University of the Free State

University of the Free State
Faculty of Health sciences: School of Medicine
Division of Nephrology, Dept of Internal Medicine
Prof BW Janse van Rensburg 2011
Nephrology topics:
1 Water, Electrolytes and acid-base disturbances (SELF STUDY and Preparation for topics 2-6)
2 Hypertension
3 Renal failure and renal replacement therapy
4 Glomerulopathies including glomerulonephritis (GN)
5 Tubulo-Interstitial Nephropathies (TIN) including urinary tract infections
6 The Kidney in systemic diseases and congenital conditions presenting in adult nephrology
Water, Electrolytes and acid-base disturbances
(SELF STUDY and Preparation for topics 2-6)
The human body consists mainly of water, control of the water in the body is accomplished by several systems
acting in harmony. It is helpful to think of the following:
1. Volumetric control: Sodium with the hormones involved in its homeostasis - especially aldosterone.
2. Osmotic control:
ADH and the thirst sensation
Disturbances of water balance:
Depending on the amount of sodium and electrolytes lost with water the patient may have hypertonic, isotonic or
hypotonic dehydration and serum osmol is not a good indication of dehydration, especially if renal failure is
Clinical picture: An early indication of dehydration may be orthostatic hypotension, later loss of skinturgor and the
thirst sensation, later CNS depression. It is notoriously difficult to clinically assess intravascular volume correctly
in marginal cases and this is an important reversible cause acute prerenal failure.
If there is any doubt about the i/v volume it is of value to put in a central venous line and to replace the fluid
according to the measured pressure. In hypotomic dehydration 0,9% saline or ringerslactate will be a good
choice and with hypertonic dehydration 5% Dextrose or 0,45% saline. The electrolytes and CVP should be
reassessed regularly and adjustments made accordingly. Remember in all cases to treat the cause as well.
Water intoxication:
Water intake exceeds the losses as well as maximal urine output in the patient.
Iatrogenic. Overhydration with 5% Dextrose especially in patients with poor renal function.
Psychotic patients.
Water enemas.
Clinical picture: CNS disturbances with restlessness, convulsions and coma.
Management: Water restriction, hypertonic sodium solutions are dangerous as they may cause pulmonary
Here there is a shift of water and electrolytes from the intravascular compartment to the interstitial compartment
and it is important not to make deductions of the i/v compartment (overloaded) just because the patient is
There are two theories / mechanisms postulated to explain oedema in the hypoproteinemic diseases such as
nephrotic syndrome and liver failure: the so-called “underfill” theory: Here there is a low i/v volume (low oncotic
pressure causes fluid loss extravascularly) that stimulates sodium retention via amongst others aldosterone. The
second theory “overfill” postulates a primary defect in renal water and sodium excretion with its retention and
swelling. (It may be tubular insensitivity to atrial natriuretic peptide.)
The factors that play a role in oedema formation are the following (Starling forces): Increased permeability of
capillary membrane, high hydrostatic pressure in the capillary and low oncotic pressure. It may be clinically
grouped as follows:
Local oedema:
High hydrostatic pressure e.g. DVT
Increased permeability e.g. cellulitis or a bee sting.
Generalised oedema:
High hydrostatic pressure e.g. CCF and renal failure.
Low oncotic pressure due to hypoproteinemia such as nephrotic syndrome or
Increased permeability e.g. anaphylaxis, endotoxins, shock of multi-organ
Idiopathic oedema / cyclic oedema of females.
Some ladies may have fluid retention that may involve a few kilogram / day in terms of body weight. Especially
those that are overweight may pressurise their GP’s to provide them with diuretics to lose weight without eating
less. This is a benign problem and the diuretics will do more harm than good, in severe cases ACE-I may be of
value. The diagnosis is made by excluding other causes of oedema.
The most important extracellular electrolyte is sodium and intracellular is potassium. The serum osmol can be
calculated as follows:
2(Na + K ) + Ureum + Glucose = 280 - 295 mosmols / L
but the true s-osmol is done in the laboratory by measuring the difference in freezing temperature with distilled
Clinical approach to electrolyte disturbances:
Clinically changes in the following electrolytes are of importance: sodium, potassium, calcium, phosphate and
Hyponatremia (S-sodium < 135 mmol/L.)
The clinical picture is dominated by CNS depression and later convulsions.
Firstly pseudohyponatremia should be excluded (osmol is normal or increased) - two mechanisms may be
involved nl:
Other osmotic active small molecules for e.g.. urea may be present or:
large molecules that replace part of the plasma water such as hyperlipedemia and para proteienemia.
Assessment of the patient should include: evaluating the hydration status of the patient and sending the
following lab tests: s-osmol, s-sodium, urine osmol and urine sodium in casualty before any treatment is
started because giving saline may influence the values and a definite diagnosis will then be very difficult
to make.
step1 S- osmol
> 280 = Pseudohyponatremia
< 280
hydration status
Step 3 Urine values
U Na:
U osmol:
GIT loss:
like serum
like serum
Renal failure
Will depend on the cause and a general recipe for all patients with hyponatremia is not possible. A patient with
hyponatremia due to diuretic induced renal loss should respond well to 0,9% saline, while someone with
inappropriate APH only needs fluid restriction and may be harmed by giving normal saline.
hyponatremia can be hazardous and the following general principles that should be adhered to;
Correction of sodium should occur slowly at ± 1 mmol/L/h. it may be faster if the hyponatremia is acute.
If it is replaced too rapidly there may be an association with the occurrence of central pontine
Sodium need not be corrected totally in the initial phases. a Reasonable target may be ± 125 mmol/L.
It is important to do serial determinations of sodium to monitor the progress and make timely
Hypertonic solutions of sodium are seldom necessary, mostly it is reserved for severe
with convulsions.
Acute hypernatremia is usually due to water loss in the urine in situations such as diabetes insipidus. Conscious
patients usually respond by their thirst sensation and ingesting more fluids, the result is thus rather polyuria than
hypernatremia. Chronic hypernatremia is nearly always a problem of the thirst mechanism (hypothalamic
disease) and is called essential hypernatremia. These are examples of hypovolemic hypernatremia
Mineralocorticoid effects usually present with hypertension (water is retained as well as sodium) and hypokalemia
rather than hypernatremia.
Major problem is arrhythmia, symptoms may include muscle weakness.
Potassium moves intracellularly with insulin, bicarbonate and vitamin B12 therapy. It is usually lost in the urine
(diuretics) and sometimes in the stools (laxatives).
In most patients with hypertension and hypokalemia the cause is essential hypertension with diuretic therapy, and
the usual advice is to repeat the test after the diuretic has been stopped for 10 days. There are a lot of secondary
causes of hypertension with hypokalemia, mediated by mineralocorticoid effects: (Conn syndrome, renal artery
stenosis, eccessive liqourice intake, cushing syndrome, renin secreting tumours and adrenal enzyme defects )
The combination should never be ignored when evaluating a patient with hypertension.
The danger is asystole with cardiac arrest.
Pseudohyperkalemia: Leucocytoses
Hemolysis in vitro
Insulin deficiency
Tissue necrosis. (as Rhabdomiolysis)
True hyperkalemia:
Iatrogenic: Bad choice of medication such as an ACE I + spironolactone
Renal failure.
The management of hyperkalemia is discussed in the lecture on renal failure.
Presents as renal stones, metastatic calcification or psychiatric disturbances.
When interpreting total s-calcium remember to correct for the s-albumin, for each 1 mg/L the albumin differs from
the middle of the reference laboratory 0,02 mmol/L should be added or subtracted from the total measured scalcium. It is better to do a free s-calcium as well as a s-parathyroid hormone level. Then the causes can be
divided as follows.
High or normal PTH:
Low PTH:
Primary and Tertiary hyperparathyroidism
Familial hypocalciuric hypercalceamia.
Malignancies as myelomatosis.
Thiaside diuretics.
Vit D intoxication.
Other endocrine disease such as:
Thyrotoxicosis and Addissons.
Treat the cause
Keep the patient well-hydrated 0,9% saline with furosemide
Difosfonates. (“aredia” - inhibits osteoclasts)
Manifestation is tetani - (note the s-albumin)
Renal failure.
Massive blood transfusions.
Unsure of the clinical effect.
Manifestation: arrhythmia’s.
Danger is rhabdomiolysis
Mainly renal failure
Diabetes Mellitus.
glucose administration (hyperalimentation), diabetic keto acidosis
Renal losses (Fanconi syndrome)
May cause metastatic calcification.
