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DR ADRI AN G MI L L E R

ROYAL L I VE RPOOL HOS PI T AL


An Introduction to
Kidney Disorders
Aims of this session
To briefly revise kidney function
To revisit means of assessing kidney function
Gain an understanding of common kidney disorders
Understand pre-renal, intra-renal and post-renal
concepts
Learn how to investigate and manage renal
disease
Apply knowledge to clinical scenarios (cases)
Important points to remember
Renal disease is rarely straight-forward this session
will not teach you everything you need to know but
were afraid to ask about renal disease
Use the references cited to expand your knowledge
Use Textbooks (Tietz, Marshall etc)

Make a friend of the kidney and its role in health
and disease
Although sometimes (!) complicated, the kidneys role is
crucial to understanding many disease processes
Use a multi-disciplinary approach to clinical problems

THE KIDNEY A REFRESHER
KIDNEY FUNCTIONS
Maintains water and electrolyte homeostasis
Controls volume and composition of ECF

Removes water-soluble waste products and toxins
Nitrogenous compounds
Maintains acid-base balance (excretion of H
+
)

Produces (and responds to) chemical messengers
Role in Vitamin D metabolism
Role in haemoglobin synthesis
When renal function is impaired, for WHATEVER reason, it
will hinder the kidneys ability to perform these functions
KIDNEY FUNCTIONS
Maintains water and electrolyte homeostasis
Sodium, glucose, bicarbonate reabsorption
Potassium, phosphate, acid (H+) excretion
Water control
Electroneutrality

In order to function, the kidney needs
Adequate perfusion (blood supply)
Positive pressure differential at the glomerulus
Viable, semi-permeable glomerular membrane
Intact, functioning tubular endothelium
Channels
Transporters
Gradients (electrochemical, concentration)
Clear passage for filtrate to travel
Appropriate hormonal activity (and ability to
respond)
Energy!
ASSESSING RENAL FUNCTION
Which function to measure.?

Ability to maintain water and electrolyte balance?

Ability to select what is allowed to enter the tubule?

Ability to remove waste products?

Ability to produce (and respond to) chemical
mediators?


ASSESSING RENAL FUNCTION
Broadly divided into:

Assessment of glomerular filtration
Ability to remove waste products
Assessment of glomerular integrity
Ability to select what is allowed to enter the tubule
Assessment of tubular cell function
Ability to reabsorb or secrete compounds
Ability to respond to stimulation


AT THE MACROSCOPIC LEVEL
Imaging studies are used to indicate anatomical
changes
Radiography
Ultrasonography
CT, MRI
Angiography
Urinalysis is a simple way to indicate renal pathology
Appearance (cloudy? Bloody? Strange colour? Smell?)
Specific gravity and osmolality
pH
Protein
Sediment
Other substances
AT THE MICROSCOPIC LEVEL
Immunological analysis
Auto-antibodies against renal components
Immuno-histochemical analysis

Biochemical analysis is the mainstay of renal
investigations
ASSESSING GLOMERULAR FILTRATION
As Biochemists, our frontline test measures the ability
of the kidneys to excrete nitrogenous (azotemic)
waste products.
Creatinine
Urea
Borne from the (uneasy) relationship between serum creatinine
concentration and glomerular filtration rate. Urea used as a side-kick.
Although beyond the scope of this lecture to discuss the
advantages and disadvantages of estimating glomerular
filtration rate (eGFR) as a function of serum creatinine
concentration (and other confounding variables), it would be
prudent to read the following:
Assessing Kidney Function Measured and Estimated Glomerular Filtration Rate
L. Stevens et al., New England Journal of Medicine (2006), 354 2473-83

Creatinine and glomerular filtration rate: evolution of an accommodation
C. Diskin, Annals of Clinical Biochemistry (2007), 44 1619
Creatinine clearance is not and has never been synonymous with
GFR, and no regression analysis will make it so, because the
serum creatinine depends upon many other factors than filtration.
ASSESSING GLOMERULAR INTEGRITY
Detection of compounds not normally present in the urine due
to the selectivity of the glomerular basement membrane
Albumin is the predominant plasma protein responsible for
many physiological functions (solute transport, oncotic pressure
etc). Normally not filtered at the glomerulus due to
Size (~66 kDa)
Charge (net negative charge)

Its presence in urine signals
loss of glomerular integrity
Microalbuminuria
Used to monitor CKD

ASSESSING TUBULAR FUNCTION
The most common tests of tubular function assess:
Ability to excrete an acid load (Urine pH e.g. RTA)
Ability to concentrate urine (Urine osmo. e.g. SIADH, DI)
Ability to respond to hormones (plasma and urine
electrolytes e.g. Addisons)
Ability to reabsorb solutes (urine glucose e.g. DM)
NB. Many re-absorption mechanisms are saturable. The presence of
small molecular weight solutes in the urine that arent normally there
may reflect over-production rather than under-reabsorption e.g.
Glucose in Diabetes Mellitus
Amino acids in some inborn errors of metabolism
RENAL DISORDERS
Acute Renal Failure (ARF)
More recently referred to as Acute Kidney Injury (AKI)
Describes a clinical scenario of kidney failure that develops over
hours or days (as opposed to weeks or months)
May be superimposed on established, chronic renal failure
(CRF) and is then referred to as acute on chronic RF

