RENAL DISEASE
Introuduction
Renal function is required:
 to maintain normal body fluid volumes and composition including acid-base
balance
 to excrete many metabolites and drugs
 to synthesize vitamin D and erythropoietin.
The nephron makes urine by filtering small molecules and ions from the blood
and then reclaiming useful materials.
The nephron consists of a:
1. Bowman's capsule
2. glomerulus. This is a capillary network within the Bowman's capsule.
Blood leaving the glomerulus passes into a second capillary network
3. proximal convoluted tubule. This, by active transport, reabsorbs all the
glucose, and amino acids, and most of the uric acid and inorganic salts.
4. loop of Henle. Here water continues to leave by osmosis
5. distal convoluted tubule. Here more Na"1" is reclaimed by active transport,
and still more water follows by osmosis
6. collecting tubule. Here there is a final adjustment of the Na+ and water
content of the body, and the surplus or waste molecules and ions are left to
flow out as urine, which passes to the pelvis of the kidney, from where it
flows to the bladder and, periodically, on to the outside world.
Nearly one-quarter of the blood volume perfuses the kidneys each minute. The
glomerular filtration rate (GFR) is calculated from creatinine clearance, inulin
clearance, or using chromium-labelled EDTA, or plasma creatinine levels, and in
health is normally 120 ml/min/1.73 m2 for women and 130 ml/min/1.73 m2 for
men.
The kidneys also act in the excretion of drugs and hormones. ^ The kidneys also
act as endocrine organs for the synthesis of hydroxycholecalciferol (active
vitamin D), erythropoietin, renin and prostaglandins, and are target organs for
parathyroid hormone and aldosterone.
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RENAL FAILURE
Loss of renal function results in a low GFR (renal failure).
Renal failure may be caused by:
o pre-renal conditions such as renal hypoperfusion in severe shock or
haemorrhage, renal disease such as trauma, disease or drug damage
o post-renal disorders such as obstruction of renal outflow by calculi,
prostatic hypertrophy or tumour.
Renal failure can come on suddenly (acute renal failure: ARF), as after surgery
or severe injuries, or when blood vessels leading to the kidneys become
obstructed.
Renal failure more usually develops slowly (chronic renal failure; CRF).
Renal failure results in:
a. fluid retention
b. acidosis
c. accumulation of metabolites and drugs
d. damage to platelets, leading to a bleeding tendency
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e. hypertension, anaemia and endocrine effects.
Acute renal failure
Acute renal failure (ARF) can be caused by:
A. pre-renal factors (55%)
1. renal ischaemia, severe burns - as a result of shock or dehydration, or
renal thrombosis
2. hypotension
3. sepsis
4. heat stroke
5. drugs causing renal shutdown (NSAIDs, ACE inhibitors)
B. renal factors (15%) renal disease such as interstitial nephritis, etc.
C. obstructed urine flow (10%)
D. toxic acute tubular necrosis (5%)
1. complicated surgery or trauma - myoglobin blocks tubular function
2. drugs: contrast dyes used in arteriography, antibiotics (especially
streptomycin or gentamicin or amphotericin), aspirin, ibuprofen and other
NSAIDs, acetaminophen overdose
3. toxins: heavy metals, solvents and excessive amounts of alcohol
4. multiple organ failure: in which the heart, lungs, liver, brain and kidneys
totally or partially shut down. This is most often the result of major trauma
or sepsis
5. haemolytic uraemic syndrome (HUS): a complex condition caused by
strains of Escherichia coli.
Clinical features
ARF is a medical emergency, which causes: fluid retention, bleeding, often in
the stomach or intestines, confusion, seizure, and coma.
Management: Dialysis is often required.
Chronic renal failure
General aspects
Chronic renal failure (CRF) results from progressive and irreversible renal
damage and is shown by a low glomerular filtration rate (GFR) persisting for
more than 3 months.