Renal failure
Iatrogenic: phosphate enemas
Acid – base balance
Arterial pH is held consantly between 7,35 and 7,45 (< 6,8 and> 7,8 probably not compatible with life) The
hydrogen ions form during metabolism daily is managed by 3 mechanisms:
1Buffers Serves as immediate defence agains abrupt shifts in pH. The most important buffer is bicarbonate, the
relation of its components can be summarised by the Henderson – hasselbalch formula:
pH = pK + Log
[H2CO3 (of pCO2)]
This does not have to be memorised but it explaines why the compensatory response is always in the same
direction as the primary change. To keep the pH constant a drop in bicarbonate as in metabolic acidosis must
be followed by a drop in pCO2. The same is true for the other forms of compensation.
2 Lungs: a drop in CSF pH stimulates respiration and causes hyperventilation. A change in the pCO2 thus
represents the respiratory component and is another temporary measure because H+ is not removed from the
3 Kidneys: This is the only way that can get rid of H+ from the body, by:
a) Generation and reabsorbing bicarbonate
b) Buffering H in the urine by phosphates and NH3
Changes in [HCO3] represents the metabolic component remember the CO2 on a U K+E or SMAC represents
the HCO3 and not the pCO2!
Evaluation of the acid base status in a patient;
1 Only look at the pH, bicarbonate and pCO2 (and the clinical picture of course)
2 First look at the pH
3 pCO2 = respiratory component, HCO3 = metabolic component
4 the compensatory response should be in the same direction as the primary response
5 overcompensation cannot occur. (in a longstanding respiratory acidosis the compensatory
metabolic acidosis may be revealed if such a patient is started on a ventilator, because the
metabolic component takes longer to change.
6 Formulas may be used to evaluate the compensatory if it is adequate, but this is used seldom
in practise
pCO2 and HCO3
pCO2 and HCO3
fully compensated
mixed acid base defect
HCO3 and pCO2 changing in different directions implies a mixed problem
Which change is the largest? PCO2 = resp, HCO3 = metabolic
Use formulas to see if compensation is adequate
Evaluating specific problems further:
Metabolic acidosis
Firstly check the anion gap:
AG = Sodium – (chloride + bicarbonate) = normally 8-12
High anion gap metabolic acidosis: (>12)
Primary problem is retension of acids like in:
Renal failure
Lactic acidosis as in systemic shock with tissue hypoperfusion
Poisonings such as salisilates
Normal aniongap metabolic acidosis: (<12)
Primary problem is mainly loss of bicarbonate with retension of chloride
Renal tubular acidosis
Bowel losses: diahrea, laxatives, fistuli, ureterosigmoidostomy
iliostomy bladder
Carbonicaciddehydrogenase (Diamox)
The clinical picture is dominated by hyperventilation (Kussmaul) that may be mistaken for primary lung disease
like asthma
Management:: A pH below 7,2 may be treated by giving bicarbonate. 8,5% bicarbonate solution 1ml = 1mekw.
Respiratory acidosis
Causes Acute:
bronchospasm, pneumothorax, aspiration
parenchymal disease, COPD
Chest wall kifoscoliosis, pleural effusion, ankilosing spondilitis
Respiratory depression: sedation oxygen therapy in type 2 resp failure
Clinical picture is cyanosis and if the cause cannot be treated rapidly the patient may have to be mechanically
Metabolic alcalosis
HCL loss
KCl loss:
nasogastric suction
Mineralocorticoid effect: Cushing Conn liquorice
Villeus pappiloma of the colon
Alcali administration (bicarbonate or citrate)
Clinical picture: hypoventilation and arythmias
Management: 1 Cause
2 Measure u-chloride chloride sensitive (u-cl<20mekw/L)
Eg vomiting, diuretics
Treatment is saline
Chloride resistent (u-cl >20mekw/L)
Rx spironolaktone may be tried
3 Induction of a metabolic acidosis with carbonic acid anhydrase
4 correct hypokalemia and hypomagnesemia
Respiratory alcalosis
Hyperventilation syndrome
SSS lesions
Salisilate poisoning (early – later metabolic acidosis)
Liver disease
Mixed acid – base changes: (more than one factor causing acid – base changes are present)
Metabolic alkalosis and resp alkalosis;
Surgical patient that hperventilates due to pain or is ventilated with nasogastric suction and antacids
Pregnant patient tha hyperventilates and vomits
Metabolicalkalosis and respiratory acidosis
COPD patient with diuretics and steroids
Metabolic acidosis and resp acidosis
Cardiac arrest
Metabolic acidosis and respiratory alkalosis
Liver disease
Hypertension has been identified as one of the 5 priority health issues in the RSA and with urinary tract infections
are the 2 most common problems that a GP will encounter of all the diseases covered by these lectures and
must therefore be known well.
The cause of hypertension is probably multifactorial with genetic as well as several environmental factors playing
a role. Hypertension should rather be viewed by the clinician as part of the risk factors for atherosclerosis and
not as a single entity. What a normal bloodpressure is in the community is not determined by the average of
normal people but rather at what pressure the risk of cardiovascular disease increases significantly or better still,
below what pressure treatment has been shown to reduce this risk.
Unfortunately these two aspects are dependent on good prospective randomised trials to provide definite
answers and these are lacking at this time. It does seem that the optimal bloodpressure (with regard to the risk
for cardiovascular disease) may be below 120/80.
Complications of hypertension:
(The statement is often made that the individual is as old as his arteries)
Cardio vascular:
LV hypertrophy.
Heart failure
Ischeamic heart disease
grade 1=
Arterial spasm
grade 2=
A/V nipping and copper/silver wiring.
grade 3=
exudates and haemorrhages.
grade 4=
Renal failure
Intermittent claudication.
Clinical evaluation:
Base line for follow-up.
Exclude secondary (treatable) causes.
Document target organ involvement.
Identify additional risk factors for atherosclerosis: family history of IHD or stroke,
smoking, hyper cholesterolemia.
A thorough history and physical examination is necessary, note especially a family history of hypertension (may
be essential HT) diet, mass, alcohol and smoking etc. During examination check the BP in both arms (take the
highest value as the reference arm) fundoscopy, murmurs over the large vessels including the renal arteries, LV
hypertrophy and peripheral pulses.
The following precautions should be taken when measuring BP.
Seated for 5 min, no coffee, tea, food or cigarettes in the previous 30 min, take the BP
in the standing
position as well, in patients where autonomic dysfunction is suspected like elderly people, diabetics and
renal failure to evaluate postural hypotension.
Cuff size should be appropriate: (> 33 cm arm - 15 cm cuff)
Diastolic = karotkoff phase 5, (In pregnancy both 4 and 5 may be noted if clearly audible)
Repeat measurements three times when SBP is 140-160 and diastolic is 90-100, this should be done
over a 2 month period
24h BP monitor is available: a recording of the bloodpressure for a 24h period is obtained by hourly
measurements that are graphically presented during normal working day. Average values are considerably lower
than normal conventional values. Potential uses include the following: (adequate data is still lacking)
“White coat” hypertension. These patients have high bloodpressure recordings in the stressful
environment of the doctor’s office but not at home. Currently it is still regarded as benign although
evidence to the contrary is mounting.
“Dippers and non-dippers” Normally the BP drops during sleep (“dipper”) if it does not occur it may be a
marker for patients who will later develop target organ involvement.
The adequacy of therapy may be evaluated.
Refractory hypertension
Borderline hypertension
Special investigations routinely advised in hypertensives:
Urine analysis.
(fasting) glucose.
Lipogram with total cholesterol, HDL and trigliserides.
Further evaluation where secondary hypertension is suspected will be discussed later.
Life style modification: (“non-pharmacological therapy”)
Body mass Index should preferably be below 25: BMI = mass(kg) / length(m)
Fat distribution: android (apples) are worse than gynecoid (pears) and can be assessed as
waist / hip ratio of > 85 in females and 0.95 in males.
Alcohol maximally 2 tots / day.
Exercise: ± 3 - 5 × / week for 30 - 45 minutes brisk walking (should be able to converse during exercise)
The so called “DASH” diet (Dietary Approaches to Stop Hypertension) This is a diet that emphasizes fruits,
vegetables and low fat dairy products, that contains whole grains, poultry, fish and nuts, and only small amounts
of red meat, sweats and sugar containing beverages and that contains decreased amounts of total and saturated
fat and cholesterol. This has been shown to reduce systolic blood pressure in hypertensives by 11,5mmHg.
Sodium is usually restricted to less than 100 mmol/day. (Salt should not be added at the table and chips etc.
Stop smoking.
Guidelines for drug therapy:
There are different guidelines for the pharmacological management of hypertension in different countries, these
differences does not imply that the disease and its risks differ geographically but is rather based on economical
factors. The RSA guidelines for primary care is available in SAMJ April 2006,vol96 no4. I would suggest that
two factors be taken into account when therapy is decided on, namely the presence of other risk factors for
atherosclerosis and the presence of target organ involvement.
