GFR

• Kidneys process about 50 gallons (180 liters) of blood every day to produce
about 50 ounces (1.5 liters) of urine.
• GFR is affected by many factors,
• Time of day
• Dietary protein intake
• Exercise
• Age
• Pregnancy
• Obesity
• High blood sugar (hyperglycemia)
• Antihypertensive drugs (used for reducing high blood pressure)
• Acute and chronic kidney disease
Creatinine-derived eGFR

• These factors can decrease eGFR:(increase creatinine)

• Eating cooked meat before the test – this increases creatinine levels in the blood
• Starvation and long fasting periods
• Bodybuilding and creatine supplementation [15]
• Other factors that can increase , such as dehydration [16]
• Medication, including NSAIDs and ACE inhibitors (or angiotensin receptor
blockers) [
Stage Ml/min/ Description color
1.73m2
1 >90 Slight kidney damage with normal/
2 60-89 Mild decrease in kidney function
3 30-59 Moderate decrease in kidney function
4 15-29 Severe decrease in kidney function
5 <15 End stage kidney failure
 eGFR
A calculation used to estimate how well
your kidneys are filtering certain
agents produced by your body, such
as:creatinine (a waste product that comes
from the normal wear and tear on
muscles)cystatin C (a protein that slows
down the breakdown of other protein cells)
Availability widely available
Cost Less expensive
Time for test Less time needed
Accuracy Possible inaccurate estimates of GFR,
especially in early stages of kidney disease
(stages 1 and 2)*
Precision Can miss early GFR changes, such as a
rapid decrease in levels, which may be a
sign of diabetic kidney disease
mGFR
A measurement of how well your kidneys are
filtering certain agents not produced by your
body, such as: inulin (a kind of fiber that is found
in some plant foods)
iohexol (contrast agent used in imaging tests)
Not widely available
More expensive
More time consuming
Accurate measures of GFR, including early
stages of kidney disease (stages 1 and 2)
Can identify early GFR changes, such as a rapid
decrease in levels, which may be a sign of diabetic
kidney disease
• Later stage CKD does cause symptoms. So, you may need an eGFR test if you
have any of the following CKD symptoms:
• Urinating more often or less often
• Itching
• Feeling tired
• Swelling in your arms, legs, or feet
• Muscle cramps
• Nausea and vomiting
• Loss of appetite
SECONDARY HYPERPARATHYROIDISM IN CKD –
SEQUENCE OF PLASMA BIOCHEMISTRY
CHANGES IN EARLY CKD STAGES
Chronic kidney disease-associated mineral and bone disorder (CKD-
MBD)

Complex interactions between phosphate,

FGF23, FGF receptor-1c (FGFR1c), Klotho,
1,25diOH vitamin D (calcitriol), renal 1α
25OH vitamin D hydroxylase (1α
hydroxylase), vitamin D receptor (VDR),
calcium, Ca-sensing receptor (CaSR), and
parathyroid hormone (PTH).
• The terminology is also somewhat hard to follow, so here goes:
• eGFRcr: formula with creatinine (not cystatin C)
• eGFRcys: equation with cystatin C (not creatinine)
• eGFRcr-cys: equation with both creatinine and cystatin C
• Then the demographic factors get added on
• ASR: equation with age, sex and race
• AS: age and sex (but not race)
Creatinine clearance equation

• SI units
• urea mmol/L (Normal 2-7)
• Creatinine umol/L (Normal 49-90)
• Conversion umol/L to mg/dL (umol/L x 88.4)
mg/dL to umol/L (mg/dL x 0.0113)
• Normal creatinine clearance for adults 80-120 ml/min
• Abnormal when woman creatinine 1.2 x normal; male 1.4x normal
• Creatinine clearance ={Creatinine (24 hour urine in mg/dL) / Creatinine
(serum in mg/dL)}X{Volume (24 hour urine in ml) / Time (hours x 60min)
Estimation of GFR (eGFR)

