Mucociliary clearance (MC) is a critical defense mechanism for the protection of the entire respiratory system. Nasal or lower airways can also be cleaned with a sneeze or cough reflex, however, the paranasal sinuses solely depend on MC for cleaning.1 Effective MC requires appropriate mucus/periciliary fluid production and coordinated ciliary activity.2 Several tests have been used to investigate MC, and the saccharin transit test (STT) is the easiest, cheapest and most widely used one.3

Chronic kidney disease (CKD) refers to the progressive loss in renal functions over a period of months or years with important extrarenal systemic consequences such as metabolic, cardiovascular and respiratory system problems.4 For the patients with CKD, peritonitis is currently one of the leading complications of continuous ambulatory peritoneal dialysis (CAPD).5 Nasal colonization of some pathogens and chronical nasal infections are important risk factors for peritonitis. Recent studies have reported deteriorated nasal mucociliary activity in patients with CKD.6,7 Any disturbance in the MC causes stasis of secretions and secondary infections. In other words, disordered MC leads to impaired health of respiratory tract and can manifest as chronical infections of the nose, sinuses and the whole airway which can be risky in CKD patients, especially ones receiving CAPD.8 Our aim of this study was to evaluate the patients with CKD receiving CAPD in terms of nasal MC and to investigate whether there is a relation between the MC and risk of infection for this particular patient group.

A total of 40 patients with CKD, 16 females/24 males with a mean age of 32.4 years (range 22–52 years); and 39 healthy individuals in the control group, 17 females/22 males with a mean age of 33.3 years (range 20–56 years) completed the study. There were no significant differences between the CKD and control groups in terms of age (p>0.05). Table 1 shows the clinical and demographical features of patients. Also the etiological spectrum of peritonitis in CAPD patients are listed in Table 2.

The nasal swab results were positive for S. aureus in only 4 patients who had a history of peritonitis. As the number was low, these results were not included in analysis.

Mean MC times in the CKD and control groups were 382.55s (range 90–941s) and 373.33s (range 115–616s) respectively. There was not a significant difference in terms of mean MC time in patients with CKD when compared with the individuals in the control group (p>0.05).

There were no correlations between the MC time and age, gender, body mass index and the duration of CAPD. The correlation analysis between the MC time and blood glucose was significant (p=0.004).

In the patient group, there were 16 patients who had had at least one peritonitis episode. The mean MC time in the patients who had a history of peritonitis was 588.8s while it was 256.5s in the 24 patients without peritonitis which revealed a statistically significant difference (p<0.05).

The predictive role of MC time in determination of peritonitis risk was first measured in ROC analysis. The sensitivity and specificity of MC time were 93.7% and 91.7% when the cut-off level was accepted as 412s during the evaluation of the patient group in terms of a previous history of peritonitis. ROC area was measured as 0.940 (95% CI: 0.697–0.990, p<0.001) (Fig. 1).

Fig. 1.

Figure showing the cut-off value for STT in patients with CAPD.

(0.1MB).

The Omnibus test (χ2=38.089, p=0.008) revealed that the built multiple model is significantly better than the baseline logistic regression model. Nagelkerke R2 statistic was calculated as 0.830. The WBC and MC time variables in the multiple model predicted 83% of the variability of peritonitis. Not surprisingly, the WBC is related to the inflammatory process and is a predictor. The Hosmer–Lemeshow test resulted as χ2=8.172, p=0.417. These results revealed the appropriateness of the built multiple binary logistic regression model in order to predict the peritonitis (Table 3). In the multivariate analysis, the OR (95% CI) of WBC and MC were 1.74(1.05–2.88) (p=0.032) and 0.98(0.97–0.99) (p=0.008) respectively.

