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Biochemical Assessment of

Renal Disease
Dr Suzannah Phillips
Senior Clinical Scientist
Royal Liverpool Hospital
Overview
Presentation of renal disease

Biochemical assessment
glomerular function
tubular function
urinalysis

Other tests

Renal Disease
Retention of waste products
Disorders in
electrolyte
balance
Disorders in water
balance - alterations in
urine output
Disorders in red
cell production
and vitamin D
Changes in urine output
Anuria
No urine output <50 mL/24hrs

Oligouria
Reduced volume of urine output <400 mL/24hrs in adults

Polyuria
Increased volume of urine output >3 L/24hrs

Frequency - increased urination but total daily volume is normal (nocturia)
Dysuria - pain on urination


Presentation
Uraemic syndrome
Cardiovascular
Hypertension
Percarditis
CCF
Anaemia
Neurological
Lethargy
Headache
Peripheral neuropathy
Muscle weakness
Skeletal
Renal osteodystrophy
Stunted growth

Gastrointestinal
Vomiting
Nausea
anorexia
Dermatological
Pruritus
Pigmentation
Slow wound healing
Genitourinary
Impotence
Polyuria/Nocturia

Immunological
Increased susceptibility to infection
Presentation
Azotaemia increased
urea
Effect of Renal Disease
Glomerular
Tubular
Reduced filtration
Anuria/oliguria
Increased plasma creatinine /urea
Hyperkalaemia
Hyperphosphataemia
Metabolic acidosis

Damage to glomerular membrane
Proteinuria large proteins
Haematuria
Reduced reabsorption (general or
specific inherited conditions).
Polyuria, low urine osmolality
Metabolic acidosis
Proteinuria - small proteins
(2 microglobulin, amino acids)
Glycosuria

Anaemia,
Hypocalcaemia
Hormonal
Presentation will depend on the cause, the relative glomerular to tubular
dysfunction and the number of nephrons affected.
Nephrotic syndrome
Proteinuria (>3g/24hrs), hypoalbuminaemia,
oedema, hyperlipidaemia

Nephritic syndrome
Haematuria, proteinuria, oligouria,
hypertension, azotemia



Fanconi syndrome
Glycosuria, aminoaciduria, hypokalaemia,
hypophosphataemia, hypouricaemia,
metabolic acidosis)

Presentation

Tests for Glomerular function -
ability to remove waste products
integrity of glomerular membrane and ability to prevent large particles
entering the filtrate

Tests for Tubular function
ability to adjust Na+, K+, H+ ions, water composition of filtrate &
reabsorb small proteins, amino acids & glucose
e.g. urine volume/osmolality, urine glucose, urine electrolytes, urine aminoacids.


Urinalysis
detect disease

Assessment
1. Glomerular filtration rate (GFR)
Clearance (ability to remove waste products)
The volume of plasma that is filtered by the kidneys and from which a
substance is completely cleared per unit of time


Assessment of Glomerular function
Clearance = Urine concentration (umol/L) x Urine Volume (mL)
Plasma concentration (umol/L) x time (min)
= mL.min
-1
Ideal Marker (clearance = GFR)
Stable plasma concentration
Freely filtered at the glomerulus
Not secreted or reabsorbed by renal tubular cells
Renal excretion ONLY (i.e. not metabolised by liver)
Easy and cheap to measure
!! No marker fulfils
all these criteria
WATCH
UNITS
1. Glomerular filtration rate (GFR)
Assessment of Glomerular function
How to collect 24 hr urine
Day 1 8am empty bladder (discard output)
Commence 24h urine collection
All urine now passed until 8am next day must be collected into container.
Day 2 8am collect final urine output into container
Clearance need blood and urine sample - relies on accurate 24 hr urine
collection
Indirect measure of clearance - use plasma concentration of marker
increased levels reflect reduced clearance.
1. Glomerular filtration rate (GFR)
Assessment of Glomerular function
Exogenous markers
Bolus injection disappearance from plasma
IV infusion clearance

Inulin Clearance - gold standard.
- difficult and expensive to measure

51
Cr-EDTA - clinical standard
- difficult and expensive to measure

99
m
Tc-DTPA (diethylenetriaminepentacetic acid)
- difficult and expensive to measure
- allows imaging of kidney

P-aminohippuric acid - determines renal plasma flow
- completely cleared in single passage through kidney

1. Glomerular filtration rate (GFR)
Assessment of Glomerular function
Endogenous markers
Clearance
Plasma concentration

Cystatin C
Protein produced by all nucleated cells
Expensive assay

Urea

- End product of nitrogenous compound metabolism (esp amino acids)
- Freely filtered at glomerulus
- Quick, cheap & convenient
- NOT steady plasma levels effected by diet and protein catabolism e.g.
raised in GI bleed
- Low in liver disease
- Some passive reabsorption in renal tubules
- Under estimation of GFR
Assessment of Glomerular function
Creatinine clearance / plasma

