Renal disease

Renal disease 4,5,6,34-43

More often the dentist treats patient with chronic kidney disease. Chronic renal

failure can result from any condition that affects renal function permanently or

irreversibly. Congenital anomalies of the renal and urinary tract tend to produce CRF

before the age of 5 yrs. After 5, glomerular and hereditary renal diseases become

more prominent. Glomerular conditions include membranoproliferative

glomerulonephritis, the glomeruloscleroses, and the glomerulopathies of lupus

erythematosis and anaphlactoid purpura.

Clinical manifestations –

- The clinical manifestations of chronic renal failure often begin gradually with

complaints of fatigue, weakness, headache, nausea, vomiting, diarrhea,

anorexia and sometimes neurological disturbances.

- As the condition progresses, polyuria, polydipsia, muscle cramps and

paresthesia may develop.

- Physical examination usually reveals pallor due to severe anemia, peripheral

oedema, elevated blood pressure and skeletal deformities.

- Brown hyperpigmentation of the nails and skin due to the retention of dietary

pigments, and skin excoriations or scratches produced by intense generalized

itching secondary to the accumulation of calcium and phosphate

microcrystals.

- Patients also suffer from dyspnea, as well as an increased incidence of

gastrointestinal bleeding episodes.

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- Hemostasis is altered as a result of platelet dysfunction, and of the

anticoagulants used in dialysis. The mechanical trauma to which the platelets

are exposed dialysis can reduce their count. In addition diminished platelet

adhesion is observed, together with an increase in prostacyclin activity, lesser

availability of platelet factor 3, and increased capillary fragility. All these

factors can lead to an increased risk of bleeding problems.

- Involvement of the central nervous system is expressed in the form of

restlessness, apathy and insomnia.

- Facial puffiness, dryness and itchiness of the skin and specific sensory or

motor loss are also possible. Advanced CRF creates hypertension, fluid

retention, anemia and acidosis. These complications can lead to symptoms of

cardiac failure and circulatory congestion. General appraisal of the dental

patient with chronic renal failure reveals a pale brownish complexion, growth

retardation, and muscle weakness and wasting.

- Skeletal deformities commonly seen in children with renal obstructive

disorder related to chronic kidney disease and is most apparent in the bones

that are growing most rapidly at given age.

- A delay in tooth age and bone age in these patients with bone maturation

more frequently delayed has been observed. Bone development followed a

slower course compared to chronological age development in patients with

CRF.

- Growth retardation is a hallmark of chronic renal failure in children. Factors

that contribute to growth retardation are reduced food intake and chronic

metabolic acidosis. The main factor causing growth retardation is impairment

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of the biological activity of insulin like growth factor, the mediator of growth

hormone action.

- The breath may be suggestive of uremia and the skin may show areas of

bruising due to altered platelet function.

Oral manifestations –

About 90% of all patients with CRF suffer oral signs and symptoms affecting both

the bone and soft tissue structures.

- Bad odour (secondary to uremia) and metallic taste resulting from the increased

concentration of urea in saliva.

- Calculus formation is seen to be more in patients with dialysis, it has been found to

be in greater thickness.

- Gingival inflammation has been reported due to plaque accumulation and poor oral

hygiene habits.

- Reduced prevalence of dental caries are related to increased pH, resulting from urea

hydrolization in the saliva.

- Xerostomia, possible causes includes restricted fluid intake, effects of drug therapy,

and/or mouth breathing. Paleness of the mucosal membranes due to anemia, uremic

stomatitis, and uncommon clinical observation associated to uremia.

- Gingival bleeding, petechiae and ecchymosis resulting from platelet dysfunction and

the effects of anticoagulants.

- Gingival hyperplasia secondary to drug treatment, Periodontal problems with

important attachment loss, recesses and deep pockets.

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- Enamel hypoplasia secondary to alterations in calcium and phosphorus metabolism

which can affect both the primary and permanent dentition. Severe erosions on the

lingual surfaces of the teeth, Pulp obliteration, Delays or alterations in eruption

pattern is seen. The patient with chronic renal failure and on chronic hemodialysis

exhibited a more predentin thickness.

- Amelogenesis imperfecta may be associated with chronic renal failure.

- The often cited radiologic features, are the loss of lamina dura, changes in the

trabecular pattern in the jaw bones, a ground glass appearance of the bone, all seen in

hyperparathyroidism secondary to chronic failure.

