274 9. Jeantet A, Piccoli GB, Malfi B et al. Preparation of candidates for renal transplantations: cost analysis. Transplant Proc 2004; 36: 455– 456 10. Brekke IB, Lien B, Jakobsen A et al. Aortoiliac reconstruction in preparation for renal transplantation. Transplant Int 1993; 6: 161– 163 11. Andres A, Revilla Y, Ramos et al. Helical computed tomography angiography is the most efficient test to assess vascular calcifications
A. M. Abdelaziz et al. in the iliac arterial sector in renal transplant candidates. Transplant Proc 2003; 35: 1682–1683 12. Gill JS, Pereira BJ. Death in the first year after kidney transplantation: implications for patients on the transplant waiting list. Transplantation 2003; 75: 113 13. Matas AJ, Kasiske B, Miller L. Proposed guidelines for re-evaluation of patients on the waiting list cadaver transplantation. Transplantation 2002; 15: 811–812 Received for publication: 4.8.09; Accepted in revised form: 13.8.09
Nephrol Dial Transplant (2010) 25: 274–277 doi: 10.1093/ndt/gfp486 Advance Access publication 19 September 2009
Nail changes in kidney transplant recipients Abeer M. Abdelaziz1 , Khaled M. Mahmoud2 , Essam M. Elsawy2 and Mohamed A. Bakr2 1
Department of Dermatology and 2 Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
Correspondence and offprint requests to: Khaled Mahmoud; E-mail:
[email protected]
Abstract Background. Nail changes are common complications of end-stage renal disease, and reports of nail changes in kidney transplant recipients (KTR) are rare. Few reports have documented a higher prevalence of onychomycosis in KTR compared with controls, while others found no significant differences. In this study, we investigated the prevalence and nature of nail changes in a large series of KTR. Methods. Three hundred and two KTR (216 males and 86 females) were included in this study, and the mean transplant duration was 6.57 years (range 1.5 month–23 years). They were screened for the presence of nail changes. Nail clippings were collected when indicated and cultures were performed for patients with suspected onychomycosis. The patients were compared with 302 age- and sex-matched healthy controls (220 males and 82 females). Results. One hundred and twenty-one KTR (40.1%) had nail changes compared with 104 (34.4%) in controls. Onychomycosis, Muehrcke’s nail and leuconychia were significantly more common in KTR [23 (7.6%), 13.3 (4.3%), 11 (3.6%), respectively] compared with controls [7 (2.3%), 1(0.3%), 2 (0.66%), P = 0.002, 0.001 and 0.02, respectively]. However, the most frequent nail change among KTR and controls was absent lunula, 90 (29.8%) and 80 (26.5%), respectively P = 0.36. Longitudinal ridging was also a frequent nail pathology among KTR and controls, 21 (6.9%) and 19 (6.3%), respectively, P = 0.74. Conclusion. KTR have higher prevalence rates of onychomycosis, Muehrcke’s nail and leuconychia than the healthy population. On the other hand, absent lunula could be a normal variation among Egyptian people. Keywords: kidney; nail; transplantation
Introduction A significantly higher incidence of nail changes was reported in end-stage renal disease (ESRD) patients [1,2] and in those on haemodialysis [2,3]. Several nail changes have been described which may occur in up to 60.3% of patients with ESRD and in up to 62.3–69.8% of haemodialysis patients [2,4]. Whether similar nail changes could be present after kidney transplantation, there is only one published casecontrol study of 205 patients that showed that 56.6% of kidney transplant recipients (KTR) had at least one type of nail pathology [4]. On the other hand, there are a few reports on nail changes in patients receiving immunosuppressive drugs for indications other than kidney transplantation [5,6]. The aim of this study was to determine the prevalence and the nature of nail lesions in a large series of KTR. Subjects and methods This study was conducted on two groups of patients, group I which included 302 kidney transplant patients (216 males and 86 females) and group II which included 302 healthy individuals who served as a control (220 males and 82 females). Group I received kidneys from living-related donors in the Urology and Nephrology Center, Mansoura University, Egypt. They were followed up and examined in the out-patient clinic during the period from July 2004 to July 2006. Their ages ranged from 11 to 64 years (mean 35.9 ± 11.3). They were receiving immunosuppressive protocols in different combinations of steroid, azathioprine, mycophenolate mofetil, cyclosporine and tacrolimus. The time since transplantation ranged from 1.5 months to 23 years (mean 6.57 ± 5.2 years). Group II was randomly selected from healthy hospital staffs and from healthy companions of ill patients. Controls were matched with cases by sex and age. Their ages ranged from 14 to 66 years (mean 33.9 ± 11.2).