Chronic renal disease can be compensated by structural and functional
hypertrophy of surviving nephrons, to a point at which around 50% of renal
function remains, when chronic renal insufficiency (CRI) ensues. CRI inevitably
progresses to end-stage renal disease (ESRD). CRF is not a specific disease, but
a sequel to many renal and systemic disorders, including:
 hypertension - the leading cause of CRF
 diabetes mellitus. This is another important cause of CRF. Approximately
5-10% of people with type 2 diabetes living for at least 20 years also
develop renal disease.
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 renal diseases such as: chronic glomerulonephritis, polycystic renal disease.
Associated mitral valve prolapse can lead to dysrhythmias, embolism or
sudden death.
 renal artery stenosis: blockage of the renal artery is usually by
atherosclerosis. Renal artery stenosis can also affect young women with
fibromuscular dysplasia, which causes the walls of the arteries to become
thicker. Both these conditions are often associated with high blood pressure
 systemic lupus erythematosus
 myeloma and amyloid
 poisoning. Examples include lead poisoning from lead-based paint, lead
pipes, soldering materials, jewelry and even alcohol distilled from old car
radiators
 drugs: Analgesic nephropathy the long-term use of aspirin or other
(NSAIDs) or large amounts of acetaminophen. Chronic renal failure can be
exacerbated by various nephrotoxic drugs such as aminoglycosides or
amphotericin used systemically or NSAIDs.
Clinical features
Chronic renal failure is asymptomatic at first. Symptoms and signs of CRF
depend on the degree of renal malfunction, often with few symptoms until
kidney function has fallen to less than 25% of normal. Chronic renal failure then
manifests with nocturia and anorexia, and raised serum levels of nitrogenous
compounds such as urea and creatinine, from normal metabolic processes and
changes in electrolytes.
clinical features
A. Metabolic
1. Nocturia and polyuria
2. Thirst
3. Glycosuria
4. Raised serum urea, creatinine, lipids and uric acid
5. Electrolyte disturbances
6. Secondary hyperparathyroidism
B. Cardiovascular
1. Hypertension
2. Congestive cardiac failure
3. Pericarditis
4. Cardiomyopathy
5. Atheroma
C. Gastrointestinal
1. Anorexia
2. Nausea and vomiting
3. Hiccup
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4. Peptic ulcer and gastrointestinal bleeding
D. Neuromuscular
1. Weakness and lassitude
2. Drowsiness leading to coma
3. Headaches
4. Disturbances of vision
5. Sensory disturbances
6. Tremor
Dermatological
1. Pruritus
2. Bruising
3. Hyperpigmentation
Haematological
1. Bleeding
2. Anaemia
3. Lymphopenia
Immunological: Liability to infections
Advanced CRF causes significant impairment of all renal functions and affects
virtually all body systems, and causes changes in urea and electrolytes, and other
blood constituents. Laboratory features of chronic renal failure: raised in blood
urea, creatinine, potassium, and phosphate, low in calcium and haemoglobin.
Hypertension is common. Electrolytes such as potassium and hydrogen ions
accumulate.
Anaemia is common. This is caused by lack of renal production of erythropoietin
(EPO), blood loss in the gut, toxic suppression of the bone marrow and by
haemolysis and by shortened red cell survival from hypersplenism.
Renal osteodystrophy is common and appears to cause worsening symptoms
after the start of regular dialysis. Phosphate retention in CRF leads to depression
of plasma calcium levels and subsequently raised parathyroid activity (secondary
hyperparathyroidism).
There is also deficiency of renal production of 1,25 dihydroxycholecalciferol
(vitamin D3), and calcium absorption is thereby impaired. Parathyroid
hyperplasia may eventually become adenomatous and irreversible (tertiary
hyperparathyroidism).
Purpura and a bleeding tendency. The bleeding time is often prolonged not
because of a defined clotting defect but mainly from abnormal platelet
production, diminished platelet Factor 3 (thromboxane), which impairs
conversion of prothrombin to thrombin, raised prostacyclin (prostaglandin I),
leading to vasodilatation and poor platelet aggregation, and defective von
Willebrand's factor.