- The metabolic changes related to renal dysfunction or its treatment has also been

related to eruption of rootless teeth and cysts.

- Gingival overgrowth may be site for development of oral carcinoma.

- The oral manifestations of CRF include ammonia-like smell, dysgeusia, stomatitis,

decreased salivary flow, and parotitis.

- Cytomegalovirus infection may occur most commonly in the first few months after

transplantation, coinciding with the maximal immunosuppression.

- Intrinsic stains are also seen in some hemodialysis patients resulting from the use of

tetracycline to treat infection during the period of calcification of the primary and

permanent teeth. Extrinsic staining was found in pediatric patients being treated for

anemia with ferrous sulphate in syrup form, which caused a black-brown extrinsic

staining on the teeth.

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Dental management –

- Gingival inflammation has been reported due to plaque accumulation and

poor oral hygiene due to accumulation and poor oral hygiene habits. Oral

hygiene has the potential to reduce the inflammatory component of gingival

disease in patients with renal failure. Hence thorough oral prophylaxis is

recommended in children with renal failure.

- Gingival overgrowth is believed to be related to an alteration of the fibroblast

metabolism due to cyclosporine and/or its metabolites, increasing protein

synthesis, collagen, and extracellular matrix formation. Gingival overgrowth

treatment may be conservative with meticulous professional and personal

oral hygiene and/or by surgically by laser or traditional scalpel surgery. The

recurrence is considered inevitable. A delay in surgery for atleast 3yrs

however, may be beneficial in reducing the recurrence rate.

- An additional possibility of gingival overgrowth treatment is the use of

antibiotics such as azithromycin, metronidazole, and clarithromycin. The

mechanism of action of which is attributed to their antibacterial action,

reduction in the local inflammation and possible suppression of protein

synthesis in the fibroblasts before severe gingival overgrowth is established.

- Cyclosporin associated gingival enlargement may reduce or resolve when

cyclosporin is replaced by tacrolimus.

- The oral hygiene habits of these children should be improved and monitored

closely through periodic dental check-ups. The prescription of additional

fluorides (other than from fluoridated water and tooth pastes) for these

patients is contraindicated because of their renal impairment.

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- Disturbed calcium and phosphate metabolism may cause developmental

enamel disturbances, including enamel hypoplasia. The age in which the

metabolic disturbances take place correlate with the dental developmental

disturbances, as reflected by prominent incremental lines. The treatment of

these defects should be based on the defect’s severity and extent and the

patient’s dental developmental stage and may vary from bonded composite

conservative restorations to full crown coverage.

- All pediatric dentists should consider referral of patients with amelogenesis

imperfecta for renal ultrasound examination to establish its association to

renal disease.

- It is essential to eliminate any infection in the oral cavity as soon as possible,

with the consideration of antibiotic prophylaxis when bleeding and/or a risk of

septicaemia is expected (extractions, periodontal treatments, endodontics and

periapical surgery, the placement of orthodontic braces, implant surgery, and

the reimplantation of avulsed teeth).

- Patients with arterio-venous shunts are at greater risk of infection following

dental manipulation. It is speculated that changes in fluid volume and

hemodialysis itself affect heart behaviour, creating mechanical stresses that

may play a role in the development of infective endocarditis. Hence AHA

protocol for prevention of infective endocarditis should be used.

Drug interactions

- The metabolism and elimination of certain drugs are altered in situations of

renal failure. In such cases dose adjustment or modification of the dosing

frequency is needed. The prescription of aminoglycoside antibiotics and

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tetracyclines is to be avoided, because of their nephrotoxicity. Penicillins,

clindamycin and cephalosporins can be administered at the usual doses, and

are the antibiotics of choice – though the dosing interval should be prolonged.