C The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail:
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Nail changes in kidney transplant recipients
275
Table 1. The prevalence rates of nail lesions in KTR and controls KTR (n = 302)
Controls (n = 302)
Nail lesion
No.
%
No.
%
P-value
Absence of lunula Onychomycosis Longitudinal ridging Muehrcke’s nail Leuconychia Koilonychia Thickening Transverse ridging Half and half nail
90 23 21 13 11 7 5 4 1
29.8 7.6 6.9 4.3 3.6 2.3 1.7 1.3 0.3
80 7 19 1 2 5 11 4 1
26.5 2.3 6.3 0.3 0.66 1.66 3.6 1.3 0.3
0.36 0.002 0.74 0.001 0.021 0.56 0.12 1 1
Total
121
40.1
104
34.4
0.15
All of them had no history of renal diseases, treatment with immunosuppressive drugs or irradiation. We excluded patients and controls who were anaemic or severely ill due to liver cell failure or cardiopulmonary diseases from the study to avoid their effect on the nails. The study was approved by the ethics committee of the university before its initiation, and the protocols used conformed to the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from the participants. For both groups, a standardized nail examination of all fingers and toes was performed by one dermatologist of 2 years’ duration. Changes in surface, colour, thickness and curvature of nail plates were noted. The presence or absence of paired white transverse lines on the nail (Muehrcke’s nails) or leuconychia (white discolouration of the nail plate) was recorded. In case onychomycosis was suspected, mycological culture was carried out for these patients. Two types of growth media were used, one with cyclohexamide (dermatophyte test medium) for dermatophytes and one without cyclohexamide (Sabouraud’s dextrose agar) to isolate yeasts and non-dermatophyte moulds. Dermatophytes and mould growth were identified by gross colony morphology and microscopic examination with lactophenol blue preparation; yeast colonies were confirmed microscopically by gram stain. When the diagnosis of onychomycosis was established, the other abnormal findings on the same nail were not recorded, since discolouration and changes in consistency of the nail plate are mainly due to onychomycosis. KTR were subjected to routine laboratory investigations including complete blood picture, serum creatinine, creatinine clearance, blood sugar and liver function tests. Statistical analysis The statistical analysis of data was carried out by using the Excel program and the SPSS program (Statistical Package for Social Science Version 10 on Windows 98). The description of the data was done in the form of mean ± SD for quantitative data, and frequency and proportion for qualitative data. The analysis of the data was carried out to test statistical significant difference between groups for quantitative data (mean ± SD). Student’s t-test was used to compare between two groups. One-way ANOVA was used to compare more than two groups. For qualitative data (frequency and proportion), the chi-square test was used. A P-value was significant if ≤ 0.05 at confidence interval 95%.
Results One hundred and twenty-one (40.1%) KTR and 104 (34.4%) healthy controls had at least one type of nail pathology. The prevalence rates in both groups are summarized in Table 1. The prevalence rate of overall nail changes was not significantly different in KTR compared with the controls (P = 0.15). Analysis revealed no significant differences in age, gender, duration of transplantation, blood picture and renal and hepatic function among KTR with nail changes compared
Fig. 1. Loss of lunula in a 14-year-old male KTR.