Definitions and Classification
High normal:
Stage 1 (mild):
Stage 2 (moderate):
Stage 3 (Severe):
( The mean bloodpressure can be calculated: (2xSBP+DBP)/3)
All patients with bloodpressures >140/90 are regarded as hypertensive and should receive appropriate lifestyle
Choice of an antihypertensive drug.
The first drug to use is a thiazide diuretic unless there is a specific reason not to use it in that particular patient. If
the first drug does not work (all have an ± 50 - 60 % chance of working - luckily it is not the same patients that do
not respond to all drugs) one of two strategies may be adopted:
“Stepped Care” - Where a drug from another class may be added, the advantage is that control will be obtained
quicker. “Sequential monotherapy” The drug is stopped and replaced by another in a different class, the
advantage is that more patients may be controlled on a single drug, but patients tend to think the doctor is
Patient characteristics should influence the choice of the drugs used. (“Tailored therapy”)
Renal failure
good choice
b blocker ca-ant
Loop diuretic
ACE –I/ Angt2 ant
Beta locker, verapamil, diltiazem
? ca antagonist
Ca antagonist
Alpha blocker ACE - I
ACE - I / All-ant .
aldomet hydrallasin
B Blockers
alpha blocker
ACE-I / Angiot2 ant
be careful
direct vasodilators
B Blocker
Potassium supplements
or potassium sparing
beta blocker
vasodilators diuretics
B blocker
B Blocker
B blocker, diuretic.
B blocker, diuretic.
ACE - I Angiot ant (both never used!)
loop diuretic
?dihidropiridin ca ant
Isolated systolic hypertension (systolic > 160 and diastolic < 90) is important and should be treated, It is often
seen in the elderly and should be carefully and slowly brought under control. The drugs used in most trials are
thiazides (12,5 - 25 mg) and atenolol (25 - 50 mg) or a long acting calcium antagonist.
Good Combinations:
ACE - I or Angiotensin antagonist + diuretic
Alpha blocker + B blocker
B Blocker + diuretic + vasodilator.
Bad combinations:
ACE I or angiotensin antagonist + potassium sparing diuretic (hyperkalemia)
B blocker + Verapamil (bradi - arrhythmia)
Refractory hypertension
BP > 160/110 on maximal dose of 3 drugs if pre BP was > 180/115
BP > 140/90 on maximal doses of 3 drugs if pre BP was <180/115
1 Poor compliance
> 2×/day dosage regimen
Side effects.
2 Other drugs NSAIM, oral contraceptives, TAD liquorice.
3 Pseudohypertension: Thick arm with a small cuff.
Atherosclerosis: - Oslers’ sign may help to identify these patients
If these causes are not present, evaluate for a secondary cause of the hypertension.
The following definitions are used in severe hypertension:
Accelerated hypertension:
Hypertension with rapid vascular damage (fresh retinal haemorrhages and exudates, without pappiledeama)
Malignant hypertension: Diastolic hypertension (usually above 120) with papiledeama or gr3 retinopathy
Hypertensive encephalophally neurological symptoms due to hypertension.
Hypertensive crisis.
Unfortunately a uniform definition is not used in the literature at this stage but probably one of the most usefull
consists of two entities.
This is symptomatic hypertension with evidence of target organ damage, but no
Hypertensive urgencies:
immediate life threatening complication as in hypertensive emergencies (Control is needed in days - oral
medication is started with 2 drugs and the patient is managed in a general ward to reach a diastolic blood
pressure of 100 in 48-72 hours)
Accelerated hypertension
Malignant hypertension.
Severe post operative hypertension.
Left heart failure without pulmonary oedema.
Hypertensive emergencies: This is a rare life threatening situation (Control needed in hours, thus admission
needed in the ICU and drugs are given intravenously. Do not reduce the mean bloodpressure by >25% in 1 - 2h
and try to achieve 160/100 in about 6 hours)
Hypertensive encephalopathy.
with acute left heart failure with pulmonary oedema.
with unstable angina.
Aortic dissection
pheochromocytoma crisis.
Drugs: Sodium nitroprusside, diasoxide, labetalol
It is important to differentiate between a stroke and hypertensive encephalopathy (usually with a CT scan of
the brain) because the bloodpressure should be controlled quickly in encephalopathy and the opposite is needed
with a stroke, here the high blood pressure is needed to maintain cerebral perfusion and a bloodpressure of
220/120 may be acceptable. With higher blood pressures in the setting of a stroke blood pressure should only
be reduced by 15-20% in 24hours.
Secondary Hypertension:
Although it is the minority of patients (±5%) with hypertension that have a treatable cause, it remains important
and worthwhile to identify them. It is obvious that all the tests cannot be done on all patients (>95% would be
fruitless) to exclude a secondary cause and it is therefore important to devise an individual plan for each patient
according to the guidelines that follow.
The following may be clues to secondary HT and further special investigations should be done:
Age at onset: young patients (<35y) and older patients (>55y).
Refractory hypertension.
Murmurs over the large vessels.
Difference in BP between the arms or arms and legs.
Malignant hypertension or evidence of severe target organ involvement.
a Diagnosis may be suspected during the clinical examination: e.g. Hyperthyroidism,
acromegaly etc.
A patient that was controlled adequately and suddenly requires more and more therapy.
Causes of secondary hypertension:
Renal parenchymal disease.*
Endocrine. Adrenals:
Conn*, cushing, adrenal hyperplasia, pheochromocytoma.*
Hyperthyroidism and hypothyroidism.
Hypophysis: cushing, acromegaly.
Coarctation of the aorta.
*(Will be briefly discussed)
Renovascular hypertension:
It may present as follows:
A murmur may be heard over the renal arteries during initial examination.
Difference in renal size noted on echo, abdominal X-ray, CT or IVP.
A patient that develops acute renal failure when started on an ACE - I or angiotensin2 antagonist
Screening tests available for renovascular hypertension:
Captopril (Isotope) renogram: here the renal function in the kidney with the stenosis is temporarily impaired and
documented by a Isotope renogram done before and after the administration of Captopril.
Captopril test: blood is taken before and after administering captopril and if the plasma rennin raises more than a
specified value it is indicative of renal artery stenosis.
Doppler of the renal arteries during echography, it may be the test of the future.
Fibromuscular dysplasia usually younger patients (females). They seldom cause osteal lesions and are thus
more amenable to angioplasty.
Aterosclerosis. Older patients with evidence of vascular involvement elsewhere, osteal lesions are common (this
is aortic disease) and bypass surgery is done more commonly but angioplasty with stenting is becoming more
Renal parenchymal disease:
±All the glomerular and tubulo-interstitial diseases may cause hypertension. The important markers are renal
failure (initial urea and createnine elevated) and blood, protein or specially casts in the initial urine examination.
A common clinical problem is to decide if hypertension is the cause or result of renal failure and the following
may be of value:
Urine sediment: casts may indicate primary renal disease (except in a malignant phase of hypertension)
Target organ involvement in other organs is more in favour of hypertension as the cause.
Renal size: Small contracted kidneys (7-8cm) are usually due to parenchymal disease, while renal size in
essential hypertension is typically low normal (9cm)
Serological evidence such as a positive ANF, hepatitis BsAg or low complement my indicate a secondary
Presents mostly with hypertension and hypokalemia as well as easily induced hypokalemia on low dose diuretics.
More cases are now also found without hypokalemia.
Differential diagnosis of hypertension and hypokalemia:
Primary Aldosteronism (Conn)
Renal artery stenosis.
Rennin secreting tumour (very rare)
Congenital adrenal hyperplasia (enzyme defect)
Iatrogenic: Steroid therapy.
Malignant hypertension.
Evaluation: (screen)
Aldosterone / rennin ratio: if high = primary, if low = secondary.
Clinical triad of headache, sweat and palpitations may be important. Hypertension may be sporadic or
permanent. May be part of a familial disease (phakomatosis or MEN) - especially if it is present bilaterally.
Diagnosis by 24h urine VMA and metanephrines that are elevated, it should be repeated several times.
Remember to use an alpha-blocker before a beta-blocker is started, to prevent vasoconstriction that may follow
the reverse order.
The other endocrine causes are usually suspected during the clinical examination. Elderly people with
hyperthyroidism may just present with hypertension. Coarctation with delayed pulses and lower bloodpressure in
the legs. The mechanism of hypertension is like bilateral renal artery stenosis. X-ray of the chest may show
ribnotching on the lower border of the ribs due to dilated collateral vessels. Differential diagnosis includes mid
aorta syndrome and takayasu’s arteritis.