As regards analgesics, paracetamol is the non-narcotic analgesic of choice in

application to episodic pain. Aspirin possesses antiplatelet activity, and as

such should be avoided in uremic patients. As regards the rest of nonsteroidal

anti-inflammatory drugs (indomethacin, ibuprofen, naproxen and sodium

diclofenac), dose reduction or even avoidance is indicated in the more

advanced stages of renal failure, since they inhibit prostaglandins and generate

a hypertensive effect. Benzodiazepines can be prescribed without the need of

dose adjustments, though excessive sedation may occur. The narcotic

analgesics (codeine, morphine, fentanyl) are metabolized by the liver, and so

usually do not require dose adjustment. Antifungal drugs like fluconazole and

Miconazole increases the plasma-cyclosporin concentration and thus, usually

following the initial dose is then halved in the subsequent doses. Amphotercin

is used only if there is no alternative as that may also increase the risk of

nephrotoxicity. Povidone-iodine and ephedrine are generally avoided or used

with caution.

Analgesic nephropathy

- Long term ingestion of analgesic drug can cause renal papillary necrosis and

chronic interstitial nephritis. Mixtures containing aspirin and phenacetin have

been associated with analgesic nephropathy. A fall in the incidence of

analgesic nephropathy on withdrawal of phenacetin was observed. It is caused

by the frequent use of over the counter drugs. Dehydration is contributory

factor which acts by reducing medullary blood flow, resulting in increased

concentration of the drugs in the renal medulla.

- Proper kidney function depends upon adequate blood flow to the kidney.

Kidney blood flow is a complex, tightly regulated process that relies on a

number of hormones and other small molecules, such as prostaglandins. Under

normal circumstances, PGE2 produceed by the kidney is necessary to support

adequate blood flow to the kidney. But PGE2 synthesis depends on the

cyclooxygenases. Aspirin and other NSAIDS are inhibitors of the

cyclooxygenases. This result in decreased concentration of PGE2 causing

reduction in blood flow. Because blood flow to the kidney reaches first the

renal cortex and then the renal medulla, the deeper structures of the kidney,

called the renal papillae, are especially dependent on prostaglandin synthesis

to maintain adequate blood flow. Inhibition of cyclooxygenases, therefore

rather selectively damages the renal papillae, increasing the risk of renal

papillary necrosis.

- It has been proposed that Phenacetin and acetoaminophen metabolites lead to

lipid peroxidation that damages cells of the kidney. In cells of the kidney,

COX catalyse the conversion of paracetamol into N acetyl p

benzoquinoneimine. NAPQI depletes glutathione via non enzymatic

conjugation of glutathione, a naturally occurring antioxidant. Hence, kidney

become particularly sensitive to oxidative damage.

Nephritic syndrome

- Substantial amounts of protein are lost in the urine. Proteinuria itself is an

underlying pathogenic abnormality in nephrosis, which results from an

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increase in glomerular capillary wall permeability. The consequences of the

disease leads to oedema, hypercoagulability, hypercholesterolaemia and

infection.

Hemostasis

- Bleeding tendencies in these patients are attributed to a combination of factors,

including anticoagulants used with hemodialysis therapy and vascular access

maintenance. Mechanical trauma to platelets during dialysis treatments can

reduce the platelet count. Apart from these, decreased platelet adhesiveness,

increased prostacyclin activity, decreased availability of platelet factor 3 and

increased capillary fragility, all of which can lead to increased loss of blood.

- Prior to invasive procedures, it is important to request a complete blood count

and coagulation tests, and to ensure that local hemostatic measures are

available: mechanical compression, sutures, topical thrombin, microfibrilar

collagen and oxidized regenerated cellulose. Desmopressin has been proposed

for the control of severe bleeding in patients with renal failure, and conjugated

estrogens can be used to achieve longer term hemostasis. Tranexamic acid in

the form of a rinse or administered via the oral route at a dose of 10-15 mg/kg

body weight a day distributed in 2-3 doses, may also prove useful.

Patients undergoing hemodialysis

- Renal patients receiving dialysis have been shown to have altered immune

function. Research has shown elevated levels of the pro inflammatory

cytokines, particularly the tumour necrosis factor, IL-10 and IL-6. Local

stimulators of bone metabolism such as cytokine are particularly involved in

the coordination of many events leading to the overall loss of bone seen in

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periodontal disease. IL-1, TNF, IL-6 and PGE1 have been shown to regulate

osteoclast generation. Stashencko, demonstrated a positive correlation

between IL1b levels in periodontal tissue and attachment loss in humans.

- Dialyzed patients are subjected to numerous transfusions and blood

exchanges, and this implies an increased risk of infection in the form of HIV,

HBV, HCV and tuberculosis. Periodic monitoring is required, with the

adoption of measures to avoid both personal contagion on the part of the

dental professional and cross-contamination in the dental clinic.