Fig. 2. Loss of lunula in a 54-year-old female (control); the lunula is present only on the right thumb (arrow) due to paronychia.
with those without. Furthermore, only 25 (8.3%) patients had no history of arteriovenous (AV) fistula for a previous haemodialysis therapy, while the other 277 (91.7%) had scars of one or more previous AV fistula, but there was no statistical difference in nail changes between patients with history of AV fistula and those without; also there was no difference in the prevalence of nail changes on the fistula side versus the other side (P > 0.05). Absent lunula from all nails (fingers and toes) (Figures 1 and 2) was the most frequent nail change in both KTR and controls, 90 (29.8%) and 80 (26.5%), respectively (P > 0.05). Clinical diagnosis of onychomycosis was established in 26 KTR (8.6%) and in 8 controls (2.6%). Positive mycological culture was noted in 23 KTR (88.5% of patients with a clinical diagnosis of onychomycosis) and in 7 controls. The distal and lateral subungual onychomycosis (DLSO) was the most common clinical presentation of onychomycosis in this study. It was detected in 20 out of 26 cases (76.9%) followed by total dystrophic onychomycosis in 4 patients and proximal subungual onychomycosis in 2 patients. All controls with onychomycosis had DLSO. Table 2 shows
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A. M. Abdelaziz et al.
Table 2. Fungal isolates from KTR diagnosed clinically and mycologically as onychomycosis
Dermatophytes
Moulds Yeasts
KTR (n = 23)
Control (n = 7)
Fungal isolate
No.
%
No.
%
T. rubrum T. mentagrophytes E. floccosum T. tonsurans T. violaceum T. verrucosa Aspergillus Candida
6 3 3 1 1 1 4 4
26.1 13 13 4.3 4.3 4.3 17.4 17.4
4 2
57.1 28.6
1
14.3
T. rubrum, Trichophyton rubrum; E. floccosum, Epidermophyton floccosum.
Fig. 3. Muehrcke’s lines in KTR.
fungal species isolated by the culture of onychomycosis in both KTR and controls. The mean age of KTR with onychomycosis was 41.7 ± 6.3 years which was significantly higher than those without onychomycosis 35.6 ± 7.2 years (P = 0.047). On the other hand, the sex, time since renal transplantation and immunosuppressive regimens showed no significant differences between KTR with onychomycosis and those without (P > 0.05). The presence of paired white transverse lines on the nail (Muehrcke’s nails) was significantly higher in KTR not under corticosteroid medication (P = 0.002) (Figure 3). On the other hand, their presence was higher among those receiving cyclosporine treatment than those on regimens not including cyclosporine, but without statistical significance (P = .070). Muehrcke’s nails were obvious only in fingernails. We detected 11 cases of true leuconychia (3.6%) of KTR and most of them were of subtotal and punctuate types. In true leuconychia, the nail appears opaque and white in colour. Leuconychia was present in some of the fingernails only. The presence of true leuconychia was not significantly related to either age, sex, duration of transplantation or immunosuppressive regimens (P > 0.05).