Renal failure and renal replacement therapy
When managing a patient with renal failure the following questions should be answered:
1 Is the patient in immediate danger? (usually means hiperkalemia or pulmonary oedema)
2 am I dealing with acute or chronic renal failure? (renal size helps to differentiate)
3 What is the cause of the renal failure?
Definitions and terminology
1 Renal failure: Deterioration in renal function to such an extent that waste products accumulate in the blood. It
can further be subdivided into acute, chronic and endstage renal failure. Acute and chronic renal failure:
although a time frame is suggested to differentiate the two it is usually understood that acute renal failure is
potentially reversible while chronic renal failure is not. If a time should be used it usually implies that less than 3
months from the beginning of the disease is acute and longer chronic. In practise it is usually not known when the
disease actually started and we rely more on renal size (by ultrasound) with small kidneys implying chronic
disease and large kidneys acute renal failure. "Endstage renal failu" is differentiated from chronic renal failure
because dialysis is necessary in endstage renal failure while conservative measures may be adequate for
chronic renal failure. The current consensus is to use the following stages for Chronic renal disease. It may at
first not result in a reduced GFR, for e.g. diabetic nephropathy, where early on hyperfitration (which is harmfull to
nephrons) may be present. This patient early on has chronic renal disease but not renal failure.
Chronic renal disease (>3 months present) can be subdivided into stages that has implications for management:
Stage: GFR ml/min
Renal disease with:
normal or hyperfiltration
diagnosis, reduce hyperfitration
Mildly impaired GFR
+estimate and prevent progression
Moderately impaired GFR
continue preventing progression
Severely impaired GFR
+ prepare for replacement therapy
Renal failure or dialysis
Replacement therapy if uremic
2.Oliguria: urine volume < 400 ml/24h.
3.Anuria: urine volume < 100 ml/24h.
4. Poli-uria > 3L/24h
These are arbitrary cut off points and not universally accepted
Acute renal failure
Causes of acute renal failure:
1.Prerenal (hypoperfusion of the kidneys): systemic shock (trauma, septicaemia) or low cardiac output (CCF)
80% is acute tubular necrosis (follows on prerenal if it is not corrected in time).
Drugs: Aminoglycosides, NSAIDs. Radiographic contrast
Toxins: Ethilynglycol, metals / traditional medications.
Rhabdomiolysis, severe hemolysis
Infections; Malaria, HIV associated septicaemia
Thrombotic micro-angiopathies.
Pre-eclampsia and eclampsia with HELLP syndrome
3. Postrenal:
Obstruction to flow.
Stones / necrotic papillae, Tumours, Prostate, Urethral stricture,
Catheter blocked.
After a patient has had a prolonged hypotensive episode the renal failure gradually changes from prerenal to
acute tubular necroses (ATN) if the blood pressure is not corrected in time. The course of ATN has 3 stages:
1. Oliguric phase: (hours - weeks) urine volume < 400 ml/day
Problem in managing the patient is fluid overload.
2. Polyuric phase (days - weeks) urine volume 3 - 10 L/day.
causes: Tubular concentrating ability inhibited as well as sodium loss in the urine.
Problem in managing the patient is dehydration.
3. Recovery phase (months)
Progressive improvement in renal concentrating ability and GFR, the patient may have residual permanent
damage. In pregnant patients cortical necrosis may occur in the setting of ATN with the development of
chronic renal failure and calcification of the renal cortex in the long-term.
Evaluating a patient with acute renal failure:
Toxin exposure (traditional healers.)
Medication (aminoglycosides, radiographic contrast, NSAIDS)
Ureter colic
Muscle breakdown (excessive exercise,
Previous renal disease / familial disease.
Examination: Fluid balance - Dehydrated or overloaded.
Pain: renal angles.
Bladder: full/ empty.
Urine microscopy: hematuria, proteinuria and casts make prerenal disease unlikely.
Urine biochemistry:
Urine [Na ]
High (>600)
FeNa (%) (u-Na /s-Na × s-Cr/u-Cr)
High > 1020
Renal (ATN)
Often iso-osmotic to
± 250 - 300
± 1010
In prerenal failure the urea raises quicker than the creatinine because urea can diffuse back to the blood and
creatinine is actively secreted by the tubules.
Structural evaluation: renal ultrasound to exclude obstruction (hydronephrosis) and to document renal
size (acute renal failure should have normal to large kidneys >10-11cm)
Management of a patient with acute renal failure:
Treat the cause (Infection, toxin, hypotension) look out for acute on chronic disease. Make sure of the
hydration status if the patient, If the i/v volume is not clear a CVP will be of help.
Determine urine flow - if reduced (oliguric phase) with a normal i/v volume (CVP 10-15).
restrict fluid to 500 ml/day + previous 24h urine output, or 20 ml + previous hours output.
patients passing less than 500 ml of urine will probably have to be dialysed.
diuretics: furosemide starting with low dosis (40mg iv) increasing rapidly to 250mg 6 h iv may be
combined with metasolone.
S-[Na ]
Type of i/v fluid: Usually 5% Dextrose adding 8,5% Na HCO3 depending on the pH,
and if the patient is passing any urine.
Electrolytes: hyperkalemia is the most dangerous electrolyte problem that arises and the S-potassium
should be assessed with an ECG to evaluate the urgency of the situation it gives an idea of the
physiological effect of the high potassium on the conducting tissue that a s-potassium alone does not do.
Patients also respond differently to the same level of potassium.
Management of hyperkalemia:
(a) Stop all potassium containing medication, or drugs that may increase the s-potassium: Slow K, potassium
sparing diuretics, maintelite infusion, ACE – I etc.
(b) If the potassium is high with severe ECG changes it is an emergency, and 10 ml 10% Ca gluconate is given
i/v slowly and may be repeated. This is the first line in an emergency, it does not lower potassium but is a
physiological antagonist of hyperkalemia. The rest of the following therapeutic measures may then be added as
(c) Potassium high without severe ECG changes: 100ml 50% Dextrose + 10U rapid acting insulin (Check sglucose and potassium afterwards) if needed add 50 ml 8,5% NaHCO3 over 20 - 30 min (problem with repeated
NaHCO3 is volume overload). These two measures drive the potassium intracellular and are only of temporary
help to either improve the patient / precipitant factors or to arrange dialysis.
(d) Kay exelate 15 - 60g PO or retention enema. This removes potassium from the body.
(f) Dialysis.
Diet: protein should not be reduced in acute renal failure because it may prevent recovery of injured
tissues. Patients should rather be dialysed early if needed and available. Sodium and potassium should be
restricted in the oliguric phase as needed.
Indications for dialysis.
refractory pulmonary oedema due to fluid overload.
refractory hyperkalemia.
refractory acidosis.
symptomatic uraemia:
GIT: vomiting, hiccup.
CNS: coma, convulsions.
Cardio vascular: pericarditis.
Haematological: bleeding tendency evaluated by a bleeding time not by
Biochemical parameters.
These are not absolute, but may depend on fluid balance:
Mostly creat > 500 - 600 mmol/L. Urea > 30-35 mmol/L. especially if the values are rising rapidly.(creat >
100/day) or urea > 10/day and the patient is passing less than 1L of urine / 24h. Changes in sodium severe
Prolonged oliguria or anuria
The life threatening indications are pulmonary oedema and hyperkalemia and these patient should be dialysed
immediately while there may time to do the patients with the other indications a few hours later when it is more
convenient if they are stable enough.
Chronic renal failure;
The clinical syndrome that occurs if the renal function deteriorates of over a long period (??>3 months) to such
and extent that the waste products accumulate in the blood. It is irreversible. Acute on chronic renal failure may
be present and additional reversable causes for renal disease must allways be excluded.
Diabetic nephropathy. (most important cause in caucasians)
Malignant hypertension (most important cause in blacks) may be partially reversable.
Chronic glomerulonephritis.
Chronic pyelonephritis.
Analgesic nephropathy.
Congenital renal disease like polycystic kidneys and Allport syndrome.
HIV associated nephropathy (HIVAN)
Ischeamic nephropathy (elderly - atherosclerotic renal artery stenosis)
All functions of the kidney are affected in varying degrees:
Excretion of metabolic waste products and drugs / toxins.
Water and electrolyte homeostasis.
Acid-base balance (metabolic acidosis)
Vit D activation.
Renin-Angiotensin system.
The concentrations of the following increase in the serum, (while calcium declines):
Peptide hormones such as PTH prolactin, FSH, LH etc.
Clinical picture of chronic renal failure (All the systems are involved)
Heamatological: Normocytic normochromic anaemia (erythropoetin deficit)
Thrombocytopathy - bleeding tendency.
