1. Assessment of Kidney function Assessment of Kidney function Challenges and opportunities George Moturi Physician/Nephrologist Aga Khan University Hospital Nairobi 25.04.2015

2. Road map Introduction Why do you want to know the kidney function? Challenges: assessing kidney function in devolved HCS Opportunities: assessing kidney function in devolved in HCS Integrating e-medicine in assessing kidney function Conclusions

3. Road map Introduction Why do you want to know the kidney function? Challenges in assessing kidney function in devolved HCS Opportunities in a assessing kidney function devolved in HCS Integrating e-medicine in assessing kidney function Conclusions

4. 2020

5. 3. Secretion of erythropoitin 1,25-dihydroxy vitamin D 3 (vitamin D activation) renin prostaglandin Major Functions of the Kidneys 2. Excretion of metabolic products foreign substances (pesticides, chemicals etc.) excess substance (water, etc) 1. Regulation of: body fluid osmolarity and volume electrolyte balance acid-base balance blood pressure

6. What is kidney disease? Acute kidney injury (AKI) Acute kidney injury (AKI) Acute kidney disease (AKD) Acute kidney disease (AKD) Chronic kidney disease (CKD) Chronic kidney disease (CKD) No kidney disease (NKD) No kidney disease (NKD)

7. Definition of CKD Structural or functional abnormalities of the kidneys for >3 months ( ≤ 3 months), as manifested by either: 1. Kidney damage, with or without decreased GFR, as defined by pathologic abnormalities markers of kidney damage urinary abnormalities (proteinuria) blood abnormalities (renal tubular syndromes) imaging abnormalities kidney transplantation 2. GFR <60 ml/min/1.73 m 2, with or without kidney damage NKF-K/DOQI

9. CKD death ComplicationsComplications Screening for CKD risk factors: diabetes hypertension age >60 family history US ethnic minorities CKD risk reduction; Screening for CKD Diagnosis & treatment; Treat comorbid conditions; Slow progression Estimate progression; Treat complications; Prepare for replacement Replacement by dialysis & transplant NormalNormal Increased risk Kidney failure DamageDamage  GFR 11.3 m 5.6% 7.7 m 3.8% 0.3 m 0.2% Conceptual Model for CKD

10. How do you assess kidney function?

11. Answer- Glomerular filtration rate

12. Glomerular filtration rate does not spell etiology of kidney disease. What does? Urinalysis Urinary protein excretion Radiologic studies Kidney biopsy

13. The quagmire of kidney disease Largely asymptomatic Mitchell AJKD 2006

14. Frequency of GFR monitoring per year NICE 2014

15. Road map Introduction Why do you want to know the kidney function? Challenges in assessing kidney function in devolved HCS Opportunities in a assessing kidney function devolved in HCS Integrating e-medicine in assessing kidney function Conclusions

16. CKD is a Public Health Problem CKD is common CKD is harmful We have treatment

17. Adjusted Hazard Ratio for Death from Any Cause, Cardiovascular Events, and Hospitalization among 1,120,295 Ambulatory Adults, According to the Estimated GFR Alan et al NEJM 2004

18. Stevens NEJM 2006

19. Road map Introduction Why do you want to know the kidney function? Challenges: assessing kidney function in devolved HCS Opportunities in a assessing kidney function devolved in HCS Integrating e-medicine in assessing kidney function Conclusions

20. What are the hurdles to diagnosing Kidney diseases in Africa? Naicker et al. NDT 2010; 25: 649-650

22. Glomerular filtration rate (GFR) The physiological mechanism of glomerular filtration is generally well understood A more complex issue, however, is the measurement of GFR in clinical practice and especially the definition of “normal” renal function

23. Normal value : Men- 130 ml/min Female - 120 ml/min

24. Screening for CKD is not a preserve of the Nephrologist The large number of patients who have CKD, together with the number of people at increased risk for it, requires primary care providers, as well as specialists in areas other than nephrology, to increase their familiarity with the use of GFR estimates

25. Assessing function - Tools Urine output GFR Urinalysis Novel biomarkers Imaging Biopsy

27. Production of creatinine Non-enzymatic breakdown product of phosphocreatine in muscle Produced at a relatively constant rate based on age, gender,race, and muscle mass Not affected by diet