Used routinely
From breakdown of skeletal muscle cells.
Constant daily production
Normally filtered and excreted in the urine.
Some secretion.
Over estimation of GFR
Can correct for BSA (mL/min/1.73m
2)
CrCl x 1.73
BSA

Quick, cheap & convenient
Effected by body mass /ethnicity.
Interferences (ketones & bilirubin).
GFR falls to <50ml/min before creatinine rises

Calculated Glomerular filtration rate
Assessment of Glomerular function
Cr Cl (mL/min) = [(140 age) x weight / 0.814 x serum creatinine (umol/L)]
a. Cockcroft and Gault
x 0.85 if female
b. Schwartz Formula (children)
eGFR = K x height / serum creatinine
K= constant, dependent on age
Estimated Glomerular filtration rate (eGFR)
Assessment of Glomerular function
c. Modification of Diet in Renal Disease (MDRD)
eGFR = 175 x (Creat / 88.4)
-1.154
x (Age)
-0.203
x (0.742 if female) x (1.210 if black)
4 variable (creatinine, age, sex, ethnicity)
6 variable (includes serum urea & albumin)
NOT validated for use in
Children
Acute kidney injury
Amputees
pregnancy
Malnourished
Odematous
Muscle wasting
Only black ethnicity accounted for ?others
Under-estimates GFR (>60 mL/min)

? Differences in assay performance:
175 if method traceable to IDMS
NEQAS (2006) slope and intercept adjustment
factors.
Estimated Glomerular filtration rate (eGFR)
Assessment of Glomerular function
d. CKD Epidemiology collaboration (CKD-EPI) (2009)
More accurate than MDRD esp when GFR >60 mL/min
2. Proteinuria (glomerular membrane integrity)
24h protein excretion (<0.15g/24h) >50% Tamm-Horsfall mucoprotein.
24 hr albumin excretion (<30mg/24)
Albumin main protein lost when glomerular disease most abundant protein
in plasma.
More severe glomerular damage loss of larger proteins (Igs).
Assessment of Glomerular function
Classification of proteinuria
Assessment of Glomerular function
Tests for glomerular proteinuria
24 hr total protein
Random urine - Protein:creatinine ratio (PCR)
Protein Selectivity

Microalbumin (ability to detect albumin at low levels in urine)
Random urine - Albumin:creatinine ratio (ACR)
http://www.nice.org.uk/nicemedia/pdf/CG073NICEGuideline.pdf

Assessment of Tubular function
1. Ability to excrete / retain water
Determined by ability to concentrate / dilute urine
Tests
Urine sodium, osmolality and volume
Serum sodium & osmolaltity
Fluid deprivation test

2. Ability to maintain acid-base balance
Usually see metabolic acidosis
Renal tubular acidosis
Urine / blood pH
Anion gap
Serum bicarbonate
Assessment of Tubular function
3. Ability to maintain electrolyte balance
Tubular proteinuria low molecular weight proteins (1-microglobin, Retinol
binding protein, RBP & 2-microglobin)
Serum and urine aminoacids. (specific defects aminoaciduria).
Urine glucose renal threshold ~10 mmol/L
4. Ability to reabsorb small proteins, amino acids & glucose
Serum sodium & potassium
Random Urine sodium & potassium
Fractional excretion of sodium (FeNa) = 100 x ((Ur Na/Serum Na) / (Ur creat/serum creat))
Trans-tubular K gradient (TTKG) = ((UrK / serum K) / (Ur osmo / serum osmo))
Urinalysis
1. Dipstick (random)
Urinalysis
2. Microscopy
Urine casts due to aggregation in distal / collecting duct
Red cell


Granular (cell debris)


Hyaline (Tamm-Horsfall protein)


White cell


Urinalysis
3. Renal stones
Types of stone
(67%) Calcium oxalate phosphate (hypercalcaemia)

(12%) Triple phosphate/struvite (Mg, Ca, NH
4
) (UTI)

(8%) Calcium phosphate (alkaline urine)

(8%) Uric acid (purine metabolism)

(1-2%) Cystine (cystinuria)

Urinalysis
3. Renal stones
Formation induced by:
Increased concentration of urinary constituents above natural solubility

Lack of physiological inhibitors of stone growth (e.g mucopolysaccarides,citrate &
pyrophosphate)

Changes in urine pH (alkaline pH favours NH
4
ion formation precipitate)

Seeding (i.e stone formed can be different to the nucleus that the stone started
from & colonisation of bacteria can accelerate stone growth)
Urinalysis
3. Renal stones
Urine analysis
Calcium
Phosphate
Urate
Oxalate
Cystine
pH
Sodium
Magnesium
Citrate
Microbiology

Stone analysis

Other Specific Tests
NGAL- Neutrophil Gelatinase Associated Lipocalin
Marker of acute kidney injury (urine & serum)
Early detection of AKI
Serum glucose / HbA1c Diabetic renal disease
Bence Jones Protein (BJP) Multiple myeloma
Also serum Igs & electrophoresis
Immunology Tests
ANCA, Anti-GBM
Imaging
Ultrasound
MRI
CT
Angiography (renal artery stenosis)