Immunological suppression.
Cardiac failure.
Pleural effusions.
Pulmonary oedema.
Anorexia, nausia and vomiting.
Gastro enteritis.
GIT Bleeding.
Renal osteodystrophy.
Peripheral neuropathy.
Diabetic nephropathy.
Obstructive uropathy.
Secondary GN.
Ischeamic nephropathy
Analgesic abuse
2. Measures to retard progression of renal failure: (any renal disease has a tendency to progress if a certain
critical amount of renal mass has been damaged, this is due to several mechanisms including hyperfiltration
of the remaining glomeruli). These measures are very important for a GP to know because they may
prevent or delay the need for dialysis in patients.
a) Bloodpressure control: preferably with ACE-I or an Angiotensin2 antagonist to reduce hyperfiltration, care
should be take to check for hyperkalemia or hemodynamically mediated drop in renal function. Resrict sodium.
b) Reduction in proteinuria, again ACE-I or angiotensin antagonist should be used, even if the blood pressure is
normal to reduce the proteinuria. Proteinuria should be checked regularly to try to reduce it to less than 3g or
even 1g/day. (antiangiotensin drugs dilate efferent glomerular arterioles and thus reducing intraglomerular
pressure and hyperfitration as well as proteinuria).
c) Protein restriction - 0,8g/Kg/day. This has become controversial do to the malnutrition that occurs and patients
with low albumin’s do worse on dialysis, thus some would advocate to rather start dialysis early than to severely
restrict protein in the diet. In the RSA with our limited services it is still applicable.
d) treat metabolic acidosis
e) Control of phosphate and calcium homeostasis: These patients have a lack of active vit D with low calcium
and high phosphate and secondary hyperparathyroidism. This is done by reducing phosphate in the diet, using
oral phosphate binders and adding oral vit D in sequential order and monitoring the Ca, PO4 product regularly.
f) Control of s-lipids
h) prevent severe prolonged hypokalemia
i) other measures to prevent atherosclerosis may be of benefit
j) Do not advise excessive fluid intake if not appropriate
3. Other medication:
Fuid overload: diuretics usually furosemide if CrCl < 40 ml/min
Anaemia - no routine bloodtransfusions, subcutaneous erythropoetin.
Control potassium by reduction in the diet as needed
Renal function, proteinuria and blood pressure is very important to monitor
a) estimated GFR
eGFR =
(140-age)x mass
s creat (µmol/L)
(x I,23 in males)
b) protein/creatinine ratio in the urine
c) BP target of < 130/80
refer to a renal unit to plan renal replacement therapy if the s-creat > 300 – 400mmol/L or if eGFR < 30 ml/min
Renal replacement therapy:
3 methods are available:
1) Peritoneal dialysis:
2) Haemodialysis:
3) Renal transplantation:
CAPD (Continuous ambulatory PD)
IPD (Intermitted PD)
Living related donor.
Emotionally related donor
Cadaver donor.
Peritoneal dialysis.
A catheter is placed in the abdominal cavity (opening in the pouch of Douglas) fluid (dialysate) is introduced by
gravitation and after a few hours the empty bag is placed on the ground and it flows out again by gravitation. The
composition of the fluid is similar to a normal U+E except the electrolytes that accumulate in renal failure (K ,
phosphate magnesium) are lower. Dextrose is added in varying concentrations to remove fluid by osmotic
suction. The patients usually do their own exchanges at home manually 4-5 times per day (CAPD) or they use a
cycler (machine) that automatically does the exchanges at night time.
No expensive equipment needed (except if the cycler is used)
No anticoagulation needed.
Patients are more independent and can be managed in remote areas or go on holidays without arranging
hemodialysis at their destination.
Diet restrictions are less.
Aseptic technique.
Peritonitis risk.
Previous abdominal surgery may produce adhesions that may make PD impossible.
Blood is pumped through capillary tubes or plates (to enlarge the diffusion surface) in a counter current
arrangement with dialysate and exchange is through diffusion. The transmembrane pressure determines the
amount of fluid removed.
Peritoneal adhesions of no importance.
No personal dexterity needed.
Vascular access (fistula) needed.
Heparinization during the procedure.
Should stay near the hospital. (Dialysis always 3× / week for 3 - 5h each session).
Cost of equipment.
Renal transplantation:
The biggest problem with dialysis therapy is the cost involved (±R130 000 per year per patient, both hemo and
PD). This therapy cannot be given to all possible patients who may benefit, due to financial constraints. Luckily
renal transplantation is both the best and the cheapest (halving the cost approximately). Thus only patients that
are transplantable are accepted onto the program for both hemodialysis as well as peritonial dialysis in the public
sector in the RSA. With this policy both hemodialysis and peritoneal dialysis are seen as temporary measures to
have an eventual transplantation. In this way the resources are available to the most patients and slots on
dialysis are not permanently blocked by untransplantable patients making it impossible to accommodate new
Contra indications for transplantation in the RSA (in more affluent countries it is less restrictive):
Age over 60 years (relative)
Underlying sepsis or HIV.
Severe vascular impairment.
Poor compliance.
Severe extrarenal medical or psychiatric disease
ABO compatibility with a negative white cell cross match, HLA B and class II antigens improve the chances of
long-term survival but chances of a good match is remote with short waiting lists.
Transplantation is done in the fossa iliaca to make the ureter as short as possible and the patients own kidneys
are left. From one cadaver donor 2 patients may thus benefit
Best rehabilitation
Disadvantages: Immunosuppression (Steroids, Azathioprine) for the rest of his/her life with the associated side
effects. Prognosis: 2 years survival > 80%.
Glomerulonephritis (GN)
a Definition of Glomerulonephritis:
Renal disease where the main pathology is located in the glomeruli. Although an inflammatory response is
implied, the term is also used (probably wrongly) in other glomerular diseases. When the pathology is mainly in
the glomeruli without an obvious inflammatory component the preferred term is glomerulopathy. Most GN are
immunologically mediated and the glomerulus has a limited number of ways to respond to injury- the final
histological picture may thus be similar although the causes may differ.
There are different ways in which a glomerulonephritis may be classified, they do not necessarily correlate with
one another: in other words a certain histological type will not always present with a predictable clinical picture,
and other diseases (not GN) may also present in a similar manner, e.g. asymptomatic hematuria with a
neoplasm or nephrotic syndrome with diabetes mellitus. The general practitioner should be familiar with the
clinical and etiological classifications.
Four different ways to classify glomerulonephritis (pathogenetic, etiological, clinical and histopathological):
Pathogenetic: 1.
Humeral immunity.
AG - AB complexes circulating, or in situ.
Antibasal membrane antibodies.
Reticulo endothelial.
Cellular Immunity.
Other mechanisms.
Causes of a secondary GN*:
Primary GN implies the antigen involved is unknown
Secondary GN - antigen known.
Streptococci, staphyllococci and
Schistosoma Mansoni
Plasmodium Malariae.
Hepatitis B.
Drugs: Gold + d-penissillamine.
Tumour antigens.
Acute nephritis syndrome.
Acute renal failure (sub-acute nephritis).
Chronic renal failure.
Nephrotic syndrome
Asymptomatic urinary changes: - hematuria, proteinuria or casts.
(these are really glomerulopathies –no inflammation on biopsy, they tend to present more with proteinuria or
nephrotic syndrome)
1 Minimal change disease*.
2. Focal glomerulosclerosis.
3. Membranous nephropathy.
b)proliferative types:
(term glomerulonephritis applies here accurately, they tend to present more with nephritic syndrome, although
this may vary considerably)
1. Acute exudative or diffuse proliferative.GN*
2. Mesangial proliferative including IgA
3. Mesangio capillary or membranoproliferative GN .
4. Rapidly progressive GN*.
5. Focal proliferative GN.
(Students should be very familiar with the parts marked*)
Acute nephritic syndrome:
Defined as:
1) Hematuria, 2) Hypertension and 3) Oedema with a varying drop in glomerular filtration.
Hematuria: May be red blood but commonly dark brown (Coca-Cola) at times microscopic hematuria.
Hypertension: Commonly without retinopathy.
Oedema: Commonly periorbital, signs of fluid overload and possibly pulmonary oedema. Classic prototype is
post-streptococcal GN. Infections of the pharynx and skin (scabies secondarily infected) by beta haemolytic
streptococci - only certain strains are involved (4,12), a latent period of 10-14 follows after which a nephritis
syndrome follows. Remember IgA nephropathy may develop hematuria with resp infections, but here it occurs
simultaneously. Most patients recover but adults and sporadic cases do worse. (Epidemics and children better).
