Renal Disease

Dental and Medical Considerations of Patients with Renal Disease

John A Svirsky, DDS, MEd, Julia Nunley, MD, C. Daniel Dent, DDS, Don Yeatts, DDS, MD

Copyright 1998 Journal of the California Dental Association.

Dr. John A. Svirsky will present "Oral Pathology For the Fun of It" at the ADA Annual Session in San Francisco on Sunday, Oct. 25, from 8:30 am - 11 am and 1 pm - 3:30 pm in Room 307 at the Moscone Center. Dr. Svirsky will also be part of the OSHA Infection-Control Panel, Monday, October 26, from 8:30 am - 11 am and repeating at 1 pm - 3:30 pm in room 307 at the Monscone Center.

Often a dentist will have a patient with a complicated medical condition that needs to be considered when providing treatment. Following is an in-depth discussion of the medical and dental considerations of patients with renal disease.

Of the over 260 million people in the United States approximately 257,000 have End Stage Renal Disease (ESRD) of such severity that dialysis or renal transplantation is necessary to maintain life.1 This population of patients with ESRD increases by roughly 10 percent per year,1 despite a significant coexistent mortality rate of approximately 20 to 25 percent per year.2 The more common causes of ESRD in the United States are diabetes mellitus, hypertension, glomerulonephritis, chronic pyelonephritis, urologic disorders and autoimmune diseases. The primary causes of death in patients with renal failure include cardiovascular disease, accounting for 48 percent of all deaths, and overwhelming sepsis, which accounts for 12 to 38 percent of all deaths;3,4 Diabetes and hypertension have been shown to be major contributing co-morbid factors.3

Normal Renal Physiology

The functional unit within the kidney is termed the nephron and each kidney contains approximately 1 million nephrons. The major components of the nephron are the glomerulus, where filtration occurs, the renal tubule, where a combination of reabsorptive and secretive processes alter the filtrate, and the collecting system, where final modification occurs, resulting in the waste product urine.5 Renal failure evolves over time through progressive deterioration and destruction of the nephron units. Though different diseases affect different segments of the nephron initially, the entire nephron is eventually destroyed. Once a nephron is lost, it is not replaced.

The kidney maintains sodium, water and acid-base homeostasis via glomerular filtration, tubular reabsorption and secretion, Renal excretion is also the major route of elimination for many drugs and for most end products of metabolism. As renal blood flow accounts for approximately 20 percent of the cardiac output, the kidneys can efficiently affect blood composition.5

The kidney also functions as an endocrine organ. Ninety percent of the body's erythropoietin, a hormone that stimulates red blood cell production, is renally produced.6 The renin-angiotensin-aldosterone axis, which is crucial for volume status and significantly affects blood pressure, is largely renally regulated.7 In addition, the kidneys are responsible for the activation of vitamin D, essential for normal bone and calcium metabolism.8

Chronic Renal Disease

Renal function is defined by the rate of glomerular filtration (GFR) and frequently determines the metabolic milieu. A normal GFR is 100-120 cc/min. Physiologic homeostasis can be maintained until approximately 75-80 percent of the nephrons are destroyed and the GFR falls below 20-25 cc/min.5 When this severe reduction is attained, normal volume and acid-base balance can no longer be maintained and medical intervention with diuretics, dietary restriction, bicarbonate therapy, or other modalities becomes necessary.

Abnormal laboratory tests are common in renal disease. Routine blood chemistries in a patient with advanced renal failure may show hyperkalemia, metabolic acidosis, hypocalcemia, and hyperphosphatemia, as well as the usual markers of renal disease, an elevated blood urea nitrogen (BUN) and creatinine. As renal failure progresses, most patient will develop a normochromic, normocytic, anemia due primarily to erythropoietin deficiency.9 Though the plasma creatinine is a rough estimate of GFR, glomerular filtration rate is more accurately determined by calculating the renal creatinine clearance from a 24-hour urine collection.5

End Stage Renal Disease

Renal failure becomes symptomatic only when metabolic abnormalities become severe. End Stage Renal Disease (ESRD) occurs and treatment is initiated when the patient is clinically "uremic" and/or cannot adequately maintain physiologic balance, despite medical intervention. Symptoms of uremia are nonspecific and include gastrointestinal symptoms, sleep disturbances, mental changes, and an overall failure to thrive. When uremia develops, the patient's GFR will be as low as 5-12 cc/min. Treatment options for ESRD include hemodialysis, peritoneal dialysis, chronic ambulatory peritoneal dialysis, and renal allograft transplantation. If one of these options is not initiated when renal failure becomes severe, the patient will die within a fairly short period, usually weeks.