- Hemodialysis can affect the serum concentrations of different drugs used by

CRF patients, when such substances are administered before the dialysis

session, supplementary dosing after dialysis therefore may be needed. Hence

procedures involving bleeding or requiring antibiotic administration

should not be performed on the dialysis session day, other dental

treatment can be performed at any time.

- Elective dental procedures should be performed on the day after dialysis

treatment when the patient is best able to tolerate treatment. Dialyzed patients

are at an increased risk of bleeding. It is advisable to provide dental

treatment on non-dialysis days, to ensure the absence of circulating

heparin, which has a half-life of about four hours.

- Apart from serving as a potential site for infection, arterio venous access sites

must not be jeopardized, blood pressure monitoring is prudent, but the

affected arm should never be used for the intravenous or intramuscular

injection of any medications, nor should the circulation be impeded by a

blood pressure cuff.

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- In addition patients should not be kept in cramped positions in the dental

chair and should be allowed to stand or walk occasionally to minimize the

risk of access obstruction.

- Hypertension in patients with renal disease leads to significant cerebral,

coronary, and peripheral vascular effects. Although patients are often treated

with antihypertensive medications dentists should take precautions to avoid

excessive stress in dental chair that could elevate the systolic pressure.

General anesthesia –

- Insulin and corticosteroid replacement regimens may require alteration.

Signs of digitalis toxicity should be sought in treated patients, emphasizing the

role of renal clearance of this and other drugs.

- Antihypertensive drug therapy is usually continued.

- Preoperative medication must be individualized, remembering that these

patients may have increased gastric fluid volumes and at the same time exhibit

unexpected sensitivity to central nervous system depressants.

- Induction of anesthesia and intubation of the trachea can be safely

accomplished with intravenous drugs including barbiturates, benzodiazepines,

or etomidate plus succinylcholine. An alternative to succinylcholine would be

intermediate acting muscle relaxants especially atracurium.

- Exaggerated pharmacologic effects produced by barbiturates could also reflect

reduced protein binding of drugs, resulting in more unbound drug to act at

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receptor sites. The amount of pharmacologically active thiopental in plasma is

increased in patients with chronic renal failure.

- The blood brain barrier may not be intact in the presence of uremia. This

could also increase the incidence of excessive drug effects, particularly as

reflected by central nervous system depression.

- The most serious electrolyte abnormality in patients with chronic renal failure

is hyperkalemia. Hazards of hyperkalaemia are cardiac conduction

abnormalities and dysrhytmias. Because of the potential dangers of

hyperkalaemia, it is a common recommendation not to perform elective

surgery unless plasma potassium concentrations are less than 5.5 mEq/L.

- Potassium release after administration of succinylcholine is not exaggerated

in patients with chronic renal failure. Caution is necessary, however when the

preoperative plasma potassium levels are in high normal ranges, since this

combined with maximum drug induced potassium release could result in

dangerous hyperkalaemia.

- Minor oral surgical procedures can be monitored by non invasive methods.

Permanent vascular shunts should be protected and their patency

monitored with a Doppler sensor to confirm continued patency during the

operative procedure.

- Continuous monitoring of intra arterial blood pressure is helpful when major

operative procedures are being performed.

- Caution must be exercised in the use of opioids for post operative

analgesia, in view of reports describing exaggerated central nervous

system and ventilator depression after even small doses of opioids.

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Fluid management –

- Ringer lactate solution or other potassium containing fluids should not be

administered to renal failure patients.

- Urine output should be maintained between 0.5/ml/kg/hr - 1ml/kg/hr in

the operative and immediate post operative period. This is best achieved

by intravenous fluid replacement with balanced salt solutions, 3ml/kg/hr

– 5ml/kg/hr.

Transplant patients

- Transplant patients who are immunosupressed often experience a change in

oral flora predisposing the patient to oral candidiasis in addition cyclosporine

and calcium channel blockers are known to contribute to gingival hyperplasia

which is exacerbated by poor oral hygiene.

- Before treating a prospective transplant recipient, obtain and review the

patient’s medical and dental histories and perform a non invasive initial

oral examination i.e without any probing.

