This document discusses evaluation of kidney function through both qualitative and quantitative methods. It begins by covering renal anatomy and physiology, then describes various laboratory tests that can detect and monitor kidney disease, including urinalysis, blood tests of creatinine and BUN, and estimates of glomerular filtration rate (GFR) using equations. Quantitative indices like GFR are important for identifying and monitoring chronic kidney disease. Qualitative tests like imaging and biopsy can help differentiate specific kidney diseases and guide treatment.

1. Renal Disorders Pharmacotherapy
By: Tsegaye Melaku
[B.Pharm, MSc, Clinical Pharmacist]
February, 2017
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et
+251913765609
Chapter 1
Evaluation of Kidney Function

2. Lesson Objectives
 Upon completion of the chapter, you will be able to:
Understand the anatomy and physiology of urinary system
Understand the role of urinalysis (chemical and microscopic) in detecting and
monitoring renal disease.
Describe qualitative and quantitative assessment of kidney function
Compare and contrast various methods to estimate and measure creatinine
clearance and GFR in patients with CKD and acute renal failure.
Describe the appropriate use of creatinine clearance and estimated GFR
equations for renal drug dose adjustments.
Discuss the role of qualitative tests such as CT, MRI, ultrasonography, and
biopsy on renal function evaluation.

3. Functions
 Regulation of the volume of blood by excretion or conservation of
water.
 Regulation of the electrolyte content of the blood by the excretion
or conservation of minerals.
 Regulation of the acid-base balance of the blood by excretion or
conservation of ions
 Regulation of all of the above in tissue fluid.
Renal anatomy & physiology

4. Functions….
 Synthesizes and secretes many hormones involved in maintaining
fluid and electrolyte homeostasis
Renin [juxtaglomerular apparatus]
production and metabolism of prostaglandins and kinins
Erythropoietin by peritubular fibroblasts; in response to
decreased oxygen tension in the blood.
 Activation of vitamin D, gluconeogenesis, and metabolism of
endogenous compounds such as insulin, steroids, and xenobiotics.

5. Parts of Renal/uirinary System
 Kidneys
 Ureter
 Bladder
 Urethra

6. Parts of Renal System
Kidneys
Is to separate urea, mineral salts, toxins and other waste
products from the blood.
Filtering out wastes to be excreted in the urine.
Regulating BP
Regulating an acid-base balance
Stimulating RBC production

7. Parts of Renal System
Ureters
Transports urine from the renal pelvis of the kidney to which it is
attracted, to the bladder.
Pass beneath the urinary bladder, which results in the bladder
compressing the ureters and hence preventing back-flow of urine
when pressure in the bladder is high during urination.

8. Parts of Renal System
Bladder
Store urine
Expels urine into the urethra (Micturation)
 Micturation – involves both voluntary and involutary muscles.

9. Parts of Renal System
Urethra
Is the passageway through which urine is discharged from
the body.
FACT: Maindifference between the urinary systemof male and femaleis the
“lengthof urethra.”

10.  Nephrons – functional unit of kidney. Each kidney is formed of
about one million nephrons.
 Glomerulus – filters the blood
 Bowman’s Capsule – is a large double walled cup. It lies in the
renal cortex
 Tubular Component – necessary substances are being reabsorbed
 Loop of Henle – create a concentration gradient in the medulla of
the kidney. Reabsorb water and important nutrients in the filtrate.
 Renal Vein – a blood vessel that carries deoxygenated blood out
of the kidneys
 Renal Artery – supply clean, oxygen-rich blood to the kidneys
 Adrenal Gland (Suprarenal Gland) – located on top of the
kidneys and is essential for balancing salt and water in the body
Other Parts of Renal System

11. Three process in Urine Formation

12. Glomerular filtration
 Beginning of the process.
 A process by which the blood courses through the glomeruli, much
of its fluid, containing both useful chemicals and dissolve waste
materials, soaks out the blood through membranes where it is
filtered and then flows into Bowman’s capsule.

13. Tubular Reabsorption
 A movement of substances out of the renal tubules back into the
blood capillaries located around the tubules (peritubular
capillaries).

14. Tubular Secretion
 Disposing of substances not already in the filtrate (drugs)
 Eliminating undesirable substances that have been reabsorbed by
passive processes (urea and uric acid)
 Ridding the body of excess potassium ions
 Controlling pH

15. Glomerular Filtration Rate
 Is the amount of fluid filtered from the blood into the capsule
each minute.
 Factors governing the filtration rate at the capillary beds are:
total surface area available for filtration
filtration membrane permeability
net filtration pressure

17. How to assess kidney function
 Assessment of kidney function፡ qualitative and quantitative methods.
Determine the pathology and etiology of kidney disease.
Urinalysis (U/A): give clues to the primary location
(glomerular/tubular)
Imaging procedures/kidney biopsy: differentiate the
specific cause.
Ultimate: Guide the selection of the optimal therapeutic intervention

18. Cont’d…
 Quantitative indices [GFR or CLcr]: identifying the presence and
monitoring the progression of CKD.
Quantify changes in function [as a result of disease
progression, therapeutic intervention, or a toxic insult].