• CKD-EPI also reported as ml/min/1.73m3

• Equations are adjusted for BSA as kidney function is proportional to kidney size
which is proportional to BSA. 1.73m3 is the normal mean for young adults.
• Why adjust for race and sex?
- African-American was found to have a higher GFR than Caucasians and other
races at the same serum creatinine. Due to higher average muscle mass and
creatinine generation.
- Adjusted for sex as male has higher average muscle.
- Modifications for MDRD and CKD-EPI for Japanese and Chinese population
but yet to be validated
All 3 equations estimate GFR from serum creatinine.
• 1) Cockcroft-Gault- Developed 1970s from 250 men with a wide range of CrClr.
- Not adjusted for BSA. Adjusted for age, lean body weight and sex
- Since unadjusted for BSA, can be used for drug doing
- Pharmacokinetics used Cockcroft-Gault to determine level of kidney function
and drug dosage adjustment. NOTE! The creatinine assays were not standardised,
therefore still inconsistent translation into clinical practice
• 2) MDRD (Modification of Diet in renal Disease)
- Developed from 1630 patients with CKD. It is more accurate than Cockcroft Gault.
- It is adjusted for BSA, age, sex and race (if African American) but not weight
- Less accurate at eGFR >60ml/min/1.73m3
- Not validated in <18 years old, pregnant and elderly
- For drug dosing, MDRD needs to be unadjusted for BSA
• 3) CKD-EPI (CKD Epidemiology Collaboration)
- Accurate as MDRD in the subgroup with eGFR <50ml/min/1.73m3 but also
accurate in the subgroup with eGFR>60ml/min/1.73m3
- Adjusted for age, sex and race
- Not validated for children <18, pregnant and some ethnic subgroups
Problems associated using eGFR:

• Using serum creatinine as filtration marker

- Decreased accuracy at higher eGFR
- non-steady state conditions for filtration marker when GFR is changing
- Serum creatinine is affected by production (muscle and diet), PCT
secretion and extrarenal (GIT and liver) excretion which causes a wide variation
amongst individuals therefore wide-range of abnormal cutoffs. As such GFR must
decline to approximately 50% of normal before serum creatinine concentration
rises above the upper limit of normal. Always remember drug interactions, some
can inhibit creatinine secretion e.g. cimetidine
How is GFR measured or estimated?
• GFR cannot be measured directly.Clinically rather estimated via filtration markers. The perfect marker
wound be freely filtered, not reabsorbed or secreted.
• Normal
-Young: eGFR >= 90ml/min/1.73m3
-Elderly (>60 years old) or Infants: 60-89ml/min/1.73m3 may be normal
• Abnormal
- eGFR 60-89ml/min/1.73m3 for 3 months long with kidney damage = signs of early kidney
disease - eGFR <60ml/min/1.73m3 for 3 months or more indicate CKD
- eGFR <60ml/min/1.73m3 is associated with increased prevalence of complications of CKD and
risks of CVS disease
• 1) Creatinine (urine and serum): Filtered but also mildly secreted in PCT (therefore overestimates)
Endogenously produced, a product of muscle metabolism with near constant production.
2) Inulin (gold standard): Filtered only. Not made endogenously and must be injected.
3) Urea: Endogenous product of protein intake. It is filtered and reabsorbed therefore
not an ideal marker. 4) Cystatin C: non-glyosylated protein produced by all nucleated cells that
is less variable and less affected by age and sex. Freely filtered and reabsorbed plus catabolised by tubular