This prospective study aimed to investigate the nasal MC in patients with CKD receiving CAPD. Although an alteration in the nasal functions and MC were reported in the literature, which might be an expected consequence of CKD, no significant difference was observed between the patients with CKD and healthy individuals in the control group in terms of nasal MC in this study. However, in the patient group, the MC of the subjects who had a history of peritonitis was found to be significantly altered. This interesting finding may prompt a conception that a relation between the peritonitis and MC exists and needs further investigation in this particular patient group.

Mucociliary clearance is an important mechanism for protecting upper and lower airways by eliminating foreign particles and pathogens and keeping the mucosa moist and fresh. Mucociliary clearance is dependent on the volume and composition of mucus and periciliary fluid, the ciliary structure and function, and the mucociliary interaction.10 The ciliary cells line upper and lower airways; so as any alteration in any mechanism MC depends on, such as cystic fibrosis or sinonasal manifestations of systemic diseases, leads to the stasis of secretions and recurrent middle ear, sinonasal, and lower respiratory tract infections.11

Many factors are known for affecting ciliary function and mucus production, thus the MC. Moisture, temperature, smoking, partial oxygen pressure and pH are modifiable environmental factors affecting MC; however, systemic diseases such as hypothyroidism and cystic fibrosis, obstructive nasal pathologies such as septal deviation and adenoid vegetations, infectious or allergic rhinitis also affect MC by altering ciliary function, production of mucus or obstructing the airway.12 Hence, the study was conducted in the same environmental condition; smokers and subjects with rhinosinusitis, nasal polyps, allergic rhinitis, septal deviations or perforations, a history of previous nasal surgery, obstructive adenoid vegetation, cystic fibrosis or other subjects with chronical pulmonary infections, immunodeficiency, ciliary dyskinesia were excluded from study.

Many techniques have been reported for measuring MC, but the easiest, cheapest and most widely used one is the STT. Originally described by Andersen et al.,9 then modified by Rutland and Cole,3 STT is conducted by placing a 1mm saccharin on inferior turbinate, 1cm behind the mucocutaneous junction, under direct visualization. Time between the placement of saccharin and first sensation of sweet taste on the tongue is measured with a timer.13 Broad range of times for normal MC have been reported in the literature from 4.4 to 20min.14–17 If there was no perception within 30min, another saccharin particle was placed directly on the tongue to determine if the patient tastes saccharin at all. Some authors dissolve saccharin with methylene blue and confirm the patient's taste perception by presence of blue dye in oropharynx.18

Other methods for measuring MC consist of a variety of in vivo and in vitro techniques. Technetium-99 scintigraphy 19 and microdialysis probes20 are other in vivo choices, more objective than STT, but also more expensive and invasive. In vitro techniques consist of human airway cell cultures,21 photodiodide, photomultiplier and digital high-speed video capturing as an indirect method for quantifying ciliary beat frequency.13,22 Among all these different techniques, the STT is the most serviceable, easiest and cheapest technique for measuring MC; therefore, it was used in this study.

Chronic renal disease is an irreversible pathophysiological renal process resulting in the inevitable destruction of renal structure and function with many extrarenal manifestations. Oxidative stress, hypoxia and endothelial dysfunctions are some of blamed mechanisms behind end-organ damage and the extrarenal manifestations. It has been reported in previous studies that patients with CKD have increased rate of nasal problems such as epistaxis, spontaneous perforations of nasal septum and deteriorated mucociliary clearance rate.6,7

Possible and unclear causes have been reported in previous studies for deteriorated MC in patients with CKD. Chronic renal disease causes progression of atherosclerosis and microvascular disease of small vessels, and these processes may affect MC by altering production of mucus or ciliary cell function on a cellular basis.4,6 Another study speculated that damage of dynein arms and microtubules by free oxygen radicals and uremic toxins and endothelial dysfunction, vasoconstriction and hypoxia in ciliary cells may have a role on decreased mucociliary function.7 Increased mucoid viscosity by liquid–electrolyte imbalance is also blamed for making MC ineffective.7 In another study, it has been shown that CKD patients have fibrosis, metaplasia and chronic inflammation in nasal biopsies, and all these pathophysiologies may have a role in this.23 In the current study, however, there was no significant difference between the MC of patient and control groups. Furthermore, the correlation analysis between the MC time and blood glucose was significant (p=0.004) in the current study, parallel to what has also been previously mentioned in the literature.24