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There is a liability to infection. This is because of defective phagocyte function,
which results from impaired interleukin-2 (IL-2), but increases in other cytokines
(IL-1, IL-6, tumour necrosis factor)
End-stage renal disease (ESRD; uraemia) is the term used when more than 90%
renal function is lost and may be complicated particularly by: anaemia, bleeding,
bone disease, congestive.
Stages of chronic renal failure
Features
GFRml/min/ 1.73m2
Renal health
_
130
Normal
Plasma biochemistry
50-100
Diminished renal
normal
Raised plasma urea and
reserve (early CRF]
25-50
creatinine
Moderate CRF
(azotaemia)
Uraemic symptoms
<25
Severe CRF
Life-threatening
<10
End-stage renal
failure (ESRF)
General management
CRF is measured by a falling glomerular filtration rate (GFR) and rising plasma
urea and rising creatinine levels. The creatinine clearance is an approximation of
the GFR but more accurate assessments are by inulin clearance
Renal function may remain relatively adequate for long periods if the progress of
the renal lesion is slow, but any stress, infection or urinary tract obstruction
should be treated, as they may precipitate symptoms. Underlying causes of CRF
should be treated where possible. Drugs that are nephrotoxic such as NSAIDs,
tetracyclines or cephaloridine should be avoided, as should those that can
accumulate in the body when there is impaired renal drug excretion, and can
produce encephalopathy, such as penicillins, cephalosporins and erythromycin.
Initial management aims to lower the:
1. blood pressure by using ACE and angiotensin-2 blockers. These also
minimize proteinuria
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2. level of blood urea, electrolytes, etc., by: normal diet (low protein diets are
now rarely advocated), potassium restriction, salt or water control.
Symptoms and complications such as hiccup, vomiting, fits and calcium loss
should be treated.
Epoietin (recombinant erythropoietin) or darbepoietin, which has a longer halflife, is the main treatment for anaemia.
Calcium carbonate, vitamin D3 or its synthetic analogue, a low phosphate diet, or
intravenous clodronate help inhibit bone resorption. Parathyroidectomy may be
necessary in resistant cases.
Dialysis is used to remove metabolites, by exposing the patient's blood across a
semi-permeable membrane to a hypotonic solution. Dialysis becomes essential if
renal function deteriorates to ESRD and can totally rehabilitate up to 20% of
patients but cannot prevent all complications and is itself associated with some
adverse effects. Dialysis effects include:
 worsened cardiovascular disease
 cardiac valve calcification (especially affecting the aortic valve)
 dialysis-related amyloid.
Dialysis may be by continuous ambulatory peritoneal dialysis (CAPD) or
continuous cyclic peritoneal dialysis (CCPD) or extra-corporeal haemodialysis.
Patients on CAPD undergo around five manual changes daily, whereas with
CCPD, a machine does the exchanges at night. Haemodialysis is carried out,
often at home or as an outpatient, for two to three, 3- to 6-hourly sessions per
week. An arteriovenous fistula is usually created surgically at the wrist to
facilitate the introduction of infusion lines; alternatively, a Gortex or PTFE graft
is placed, or an indwelling tunnelled cuffed catheter used. These, particularly the
grafts and catheters, may be at risk of infection. The patient is heparinized during
dialysis to keep both the infusion lines and the dialysis machine tubing patent.
The patient also has an additional bleeding tendency from the mechanical
damage to platelets from the procedure. Control of infection is also of paramount
importance during haemodialysis, as infection with hepatitis viruses, or HIV or
other blood-borne agents, and tuberculosis, was common in the past. Over 70%
of patients on haemodialysis survive at least 5 years.
Renal transplantation may then become necessary.
Dental aspects
The main management problems in patients in CRF include:
o bleeding tendencies. Careful haemostasis should be ensured if oral surgical
procedures are necessary. Dental treatment is best carried out on the day after
dialysis, when there has been maximal benefit from the dialysis and the effect
of the heparin has worn off. The haematologist should first be consulted.