Hemodialysis is a procedure during which blood is removed from the body, passed along one side of a biocompatible semipermeable membrane, and returned to the body.10 Simultaneously a "dialysate" (contrived solution) flows in a countercurrent direction on the other side of the membrane. The dialysate contains constituents that will diffuse into the patient's blood and lacks those that are to be removed.11 Thus, solutes diffuse across the semipermeable membrane according to the concentration gradient of each. Volume is removed by manipulating pressure across the same semipermeable membrane.

Each patient is required to undergo hemodialysis three times a week for about four hours per session. Because adequate hemodialysis requires a high rate of blood flow through the hemodialysis system (250-350 cc/min), surgical creation of an arterio-venous fistula or graft is necessary for sufficiently large size needle for vascular access. The vascular access must be protected at all times, for it is the patient's lifeline. Under no circumstances should there ever be a blood pressure measurement taken or a needle for intravenous access be placed in the access arm.

Peritoneal dialysis also uses the principle of a diffusion gradient to effectively dialyze the patient. However, the semipermeable membrane used is the peritoneal membrane itself.10 Again, the dialysate, which is infused into and out of the peritoneal cavity at regular intervals (usually four exchanges per day), is a contrived solution containing solutes to be given to the patient and lacking those to be removed. Volume is removed by manipulating the osmolality of the peritoneal dialysate. Surgical intervention is needed to place the peritoneal catheter, which remains in place permanently unless removed surgically.

From those 257,000 patients within the ESRD pool, an estimated 11,900 per year will receive renal allografts,1 mostly from cadaveric donors. One year kidney survival is approximately 97.5 percent for kidneys donated from living relatives, and about 93.5 percent for cadaver kidneys.1 After five years these figures fall to approximately 90 percent for related donor transplants and 78 percent for cadaver transplants.1 The primary cause of graft loss is rejection, despite the use of potent immunosuppressive drugs such as imuran, prednisone, and cyclosporine. Moreover even with close monitoring, transplant recipients have a higher incidence of bacterial, viral and opportunistic infections than the general population, as well as an increased risk of developing an occult malignancy, due to chronic immunosuppression.12

Complications of ESRD

Fluid and electrolyte disturbances

Volume

Patients with chronic renal failure can neither concentrate nor dilute their urine properly, and they are extremely sensitive to both volume expansion and volume depletion. Most patients on dialysis make little or no urine, so fluid administration should usually be limited, and possibly avoided. Volume expansion may cause hypertension, pulmonary edema with cardiomegaly, and/or peripheral edema. Many patients have an underlying cardiac condition and can easily develop congestive heart failure.

Electrolytes

The major route for elimination of potassium, magnesium, and phosphate is via the kidney. Therefore, ESRD patients should never be given these substances unless deficiencies are clearly documented and blood levels are monitored. Hyperkalemia can be life-threatening because it increases neuromuscular excitability and can result in heart block, ventricular arrhythmias and cardiac arrest. Hypermagnesemia may suppress muscular contraction and lead to ventilatory collapse.13 Hypocalcemia and hyperphosphatemia are common in renal failure due to the decreased urinary excretion of phosphate and decreased production of vitamin D and the rise in parathyroid hormone.8 Conscientious management of calcium and phosphorus levels is crucial to prevent osteodystrophy.

Acidosis

Almost all patients with renal failure develop a metabolic acidosis due to decreased hydrogen ion excretion.14 Symptoms such as anorexia, lassitude, and dyspnea may occur. This acidosis is classified as an "anion gap" metabolic acidosis due to the excessive accumulation of plasma anions (sulfates, phosphates, etc.) That would normally be excreted in the urine. Physiologic pH is partially maintained by compensatory hyperventilation. Alkali therapy with sodium bicarbonate or sodium choate can help ameliorate symptoms.

Hematologic and immunologic disturbances
Anemia

Most patients with chronic renal insufficiency (CRI) and ESRD have a normochromic normocytic anemia with hemoglobin ranging from 7-9 grams per deciliter (20-27 percent hematocrit). This anemia is multifactorial, resulting from to a decrease in red blood cell (RBC) production, a shorter half-life of those cells produced, and blood loss.15 The factors responsible for decreased production include erythropoietin deficiency; possibly iron, folate and vitamin B12 deficiencies; and aluminum toxicity. The exact mechanism for the shortened RBC survival is unknown, but perhaps the uremic milieu, along with the acidosis, is responsible. Many patients have chronic blood loss through the gastrointestinal tract and some blood loss is obligatory with hemodialysis.16 Parenteral use of human recombinant erythropoietin helps alleviate the anemia in ESRD patients. Blood transfusions are reserved only for severe symptomatic anemia because they may cause production of an antibody response that can make future transplants difficult.

