The document emphasizes the significance of the rate of kidney function decline (KFD) as a predictive measure for chronic kidney disease (CKD) progression to end-stage renal disease (ESRD) while discussing various factors influencing CKD in Egypt. It highlights recommendations from the 2016 ISN Global Kidney Health Summit regarding monitoring CKD prevalence, potential therapeutic targets, and the importance of early intervention. The analysis includes the variable decline rates in eGFR among different CKD stages and the need for standardized outcome measures in clinical studies.

1. RATE of KIDNEY FUNCTION
DECLINE (KFD) and
SUBSEQUENT ESRD
Ahmed Shoker

3. KFD
•Aim:
• Highlight SIGNIFICANCE of rate of
kidney function decline (KFD) as a
potential Predictive outcome
measure to manage and study CKD
progression to ESRD, and perhaps
for the study of CKD in Egypt
• as highlighted in the 2016 ISN Global kidney health Summit
outputs published in KI , volume 7, issue 2, October 2017 and
thereafter

4. Kidney function decline
•Background:
• ISN Global kidney health Summit
outputs published in KI , volume
7, issue 2, October 2017

5. KFD
•Background
• Output of summit included
suggested plans to :
• 1) determine and monitor prevalence of
CKD

6. KFD
•Background
• Output of summit included suggested plans to :
• 2) Genetic and environmental risk factors for CKD
• Heavy metals
• Agriculture chemicals
• Occupational exposure
• Traditional herbals
• Sugary beverages
• Salty foods
• Infections

7. Kidney function decline
•Background
• Output of summit included suggested
plans to :
• 3) Closing the gap between evidence and practice in
CKD
• 4) Systemic kidney disease and complications
associated with decline in kidney function
• 5) Establish and validate novel therapeutic targets
to retard progression of CKD
• 6) optimize design of clinical trials in CKD

8. Kidney Function decline
•Background
• Output of summit included suggested
plans to :
• 7) Strategies to improve
monitoring disease progression,
assessing CVD risk, and defining
prognostic biomarkers in CKD

9. KFD
•Aim:
• Highlight SIGNIFICANCE of rate of
kidney function decline (KFD) as a
potential predictive outcome
measure to study CKD
progression to ESRD, and perhaps
for the study of CKD in Egypt.

10. KFD
• GFR
TIME
Threshold for intervention
Rate of decline in kidney function=
delta change in GFR per time unit

11. KFD
•Aim:• highlight SIGNIFICANCE of rate of kidney function decline (KFD) as a potential predictive
outcome measure to study CKD progression to ESKD, and perhaps for the study of CKD in
Egypt.
•Q # 1
•Why is the focus on
Study of CKD?

12. KFD
•Quiz
• In population studies of kidney disease, what is
the percentage of CKD patients who will make it
to ESRD
• 1-2 %
• 10- 20 %
• 40- 60%
• 70- 80 %
• 90%

13. KFD
• Incidence/Prevalence of ESRD,
• 150/1800 per million= .0001%
• Incidence/ Prevalence of CKD= 3- 11%
• Ratio (Incidence/Prevalence) of ESRD/CKD=
• 1/500
• 1/1000
• eGFR< 60 ml/min is attributed to 4% of
deaths worldwide
• Thomas B, JASN, 2017

14. Risk of nephrectomy
• Study natural history of CKD in 27,998 with
eGFR below 90 ml/m
• 5 yrs follow up
• ESRD= 1.1% (stage 2) ****Mortality= 19.5%
• ESRD= 1.3% (stage 3) ****mortality= 24.3%
• ESRD= 19.9% (stage 4)****Mortality= 45.7%
• Conclusion” Only 2% will progress to ESRD”
• Keith D,et al
• Arch Intern Med 2004;164: 659

15. KFD
• Why is the focus on CKD?
• 1) 9 out of 10 will die before ESRD
• 2) Manage CKD differs by stage
• 3) High prevalence of CKD and it’s association
with modifiable causes and increased CVD
and mortality rates, long before dialysis
• 4) Early intervention and avoidance of
nephrotoxic exposure can be done

16. KFD
• Why is the focus on CKD?, because; Early intervention
before it’s to late
•Q #2
• Can we predict patients who progresses
to ESRD/ high risk mortality?
•Q # 3
• Can we develop Predictor outcome
measures ( ESRD, etc) for clinical studies
and patient management with CKD?