Discussion There were no significant differences between KTR and controls in the overall prevalence of nail changes. These findings are reassuring on first viewing. However, the study showed a higher prevalence of onychomycosis, Muehrcke’s nail and leuconychia among KTR compared with the controls. The increased frequency of absent lunula among both KTR and controls could be responsible for the non-specific difference in the overall prevalence of nail changes. Although absent lunula have been described in association with several disorders such as atherosclerosis, chronic obstructive pulmonary disease, rheumatoid arthritis and renal failure [7,8], our data showed that there were no significant differences in graft function, haemoglobin concentration, total protein or serum transaminases levels between those with absent lunula compared with those without. This implies that absent lunula could be due to pallor of the nail bed caused by anaemia or long proximal nail fold as a normal finding in some of our Egyptian people. Anaemia is excluded because it was one of the exclusion criteria. So, the condition could be due to a long proximal nail fold obscuring the lunula as a normal variation in our Egyptian people. There is some evidence from the literature that absent lunula is a normal variation in people of Africo-Caribbean origin [9]. This could explain the difference between our results and that of Saray et al. [4] because it seems that absent lunula is not common in their populations and this pathology occurs mainly after dialysis and transplantation; thus, they noted the high prevalence of absent lunula among haemodialysis patients (31%) and KTR (17.1%) compared with their controls (2.8%). However, they did not mention the exact pathogenesis of this pathology. The significantly increased rate of mycologically proven onychomycosis (7.6%) among KTR compared with the controls (2.3%) could be explained on the basis of decreased cell-mediated immunity related to immunosuppressive therapy used to prevent graft rejection. Other casecontrol studies showed slightly higher figures (12.7%) [4,10]. However, these latter studies found no significant differences between KTR and controls. The difference between our results and these two studies could be attributed to racial differences (both studies were undertaken in Turkey), differences in the number of KTR (higher number in our study) or longer transplantation duration in our patients (6.5 ± 5.1 years). In addition, in our study there is a trend towards a higher frequency of onychomycosis in older patients and Trichophyton rubrum was the most frequently isolated dermatophyte in both KTR and controls, a finding similar to that demonstrated in other studies [11,12]. Muehrcke’s nail was the second frequent nail change in the KTR. Muehrcke’s lines are paired, white transverse lines that signify an abnormality in the vascular bed of the nail. Muehrcke first described those lines in a series of 65 patients with severe, chronic hypoalbuminaemia [13]. However, white finger nails preceded by multiple transverse white bands have been reported with normal serum albumin levels in association with other conditions as Hodgkin disease [14] and ESRD [15] and with different combinations of drugs used in the treatment of cancers. Reports
Nail changes in kidney transplant recipients
also exist of patients receiving multiple chemotherapeutic agents in whom the characteristic nail changes associated with Muehrcke’s lines were seen with slightly decreased serum albumin levels [16]. The condition has been reported with more or less similar figures to our study among ESRD patients on haemodialysis [17], KTR [4] and some cases of heart transplant recipients [18,19]. Moreover, Alam et al. [19] suggested that Muehrcke’s lines may be a predictable outcome of heart transplant surgery and noted significant hypoalbuminaemia and transient severe anaemia preceding the Muehrcke’s nails. The pathogenesis of Muehrcke’s lines is suggested by Daniel et al. [20] that a localized oedematous state in the nail bed may exert pressure on the underlying vasculature, thereby decreasing the normal erythema typically seen through the nail plate. We observed a significantly higher prevalence of Muehrcke’s nail in KTR not under steroid medication. This could be explained on the basis that corticosteroids inhibit oedema formation in the skin [21] and thereby decreasing the prevalence of Muehrcke’s nail. Several reports have documented the appearance of true leuconychia during the course of various chemotherapy protocols [22,23]. Leuconychia was also described in association with systemic illness, exposure to toxins, medications and HIV infections [24–26]. Saray et al. [4] proposed that either immunosuppressive treatment interferes with the cornification process in the nail matrix leading to leuconychia, or the immunosuppressive state itself somehow leads to this change. In this study, leuconychia was not found to be related to age, sex, time since transplantation or any of the immunosuppressive regimens; this was in agreement with another study [4] that did not find a relationship between this condition and post-transplantation interval, sex or treatment protocol. However, the higher prevalence rate of leuconychia in their KTR (21.5%) than in our patients may be due to the very high rate of presence of leuconychia (11.2%) in their controls. In conclusion, the prevalence rate of different nail changes in renal transplant recipients vary widely from one locality to another according to the normal variation in the nail shape and colour in a different population. In our locality, KTR have higher prevalence rates of onychomycosis, Muehrcke’s nail and leuconychia than the healthy population. Absent lunula is a normal variant in Egyptian people. On the other hand, further studies are required in order to clarify the exact pathogenesis of these lesions in KTR. Conflict of interest statement. None declared.
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