Bleeding disorder

Hemorrhage a frequent complication of uremia and presents as prolonged bleeding, bruising, nose bleeds, gastrointestinal bleeding, gingival bleeding, etc.15 Measurement of routine laboratory parameters of hemostasis, prothrombin time, partial thromboplastin time, and the platelet count are normal. However, template bleeding time, however, will frequently be prolonged.16 Prolonged bleeding is due primarily to a qualitative, not a quantitative, platelet disorder involving abnormal platelet aggregation, a decrease in platelet factor III, and possibly, a defect in factor VIII affecting the clotting cascade. Platelet function may be improved by chronic dialysis. In acute situations, bleeding can be treated with either cryoprecipitate and/or a synthetic analogue of antidiuretic hormone, 1-deamino-8-D-arginine vasopressin, desmopressin or conjugated estrogens.17

Compounding the already tenuous state of hemostasis in these individuals is the routine use of heparin during hemodialysis. Anticoagulation is necessary to prevent blood from clotting the dialysis system, although a minimal amount of heparin is used. Even though the half-life of heparin is short at three to four hours, most surgical procedures should be scheduled on non-dialysis days, if possible. Less efficacious alternatives to anticoagulation may be used by the dialysis center, if necessary.15

Immunocompromise

Azotemia is associated with abnormalities of the immune system and involves both cellular and humoral immunity.18 A higher incidence of infection exists in renal failure patients, implying the need for special precautions. Many centers recommend prophylactic antibiotic therapy prior to invasive dental treatment and various other procedures to avoid bacterial seeding of the patient's vascular access and also cardiac valves.

Because of the even higher risk of infection in transplant patients, dental clearance thorough oral examination and treatment to reduce possible oral sources of infection is necessary prior to transplantation. Maintenance of oral hygiene is crucial. Peculiar to all post-transplant patients maintained on cyclosporine is the potential development of gingival hyperplasia, which often requires resection.

Viral Infections

All dialysis units routinely screen patients for hepatitis B. Many patients have been exposed to the virus usually due to transfusions, drug use, etc., and about 3-10 percent carry the antigen for hepatitis B. Many dialysis units now vaccinate patients with the hepatitis B vaccine. The patient's serology status can be obtained from the dialysis center or checked by determining the HbsAg level in the blood. Approximately 1 percent to 30 percent of dialysis patients also carry the diagnosis of hepatitis C (nonA-nonB).20 Most of these patients are positive for antibody to hepatitis C (anti-HCV), but not all units routinely screen for anti-HCV.

Most centers also screen for the HIV virus, and renal failure is not uncommon in patients with HIV/AIDS. Patients who have renal dysfunction due to the virus are usually quite ill and have a poor prognosis.

Endocrine-metabolic disturbances

Aberrancies can be found in almost all of the endocrine axes.21 Renal osteodystrophy is one of the more clinically prominent and serious of the metabolic disturbances,8 and stems initially from the body's inability to clear phosphate. Hyperphosphatemia, in conjunction with a decreased vitamin D production, leads to hypocalcemia which, in turn, induces hyperparathyroidism. Under normal conditions, parathyroid hormone will inhibit renal reabsorption of phosphate, stimulate production of vitamin D, and enhance gastrointestinal absorption of vitamin D. However, in renal failure, these effects are blunted and the results can be disastrous. The increase in calcium mobilization, along with defective bone mineralization, can lead to osteomalacia, osteitis fibrosa, and metastatic calcification of soft tissues and blood vessels. It has been shown that aluminum accumulation complicates the bone disease in many patients.22 Severe bone loss after years of renal failure predisposes patients to spontaneous fractures, aseptic necrosis, and tooth loss.

Cardiovascular disease:

Patients on dialysis experience a substantially increased risk of atherosclerosis.23 Many patients have peripheral vascular insufficiency, cerebral vascular compromise, and coronary artery occlusion. These processes are complicated by the high incidence of hypertension (usually due to hypervolemia and occasionally elevated serum angiotensin levels) and hypercholesterolemia found in this population.24 Another cardiac finding, not uncommon in chronic uremia, is pericarditis.