Urine: Oliguria with red cell or granular casts, non-selective proteinuria (usually less than 2g/24h.) Urine
biochemistry may look like prerenal failure in the acute phase: Osmol and SG high. Urine [sodium] < 20 mmol/L.
Here is a pure glomerular lesion with normal tubular function.
Investigations: 1.Culture - throat and puss swab of skin lesions.
2.Serological evidence of streptococcal infections: raising ASO titre.
3.Low complement (C3)
Differential diagnosis includes: other primary GN, vasculitis (adults > 50y) children: Henoch Schonlein purpera
acute interstitial nephritis, malignant hypertension. The differential of a hypocomplementemic GN is: post-strep,
lupus nephritis, infective endocarditis, primary mesangiocappilary and membranous GN
When should a renal biopsy be considered in the acute nephritic syndrome?
These decisions should be individualised according to the patient, but when the patient does not follow the usual
course of a post-infective glomerulonephritis a biopsy may be indicated to exclude another treatable form of GN:
As soon as possible (if patient is stabilised) If uraemia or resistant oliguria to large doses of furosemide
occurs that cannot be differentiated from rapidly progressive GN.
Biopsy between 4-8 w:
Nephrotic syndrome longer than 4 weeks.
Hypocomplementemia that does not normalise in ± 8 weeks.
If renal function does not recover in 4 weeks.
Persistent hypertension longer than 4 weeks.
Biopsy later:
Hematuria longer than 18 months.
Proteinuria > 1g/24h. longer than ± 6 months.
Biopsy usually reveals exudative proliferative glomerulonephritis (diffuse proliferative GN) and no specific therapy
is proven.
Acute renal failure.
Rapidly progressive GN Here renal function is lost rapidly and patients may become ureamic within weeks.
(From a day or two, to 3 months) A lot of non-glomerular causes should be excluded. (Prerenal, renal and
postrenal) With glomerular disease hematuria and red cell casts and proteinuria occurs. Several renal causes
that are clinically similar to this form of GN:
Malignant hypertension (Although rapidly progressive GN seldom has hypertension)
Systemic sclerosis.
Thrombotic microangiopathies.
Acute Interstitial nephitis including acute pyelonephritis.
Renal vein thrombosis.
Types of glomerulonephritis that may present in this way:
Goodpasture (antibasal membrane AB).
SLE (Anti nuclear factor)
Vasculitis (ANCA positive).
When should a renal biopsy be done in acute renal failure?
If prerenal and postrenal causes are excluded and the patient is not suspected of having acute tubular necrosis a
renal biopsy should be considered in most cases. It is very important if a rapidly progressive GN may be present
because a delay in diagnosis may prevent effective immunotherapy. Histology usually reveals RPGN with more
>80% Crescents.
Chronic renal failure:
Most of these patients present with symptoms and signs of chronic renal failure with biochemical evidence and
small kidneys on ultrasound
When should a renal biopsy be done in chronic renal failure?
Although it is always important to look for reversible causes, a renal biopsy is seldom indicated in chronic renal
failure with small kidneys and usually they have to be dialysed and transplanted.
Are additional measures needed?
Progression of renal failure can be reduced by controlling bloodpressure, specifically with drugs reducing
intraglomerular pressure, by reducing proteinuria, treating hyperlipedemia and phosphates, stopping smoking
and modifying other risk factors for atherosclerosis (See management of chronic renal failure)
Nephrotic syndrome:
Defined as severe 1proteinuria > 3,5 g/24h/1,73m body surface area, hypoproteinemia, and oedema.
additionally hypercholesterolemia usually occurs.
Document nephrotic syndrome. Collect 24h urine for total proteinuria. Creatinine clearance as well as
selectivity of proteinuria and urine microscopic evaluation.
Determine cause.
Exclude causes such as diabetes mellitus or amiloidosis where a renal biopsy is not necessary.
Serological markers:
Complement, ANF, Hep BsAg, HIV, ASO, cryoglobulins should be done
as indicated
Causes of Nephrotic syndrome:
primary GN
Minimal change GN = important in kids.
Focal glomerulosclerosis - usually < 30y.
Membranous nephropathy < 40y.
Secondary to systemic diseases:
Outo-Immune = SLE
Diabetes Mellitis. (most important cause in western countries)
infections: Hepatitis B, Bilharzia, Infective endocarditis, HIV
When should a renal biopsy be done in nephrotic syndrome?
It is generally suggested that a renal biopsy be done in most adults with nephrotic syndrome without
contraindications to the procedure, and where the diagnosis is not obviuos. (such as diabetes mellitus or
amyloidosis). Impiric immunosupression is not recommended.
Are additional measures needed?
Manage the complications of nephrotic syndrome:
Low protein diet (0,8 mg/Kg/d) with low salt.
Diuretics furosemide (and low dose spironolactone if renal function is good)
Albumin i/v is seldom used because it only has a temporary effect for a few days - only
used if acute renal failure occurs due to i/v hypovolemia or cellulitis in the oedema.
Atherosclerosis: Low cholesterol diet with cholesterol lowering drugs if needed.
Hypercoagulability - especially renal vein thrombosis may occur with rapid drop in renal function
(partly due loss of anti thrombin 3 in the urine)
Opportunistic infections (a.o. primary peritonitis) due to immunoglobulin loss in the urine.
Asymptomatic urine abnormalities.
These patients are usually detected during a routine examination such as a life insurance or when applying for a
new job. Hematuria: may be microscopic, macroscopic or recurrent macroscopic (when macroscopic it may be
complicated by ureter colic) Try to differentiate early if it is a nephrological or urological reason for the hematuria it helps to look at the urine - dysmorphic RBC and casts are due to renal disease as well as significant
When should a renal biopsy be considered in asymptomatic urinary changes?
No consensus is available but the following are guidelines:
If significant proteinuria is present (> 1-2g/24h)
With renal functional impairment.
Hypocomplementemia or other serological markers positive.
Prognosis important (for work or insurance)
Casts in the urine.
In the absence of these changes it may be sufficient to follow the patient every 3 - 6 months.
Minimal change glomerular nephritis (“Nil” disease)
Clinically: Most common cause of nephrotic syndrome in children but may also occur in adults characteristically
selective proteinuria without hypertension or hematuria but it may occur especially in adults. Responds well to
Focal glomerulosclerosis (Focal segmental hyalinosis).
Clinically: Nephrotic syndrome or non-selective proteinuria. Hypertension and microscopic hematuria is more
common than in minimal change GN. They are usually primary, secondary causes include malignancies, drug
addiction (Heroin), reflux nephropathy, AIDS (HIVAN – HIV associated nephropathy), obesity, sickle cell anaemia
and this is the histologigal picture that follows longstanding hyperfiltration of glomeruli.
Steroids are used similarly as in minimal change glomerulopathy, but chances of a response is much less
Membranous nephropathy:
Present usually with nephrotic syndrome or proteinuria. More in adults, although children with HepB often present
this way. secondary causes commonly include Hepatitis B and SLE, in elderly people it may be a paraneoplastic
syndrome. Steroids and alkilating agents used in those with poor prognosis
Diffuse proliferative (exudative proliferative)
Clinical picture: Acute nephritic syndrome, seldom acute renal failure, persistent hematuria or proteinuria or
chronic renal failure. Usually spontaneous remission with diuresis and immunosupression is usually not used.
This is the histological picture seen in classical post-streptococcal GN, other infection like staphylococci may also
be involved
Mesangial proliferative:
Clinically: IgA nephropathy (“Bergers” disease - the most common GN world-wide) present classically with micro
or macroscopic hematuria, typically in young males. Sometimes proteinuria or acute renal failure may occur.
IgA: Those presenting with severe proteinuria (>3g/day) and good renal function, steroids may be used.
Mesangiocappilary (membranoproliferative).
Clinically: Nephritic, nephrotic or combination of both. Secondary causes include SLE, Hepatitis B, Bilharzia.
Immunosupession is generally not effective.
Rapidly progressive glomerulonephritis (Crescentic nephritis).
Diagnosis is made clinically and histologically - serum creatinine that doubles in less than 3 months with
glomerular crescents on renal biopsy. These patients often present with a “pulmo-renal” syndrome; hematuria
and hemoptisis. Secondary causes include Goodpasture syndrome, infective endocarditis, SLE, Wegeners,
Cryoglobulinemia. Immunosuppression is needed without delay and plasma exchange added for Goodpastures.
Prognosis is poor without early aggressive therapy.