Chronic kidney disease has a myriad of renal and extrarenal complications, but infectious complications are the second cause of mortality and main cause of morbidity in patients undergoing haemodialysis and CAPD.25,26 Increased infection rates in CKD can be explained by impaired leucocyte function and numbers, new pathways for microorganisms to enter, such as catheter exit site in patients undergoing CAPD, and ineffective defense mechanisms such as deteriorated MC.6 A vast number of prophylactic strategies have been used to reduce the occurrence of these infectious complications, including the use of oral, nasal and topical antibiotics and cautionary advice for the patients about infectious complications.6,26 Gram positive microorganisms, particularly S. aureus is an important causative microorganism in CAPD peritonitis. The microbiological evaluation of patients in the current study showed similar results in line with the current literature. Probably, these microorganisms may transfer from upper respiratory tract to peritoneal microvasculature via blood stream. It has been well established that poor glycemic control is related with increased risk of peritonitis in PD patients.27 The potential effect of nasal Staph. carriage on peritonitis rate has not been clarified yet. Moreover it has been recently demonstrated that Staph. carriage rates were similar in diabetic patients compared to general population.28 It might be speculated that diabetes may affect host-defense mechanisms in addition to lowering of MC clearance depending upon our study results. Thus further larger studies are needed to explain the relationship between MC time and peritonitis in diabetic population. Although it was stated that no data is present on the effectiveness of routine screening and eradication of S. aureus nasal carriage before catheter insertion; screening for nasal S. aureus carriage prior to PD catheter insertion, and if found, treating by topical nasal application of mupirocin is suggested, while further randomized controlled studies are needed to strengthen the evidence.29

To date, two studies evaluated MC in CKD patients. Study by Kucur et al.,6 has revealed significant difference in MC times when healthy controls and patients with CKD were compared (8.97±1.83min and 12.51±3.74min, respectively). The study by Uluyol et al.,7 has a different method; they compared pre-dialysis patients, dialysis patients and control groups for MC time. They have found that MC time was higher in patients with CKD than healthy controls, but paradoxically, higher MC times were observed in pre-dialysis patients than dialysis patients with a longer CKD duration. They suggested that haemodialysis reduces the effects of CKD on MC by filtering toxins, oxidants and balancing the electrolytes.

The patients with CAPD have a high risk of peritonitis especially when a nasal pathogenic colonization or an infection is present and ‘theoretically’, a deteriorated MC might cause such consequences. Kucur et al.,6 concluded in their study that MC time in CKD patients is prolonged and should be followed-up closely in terms of respiratory tract diseases and sinonasal and middle ear infections.

Univariate and multiple binary logistic regression analysis performed in the current study demonstrated the WBC and MC as independent risk factors for peritonitis. The WBC, in our opinion, instead is a consequence of this inflamatorry condition however the detoriated MC may be a risk factor. On the other hand, monitoring all patients with CKD in terms of MC might not be practical in daily clinical practice since the STT of those patients are similar to the ones of the healthy individuals according to the findings of the current study.

The current study, which is the first, investigating the patients receiving CAPD in terms of nasal MC however also has weaknesses. A correlation between the MC and nasal microbiological environment could not be performed although conducted during the study, which would obviously supplement the findings.

Aiming to enrich the information of MC in CKD patients, the current study is the first with a large sample size and conducted with patients with CAPD shows that, there is no significant difference in terms of MC and CKD, however a relation between the nasal MC and peritonitis occurs. We think that this relation must be taken seriously and further studies should be conducted with this patient group especially correlating with S. aureus presence in order to shed light to a possible relation between the MC, nasal colonization and peritonitis.

None.