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.
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3. CKD is reduced kidney function
and/or kidney damage
▪ Chronic Kidney Disease
− Kidney function
▪ Glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 for > 3
months with or without kidney damage
AND/OR
− Kidney damage
▪ > 3 months, with or without decreased GFR, manifested by either
− Pathological abnormalities
− Markers of kidney damage, i.e., proteinuria (albuminuria)
» Urine albumin-to-creatinine ratio (UACR) > 30 mg/g
Reference: National Kidney Foundation Kidney Disease Outcome Quality Initiative
(KDOQI). Clinical practice guidelines for chronic kidney disease: evaluation,
classification, and stratification. Amer J Kid Dis 2002; 39(2 suppl 1):S18–S266.
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Dept of Urology, GRH and
5. ▪ Severe form of CKD : Kidney failure (eGFR < 15)
▪ Kidneys cannot maintain homeostasis.
▪ Kidney failure is associated with fluid, electrolyte, and
hormonal imbalances and metabolic abnormalities.
▪ ESRD means the patient needs dialysis or renal
transplant.
▪ Uremia is the term used to describe the symptoms or
symptom complex attributable to advanced renal failure
or end-stage renal disease.
CKD vs Kidney failure v.s. ESRD v.s. uremia
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Dept of Urology, GRH and
13. ▪ Each kidney has about 1 million nephrons; slow loss may not be
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 (silent killer).
Pathogenesis of the manifestations of CKD
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Dept of Urology, GRH and
14. ▪ Urine volume may not change
− Composition of the urine changes
▪ Reduced waste excretion
− May not be apparent until CKD is advanced
▪ Altered hormone production
− Anemia (erythropoietin) and mineral & bone disorders
(vitamin D)
▪ Reduced catabolism
− Examples: Insulin, glucagon, drugs
Physiological basis of clinical manifestations
of CKD: Fewer nephrons disrupt the balance
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Dept of Urology, GRH and
15. ▪ Reduced renal clearance and accumulation of:
− Advanced glycation end products
− Pro-inflammatory cytokines
− Reactive oxygen species (oxidation)
− Metabolic acids
▪ Insulin resistance (even in people without diabetes)
− Reduces insulin-mediated glucose uptake in skeletal
muscles
− May be associated with inflammation as well
Physiological basis of clinical manifestations
of CKD: Fewer nephrons disrupt the balance
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Dept of Urology, GRH and
16. Mechanisms of adaptation
• Intact nephron
hypothesis
– more work per
nephron to
maintain
homeostasis
• Osmotic diuresis
– urea
• Functional reserve
• Hyperfiltration
• Trade-off
hypothesis
Kidney Int 2011; 79 (Suppl 121): S3–S8.
Am J Physiol. 1985 Sep;249(3 Pt 2):F324-37.
Price to pay for maintaining external
solute balance is the induction of one
or more abnormalities of uremia 16
Dept of Urology, GRH and
17. Not all solutes are regulated to the
same extent
Little regulation: Plasma concentrations
increase as nephrons are lost.
Creatinine
Urea
Partial regulation: Plasma
concentrations maintained until 50% lost.
HCO3-
Ca++
Pi
Near complete regulation: Plasma
concentration can be maintained until
approximately 90% nephron loss.
Water
Na+
K+
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Dept of Urology, GRH and
18. Disorders of erythropoiesis in CKD
• EPO is produced by the kidney
peritubular interstitial fibroblasts
• Renal EPO Producing Cells
• In CKD, REPC undergo
transdifferentiation to
myofibroblasts losing the ability
to produce EPO (erythropoietin)
Blood Rev. 2013 Jan; 27(1): 41–53.
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Dept of Urology, GRH and
24. Trade-off among renal function, PTH and
FGF23 on phosphorus homeostasis
PTH FGF23
Judith Blaine et al. CJASN doi:10.2215/CJN.09750913
Kidney International (2011) 80, 443 – 445. doi: 10.1038/ki.2011.146
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Dept of Urology, GRH and
25. Biochemical abnormalities, Bone Disease and
Extraskeletal Calcification in CKD-MBD
Adv Chronic Kidney Dis 2007 14 3-12
Multifactorial Pathogenesis:
•Phosphorus retention
•Hypocalcemia
•↑ FGF-23
•↑ PTH
•↑ Resistance to the action of
hormones (VDR,PTH,FGF-
23/klotho)
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Dept of Urology, GRH and
26. CKD leads to many bone diseases
Cardiovascular disease correlates with the presence of these
bone disorders: bones hurt and heart suffers
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Dept of Urology, GRH and
28. ▪ GFR is equal to the sum of the filtration rates in all
of the functioning nephrons.
▪ Estimation of the GFR (eGFR) gives a rough measure
of the number of functioning nephrons.
What is the glomerular filtration rate (GFR)?
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Dept of Urology, GRH and
29. ▪ eGFR is not the measured GFR.
▪ The formula to estimate GFR was derived from a population-
based study.
▪ MDRD, CKD-Epi, etc www.kidney.org/GFR.
▪ eGFR is based on serum creatinine levels.
▪ Creatinine assays are now standardized.
− Isotope Dilution Mass Spectrometry (IDMS)
eGFR estimates the measured GFR
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Dept of Urology, GRH and