19. Laboratory/diagnostic Procedures to Detect the Presence of Kidney
Disease

20. Urine consists of:
(96%)
water
Inorganic:
Cl-, Na, K.
trace amounts of:
sulfate, HCO3 etc.)
 Urine: Is an ultrafiltrate of plasma from which glucose, amino acids,
water and other substances essential to body metabolism have been
reabsorbed.
(4%)
dissolved solids:
(2%)
Urea: (half)
(2%)
Other compounds
Organic:
creatinine
uric acid
Urine analysis [U/A]

21. Urine analysis [U/A]
 Detect and differentiate various aspects of kidney disease,
Which often goes unnoticed as the result of its asymptomatic
presentation.
 Detect and monitor the progression of diseases[DM,
glomerulonephritis, and chronic UTI].
 Physical & chemical composition(volume and color) & dipstick testing.

22. Chemical analysis of Urine
I. PH
Normal urine pH: 4.5 to 7.8
Elevation   presence of urea-splitting bacteria.
Example: In patients with renal tubular acidosis, usually >5.5;
Impaired hydrogen ion secretion in the distal tubule or
collecting duct.
Urine sample must be fresh (why?)
(on standing urine become alkaline as a result of ammonia liberation due to urea
decomposition).

23. Cont’d…
Acidic urine occurs in:
Acidosis
Uncontrolled diabetes
Diarrhea
Starvation and dehydration
Respiratory diseases in which
carbon dioxide retention occurs and
acidosis develops
Alkaline urine occurs in:
Urinary tract obstruction
Pyloric obstruction
Salicylate intoxication
Renal tubular acidosis
Chronic renal failure
Respiratory diseases that involve
hyperventilation (blowing off carbon
dioxide and the development of alkalosis)

24. II. Glucose [0-0.8mmol/L]
Usually not present in the urine
 [kidney normally
completely reabsorbs all
the glucose filtered at the
glomerulus].
Above threshold for glucose
reabsorption (~180 mg/dL
[~10.0 mmol/L]) glucosuria.
Example: diabetics.
III. Ketones
Acetoacetate and acetone are not
normally found in the urine
Example: DKA, fasting or starvation,
Vomiting for long time
Acetoacetate excretion
Small (<20 mg/dL [<2 mmol/L]),
Moderate (30-40 mg/dL [3-4
mmol/L]),
Large (>80 mg/dL [>than 8
mmol/L]).

25. Nitrite is not usually present in urine.
Bacteria convert urinary nitrate to nitrite.
Example: UTI, commonly caused by GM(-)rods ; E.coli.
False (+ve) results are very rare, false (-ve) results are more
common; may be due to:
 Lack of dietary nitrate,
 Reduced urine nitrate concentration as a consequence of
diuresis, or
 Infections caused by bacteria [enterococci and Acinetobacter],
which do not reduce nitrate, and pseudomonas, which convert
nitrate to nitrogen gas.
IV. Nitrite

26. Is released from lysed
granulocytes in the urine.
Its presence is suggestive of UTI.
False(+ve): delayed processing
of the urine sample,
contamination (such as blood or
heavy mucus discharge), or
Trichomonas infection
False(-ve) presence of high levels
of protein or ascorbic acid.
VI. Heme
Indicates the presence of
hemoglobin or myoglobin .
Example: red cell hemolysis or
Rhabdomyolysis.
V. Leukocyte Esterase

27. VII. Protein Or Albumin
 Proteins [albumin, globulins] are not filtered by the glomerulus molecular
size(>40 kDa).
 Smaller proteins (<20 kDa) pass across the glomerular basement
membrane but are usually readily reabsorbed in the proximal tubule.
 Standard tool to
Characterize the severity of CKD.
Monitor the rate of disease progression or regression.
 Persistent proteinuria or albuminuria: at least three occasions over a
period of 3 to 6 months
A principal marker of kidney damage.

28.  A measure of urine weight relative to water (1.00) using a
refractometer.
 Dependent on water intake and urine-concentrating ability.
 Increase suggests:
 Decrease suggests:
VIII. Specific Gravity [1.003 to 1.030]

29. Microscopic Analysis of Urine
 Critical aspect of U/A.
 Detect: erythrocytes, leukocytes, casts, and crystals.
 RBC: >2 cells/HPF
 WBC:>1 cells/HPF
 Infection/inflammatory conditions [e.g. interstitial nephritis].
abnormal

30. Serum/Blood Urea Nitrogen
 Normal: 5 to 20 mg/dL
 Amino acids ammonia urea [in liver)
 Production dependent on protein(diet) and hepatic function.
 Increase suggests:
 Decrease Suggests:
 BUN: Scr