17. Kidney function decline
•The story of
potential outcome
measures in CKD

18. KFD
• Outcome measures in nephrology clinical studies
• Differs between CKD/ HD/ PD/TX
• Different priorities of Pts, clinicians, researchers,
caregivers
• Outcome: is something that can be measured, and
can arise or change because of a health condition or
treatment
• Core outcome set: is an agreed standardized set of
outcomes that should be measured and reported,
as a minimum, in all clinical trials in specific areas of
health or health care. Researchers may add other
outcomes to the core outcome set
• Nistor, NDT, 2017

19. KFD
• Standardized Outcomes In Nephrology (SONG)
• Initiative to establish set of outcome measures
• SONG- Tx
• SONG- Kids
• SONG-PD
• SONG-CKD
• SONG- PCKD
• SONG handbook,2017
• Transplant, 2017
• Tong, A. NDT, 2017

20. Kidney function decline
•The story of rate of kidney
function decline (KFD) as a
potential predictive
outcome measure for
subsequent ESRD

22. Kidney Function Decline
• Mean rates ( ml/min/yr) of eGFR decline ( is variable, but
constantin individual pts)
• DM .0 - 12.6
• IGA 1.4 - 9.5
• MN 4.6 - 9.5
• Chronic GN 2 - 10.4
• TID 2 - 5.4
• PCKD 3.8- 5.4
•Q # 4
• Can we grade rates of kidney function
declines into slow/ fast? to use as
outcome measure in the study CKD?

23. KFD
• Meta-analysis of 1.7 million pts
• Adjusted HR for ESRD, mortality were
higher for larger decline in eGFR over 1-
3 yrs
• JAMA, 2014,, Coresh et al

24. KFD
• AHR of ESRD for Pts with eGFR
decline over 2 yrs of
• > 57% = ESRD of 32.1
• > 30% = ESRD of 6.9
• < 30% = ESRD of 5.4
• AHR for patient mortality adjusted
for 10 yrs were similar

25. KFD
• 1) Decline in EGFR smaller than doubling SCr
occurs more commonly
• And strongly associate with risk for ESRD
• 30% reduction in eGFR over 2 years is
alternative end point for CKD progression in
10 yrs.
• JAMA, 2014,, Coresh et al
• Inker, Am j Kid Dis, 2014
• Badve,NDT,2015
• PLoS One, Tsai,2017

26. KFD
•Definition of rapid
progression as rate of
eGFR > 5 ml/min/yr.
• KI,91,issue6, june2017

27. KFD
• FDA accepts 30%- 40% decline in eGFR over
2- 3yrs in eGFR as an end point in clinical
studies
• Acceptable, shorter duration, smaller
population and simple and cheap target
• Coresh, JAMA, 2014
Coresh, JASN 2016: 27;2447
• Badve, NDT,,2016
• Carlesson CJASN, 2017. vol12
•

28. KFD
•The story of rate of kidney
function decline (KFD) as a potential
predictive outcome measure for
subsequent ESRD Continues

30. Patterns of progression of chronic
kidney disease at later stages
Fernando Caravaca-Fontán Lilia Azevedo Enrique
Luna Francisco Caravaca
Clinical Kidney Journal,
sfx083, https://doi.org/10.1093/ckj/sfx083
Published:
28 July 2017
Conclusions: A majority of patients with advanced CKD show patterns of renal function
decline different from linear, and several of the main determinants of CKD progression
are potentially modifiable.

31. From: Patterns of progression of chronic kidney disease at later stages
Clin Kidney J. Published online July 28, 2017. doi:10.1093/ckj/sfx083
Clin Kidney J | © The Author 2017.

32. From: Patterns of progression of chronic kidney disease at later stages
Clin Kidney J. Published online July 28, 2017. doi:10.1093/ckj/sfx083
Clin Kidney J | © The Author 2017.

33. Fast renal decline to end-stage renal
disease: an unrecognized feature of
nephropathy in diabetes.
Krolewski AS1, Skupien J2, Rossing P3, Warram JH4.
Kidney Int. 2017 Jun;91(6):1300-1311. doi:
10.1016/j.kint.2016.10.046. Epub 2017 Mar 31.