Focal proliferative (focal necrotising)
Look for secondary causes such as infective endocarditis or a vasculitis
Urinary tract infections and other Tubulo-Interstitial Nephropathies (TIN)
Definition of a tubulo-interstitial disease:
Renal disease where the structural and functional changes involve mostly the renal tubules and interstitium. With
the glomerulopathies, it constitutes the other large group of renal parenchymal disease.
Classification may again be made in different ways:
Clinical classification:
Acute TIN
Prototype: Penicillin induced acute TIN, but a lot of other antibiotics and drugs are associated with this disease.
clinically: Erythematous rash, renal angle pain, eusynophillia and eusynophiluria (+hematuria). May cause acute
renal failure and may present as acute nephritis syndrome.
Pathogenesis: Allergic reaction that may occur after a single dose or a longer coarse.
Treatment: Stop the drug and possibly use steroids. Other non-allergic reactions mechanisms may be involved
in some acute TIN:
Apart from medicine or toxins, infections may cause acute TIN without directly infecting the kidney. Here
infection in a remote part of the body causes TIN by immunological means (immune complexes?), analogous to
post-strep GN but here the interstitium is the main target.
Direct toxicity is found with exposure to nephrotoxins such as aminoglycosides antibiotics radiological
contrast, NSAIDS, and traditional medicine.
Chronic TIN:
Analgesic nephropathy is an important preventable cause of chronic renal failure among the first
world community, but it is becoming less common as the public are more aware of the problem.
Chronic renal disease due to analgesic overuse may include:
Urothelial carcinoma: 11× higher in analgesic abusers.
Papillary necrosis: Is the typical lesion of analgesic nephropathy but is not specific, there are other
Diabetes mellitus.
Urinary tract obstruction (+infection).
Sickle cell hemoglobinopathy.
Renal transplant rejection.
Toxic effect on tubular epithelium, the analgesic metabolites bind covalently on cellular protein, amongst
others gluthathion and induce oxidative damage, the highest concentration of these metabolites are found in the
renal interstitum.
Renal ischemia (due to reduced renal prostaglandin synthesis and thus loss of normal local
vasodilatation) with infarction and coagulation necrosis of the renal papilla. This situation is worsened by when
renal perfusion is already compromised such as dehydration, cardiac failure or with a low s-albumin. (nephrotic
syndrome or liver failure).
Causes of interstitial nephritis:
Toxins: (a)
Analgesic nephropathy*.
Lead intoxication.
Radiological contrast*. /Drugs such as
aminoglycosides* / NSAIM*.
Acute uric acid nephropathy hypercalcaemia,
Neoplasms eg. myeloma.
Hypersensitivity nephropathy.
Sickle cell nephropathy.
Hereditary:Enzyme transport defects:
Phosphate losing rickets.
Cystic renal disease.
Reflux nephropathy.
(The students should be very familiar with these*)
Urinary tract infections:
With hypertension this is the most common clinical problem that the GP will encounter from all the diseases
discussed in these lectures
The following conditions predisposes to UTI:
Underlying anatomical abnormalities of the urinary tract: obstruction, reflux or stones.
Postmenopausal state
Instrumentation / catheterisation.
Female gender.
Sexual intercourse.
Receptor density on the patients urothelium for “P” fimbriae on the bacteria. (these vary among patients
and it is therefore important to understand that some people are more prone to UTI’s without a structural or
functional defect. The most useful examination that can be done by the doctor in his rooms to screen for a
defect in the urinary tract is to do a residual volume of the bladder. If this is more than 100ml, further evaluation
by an urologist is needed.)
Entero bacteriacea - 80% of bacterial UTI’s mostly E.Coli.
Proteus: more with underlying anatomical abnormalities - especially stones.
Chlamidia and Staph. Saprohiticus - females with acute urethrocystitis.
Staph epidermidis - catheter associated infection.
Staph aureus - mostly hematogenous spread to the kidneys.
The following are 5 important questions to consider in classifying and managing urinary tract infections:
1 Is it truly infection?
Remember that other causes may cause sterile pyuria such as: SLE, TB and analgesic abuse.
2 What anatomical area is involved
Urinary tract infection is a broad term that should be better defined because management may be totally different
depending on the area involved.
3 Is the patient male or female?
Short course therapy should be used only in females while in males the prostate complicates therapy in many
4 Is it a special organism?
Such as Tuberculosis, Bilharzia or fungus, that may require special therapy or measures
5 Is it a special patient?
Such as diabetics, catheterised patients or someone with anatomical defects of the urinary tract that must be
managed in a different manner.
With these questions in mind we use the following classification of urinary tract infections:
Upper urinary tract infection.
Cortical abscess.
Perinephric abscess.
Lower urinary tract infection.
Acute prostatitis.
Chronic prostatitis
Acute urethral syndrome.
Specific problems / Complicated urinary tract infections:
Patient related
Diabetes mellitus
Catheter associated infections.
Vesico urethral reflux.
Spinal cord patients
Renal stones with infection
Post menopausal women
Organism related
Fungal infection
Evaluation and management of a UTI:
1 Is it really infection?
The two mistakes that GP’s most often make in this regard is to regard all dipstick changes as UTI’s, or to
misinterpret the finding of a u-MCS result:
a) Changes on urine dipstix may have an extensive differential diagnosis, and the presence of puss cells do not
always mean infection. The differential diagnosis of a sterile pyuria are:
Unusual infections such as TB (requires 3 morning urine specimens for culture)
Tubulointerstitial diseases such as analgesic nephropathy
Renal stones
b) Urine for MCS. (in females with lower UTI it investigation is not mandatory initially)
The 3 important aspects to assess when evaluating a report of urine MCS are:
Amount of organisms (> 100 000colonies/ml is regarded as significant bacteruria)
Is it a single organism? (more than one may be contamination).
Presence of puss cells.
2 Try to differentiate an upper from a lower tract infection,
This may be very difficult or even impossible to do clinically and the suggestions below have not proven to be
very accurate, the best way is probably with urine microscopy where white cell casts localises the disease to the
Upper UTI
Temp > or = 39C
renal angle tenderness
White cell or granular casts
Lower UTI
Seldom such a high temp.
Suprapubic tenderness
White cells.
B. Upper UTI’s
Management of an adult with pyelonephritis:
Remember the differential diagnosis:
Herpes Zoster (early).
Basal pneumonia.
Renal infarct.
Renal vein thrombosis.
and do a gynaecological examination in females or a rectal examination in males after the infection is under
When the patient is very ill and admission in hospital is required:
Do blood and urine cultures and obtain an abdominal X-ray if indicated.
I/v fluid.
community acquired:
Nosocomial :
Cefotaxime / piperasillin + Aminoglycoside.
Both may be treated with a quinolone if the patient cannot /needs not to be admitted to hospital.
The patient should improve in 48h, and the course may be completed with oral antibiotics × ± 10 days,
according to the sensitivity of the organism. Follow up culture of urine after 2 and 6 weeks and probably
an IVP (if renal function allows it and the patient is not allergic to iodine)
If the patient does not respond in 48 h. (a complicated infection or a wrong diagnosis).
Review the cultures and change antibiotic regimen accordingly
Culture negative with no response: review the diagnosis.
Anatomical assessment: ultrasound or IVP (if renal function allows and not allergic to iodine)
for: obstruction, stones, papillary necrosis and abscesses.
Repeat cultures.
Lower UTI’s (These are managed differently in males and females)
Acute dysuria of females (Cystitis or urethrites)
If the patient has gynaecological symptoms these should be treated first to see if the symptoms do not subside.
A urine culture is not cost effective before treating an uncomplicated lower UTI in females but try to differentiate
upper UTI and chlamidia urethritis, because they will not respond to short courses of antibiotics. The
uncomplicated lower tract infection may be treated for 3 days with cotrimoxasole. If the patient does not respond
then is the time to do a culture. Possible outcomes may follow depending on the outcome of the urine culture:
Chlamidia classically has leukocytes in the urine without organisms. It may be cultured on special media from a
urethral swab or a rapid antigen test is available. Treatment is doxycycline. Secondly a specific organism may be
cultured and the patient should be treated according to the sensitivity for 10 days. Thirdly no leukocytes or
organisms present only symptomatic treatment is necessary, if pyridium is used this should only be used for short
periods (e.g. 3 days) at a time. A relapse is diagnosed when the same organism is cultured within 2 weeks and
such a patient should be evaluated further for anatomical / neurological defects. Re-infection usually occurs after
2 weeks and a different organism is usually cultured - here predisposing causes such as sexual intercourse must
be looked for and prophylactic therapy may help.
In males a lower UTI usually means prostatitis and will be dealt with in detail by urology:
Acute prostatitis
Firstly check for an urethral discharge.
They usually have severe pain (especially rectally) and are feverish (up to 40 C) with acute dysuria.