28. Factors Affecting Creatinine Generation

30.  Acute changes in kidney function are not immediately apparent.  Creatinine excretion is due not only to filtration (90%– 95%) by the kidney but also to secretion (5%–10%) by the proximal tubule. If the patient with advanced CKD takes a substance that blocks tubular secretion of creatinine (eg, trimethoprim, cimetidine, cefoxitin), the serum creatinine level will increase abruptly, but the actual GFR will not change  Extra-renal elimination of creatinine occurs.. Other Limitations of Creatinine-Based eGFR Stevens NEJM. 2006

31. Cystatin C  Produced by all nucleated cells at a constant rate and freely filtered at the glomeruli  Minimally affected by diet, gender, ethnicity, age and muscle mass  Affacted by glucocorticoids and thyroid hormone

32. Early detection of acute renal failure by serum cystatin C Serum cystatin C is a useful detection markerof ARF, and may detect ARF one to two days earlier than creatinine. Stefan et al. KI 2004:66:1115–1122

33. Creatinine Equations 1. Cockroft-Gault equation – 1973 2. Original MDRD Study equation - 1999 3. “Reexpressed” MDRD Study equation for standardized – 2005 4. CKD-EPI equation - 2009

34. Cystatin C Equations 1. CKD –EPI cystatin C equation not adjusted for age, sex, and race 2. CKD – EPI cystatin C equation adjusted for age, sex, and race 3. CKD – EPI cystatin C and creatinine equation adjusted for age, sex, and race

35. Performance of Three Equations for Estimating Glomerular Filtration Rate (GFR) Inker NEJM 2012 The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease

36. Road map Introduction Why do you want to know the kidney function? Challenges in assessing kidney function in devolved HCS Opportunities: assessing kidney function in devolved HCS Integrating e-medicine in assessing kidney function Conclusions

37. Where do we start? National Vs regional kidney disease registries Standardized assessment of kidney function Referral pathways for kidney diseases Structured awareness campaigns

38. Measurement of Serum Creatinine – Current Status and Future Goals Creatinine measurement should be based on the isotope dilution- mass spectrometry (IDMS) method Standardisation of serum creatinine measurements to IDMS Jaffe Assay (since 1886) – should be abandoned Peake and Whiting Clin Biochem Rev 2006

39. Urine protein :Quantitative measurement n 24 hour collection of urine for protein normal excretion is <150 mg/24 hour n Spot urine protein/urine creatinine ratio n Microalbuminuria: 30 – 300mg/24hrs n Macroalbuminuria: ≥ 300mg/24hrs

40. Screening for Urine protein Dipstick: Gives green color, does not check for light chains Negative– 10 mg/dl Trace– 15-25 mg/dl 1-2+– 30-100 mg/dl 3+ – 300 mg/dl n Sulfosalicylic acid: white precipitate

41. Day-to-today clinical situations Determining the exact GFR is rarely necessary. Instead, it is important to determine whether renal function is stable or getting worse or better—which can usually be accomplished by monitoring serum creatinine value alone.

42. Road map Introduction Why do you want to know the kidney function? Challenges in assessing kidney function in devolved HCS Opportunities in a assessing kidney function devolved in HCS Integrating e-medicine in assessing kidney function Conclusions

43. Health in Cloud eHealth Fully integrated national health system – None in developing countries mHealth WelTel SMS System ChildCount+Register Changamka(finance)

44. Ecosystem for mobile health ICT Sector World Bank 2011

45. eTargets in Kidney diseases Mobile updates Mobile reminders Mobile eGFR

46. Road map Introduction Why do you want to know the kidney function? Challenges in assessing kidney function in devolved HCS Opportunities in a assessing kidney function devolved in HCS Integrating e-medicine in assessing kidney function Conclusions Conclusions

47. Take away Messages Often assessment of kidney function is the only indicator of renal impairment Structural defects can be present despite normal or even supra- normal kidney function

48. Take away Messages… Complete assessment kidney status will require GFR, Urinalysis, Imaging, +/- biopsy Reporting of renal function should be routine in all laboratories and if possible individualized We should and/or must assess kidney function of all our clients eHealth and mHealth can enhance kidney health in our population

49. Frequency of GFR monitoring per year NICE 2014