Chronic Kidney Disease

Chronic Kidney Disease

1. Chronic Kidney
Disease
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai 1

2. Moderators:
Professors:
Prof. Dr. G. Sivasankar, M.S., M.Ch.,
Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
Dr. J. Sivabalan, M.S., M.Ch.,
Dr. R. Bhargavi, M.S., M.Ch.,
Dr. S. Raju, M.S., M.Ch.,
Dr. K. Muthurathinam, M.S., M.Ch.,
Dr. D. Tamilselvan, M.S., M.Ch.,
Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai.
2

3. CKD is reduced kidney function
and/or kidney damage
▪Chronic KidneyDisease
−Kidneyfunction
▪Glomerular filtration rate (GFR) < 60 mL/min/1.73m
2
for>3
months with or without kidneydamage
AND/OR
−Kidneydamage
▪>3 months, with or without decreased GFR, manifested byeither
−Pathologicalabnormalities
−Markers of kidney damage, i.e., proteinuria(albuminuria)
» Urine albumin-to-creatinine ratio (UACR) > 30mg/g
Reference: National Kidney Foundation Kidney Disease OutcomeQualityInitiative
(KDOQI). Clinical practice guidelines for chronic kidneydisease:evaluation,
classification, and stratification. Amer J Kid Dis 2002; 39(2 suppl1):S18–S266.3Dept of Urology, GRH and
KMC, Chennai.

4. 4Dept of Urology, GRH and
KMC, Chennai.

5. ▪Severe form of CKD : Kidney failure (eGFR <15)
▪Kidneys cannot maintainhomeostasis.
▪Kidney failure is associated with fluid, electrolyte, and
hormonal imbalances and metabolicabnormalities.
▪ESRD means the patient needsdialysis or renal
transplant.
▪Uremia is the term used to describe the symptoms or
symptom complex attributable to advanced renalfailure
or end-stage renaldisease.
CKD vs Kidney failure v.s. ESRD v.s.uremia
5Dept of Urology, GRH and
KMC, Chennai.

6. 6Dept of Urology, GRH and
KMC, Chennai.

7. 7Dept of Urology, GRH and
KMC, Chennai.

8. 8Dept of Urology, GRH and
KMC, Chennai.

9. 9Dept of Urology, GRH and
KMC, Chennai.

10. 10Dept of Urology, GRH and
KMC, Chennai.

11. 11Dept of Urology, GRH and
KMC, Chennai.

12. 12Dept of Urology, GRH and
KMC, Chennai.

13. ▪Each kidney has about 1 million nephrons; slow loss may notbe
noticeable
▪The slow, progressive loss of function triggers a number
of maladaptive compensatory mechanisms
▪Either the loss of renal function or the adaptations to
reduced renal function lead to the manifestations of
uremia
▪The person with CKD may not feel different (silentkiller).
Pathogenesis of the manifestations ofCKD
13Dept of Urology, GRH and
KMC, Chennai.

14. ▪Urine volume may notchange
−Composition of the urinechanges
▪Reduced waste excretion
−May not be apparent until CKD isadvanced
▪Altered hormoneproduction
−Anemia (erythropoietin) and mineral & bone disorders
(vitaminD)
▪Reducedcatabolism
−Examples:Insulin, glucagon,drugs
Physiological basis of clinical manifestations
of CKD: Fewer nephrons disrupt thebalance
14Dept of Urology, GRH and
KMC, Chennai.

15. ▪Reduced renal clearance and accumulation of:
−Advanced glycation endproducts
−Pro-inflammatorycytokines
−Reactive oxygen species(oxidation)
−Metabolicacids
▪Insulin resistance (even in people withoutdiabetes)
−Reduces insulin-mediated glucose uptake in skeletal
muscles
−May be associated with inflammation aswell
Physiological basis of clinical manifestations
of CKD: Fewer nephrons disrupt thebalance
15Dept of Urology, GRH and
KMC, Chennai.