Should bleeding be prolonged, desmopressin (DDAVP) may provide
haemostasis for up to 4 h. If this fails, cryoprecipitate may be effective, has a
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peak effect at 4-12 h and lasts up to 36 h. Conjugated oestrogens may aid
haemostasis: the effect takes 2-5 days to develop, but persists for 30 days.
o infections: are poorly controlled by the patient with CRF, especially if
immunosuppressed, and may spread locally as well as giving rise to
septicaemia. They also accelerate tissue catabolism, causing clinical
deterioration. Infections can be difficult to recognize as signs of inflammation
are masked. Haemodialysis predisposes to blood-borne viral infections such as
hepatitis virus. Tuberculosis is also more frequent, but is usually
extrapulmonary and therefore does not constitute a risk to dental staff.
Odontogenic infections should be treated vigorously. Antimicrobial
considerations include: erythromycin, cloxacillin, fucidin and can be given in
standard dosage penicillins (other than phenoxymethyl penicillin and
flucloxacillin), metronidazole and cephaloridine, should be given in lower
doses, since very high serum levels can be toxic to the central nervous system.
Benzylpenicillin has a significant potassium content and may also be neurotoxic
and may therefore be contraindicated, tetracyclines, can worsen nitrogen
retention and acidosis in CRF. Only doxycycline and minocycline may be given.
Patients who should be considered for antimicrobial prophylaxis before
extractions, scaling or periodontal surgery include: those with polycystic kidneys
(who may also have mitral valve prolapse, those receiving peritoneal dialysis,
since bacteraemia can result in peritonitis, and some on haemodialysis. Vascular
access infections are usually caused by skin organisms such as Staph. aureus and
only rarely by oral microorganisms. Patients with most arteriovenous fistulas are,
therefore, not considered at risk from infection during dental treatment.
However, those with prosthetic bridge grafts of polytetrafluorethylene or
tunneled cuffed catheters may need to be managed with precautions similar to
those at risk from infective endocarditis. teicoplanin i.v. during dialysis, which
gives cover for at least a day. Antibiotic prophylaxis may also be indicated if
there is uraemia-related chemical trauma of heart valves, placing the patient at
possible long-term risk of endocarditis.
Drugs that are directly nephrotoxic must be avoided, drugs excreted mainly by
the kidney may have undesirably enhanced or prolonged activity if doses are not
lowered. Drug therapy may need to be adjusted, depending on the degree of renal
failure, the patient's dialysis schedule, or the presence of a transplant. Except in
emergency, such drugs should be prescribed only after consultation with the
renal physician. aspirin and other non-steroidal anti-inflammatory analgesics
should be avoided since they aggravate gastrointestinal irritation and bleeding
associated with CRF. Their excretion may also be delayed and they may be
nephrotoxic, especially in the elderly or where there is renal damage or cardiac
failure. Some patients have peptic ulceration, which is a further contraindication
to aspirin. Even COX-2 inhibitors may be nephrotoxic and are best avoided.
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antihistamines or drugs with antimuscarinic side-effects may cause dry mouth or
urinary retention. fluorides can usually safely be given topically for caries
prophylaxis. Systemic fluorides should not be given, because of doubt about
fluoride excretion by damaged kidneys. antacids containing magnesium salts
should not be given as there may be magnesium retention. Antacids containing
calcium or aluminium bases may impair absorption of penicillin V and
sulphonamides. Cholestyramine, sometimes used in CRF, may also interfere with
the absorption of penicillins. Many renal patients are on antihypertensive
therapy, digoxin and diuretics, which may also complicate management.
Postoperative complications:
major surgical procedures may be complicated by hyperkalaemia as a result of
tissue damage, acidaemia and blood transfusion. Hyperkalaemia predisposes to
dysrhythmias and may cause cardiac arrest. Dialysis is deferred postoperatively
if possible since heparinization is required.
Underlying diseases and complications: consideration must be given to the effect
on dental management of underlying diseases, such as hypertension, diabetes,
systemic lupus erythematosus, polyarteritis nodosa, myelomatosis, and
amyloidosis, or complications such as peptic ulceration.