Gastrointestinal abnormalities:

Anorexia, nausea and vomiting, diarrhea, and gastrointestinal ulceration and bleeding are not uncommon in these patients.25 This can lead to malnutrition and, rarely, vitamin deficiencies.

Neurologic abnormalities:

Uremic encephalopathy, ranging from mild sensorial clouding to coma, can develop in patients with severe renal dysfunction who are not yet on dialysis.26 Moreover, there can be an aluminum-related neurologic abnormality that improves with aluminum removal. Dialysis patients also develop a peripheral, stocking-glove, ascending neuropathy that can be effectively treated only with renal transplantation.

Dermatologic/oral manifestations:

Those patients with anemia appear pale and those with bleeding abnormalities may have bruises or petechiae. Yellowish-brown hyperpigmentation can occur over time due to the accumulation of carotene-like uremic toxins.27 Excoriations are common due to the severe pruritus suffered by many patients. This may respond to phototherapy and IV lidocaine. With the availability of dialysis, the classic "uremic frost" due to residual urea crystals left on the skin when perspiration evaporates is rarely seen today.

Oral findings of azotemia include stomatitis, candidiasis, xerostomia, gingivitis and the classic uremic fetor, an ammonia-like odor of the breath. An unpleasant metallic taste also may be present. Bone resorption can lead to pathologic mobility of the teeth.28 The triad of localized radiolucent jaw lesions, loss of lamina dura, and demineralized ("ground glass") bone can be seen with renal osteodystrophy.29 Particular to the patients on cyclosporine is the gingival hyperplasia previously mentioned. Tooth erosion from persistent vomiting may also be seen.

Special Considerations

Renal dysfunction is a matter when considering drug therapy. Many drugs (and/or metabolites) are excreted renally and should be administered in a reduced dose, or completely avoided.30 In general, the full dose of most drugs can be given if the patient's GFR is greater than 20-30 percent of normal (GFR>20-30 cc/minute). Patients with lower GFRs, or with ESRD, usually require dose adjustments.

Drugs

Antibiotics

Oral penicillin can be given in the standard dosage for a short course of therapy (less than a week). However, high dose intravenous penicillin therapy has been associated with seizures, and should be avoided. Aqueous penicillin exists as either a sodium salt or a potassium salt, and the potassium salt should be avoided. Other commonly used antibiotics that should be used cautiously in the patient with renal failure include tetracycline and trimethoprim/ sulfamethoxazole.30 Tetracycline has been associated with episodes of acute renal failure, and it also increases catabolism, which can cause an increase in BUN. Trimethaprim/sulfa has been associated with the development of an acute interstitial nephritis and acute renal failure, but it can also competitively inhibit renal creatinine secretion and raise plasma creatinine without a change in renal function.

Erythromycin and clindamycin are metabolized by the liver and do not require dosage adjustments in patients with renal failure. However, erythromycin decreases the metabolism of cyclosporine, and should be avoided in patients taking this drug.31

Analgesics

Aspirin cannot be used in the usual dose in most dialysis patients. It should only be used when absolutely necessary and then the interval between doses should be increased. Acetaminophen does not cause bleeding and is better tolerated. Nevertheless, chronic acetaminophen use should be avoided in the pre-dialysis patient, because the primary metabolite of acetaminophen is the renal toxin phenacetin. If it is used, the interval between doses should be lengthened.

Non-steroidal anti-inflammatory drugs (NSAID) should be avoided in patients with CRI because they can cause deterioration of already compromised renal function.32 If an NSAID is necessary, close monitoring of plasma creatinine is essential. NSAIDs can be used in patients with ESRDs where there is relatively little renal function, but one needs to be aware of the increased incidence of gastrointestinal bleeding.

Most narcotics can be safely used. The exception is meperidine, which should not be used in patients with ESRD. Meperidine is metabolized to normeperidine, which accumulates in renal failure and can cause seizures.33 Indeed, many metabolites will accumulate in renal failure; therefore, long term therapy and/or high dose use of any narcotic or hypnotic should be avoided.

The dosage of lidocaine and other local anesthetics need not be adjusted since they cause little to no problem when used properly. However, the duration of the anesthetic block can be substantially shorter in patients with renal failure than in the normal subject.34 Vasoconstrictors should be used with care due to the prevalence of hypertension in renal failure.

Antihistamines/decongestants/barbiturates/sedatives

Most of these agents are tolerated without difficulty. One should use shorter-acting rather than the longer-acting preparations and to avoid chronic use. Be aware that patients with hypertension may show an elevation in blood pressure when placed on a nasal decongestant.