epithelial cells. urinary clearance cannot be measured. May be a more accurate filtration marker than
creatinine and better predictor of adverse events in elderly (mortality, cardiac failure, peripheral arterial
disease)
 How to classify Acute Kidney Injury?
• AKI is the new term for acute renal failure
- Clinical spectrum of disease
- SCr poor marker
• Conversion of SCr mg/dL to umol/L
- 0.3mg/dl = 26.5umol/l - 4mg/dl = 353.6umol/l
• Normal renal function patients undergoing non-cardiac surgery has an incidence
of 7.5%
- sensitive marker of physiological stress
- independent contributor to mortality and morbidity
- risk factor for developing or worsening of CKD
1) RIFLE criteria (Risk, ,Injury, Failure, Loss, end-stage) - AKI defined as increase in
SCr >= 50% within 7days - Based on serum creatinine and
urinary output - 3 Stages of AKI and 2 clinical outcome stages (Loss and End-stage)
- Needs a baseline creatinine and did not incorporate RRT patients, no time
frame with the minimum change in creatinine too large
2) AKIN (Acute Kindey Injury Network) - AKI defined as Increase in
SCr>= 0.3mg/dL or 50% within 48 hours - new changes to take into account the
minor changes in serum creatinine (which may be associated with increased mortality,
serving as a prognostic factor) - 48 hours to determine the change in creatinine
with no need to correlate with baseline value and the need for RRT was taken into
account
3) KDIGO (Kidney Disease: Improving Global Outcomes AKI group)
- AKI defined as increase in SCr >= 0.3mg/dl within 48 hours or >= 50%
within 7days - Incorporates time criteria and patients <18 year old and RRT
 Types of ARF/AKI
• Usually multifactorial
1) Prerenal (FeNa <1% and BUN/Cr>20)- 30-40% in ICU
- Due to decreased effective arterial volume from volume, cardiac or vascular tone
abnormalities
- Drugs e.g. NSAIDs: inhibits cylooxygenase (which is involve in the production of
prostaglandin, PGE2 PGD2, that is responsible for vascular dilation thereby increase renal perfusion
by decreasing renal vascular resistance). Inhibition of COX results in renal vasoconstriction
(constrict afferent arteriole) and decreased GFR and medullary ischemia E.g.ACE-I or ARB: Dilate
efferent arteriole thereby decreasing glomerular filtration pressure
- Renal artery stenosis
- Urine analysis: No cells , no or hyaline cases
2) Intrinsic
- 50% in ICU
- Acute tubular necrosis (FeNa >2% +/- muddy casts [heme-granular casts] +/- hematuria)
( Due to prolonged prerenal failure, sepsis, shock, nephrotoxins: Often associated with multi-organ
injury: Urinalysis: epithelial or other cells. Coarse, granular muddy casts: Also consider
rhabdomyolysis (CPK, LDH, aldolase)
- Acute interstitial nephritis (AIN)
• : Almost any drug can cause AIN, may or may not be associated with fever, rash or
eosinophilia in urine
• : Urinalysis: WBC or granular casts, WBCs or eosinophils
• : implicating drugs: Antibiotics (Penicillin, Cipro, Rifapin), NSAIDs, Lasix
• - Small vessel Disease/ Vasculitis (emboli, HUS, TTP, DIC, PET, malignant hyperthermia
• - Glomerulonephritis
• : Urinalysis: dysmorphic RBC and RBC casts
• 3) Postrenal
• BUN = Blood urea nitrogen = Europe the whole urea molecule is assayed. USA the nitrogen
component of urea is measured. BUN is approximately 50% of blood urea.
• Convert BUN mg/dL to urea mmol/L
• :BUN 10mg/dL = urea 21.4mg/dL = 7.6mmol/L
What are the markers of kidney damage ?

