about 2%-3% in school age children It is the most common laboratory finding of renal disease

6. ©2007 RUSH University Medical Center isolated asymptomatic hematuria No proteinuria on dipstick-test Normal BUN and serum creatinine levels Negative TB test Normal serum C3, C4, CH50 Ca/Cr ratio <0.22 Normal renal ultrasound Negative urine culture

7. ©2007 RUSH University Medical Center Consider other causes Benign hematuria (TGBM disease ) IgA nephropathy Alport’s syndrome 51% 49% 1.0%

8. ©2007 RUSH University Medical Center To do the kidney biopsy! A policy of recommending renal biopsy for the diagnosis of isolated persistent hematuria would lead to a large number of patients with benign hematuria (51%)

9. ©2007 RUSH University Medical Center Not to do the kidney biopsy! A policy of deferring renal biopsy in all patients until more overt signs of a progressive nephropathy develop may delay the appropriate management of a chronic kidney disease (49%)

10. ©2007 RUSH University Medical Center To do or not to do biopsy?

11. ©2007 RUSH University Medical Center Hypothesis Inflammation is an important risk factor in the initiation of HTN, CVD, CKD, and stroke in both diabetic and non-diabetic patients Microalbuminuria (MA/Cr >30 mg/g) is a sensitive marker of inflammation and a powerful predictor of CKD, particularly in nephropathy due to diabetes

12. ©2007 RUSH University Medical Center Spesific aim To investigate the value of urinary microalbumin excretion in predicting glomerular abnormalities in children with isolated persistent hematuria

13. Design the study and develop a method Decide on a general area of interest Why does this area interest you? What is your aim? What is you hypothesis? Is your idea novel? How will patients benefit from your research? Consult colleagues and other researchers ©2007 RUSH University Medical Center

14. Obtain ethical and trust approval Why ethics are so important Applying to a research ethics committee Prepare consent forms - Prepare information sheet checklists - Prepare consent form Contact your RD office ©2007 RUSH University Medical Center

15. Collect and collate the data Issues to consider - Beware of biases - Seek statistical advice if necessary - Researchers must bear the day-to-day responsibility for the conduct of research Data protection and confidentiality - Identities should be avoided by use of codes - ©2007 RUSH University Medical Center

16. Analyze and interpret the data Quantitative data analysis - Identifying a data entry and analysis manager (SPSS) - Coding data - interpreting data Qualitative data analysis - Familiarization with the data - Development of provisional categories - Development of theory and incorporation of pre- existing knowledge ©2007 RUSH University Medical Center

17. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Patients MA/Cr 30 ug/mg N 54 (71%) 22 (29%)* Age, yrs 13 + 5 12 + 4 Female/Male (n) 20/16 19/21 Body mass index (kg/m 2 ) 24 + 3 25 + 2 Systolic BP (mmHg) 122 + 7 120 + 11 Serum Cr level (mg/dl) 0.5 + 0.2 0.6 + 0.2 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ *p=0.002 Table 1. Patients characteristics in relation to MA Results

18. ©2007 RUSH University Medical Center Results MA/Cr< 30 μg/mg Normal tissue 50% TGBM 28% IgA GN: 2% MA/Cr> 30 μg/mg IgA GN 91% 9% TGBM 9% Table 2. Glomerular lesion in relation to MA

19. ©2007 RUSH University Medical Center Fig 1. MA and glomerularl lesion IgA (n=21) TBMD (n=17) Normal (n=38) IgA (n=21) TBMD (n=17) Normal (n=38) MA/CR ( u g/mg) MA/CR ( u g/mg) 10090 80 80 70 70605040300 P=0.002

20. ©2007 RUSH University Medical Center Fig 2. MA and glomerular lesion glomerular lesion (%) MA/Cr >30 MA/Cr 30 MA/Cr<30 MA/Cr μg/mg

21. ©2007 RUSH University Medical Center Conclusions Routine measurements of urinary MA is warranted in children with isolated persistent hematuria Screening for MA usually predicts a specific morphologic type of glomerular disease It may help to identify a subgroup of patients who are at higher risk for IgA nephropathy and could benefit early therapy and closer follow-up

22. ©2007 RUSH University Medical Center Conclusions (cont’d) A renal biopsy should be considered in the child whose microscopic hematuria is associated with MA Children with isolated hematuria and strong family history of benign hematuria, in the absence of MA may not require a renal biopsy to confirm the diagnosis

23. Report on the study Publishing your research findings - Research is conducted for the benefit of patients, health care providers, and the public in general - Inform the participants of your research Presenting for conferences and seminars Assadi F. Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria. Pediatr Nephrol 2005; 20:1131-1135 ©2007 RUSH University Medical Center

24. Turning ideas into a research question Association between hyperuricemia and essential hypertension among children and adolescents. ©2007 RUSH University Medical Center

25. Turn your idea into research Essential hypertension (EHTN) is frequently associated with hyperuricemia in both adult and pediatric patients. More than 80% of children with essential HTN have serum uric acid (UA) levels above 5.5 mg/dL Elevated UA level is a predictor of incident HTN and cardiovascular disease. UA causes HTN in a rat model through the activation of the RAS, down regulation of nitric oxide, and vascular endothelial dysfunction.