16. Mechanisms ofadaptation
•Intactnephron
hypothesis
–more workper
nephron to
maintain
homeostasis
•Osmoticdiuresis
–urea
•Functionalreserve
•Hyperfiltration
•Trade-off
hypothesis
Kidney Int 2011; 79 (Suppl 121):S3–S8.
Am J Physiol. 1985 Sep;249(3 Pt2):F324-37.
Price to pay for maintaining external
solute balance is the induction of one
or more abnormalities ofuremia
16Dept of Urology, GRH and
KMC, Chennai.

17. Not all solutes are regulated to the
sameextent
Little regulation: Plasmaconcentrations
increase as nephrons arelost.
Creatinine
Urea
Partial regulation: Plasma
concentrations maintained until 50%lost.
HCO3-
Ca++
Pi
Near complete regulation: Plasma
concentration can be maintained until
approximately 90% nephronloss.
Water
Na+
K+
17Dept of Urology, GRH and
KMC, Chennai.

18. Disorders of erythropoiesis inCKD
•EPO is produced by the kidney
peritubular interstitialfibroblasts
•Renal EPO ProducingCells
•In CKD, REPC undergo
transdifferentiation to
myofibroblasts losing the ability
to produce EPO(erythropoietin)
Blood Rev. 2013 Jan; 27(1):41–53.
18Dept of Urology, GRH and
KMC, Chennai.

19. 19Dept of Urology, GRH and
KMC, Chennai.

20. 20Dept of Urology, GRH and
KMC, Chennai.

21. 21Dept of Urology, GRH and
KMC, Chennai.

22. 22Dept of Urology, GRH and
KMC, Chennai.

23. 23Dept of Urology, GRH and
KMC, Chennai.

24. Trade-off among renal function, PTH and
FGF23 on phosphorushomeostasis
PTH FGF23
Judith Blaine et al. CJASNdoi:10.2215/CJN.09750913
Kidney International (2011) 80, 443 –445. doi:10.1038/ki.2011.146
24Dept of Urology, GRH and
KMC, Chennai.

25. Biochemical abnormalities, Bone Disease and
Extraskeletal Calcification inCKD-MBD
Adv Chronic Kidney Dis 2007 143-12
MultifactorialPathogenesis:
•Phosphorusretention
•Hypocalcemia
•↑ FGF-23
•↑ PTH
•↑ Resistance to the action of
hormones (VDR,PTH,FGF-
23/klotho)
25Dept of Urology, GRH and
KMC, Chennai.

26. CKD leads to many bonediseases
Cardiovascular disease correlates with the presence of these
bone disorders: bones hurt and heartsuffers
26Dept of Urology, GRH and
KMC, Chennai.

27. eGFR andAlbuminuria
NUMEROLOGY
27Dept of Urology, GRH and
KMC, Chennai.

28. ▪GFR is equal to the sum of the filtration rates inall
of the functioningnephrons.
▪Estimation of theGFR (eGFR) gives a rough measure
of the number of functioningnephrons.
What is the glomerular filtration rate(GFR)?
28Dept of Urology, GRH and
KMC, Chennai.

29. ▪eGFR is not the measuredGFR.
▪The formula to estimate GFR was derived from a population-
basedstudy.
▪MDRD, CKD-Epi, etcwww.kidney.org/GFR.
▪eGFR is based on serum creatininelevels.
▪Creatinine assays are nowstandardized.
−Isotope Dilution Mass Spectrometry (IDMS)
eGFR estimates the measured GFR
29Dept of Urology, GRH and
KMC, Chennai.

30. 30Dept of Urology, GRH and
KMC, Chennai.

31. 31Dept of Urology, GRH and
KMC, Chennai.

32. 32Dept of Urology, GRH and
KMC, Chennai.

33. 33Dept of Urology, GRH and
KMC, Chennai.

34. Interfacebetween
PCandNephrology
KDIGOguidelines
34Dept of Urology, GRH and
KMC, Chennai.

35. 35Dept of Urology, GRH and
KMC, Chennai.

36. 36Dept of Urology, GRH and
KMC, Chennai.

37. 37Dept of Urology, GRH and
KMC, Chennai.