Other Agents

Radiologic studies using contrast media should be avoided in patients with CRI, if possible. If contrast medium is necessary, proper management with intravenous volume expansion may ameliorate some of the complications.35 However, patients on dialysis usually may undergo studies with contrast medium at no increased risk.

2) Surgery and dental treatment
For the patient with chronic renal failure and ESRD, the goal for treatment should be to establish the best oral hygiene possible and to remove all sources of infection. As the kidney disease progresses, it is important for the mouth to be in the best condition possible.

In the transplant patient, dental hygiene is crucial because these patients are even more susceptible to the highly morbid consequences of infection. Prior to transplantation, it is advisable to remove any teeth that could potentially be a focus of infection.

Dental procedures are best performed on non-dialysis days for two reasons: conflicting scheduling problems and the use of heparin during dialysis. Prior to major surgery, it is important to determine the status of hemostasis and blood potassium with routine studies that include: electrolyte, determination, complete blood cell count, prothrombin time, partial thromboplastin time, platelet count and, when indicated, a bleeding time.

Prophylactic antibiotic coverage (American Heart Association protocol, July 1997) should be considered for all transplant patients,36 and many dialysis centers also recommend this for all dialysis patients. Most routine dental treatment can be done on an outpatient basis; however, in cases of severe infection or major procedures, hospitalization may be required.

Conclusion

Due to the prevalence of chronic renal failure and end stage renal disease, it is reasonable to assume that dentists will encounter patients with this serious problem. Therefore, to provide optimum care for patients with these kidney disorders, it is important not only to understand the dental treatment but also the medical condition. (See tables 2 & 3).

As the kidneys begin to show limitation in their ability to work properly, blood and urine abnormalities start appearing. When the patient is asymptomatic, but shows only mild changes in their laboratory studies, this is called chronic renal insufficiency (CRI). As damage to the kidney continues, laboratory test values become more pronounced and the patient can show symptoms of abnormal urinary, neurologic, musculoskeletal, gastrointestinal, cardiovascular and dermatologic problems.

The goal of dental care for patients with ESRD is to achieve the best oral health possible and prevent further complications of their compromised medical condition.29 In most cases when the renal disease is under control, there are no medical contraindications to providing routine dental care. If renal disease is uncontrolled, or if there is severe infection, the dental care may be best performed in a hospital setting. Several important parameters should first be evaluated. Blood pressure should be monitored before, during, and after treatment. Bleeding tendencies, and/or anemia are common, therefore, hemoglobin, hematocrit, bleeding time, and platelet count should be obtained before doing any invasive procedure. Abnormal findings should be discussed with the patient's physician to determine if alteration in planned dental care is necessary.

Patients with CRF have an increased susceptibility to infection.37 If an infection related to the oral cavity is found, it should be treated aggressively, including culture and sensitivity tests, appropriate antibiotics, and possible hospital admission.

Pharmacologic therapy requires special care. Drugs that are excreted by the kidneys may reach toxic levels in ESRD patients, even at normal doses. The dosage schedules may need to be altered by increasing the dosing interval or decreasing the standard dose. Drugs that are nephrotoxic have the potential to further injure the already compromised kidney. Although lists of potentially dangerous drugs and nomograms for their altered administration are available, it is prudent to consult with a patients physician before administrating any of these drugs (See Table I).38

Bacterial seeding from dental procedures may result in enarteritis which may require removal or replacement of the AV shunt. Since no recognized guidelines exist for appropriate antibiotic coverage, consultation regarding antibiotics prophylaxis should be sought from the Nephrologist.

With appropriate consultation, laboratory tests, and monitoring, most CRF/ESRD patients can be safely treated in an outpatient environment which can lead to a significant improvement in health and quality of life.

Authors

John A. Svirsky, DDS, MEd, is a professor in the Department of Oral Pathology at Virginia Commonwealth University School of Dentistry in Richmond, Virginia. Julia Nunley, MD, is in the Department of Dermatology at the Virginia Commonwealth University School of Medicine. C. Daniel Dent, DDS, is Director of General Practice Residency at the Virginia Commonwealth University School of Dentistry and Veterans Administration Hospital in Richmond, Virginia. Don Yeatts, DDS, MD, has a private practice in medicine in Richmond, Virginia.

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To request a printed copy of this article, please contact / John A. Svirsky, D.D.S., M. Ed., Professor of Oral and Maxillofacial Pathology, Virginia Commonwealth University, PO Box 980566, Richmond, VA 23298