Traditionally separated into three major groups
Pre-renal (insult occurs before the kidneys)
Renal (intrinsic, tubular dysfunction)
Post-renal (blockage of the flow of urine to the ureters/bladder)
Acute Kidney Injury
J. Kellum. Crit Care Med (2008), 36 [Supplement] S141S145
Reminder: in order to function, the kidney
needs
Adequate blood/fluid supply
Positive pressure differential at the glomerulus
Viable, semi-permeable glomerular membrane
Intact, functioning tubular endothelium
Clear passage for filtrate to travel
Appropriate hormonal activity (and ability to
respond)
Energy
In Pre-Renal Conditions
Adequate blood and fluid supply?
Positive pressure differential at the glomerulus?
Pre-renal ARF implies some form of
hypoperfusion which may be a result of:
Dehydration
Haemorrhage or thrombosis
Renal artery stenosis
Acute cardiac failure
Sepsis
Pre-renal ARF can be considered an appropriate response to
hypovolaemia, conserving water and sodium at the expense of GFR
NOT AVAI L AB L E I N P R I MAR Y CAR E ( NOT AL WAY S ACCU R AT E I N
S E CONDAR Y CAR E ! ! )
FLUID BALANCE CHARTS!
INTRINSIC RENAL FAILURE
Due to their high metabolic rate, the kidneys are extremely vulnerable to
ischaemia prolonged episodes may cause renal damage that persists
after the underlying cause has been resolved - termed Acute Tubular
Necrosis
Causes of intrinsic renal failure
Glomerulonephritis
Goodpastures disease
Systemic Lupus Eryths (SLE)
Cryoglobulinaemia

Not exactly common
Pre-renal causes of ATN
Drugs
Tubular nephritis
Sarcoidosis
Poisoning
Rhabdomyolysis
Etc

A lot more common
POST-RENAL FAILURE
Obstruction is the most common cause of post-
renal failure. The main culprits are:
Renal calculi
Retroperitoneal fibrosis
Invasive bladder carcinoma
Benign or malignant prostatic disease (males)
A very un-holy
trinity!!
SOME FEATURES OF ARF
Metabolic Feature Clinical Feature
Retention of nitrogenous waste
products
Nausea, vomiting, disturbance
of consciousness, coma
Retention of sodium and water
(usually with hyponatraemia)
Peripheral and pulmonary
oedema, ascites, pleural
effusion
Hyperkalaemia ECG changes (peaked or
tented T waves, flat P waves,
QRS depression), muscle
weakness, paralysis
Retention of acid (metabolic
acidosis)
Kussmaul breathing,
hypotension
INVESTIGATING ARF/AKI
Urine dipstick testing for blood and protein suggest glomerular
disease
What if no urine is available?
Guidelines suggest serum creatinine and urine output are the
best biomarkers of AKI
UK Renal Association Guidelines issued in March 2011
MULTI-DISCIPLINARY APPROACH
Clinical
PMH
Medications

Biochemistry
Urinalysis protein and
blood
U&E, Calcium,
phosphate, CRP, CK, LFT
Arterial blood gases

Haematology
Red cell casts
Full blood count

Microbiology
Cultures and serology

Immunology
Auto-antibody screens
(ANCA, Anti-GBM etc.)
Cryoglobulin
MANAGEMENT OF ARF/AKI
Establish whether acute, chronic or acute-on-
chronic
Identify whether pre-renal and resuscitate with fluids
Discontinue nephrotoxic drugs
Treat metabolic complications
Exclude urinary tract obstruction
Investigate for intrinsic disease
Involve Nephrologists! Prognosis can be very poor.
Acute Renal Failure
R. Hilton. BMJ (2006), 333 p 7572
CHRONIC RENAL FAILURE
(CRF)
CHRONIC RENAL FAILURE
Unlike ARF/AKI, the onset of CRF is much more
gradual, presenting over months and years
Usually asymptomatic (initially, at least)
Only presents when renal functional threshold is crossed
Usually secondary to other pathologies
Natural decline of GFR with age
In many cases, progresses to End-Stage Renal Failure (ESRF)

Although there are many causes of CRF, the clinical
features tend to be similar as the condition reflects
the decline in the number of functioning nephrons
Causes of CRF
There are many, classified into 4 groups:
Vascular disease
Renal artery stenosis
Glomerular disease (primary or secondary)
Primary - Membranoproliferative glomerulonephritis
Secondary DM, SLE, BJP, Auto-immune etc
Tubulointerstitial disease
Drugs (allopurinol), infections, sarcoidosis, heavy metals
Urinary tract obstruction
Stones, tumours, fibrosis