31. Serum and Urine Creatinine
 Normal: 0.5 to 1.5 mg/dL
 Cr: Endogenous biomarker [detect kidney disease].
 It is product of creatine metabolism from muscle [dependent on
muscle mass].
 Concentration of creatinine in serum is a function of creatinine
production and renal excretion.
 Creatinine is eliminated primarily by glomerular filtration[GFR
declinesScr rises]

32. Relationship between Scr and CrCl.

33. Serum and Urine Cystatin C
 Cystatin C: 132-amino-acid (13.3-kDa) cysteine protease inhibitor.
 Produced by all nucleated cells of the body.
 Biomarker of renal function.
 Serum concentrations significantly correlated with GFR as well as Scr.
 Freely filtered at the glomerulus and undergoes both reabsorption
and catabolism in the proximal tubule.
 Its production was not affected by muscle massprovide a more
reliable estimate of renal function than Scr.

34. Measured GFR [mGFR]
 Gold standard quantitative index of kidney function.
 Important for early recognition and monitoring of patients with CKD
and as a guide for drug-dose adjustment.
 The GFR is expressed as the volume of plasma filtered across the
glomerulus per unit time
 127 ± 20 mL/min/1.73 m2 and 118 ± 20 mL/min/1.73 m2 men and
women, respectively

35. Estimation of GFR
 Direct measure of GFR in clinical settings [invasive nature and
technical difficulties].
 Many equations for estimating GFR.
 Modification of Diet in Renal Disease Study (MDRD) equation
 Inaccurate at GFR more than 60 mL/min/1.73m2
 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation
 Most appropriate for estimating GFR in individuals with eGFR values >
60 mL/min/1.73 m2
 Cockcroft-Gault (CG) equation

36. Equations for Estimation of GFR
Levey et
al.(MDRD4)
eGFR = 186 × (Scr)–1.154 × (age)–0.203 × (0.742 if patient is
female) × (1.210 if patient is black)
Levey et
al. (MDRD4-
IDMS)
eGFR = 175 × (Scr)–1.154 × (age)–0.203 × (0.742 if patient is
female) × (1.210 if patient is black)
Levey et
al.(CKD-EPI)
eGFR = 141 × min(Scr/ κ, 1)α × max(Scr/,κ, 1)–1.209 ×
0.993age × 1.018 [if female] × 1.159 [if black]
Schaeffner et
al.(BIS1)
eGFR = 3736 × (Scr)–0.87 × (age)–0.95 × (0.82 if patient is
female)
Schaeffner et
al.(BIS2)
eGFR = 767 × (cysC)–0.61 × (Scr)–0.40 × (age)–0.57 × (0.87 if
patient is female)
Larsson et al. eGFR = 77.24 × (cysC in mg/L)–1.2623
κ is 0.7 for females and 0.9 for males, α is –0.329 for females and –0.411 for males,

37. Macdonald et
al.
CKD-EPI
Equation 8
eGFR = 127.7 × (cysC in mg/L)–1.17 × (age in years)–0.13 × 0.91 (if
female) × 1.06 (if black)
*eGFR = 127.7 × (–0.105 + 1.13 × standardized ScysC)–1.17 × age–
0.13 × (0.91 if female) × (1.06 if black)
CKD-EPI
Equation 9
eGFR (mL/min/1.73 m2) = 76.7 × (cysC in mg/L)–1.19
*eGFR (mL/min/1.73 m2) = 76.7 × (–0.105 + 1.13 × cysC in mg/L)–
1.19
CKD-EPI
Equation 10
eGFR (mL/min/1.73 m2) = 177.6 × (Scr in mg/dL)–0.65 × (cysC in
mg/L)–0.57 × (age in years)–0.20 × 0.82 [if female] × 1.11 [if black]
*eGFR (mL/min/1.73 m2) = 177.6 × (Scr in mg/dL)–0.65 × (–0.105 +
1.13 × cysC in mg/L)–0.57 × (age in years)–0.20 × 0.82 [if female] ×
1.11 [if black]

38. Equations for the Estimation of CrCl
Cockroft and
Gault
Men: CLcr = (140 – age)ABW/(Scr × 72)
Women: CLcr × 0.85
Jelliffe
Men: CLcr = (100/Scr) – 12
Women: CLcr = (80/Scr) – 7
Jelliffe Men: CLcr = 98 – [0.8 (age – 20)]/Scr
Women: CLcr × 0.9
Mawer et al. Men: ABW [29.3 – (0.203 × age)] [1 – (0.03 ×
Scr)]/(14.4 × Scr)
Women: ABW [25.3 – (0.175 × age)] [1 – (0.03 ×
Scr)]/(14.4 × Scr)
Hull et al. Men: CLcr = [(145 – age)/Scr] – 3
Women: Clcr × 0.85

39. Qualitative Diagnostic Procedures
 To investigate for etiology
 Radiography, computed tomography, magnetic resonance imaging,
sonography, and biopsy