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Chronic kidney disease (CKD) is a progressive and irreversible deterioration of kidney function marked by systemic manifestations. Both the disease itself, and therapeutics used to treat disease progression, uremia and ESKD may affect oral health. Before we bite off more than we can chew, let's nibble away at this gnawing topic or oral complications of chronic kidney disease. Unfortunately, this subject might leave a bad taste in your mouth, as there is conflicting evidence regarding CKD and oral health with limited pediatric literature. CKD can lead to a dysregulation of the vitamin D-parathyroid axis, affecting tooth development and eruption, craniofacial growth, dental occlusion, and function. On the positive side, uremia may result in an alkaline oral pH that inhibits cariogenic bacteria, decreasing the risk of dental caries. However, an alkaline oral milieu may promote dental calculus accumulation, which can raise aesthetic concerns. If proper dental hygiene is not in place, the risk of dental caries rises following a kidney transplant. Both metabolism alterations and systemic medication may cause oral manifestations, such as oral pigmentation, stomatitis, gingivitis, gingival overgrowth, malodor (halitosis), dry mouth (xerostomia), and distorted taste (dysgeusia). In severe cases, there may be an increased risk of developing oral candidiasis, and oral cancers.
Chronic Kidney Disease
Tooth Development and Position
Dental impacts will occur during the tooth development timeframe, which spans from birth until the 25th year of life. Secondary parathyroid disease and bone metabolism have important roles in the different phases of tooth development. Hypocalcaemia, decreased 1,25-dihydroxycholecalciferol, elevated inorganic phosphate, elevated serum parathyroid hormone, and elevated serum fluoride can lead to defects in enamel quality and quantity, variation in the number of teeth, as well as the position of erupting teeth. Enamel defects can lead to rapid tooth destruction and an increased risk of caries. Teeth position may be influenced by the number of teeth and bone quality, leading to abnormal craniofacial development and altered occlusion (contact between upper and lower teeth). Teeth abrasion can be prevented by using fluoride toothpaste with a 1000-1500 ppm concentration, a dental split or guard during sleep and avoiding hard foods.
Dental-craniofacial development may be affected by protein and caloric deficits, metabolic acidosis, growth hormone resistance, anemia, and renal osteodystrophy. These factors may have a synergistic effect, contributing to altered occlusion. Manifestations include decreased cranial base length, more obtuse mandibular angle, and shorter mandibular length. Studies support the use of growth hormone to improve the facial profile and occlusion in selected cases. Use of growth hormone does not, however, accelerate teeth eruption. As such, growth hormone is not widely adopted in clinical practice for this indication.
Dental caries are the most frequent preventable infectious disease in the world. The pathogenesis is multifactorial, involving the host, microflora environment, food intake, and duration of risk factors. The acid produced by oral bacteria (e.g., lactobacilli) lowers oral pH resulting in demineralization of the tooth surface, allowing Streptococcus mutans proliferation in caries. Pediatric patients with CKD may be predisposed to the development of dental caries due to insufficient oral hygiene, xerostomia, and a carbohydrate-rich diet that promotes harmful microflora. In spite of this, some studies suggest these patients have lower concentration of cariogenic bacteria when compared with healthy individuals, due to an alkaline oral pH and higher salivary buffering capacity (caused by the higher concentration of ammonia from urea hydrolyzation in the mouth). Thorough dental hygiene is paramount for prevention.
Oral soft tissue manifestations like halitosis, dysgeusia, xerostomia, gingivitis, calculus accumulation, oral stomatitis, and leukoplakia are some of the reported soft tissue oral manifestations of CKD. The prevalence of these conditions is not well established but tends to increase as the patient moves towards end-stage kidney disease and kidney replacement therapy. Uremic odor, dysgeusia (metallic taste), xerostomia, and dental calculus (tartar) accumulation due to calcium deposition from saliva are more commonly observed.
Xerostomia may arise from restricted fluid intake and is associated with an increased cariogenic risk, oral sensitivity, increased Candida infections, and loss of taste. Xerostomia can be relieved with topical oral products or by chewing sugar-free gum. Dental calculi accumulation leads to inflammation of the gingival tissue (gingivitis) which can evolve into periodontitis. Periodontitis is an infection of the gingiva and the bone, which supports the teeth, which may lead to systemic infection. Systemic inflammation caused by periodontitis can lead to adverse cardiovascular morbidity and atherogenesis, already well-documented in CKD patients.To avoid hemorrhagic risk, secondary to anticoagulants used during dialysis, oral procedures with high bleeding risk should be scheduled on non-dialysis days.