• 1) Ultrasound: Increased echogenicity, small or large size, doppler interrogation.

Other signs associated with kidney disease: nephrocalcinosis

2) Proteinuria
- Albumin-specific dispstix, routeini dipstix > 1 positive, Albumin to creatinine ratio
(> 30mg/g), Total protein to creatinine ratio >200mg/g
- Microalbuminemia is when albumin-creatinine ratio between 30-300mg/g
- Macroalbuminemia >300mg/g
Chronic Kidney Disease and associated complications and comorbities

Defined as presence of kidney damage or eGFR <60ml/min/1.73m3 for 3 months or

more without knowledge of its cause
1) Metabolic: Hyperphosphatemia, hyperkalemia, hyperuricemia, acidosis,
hypocalcemia, Vitamin D deficiency, hypoalbuminemia, dyslipidemia, secondary
hyperparathyroidism
2) CVS: Hypertension, CAD/MI, arrhythmia, peripheral vascular disease,
pulmonary edema, uraemic pericarditis/effusions, vascular calcification
3) GIT: malnutrition, GIT bleed, nausea, vomiting
4) Anemia, bleeding diathesis from platelet dysfunction
5) CNS: Asterixis, encephalopathy, seizures
6) Immunocompromised: Increased risk of infection
7) Pulmonary hypertension common in ESRD, pleural effusion
 Preoperative assessment of AKI/CKD
• - PATIENT: age, sex: hypertension, diabetes : cardiac failure, liver failure, limited cardiorspiratory
reserve : sepsis
- OPERATIVE : Emergency, major hemorrhage, blood transfusion, intraop hypovolemis and
hypotension, prolonged surgery: Major surgery i.e. cardiac, liver, vascular, intraoeritoneal
- PHARMACOLOGICAL
: NSAIDs : ACE-I and ARB : Aminoglycosides : Hydroxyethylstarch solutions : Radiological
contrast
-Optimise co-morbids
-Optimise glycemic, Bp control
-Avoid nephrotoxic drugs
1) Assessment of euvolemia/fluid status
- No edema, no pulmonary edema, and urine output ability
- BP controlled
- Ease of ventilation (unless has parenchymal lung disease)
2) CVS
- presence of pulmonary hypertension (common in ESRD)
- check for uremic pereicarditis/effusion and associated tamponade
- Blood pressure: Stop ACE and ARB 2 days before due to long half life : use short acting agents
: ACE and Atenolol removed with dialysis
Preoperative assessment of AKI/CKD
• 2.1) RESP- Pulmonary edema, pleural effusions: consider tapping if affecting lung mechanics
2.2) CNS: Encephalopathy, seizures
2.3) GIT: stress ulcer, hemorrhage, anorexia, N+V
2.4) Endocrine:- Secondary Hyperparathyroidism leading to osteoporosis (secondary to
hyperphosphatemia resulting in formation of insoluble calcium phosphate causing hypocalcemia )
- Followed by tertiary hyperparathyroidism resulting in hypercalcemia
- Glucose control

3) Anemia
- Avoid transfusions
- If transfuse, use leukodepleted RBCs. This avoids HLA sensitization and maybe reduce AKI
- DDAVP/Cryoprecipitate useful for active bleeding
- Uremic patients may have bleeding tendencies due to platelet dysfunction

4) Vascular access
- Note any AV fistulas and AVOID use
- avoid areas used for future fistulas. Rather use hands or feet.
- Avoid subclavian lines, associated with increase stenosis and SVC syndrome
- Also avoid arterial lines on the same limb with fistulas
Preoperative assessment of AKI/CKD

• 5) Electrolyte assessment
- Metabolic acidosis: consider Bicarbonate when pH <7.2
- Potassium: high K are often well tolerated.
: <5.5 Sux is safe
: 5.5 - 6.0, acceptable if chronic, avoid Sux
: >6 If emergency, shift and avoid potassium containing solution. Otherwise dialyse

6) Altered drug pharmacokinetics

- Absorption/Bioavailability: Gastroparesis and gut oedema may decrease oral absorption
- Distribution
: Increased Vd due to decreased protein binding and leaky capillaries for water soluble drugs
: Loading doses therefore still required as per normal in AKI/CKD
- Excretion
: Decreased due to low GFR for water soluble drugs
: Renal excretion and metabolism of insulin DECREASES, therefore risk of hypoglycemia
: Risk of accumulation of toxins
- Maintenance dose renal adjust according to GFR
Prevention

• Stop nephrotoxic drugs :Metformin itself is not nephrotoxic but is excreted exclusively by
the kidneys, therefore may accumulate and cause lactic acidosis
• Alternative imaging e.g. ultrasound : Important to note MRI contrast using gladolinium
causes Nephrogenic systemic fibrosis (severe fibrosis of skin impeding mobility)
• Fluids : Saline at 1ml/kg/hour pre and post contrast 3-12 hours. Oral fluids have not been found
to be protective
: Bicarbonate solutions may be better than saline. KDIGO recommends either or. It
decreases radical formation due to alkaline pH
• N-Acetylcysteine: Antioxidant effects. Inconsistent results. But KDIGO recommends its use due to its
minimal side effects, potential benefits
• Theophylline: non-selective Adenosine antagonist. Promotes vasodilation. Also conflicting evidence,
with its narrow therapeutic window, also not recommended
• Statins:Pleiotropic effects (Antioxidant, anti-inflammatory and plaque stabilizing):Currently no
convincing evidence, more RCTs needed.
• CCB: Vasodilative effect. Limited data with no obvious benefits observed.
• Vitamine C: Antioxidant, controversial, inconclusive evidence. Not recommended
• Contrast: Minimise volume, avoid hyperosmolar contrasts