Local anaesthesia and conscious sedation
Local anaesthesia is safe unless there is a severe bleeding tendency. Conscious
sedation: relative analgesia may be used. The veins of the forearms and the
saphenous veins are lifelines for patients on regular haemodialysis. If it is
necessary to give intravenous sedation, or take blood, other veins such as those at
or above the elbow should be used because of the risk of consequent fistula
infection or thrombophlebitis. Midazolam is preferable to diazepam because of
the lower risk of thrombophlebitis.
General anaesthesia
CRF is invariably complicated by anaemia, which is a contraindication to general
anaesthesia if the haemoglobin is below lOg/dl. Some of the difficulties with
general anaesthesia are that patients with CRF are highly sensitive to the
myocardial depressant effects of anaesthetic agents, and may develop
hypotension at moderate levels of anaesthesia. Myocardial depression and
cardiac dysrhythmias are especially likely in those with poorly controlled
metabolic acidosis and hyperkalaemia. Enflurane is metabolized to potentially
nephrotoxic organic fluoride ions and therefore should be avoided if other
nephrotoxic agents are used concurrently. Isoflurane and sevoflurane are
probably safer. Induction with thiopentone followed by very light general
anaesthesia with nitrous oxide is generally the technique of choice.
Orofacial manifestations
Osseous lesions include loss of the lamina dura, osteoporosis and osteolytic areas
(renal osteodystrophy). Secondary hyperparathyroidism may lead to giant-cell
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lesions. There may be abnormal bone repair after extractions, with socket
sclerosis. Patients with renal disease should therefore be screened carefully for
bone disease before implant placement.
Any oral sign of infection must be examined immediately and treated
aggressively in an immunosuppressed transplant recipient.
Common complaints in CRF are of a dry mouth, halitosis and a metallic taste.
Insidious oral bleeding and purpura can also be conspicuous. The salivary glands
may swell; salivary flow is reduced; there are protein and electrolyte changes;
and there is calculus accumulation. In children with CRF, jaw growth is usually
retarded and tooth eruption may be delayed. There may be malocclusion and
enamel hypoplasia with brownish discoloration but tetracycline staining of the
teeth should no longer be seen. A lower caries rate and less periodontal disease
have been reported in children with CRF.
RENAL TRANSPLANTATION
Transplantation is now strongly recommended for all patients with end-stage
renal disease (ESRD) who are medically suitable. A successful kidney transplant
offers enhanced quality and duration of life and is more effective (medically and
economically) than chronic dialysis. Transplantation is the renal replacement
modality of choice for child patients and patients with diabetic nephropathy.
Transplants can be from cadaveric or living donors. Renal graft survival is can be
as high as 90% at 1 year, about 70% survival at 5 years, and an overall mortality
of less than 5%. The 1-year life expectancy after kidney transplantation is 9598%.
General management
All kidney transplant recipients require life-long immuno-suppression to prevent
a T-cell alloimmune rejection response. These include intravenous induction of
antirejection agents and maintenance immunotherapy. Induction therapy consists
of a short course of intensive treatment with intravenous anti-lymphocyte
antibody. Patients then need to be immuno-suppressed, usually with a
corticosteroid plus a steroid-sparing drug such as azathioprine or now more
commonly ciclosporin or tacrolimus or sirolimus, or mycophenolate mofetil.
Dental aspects
Haematological abnormalities, such as anaemia and platelet-haemostatic
dysfunction. Gastrointestinal abnormalities, such as gastritis, peptic ulcer disease
or diverticulosis. Viral hepatitis B and C. Cardiovascular disorders such as
hypertension, atherosclerotic heart disease with myocardial infarction,
congestive heart failure and left ventricular hypertrophy. Bone and joint disease,
common because of low calcium levels, high phosphorus concentrations and
elevated serum parathyroid hormone (PTH). Dental pulp narrowing has been
noted, apparently a corticosteroid effect.
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