Effects of CRF
CRF
Acid-base disturbances
Calcium, phosphate,
magnesium
Endocrinopathies (thyroid,
gonadal)
Carbohydrate and lipid
metabolism
Retention of nitrogenous waste
products
Sodium and water
disturbances
Potassium metabolism
Management of CRF/CKD
Control the underlying co-morbidity
Slow progression of kidney disease
Anti-hypertensives etc
Prevent complications (CV, anaemia etc)
Strict diet, supplementation
Prepare for renal replacement therapy (dialysis,
transplant)
www.kidney.org
CLINICAL CASES
Remember!!
Always consider (pre-)analytical causes
Patient demographics
Past medical history
Presenting symptoms
Where the patient has come from?
Medications
Multi-disciplinary approach
Multi-condition appreciation!
A wise old Biochemist once said:
When you hear hooves, think horses not zebras!
i.e. common things happen often, rare things happen rarely
Case 1
KB, 50 years old, female.
Sample received from Cardiology Outpatients
Clinical details: HF, fluid retention
Medications not stated
Assumptions?
Biochemistry
Date Sodium
(135-145 mmol/L)
Potassium
(3.5-5.5 mmol/L)
Urea

Creatinine
19/08/11 144 4.3 28.4 181
21/09/11 142 4.2 27.1 199
11/10/11 142 4.8 28.6 214
What else do we need?
Are there any Biochemistry tests wed like to add
on?
Are there any haematology or immunology tests
wed like to do?
Whats the diagnosis?
How do we manage patients with this condition?
Case 2
CC, 34 years old, female.
Patient location: Ward 6
Clinical details: HD
Medications not stated
Biochemistry
Analyte Range 15/09/11 06/10/11 06/10/11
Sodium 135 -145 mmol/L 138 139 139
Potassium 3.5 - 5.5 mmol/L 4.0 6.4 3.7
Urea 2.5 - 7.0 mmol/L 2.9 25.5 2.2
Creatinine 50 - 130 mol/L 146 735 127
Phosphate 0.70 - 1.40 mmol/L N/A 1.04 N/A
Calcium 2.20 - 2.60 mmol/L N/A 2.53 N/A
Hb 11.8 16.7 d/dL 11.2 10.9 N/A
25 (OH) Vit D >50 nmol/L N/A 60 N/A
Diagnosis and Management
What is going on in this patient?
How are these patients managed?
Dialysis
Management (continued)
As mentioned earlier:
Dietary interventions
Reduced potassium, phosphate, sodium, protein etc
Controlling blood pressure
ACEIs/ARBs
Reduce CV risk
Statins, lipid-lowering agents, anti-coagulation therapy
Control renal bone disease
Monitoring markers of turnover
Vitamin D
Monitoring other complications
Anaemia
Case 3
RD, 55 years old, male.
Patient location: Ward 2B
Clinical details: None supplied
Medications not stated
Biochemistry & Haematology
Analyte Range 17/10/09 10/10/11
Sodium
135 -145 mmol/L
133 127
Potassium
3.5 - 5.5 mmol/L
3.8 4.7
Urea 2.5 - 7.0 mmol/L 9.8 17.9
Creatinine
50 - 130 mol/L
156 244
Phosphate 0.70 - 1.40 mmol/L 1.01 1.22
Calcium 2.20 - 2.60 mmol/L 2.14 2.45
Hb
11.8 16.7 d/dL
10.1 9.6
hsTrop T
<14 ng/L
N/A 561
Diagnosis and Management
Acute-on-chronic renal failure
Presents a double whammy to the kidneys
Management revolves around treating the acute
insult while protecting the remaining renal function
Prognosis is poor
Case 4
JT, 38 years old, male.
Patient location: Ward 5Y
Clinical details: Ca GI, post-chemo
Medications not stated
Biochemistry
Analyte
Range 07/10/11 11/10/11 12/10/11
Sodium
135 -145 mmol/L
125 116 114
Potassium
3.5 - 5.5 mmol/L
4.2 4.5 3.9
Urea 2.5 - 7.0 mmol/L 3.3 23.2 22.5
Creatinine
50 - 130 mol/L
45 338 241
Phosphate 0.70 - 1.40 mmol/L 0.51 1.92 1.46
Calcium 2.20 - 2.60 mmol/L 2.17 1.72 1.86
Bilirubin
2 - 17 mol/L
179 205 206
Summary - Learning points
Look at the whole picture (and just the facts!)
Gain an appreciation for homeostatic mechanisms
and what can go wrong
Many medications are nephrotoxic (very rare that
clinicians tell us what a patient is taking)
Knowing what each wards speciality is can help
Familiarising with Consultants names also.
Think multi-disciplinary!
Renal impairment affects many organ systems