26. Hypothesis Treating EHTN with usual antihypertensive agents does not completely reduce cardiovascular risk related to uric acid (UA) levels. Lowering serum UA levels with allopurinol may provide greater benefit than simply treating HTN with the conventional therapy. Feig DI et al. JAMA 2008;300:924-932

27. Purpose of the study To investigate the potential therapeutic effects of UA-lowering agent, allopurinol in combination with an ACE inhibitor on BP in hyperuricemic children with newly diagnosed EHTN.

28. Design the study and methods Participant involvement Study design and sampling - What method will give the most useful data? - What is the probability and non-probability of sampling method? Research methods - Choosing qualitative and quantitative methods Statistical issues - Online statistics textbook from “www.Statsoft.com” Collaboration with other researchers ©2007 RUSH University Medical Center

29. Patients referred for the evaluation hypertension (n=118) Excluded (n=47) Prehypertension (n=23) Abnormal urinalysis (n=11) Stage 2 hypertension (n=5) Hydronephrosis (n=4) Cystic kidney disease (n=2) White coat hypertension (n=1) Pheochromocytoma (n=1) Patients with stage 1 hypertension (n=71) Excluded (n=19) Serum uric acid <5.5 mg/dL Patients randomized (n=52) Enalapril plus allopurinol (n=28) Excluded (n=4) poor compliance (n=4) Excluded (n=4) Poor compliance (n=3) stage 2 hypertension Completed 8 weeks study and included in analysis (n=20) Completed 8 weeks study and included in analysis (n=24) Enalapril (n=24)

30. CharacteristicEnalapril therapy(n=20) Combination therapy (n=24) P value Gender (N)Male (12) Female (8) Male (13) Female (11) NS Age (year) mean (range) 14.2 (12-17)15.9 (12-19)NS BMI (percentile) mean (range) 88 (85-99)92 (89-93)NS Serum UA (mg/dL) mean (range) 6.6 (6.0-7.3)6.8 (6.2-7.1)NS Systolic BP (mmHg) mean (range) 133 (129-136)134 (128-137)NS Diastolic BP (mmHg) Mean (range) 85 (82-86)86 (80-87)NS Baseline characteristics

31. ParameterEnalapril therapy (n=20) Combination therapy (n=24) P value Change in systolic BP (mmHg) -4.3 (-2.1 to -6.7)-8.2 (-7.2 to -9.8)0.001 Change in diastolic BP -2.4 (-1.1 to -2.2)-6.3 (-1.9 to -7.8)0.006 Serum uric acid (mg/dL) -3.3 (-2.9 to -5.2)-5.1 (-5.8 to-6.7)0.002 Results

33. ©2007 RUSH University Medical Center

34. Conclusions Allopurinol enhances the BP lowering effect of enalapril in hyperuricemic adolescents with stage-1 primary HTN by reducing serum UA level. Treatment regimen that lowers serum uric level may be indicated to decrease the incidence of CVD by reducing serum UA level. Assadi F. Allopurinol enhances the blood pressure lowering effect of enalepril in children with hyperuricemic essential hypertension. J Nephrol 27:51-56

35. Future Direction Increased dietary intake of fructose, which is a known cause of hyperuricemia, may be contributing to the current epidemic of obesity and HTN. Ongoing clinical trials will elucidate the role of UA in human HTN and will determine whether control of UA may be a new way to prevent or treat essential HTN.

36. ©2007 RUSH University Medical Center 1.Turning your ideas into research questions 2. Review the literature 3. Design the study and develop your methods 4. Writing your research proposal 5. Obtain ethical and trust approval 6. Collect and collate the data 7. Analyze the data and interpret the findings 8. Report on the study and the findings Decide on an area of research What is your aim and hypothesis? Where do I start? Libraries Links to useful websites Participant involvement Study design and methods Statistic issues Collaboration Starting your research proposal Peer review Sponsor issues Why ethics are so important? Prepare consent forms Contact your RD office Issues to consider Data protection and confidentiality Data analysis Interpreting data Publishing your research Future direction Research Process Flowchart

37. ©2007 RUSH University Medical Center