34. Distribution of categories of progressive renal decline during 6–10 years of
follow-up in patients with type 1 diabetes and type 2 diabetes in the Joslin
Kidney Studies according to category of albuminuria at entry into follow-up

35. Distribution of categories of progressive renal decline during 6–10 years of
follow-up in patients with type 1 diabetes and type 2 diabetes in the Joslin
Kidney Studies according to category of albuminuria at entry into follow-up

36. Figure 3
Kidney International 2017 91, 1300-1311DOI: (10.1016/j.kint.2016.10.046)
Copyright © 2017 International Society of Nephrology

37. Kidney function decline
• Definition of rapid progression as
rate of eGFR > 5 ml/min/yr.
• Newer definitions; very fast, fast,
moderate and slow
• KI,91,issue6, june2017

38. KFD
Suggested outcomes in measuring kidney disease
status in randomized studies
• eGFR > 45 ml/min ( Stages G1- G3a) :
• slope of eGFR or surrogate biomarkers
• Rapid progression = 30- 40 % decline over 2yrs
• Later stages.
• Slow progression = 30%- 40% decline in eGFR
• Rapid progression = > than 40% decline in GFR
• Baigent. KI, 92, 297

39. KFD
• Limitations of rate of KFD as an outcome
measure
• 1) Is the rate of decline in eGFR linear?
• 22-18% Non linear in PCKD
• 20% in DM
• 30% in GN
•Q # 5
• Can we improve on rate of KFD as
outcome measure?

40. KFD
• Limitations of rate of KFD as an outcome
• 1) Is the rate of decline in eGFR linear?
• 22-18% Non linear in PCKD
• 20% in DM
• 30% in GN
•Q # 6
• Can we further, improve on rate
of KFD as measure of progressive
CKD?

41. KFD
• Contribution of past decline VS current eGFR
and subsequent risk of ESKD
• eGFR decline of 18 ml/min /3 yrs
• AHR of 2.28
• Current eGFR of 30 ml VS 50 ml= AHR of 19.9
• Conclusion; Current eGFR and rate of decline
contribute to risk of ESRD
• Kovesdy, JASN. 2017

42. KFD
•Q # 7
• To what extend proteinuria predicts
progressive decline in eGFR???
• Remains controversial
• Proteinuria course may not be linear
• Need for improved outcome measures using
biomarkers

43. Distribution of GFR slope/ yr. and
proteinuria in the AASK study

44. Mild albuminuria is a risk factor for GFR decline in nondiabetic
normal population. Melsom,KI,2018
Optimum
ACR< 3.4
mg/mmol is
too high
ACR of .11-
.12
mg/mmol
has a .28
ml/min/yr.
steeper rate
of FGR
decline than
< .1
mg/mmol

45. Cardiovascular Disease Biomarkers
and suPAR in Predicting Decline in
Renal Function: A Prospective
Cohort Study
Salim S.Hayek1Yi
AnKo12MosaabAwad1HinaAhmed1BrandonGray1Kareem
MohammedHosny1HiroshiAida1Melissa
J.Tracy3ChangliWei3SanjaSever4JochenReiser3Arshed A.
Discussion
hs-CRP, FDP, HSP-70, and hs-TnI were not associated with eGFR decline. The
specific association of suPAR with eGFR decline supported its involvement in
pathways specific to the pathogenesis of kidney disease.

46. Figure 5
Kidney International 2017 91, 1300-1311DOI: (10.1016/j.kint.2016.10.046)
Copyright © 2017 International Society of Nephrology

47. KFD
• Plasma high- sensitive troponin T
predicts ESRD and CVD and All
Cause mortality in DM
• Desai. AM J Kidney disease
• Galsgaard. KI, 2017

48. Saulnier, diabetes care, 2017

49. Prospective study of association of circulating biomarkers (
Adrenomodulin, sTNFR1, and N- terminal prohormone brain naturetic
peptide) with renal function decline in DM type 2
1,135 pts,
GFR 76
ml/min
RFL= > 40%
decline in
GFR
Rapid
decline=
slope < -5
ml/min/yr.
diabetes
care, 2017

50. KFD Conclusions
• CKD has Variable course
• 9 out of 10 will die before reaching ESRD
• eGFR and albumin/Cr ratio slopes are
good outcome measures to study kidney
disease progression
• Surrogate biomarkers can be added to
study protocols on disease progression

51. KFD
•Conclusions
• Rates of decline in eGFR,
albumin/creatinine ratio and
biomarkers can be implemented
in National Egyptian studies as a
priority over isolated
biochemical/ molecular studies