- After the initial examination, the current status of the patient is discussed with

the physician. Decisions about timing of treatment, the need for antibiotic

prophylaxis, precautions to prevent excessive bleeding, and appropriate

medication and dosage should be considered. In some patients, it will be safer

for patients to undergo extensive treatment after transplant as the new organ

improves their health.

- Several factors should be considered before starting a treatment. Decision

regarding antibiotic prophylaxis is required to prevent systemic infection

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from invasive dental procedures. The American Heart Association’s

standard regimen to prevent endocarditis is an accepted option.

- If the patient presents with an active infection, such as purulent

periodontal infection or an abscessed tooth, antibiotics should be given to

the patient before and after dental treatment to prevent systemic

infection.

- Assess the patient’s bleeding potential with the appropriate laboratory tests

and take precautions to limit bleeding. Consult the physician regarding the

appropriate intervention, whether antifibrinolytic, Vit K, Fresh Frozen Plasma,

or others to be used.

- Aggressive suctioning techniques to be used when performing extractions

or other invasive procedures to prevent patient from swallowing blood.

The swallowed blood may increase the risk for hepatic coma.

- Patients being prepared for organ transplantation, usually take multiple

medications. Hence it is important to take precaution while prescribing

drugs to these patients, keeping in mind the drug interactions that may

occur. Consulting the patient’s physician on appropriate drug selection,

dosage and administration intervals is the best way to avoid adverse

conditions.

- All active dental treatment should be aggressively treated before

transplantation, since post-operative immunosuppression decreases a patient’s

ability to resist systemic infection.

- Teeth offering an uncertain prognosis such as non restorable teeth are to be

removed.

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- Consider removing orthodontic bands or adjusting prostheses for patients

expected to receive cyclosporine after transplant, as patients may develop

gingival hyperplasia. Gingival overgrowth can be minimized with good plaque

control.

- Instruction to the patients should be given to bring the current list of their

medications, including over the counter drugs, to every appointment and note

those that may be problematic.

- Patients who have undergone transplantation are at increased risk of serious

infection. In the first 6 months after transplantation, patients should avoid

any elective dental treatment. The decision to premedicate for invasive

dental procedures and selection of the appropriate regimen should be done in

consultation with the patient’s physician.

- Do not treat a patient when the blood pressure of the patient is well above

the baseline levels and inform the physician.

- Patient’s mouth should be thoroughly examined, since immunosuppressive

medications can hide signs of infection. As a result, infections are often more

advanced than they appear.

- Prolonged corticosteroid therapy may make it necessary to administer a

supplementary dose in situations of stress, such as when visiting the

dentist, in order to avoid an adrenal crisis.

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Drugs commonly used in dentistry and its implication in Renal disease.

Drug Caution

Antibiotics

Amoxicillin / ampicillin Reduce dose, rashes are more common

Erythromycin Increases plasma tacrolimus

concentration

Increases plasma cyclosporine

concentration

Tetracycline Avoid. Use doxycycline or minocycline if

necessary.( avoid excessive doses)

Doxycycline increases plasma

cyclosporine concentration

Cephalexin, cefradine Reduce dose.

Probenecid Avoid ( ineffective, increased toxicity)

Antifungals

Amphotericin Used only if no alternative.

Cyclosporine, tacrolimus increases risk of

nephrotoxicity.

Fluconazole Usual initial dose then half subsequent

doses.

Increases plasma tacrolimus

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concentration

Increases plasma cyclosporine

concentration

Miconazole Increases plasma cyclosporine

concentration

Antivirals

Acyclovir Reduce dose

Analgesics

Aspirin Avoid (sodium, water retention;

deterioration in renal function, risk of

gastric hemorrhage.)

Ibuprofen, diflunisal Avoid if possible/ use low effective dose,

monitor renal function.

(sodium, water retention; deterioration in

renal function.)

Cyclosporine, tacrolimus increases risk of

nephrotoxicity.

Dihydrocodiene, pethidine Reduce dose or avoid ( increased and

prolonged effect, increased cerebral

sensitivity.)

Other drugs

Carbamazepine Caution

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Reduce plasma cyclosporine

concentration.

Nitrazepam, temazepam Start with small doses. ( increased

cerebral hypersensitivity.)

Povidone iodine Avoid regular application to inflammed

or broken mucosa.

Ephedrine Avoid ( CNS toxicity)

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