Kidney Transplant Recipients
Prior to kidney transplant, a dental evaluation is recommended to evaluate for any infections or caries that could worsen once immunosuppression is started. In the immediate post-transplant period, when immunosuppression is highest, dental work should be limited to only life-threatening oral conditions to limit the risk of infection. In the post-transplant maintenance phase, regular oral treatments can be resumed, and a periodic oral evaluation should be maintained.
Antimicrobial Prophylaxis for oral procedures is not widely recommended in patients with CKD, nephrotic syndrome or immunosuppression following kidney transplant. However, on an individual basis under certain circumstances prophylactic antibiotics may be warranted. Antibiotic prophylaxis is advisable before invasive dental procedures are performed such as dental extraction or periodontal surgery, as transplant patients are more susceptible to infection.
Although rare, transplant patients may have a higher risk of oral cancers, which includes Kaposi Sarcoma and squamous cell carcinoma, due to long-term immunosuppression. Regular dental evaluation is essential in these patients, with routine follow-up to screen for these conditions. Avoiding smoking and alcohol consumption are also paramount to reduce risk factors.
Immunosuppressive medications may be used in kidney transplants and/or as a treatment for glomerular diseases such as nephrotic syndrome. They may be associated with white patches on the dorsal surface of the tongue that cannot be wiped away. Hairy tongue is benign and self-limited, and no treatment is required in most cases. In 4 to 43% of kidney transplant patients, oral Candida infection can be found in the form of oral candidiasis and angular cheilitis. Candida albicans is commonly found as part of the commensal oral flora, acting as an opportunistic pathogen following immunosuppression. Oral stomatitis or oral ulcerations may arise as a side effect of immunosuppressant medications such as sirolimus and everolimus. They tend to be self-limited and resolve in 10 to 15 days, but can be treated with topical steroids to minimize discomfort. In the case of severe and recurrent ulcers, immunosuppressant medications should be discontinued until the mucosa heals. Gingival overgrowth (GO) can be found as a consequence of immunosuppression. Cyclosporine causes GO in 25% of treated patients by inducing fibroblast production. Tacrolimus is a useful alternative in these patients. Azathioprine appears to have a protective effect in patients under cyclosporine or tacrolimus treatment, since its impact on GO is lower and allows for dose reduction of these drugs.
GO leads to delayed or ectopic teeth eruption, impaired speech, protruding appearance of the gingiva, and hinders teeth brushing. Gingivectomy is indicated when GO affects function and impairs orthodontic treatment. In selected cases, GO can be reduced or resolved by using an alternative immunosuppressant. Addressing these concerns is important to prevent patients from self-adjusting their medication and risking graft rejection.
Gingival overgrowth may also be a side effect of anti-hypertensive medications, such as calcium-channel blockers (CCB) - e.g. nifedipine (6.3% of treated patients), amlodipine (2.2%), and diltiazem (1.7%). CCBs inhibit the zona glomerulosa, increasing the secretion of ACTH by negative feedback, which then promotes testosterone production leading to gingival hyperplasia. Increased risk is observed when cyclosporine is used simultaneously with CCB (51.9%), suggesting a synergistic effect.
Angiotensin-converting enzyme inhibitors (ACEIs) can lead to angioedema in 0.1 to 0.2% of patients, oral dysesthesia, oral lichenoid reaction, and xerostomia.
CKD has an important impact on oral health.
Dysregulation of the vitamin D-parathyroid axis can cause dental-maxilo-facial dysmorphia.
Uremia decreases caries in CKD patients, but the risk can increase after a kidney transplant.
Immunosuppressants (e.g., cyclosporine) and calcium channel blockers (e.g., amlodipine, nifedipine, diltiazem) may cause gingival overgrowth.
Long-term follow-up for oral cancer screening is recommended in immunosuppressed patients.
Reviewed by S. Sudha Mannemuddhu, Brian Rifkin, Sophia Ambruso, Corina Teodosiu