Urine culture should always be done in males before antibiotics are given and short courses of antibiotics not
used. Antibiotic choice depends on the degree of disease but a 14-day course of cotrimoxasole or a quinolone is
recommended. Keep well hydrated and avoid urethral instrumentation. Watch for complications (abscess
formation) Gonorrhea may be present, especially in younger males (<35y). Follow up culture in ± 2 weeks.
Chronic prostatitis.
Subtle symptoms may be present:
This is the important cause for male patients presenting with recurrent UTI.
Treatment: antibiotics penetrate the prostate poorly. Long-term Cotrimoxasole (3 - 6 months low dose) or
quinolones for 4 - 6 weeks. Prostatodenia may respond to alpha-blockers such as prazosin.
The general rules to prevent infection must be explained to all.
Adequate fluid intake.
Regular complete bladder emptying.
Empty bladder before and after sexual intercourse.
Double micturition especially in patients with reflux nephropathy.
Adequate perineal toilet.
In males short courses of antibiotics are not recommended and evaluation for underlying structural disease
should be done in most cases. Males have a higher incidence of UTI’s in the first year of life, after which females
predominate, until they are about equal in the elderly.
The following patients should be considered for structural (anatomical) evaluation;
A male patient with a UTI
Repeated UTI’s in a female
Patients with upper UTI’s not resolving in 72 h
Patients with renal failure
The Kidney in systemic diseases
and congenital conditions presenting in adult nephrology
The kidney in systemic disease.
A systemic disease involves more then one organ system, such as:
Other outo immune disease: SLE*, systemic sclerosis
Diabetes Mellitus***.
Sickle cell disease - (not discussed)
Hepatorenal syndrome*.
(these conditions are important*)
Is an inflammatory process of blood vessels, commonly due to immune complex deposition and because the
kidney has such a rich blood supply and the glomerulus consists mainly of capillaries it is not surprising to find
that renal involvement is common.
Classification of vasculitis is made according to the size of the vessels involved and the presence or absence of
granuloma. A serological marker for vasculitis is currently available nl: ANCA (antineutrophil cytoplasmic
Small arteries (cappilaries)
Microscopic poly-angiitts Glomerulonephritis is common with positive p-ANCA
Wegeners granulomatoses:
Lung and upper airway (ulcer in the nose) involvement with a rapidly progressive GN.
A lot of other
systems may be involved. With positive c-ANCA
Hypersensitivity vasculitis = small bloodvessels with skin involvement , antigen may be a drug or
Auto-immune diseases like SLE
Henoch Schönlein purpera: More in children, Skin lesions (palpable purpera) Colic abdominal pain,
Arthralgia with a secondary glomerulonephritis (Commonly IgA nephropahy)
Medium sized arteries:
Poliarteritis Nodosa (PAN)
Fever and eusinophilia. Hypertension. Medium sized arteries are
involved with aneurysms on renal angiography.
Large arteries:
Takayasu arteritis: branches of the aorta are occluded and gives absent pulses, renal arteries may be
involved with renal artery stenosis
Systemic Lupus Erythematosis
A renal biopsy is needed in most patients with SLE manifesting with renal involvement because therapy
determined by the histological finding:
In mild or nonproliferative glomerulonephritis treatment is determined by extra-renal involvement while in
proliferative glomerulonephritis steriods and cyclophosphamide should be used.
Systemic scleroses:
Is not a vasculitis but during a scleroderma renal crisis there may be fibrinoid necrosis of arterial walls that
histologically are similar to malignant hypertension.
Treatment is angiotensien converting enzyme inhibitors.
Diabetic nephropathy:
Proteïnuria is the hallmark of clinical diabetic nephropathy and among the first world community it is the most
common cause of nephrotic syndrome in adults and is the most important cause of endstage renal failure in
developed communities. Early in the disease the GFR may be increased due to hyperfiltration, especially during
periods that the diabetes is uncontrolled. This hyperfiltration is damaging to kidneys. Nearly all patients with
diabetic nephropathy have evidence of retinopathy, the reverse is not true - if the patient has retinopathy it does
not necessarily mean that nephropathy is present.
Typical course of type 1 diabetes:
Normal renal function with periods of hyper filtration (treatment:: glucose control)
Micro albuminuria 30 - 300 mg/24h. This is a marker for those patients predisposed to develop
nephropathy (treatment is glucose control and drugs acting against angiotensin2 irrespective of the
Macro proteinuria >300mg/day = clinical nephropathy. (treatment is glucose control and drugs acting
against angiotensin2 and optimal blood pressure control)
Progressive renal failure
Endstage renal disease requiring renal replacement therapy
Management: (see also the measures to prevent progression of renal failure)
(1) Diabetic control is always important but specifically in the preclinical phase to try to postpone the
appearance of proteinuria.
Blood pressure control. ACE-I or Angiotensin receptor blockers are the first choice (look out for
hyperkalemia). There is evidence to start ACE-I or angiotensin receptor blockers as soon as microalbuminuria is constantly present to prevent renal damage even if the patient is normotensive.
Infections of the urinary tract should be looked for.
Avoid nehprotixins such as NSAID’s, radiological contrast aminoglycosides if possible.
Protein restriction, moderately (0,8gprot/kg bodymass/day).
Salt restriction and low cholesterol diet with nephrotic syndrome.
Diuretics for swelling should be used carefully.
Assessment for dialysis and transplantation should probably be earlier than in other causes of renal
failure but unfortunately a lot of them may have macrovascular involvement that excludes them from
renal replacement therapy in the RSA.
Typically proteinuria + nephrotic syndrome.
3 Ways of involving the kidney:
Acute uric acid nephropathy. Crystal deposition in the renal tubules with intra-renal obstruction. Usually
seen in the early stages of cancer chemotherapy.
Chronic urate neprhopathy. This is controversial and not all authors accept this, they regard these
changes due to other factors such as hypertension and lead poisoning.
Uric acid stones.
Hepatorenal syndrome.
Functional renal impairment that cannot be differentiated from prerenal failure. (Urine sodium < 20 mmol/L with a
high SG and osmol) Pathogenesis is intense renal vasoconstriction in patients with liver disease, usually liver
cirrhoses that has been aggressively treated with diuretics or where a large volume of ascitis was tapped, or after
a GIT bleed.
Prognosis depends on the liver disease.
The i/v volume should be increased (colloids) to be sure here is no pre-renal component because it cannot be
differentiated by the usual means.
mechanisms of renal failure:
Bence-Jones nephropathy: (deposition in the tubular lumen and is nephrotoxic).
Amiloidosis (secondary).
Uric acid nephropathy.
General: Dehydration, infection, contrast.
Congenital diseases presenting in adult patients.
Hereditary nephropathy (“nephritis”)
Alport Syndrome
Benign familial hematuria.
Cystic renal disease.
Polycystic kidneys. dominant* and recessive
Medullary cysts
Renal tubular defects.
Alport syndrome
Manifestations: Hematuria.
Progressive renal failure (mostly)
Neuronal deafness.
Eye involvement - anterior lenticonus.
Diagnosis - family history, clinical picture, E/M of the renal biopsy. There is an abnormality in type 4 collagen of
these patients’ basal membrane and the interesting finding is that the antigen that the antibasal membrane
antibodies are directed against in Goodpasture syndrome is absent in Alport syndrome. (They cannot develop
Goodpasture Syndrome).
Benign familial hematuria (thin basal membrane disease).
Commonly hematuria from childhood, microscopic or macroscopic. NB. They are not hypertensive, have no
proteinuria and have normal renal function.
Diagnosis: Thin basal membranes on E/M. Good prognosis.
Cystic renal disease:
Outosomal dominant polycystic kidneys (“Adult type”)
This is a common condition 1:1000 - 1 : 1500 (May remain asymptomatic)
Cysts are dilated tubuli, any part of the tubuli may be dilated and there are cysts with properties (content) of
proximal and dystal tubules.
The manner in which these patients may present to their doctors are:
Asymptomatic - Evaluated because a family with an involved member is screened.
Hematuria (microscopic)
Renal failure (mostly 40 - 50 years)
Macroscopic hematuria with / without ureter clot colic.
Secondary hypertension.
Urinary tract infections.
Renal masses.
Hepatomegaly (30% have liver cysts - liver function remains good)
Subarachnoidal bleeding (10% have cerebral aneurysms)
Renal ultrasound is the investigation of choice and at least 5 cysts should be present in both kidneys together,
with at least 2 in each one. Additionally there should either be a family history of polycystic kidney disease or
cysts in another organ. The cysts become larger with age and it may be missed if looked for at a young age.
Usually by 30 years of age it will manifest on ultrasound.