This document discusses chronic kidney disease (CKD), including its definition, stages, pathophysiology, clinical manifestations, and relationship to kidney failure, end-stage renal disease, and uremia. CKD is defined as glomerular filtration rate below 60 mL/min/1.73m2 or kidney damage for over 3 months. As CKD progresses, compensatory mechanisms disrupt homeostasis, leading to accumulation of waste and abnormalities. Later stages involve loss of over 90% of nephrons and inability to maintain fluid, electrolyte and hormone balance without dialysis or transplant.

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 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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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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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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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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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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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
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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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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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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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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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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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27. eGFR and Albuminuria
NUMEROLOGY
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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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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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34. Interface between
PC and Nephrology
KDIGO guidelines
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