CUTANEOUS MANIFESTATIONS IN PATIENTS WITH CHRONIC KIDNEY DISEASE ON HEMODIALYSIS AND IT ' S CORRELATION WITH RENAL FUNCTION , DIALYSIS CYCLE AND HAEMOGLOBIN

Results Among the total pa ents (n=100), 84 pa ents presented with complain of skin manifesta on but on detail examina on 97 pa ents had at least one skin disease. The causes leading to chronic kidney disease were found to be hypertension 58%, diabetes mellitus 49%, IgA nephropathy 7%, systemic lupus erythematosus 7% and glomerulonephri s 4%. Xerosis was the commonest skin disease encountered in these pa ents amoun ng to 71% among which 43 were hypertensive and 34 were diabe c. Xerosis was followed by pruritus (62%), pallor (54%), mucosal changes (39%), skin infec on (36%), hair changes (34%), pigmenta on (33%) and nail changes (29%). Serum crea nine showed sta s cally significant associa on with pruritus (p=0.030) and pigmenta on (p=0.010), similarly blood urea showed significant associa on with pruritus (p=0.001). Similarly, number of dialysis cycle showed significant associa on with pigmenta on of skin (p=<0.001).


INTRODUCTION
Chronic kidney disease (CKD) is a progressive loss of kidney func on over a period of months or years through five stages.It is defined as kidney damage or glomerular 2 filtra on rate <60 ml/min/1.73mfor months or more 1 irrespec ve of the cause.
Skin is the mirror of an internal disease, and it has always helped the clinician to diagnose systemic diseases.As we know, CKD presents with an array of skin diseases; from benign and asymptoma c to the physically disabling and life 2 threatening.Many of them, have a debilita ng effect on quality of life.These skin disease can occur before dialysis or 3 following the ini a on of hemodialysis treatment.It has been found that 82% pa ents with end stage renal disease 4 have at least one associated cutaneous change.
As the incidence and prevalence of chronic kidney disease is increasing day by day in this modern world; the incidence and prevalence of associated skin diseases are also increasing.So, their early recogni on and treatment is quite essen al 3 to reduce morbidity and mortality.The prevalence of cutaneous manifesta on is high among dialysis pa ents.This occurs because of numerous factors such as uremia, metabolic disorders, dialysis and side effects of 5 immunosuppressive drugs.Some of these skin diseases disappear following kidney transplanta on, confirming that the metabolic milieu resul ng from the malfunc oning kidney is responsible for 6 some of these changes.
Pa ents on hemodialysis (HD) are known to develop skin diseases ranging from infec ons to malignancies.In addi on, new cutaneous lesions may develop with increasing age.Some mes, cutaneous changes maybe the first 5 important sign in pa ents with chronic renal failure.Moreover, skin diseases are generally seen in pa ents with moderate renal impairment (CKD stage 3 and 4) before progressing to End Stage Renal Disease; so persistent xerosis or intractable pruritus commends for further search 7 for underlying renal impairment.
Though important for maintenance of homeostasis in pa ents with End stage renal disease (ESRD), neither dialysis is efficient in removing substances compared to healthy kidneys nor can it replace other endocrine func ons lost with renal failure leading to various metabolic disorders and 7 associated skin complica ons.With advancement of technology and improved dialysis therapy in the west, cutaneous complica ons in pa ents with renal disease are in decreasing trend; unlike the case in developing countries like Nepal.Moreover, the ignorant Nepalese popula on is subjected to harmful effects of tropical climate, with the associated higher incidence of infec ons and malnutri on; all contribu ng to the skin diseases in CKD pa ents.
Because skin diseases may have a cosme cally destruc ve effect, in addi on to complica ons such as pruritus that disturbs the pa ent's comfort, this study was done to determine the prevalence of mucocutaneous manifesta ons in pa ents on hemodialysis along with rela on of various skin disorders with the parameters of renal func on like serum crea nine, blood urea, hemoglobin and number of dialysis cycles.

METHODOLOGY
In this cross sec onal, analy c study; 100 pa ents of either sex, aged 18 years and above; admi ed with the diagnosis of CKD for dialysis in Nephrology department of Nobel Medical College and teaching hospital, Biratnagar, Nepal, recruited during the period of January 2017 to December 2017, were chosen randomly as candidates for the study a er taking ethical clearance from the ins tu onal review board.Wri en consent was obtained from all candidates.All the pa ents were examined in detail by dermatologist in a loca on with adequate light.Diagnosis of the disease was made clinically.Demographic details like age, sex, cause of renal failure, dura on on dialysis was taken from pa ent's files.Informa on about pa ents' laboratory tests was obtained from mean of three recent tests.

Inclusion criteria
Pa ents with chronic kidney disease (stage V) of age above 18 years undergoing hemodialysis.

Exclusion criteria for cases
Pa ents with acute renal failure, pa ents who had undergone renal transplanta on and who had undergone peritoneal dialysis The normal value for serum crea nine, blood urea and hemoglobin was taken to be 0.6-1.2mg/dl, 7-20 mg/dl and 12-16 gm/dl respec vely.

Sta s cal Analysis
Data were analyzed using SPSS so ware (Version 22).The Independent t-Test was used to evaluate the associa on of skin disease with serum crea nine, blood urea, hemoglobin and number of dialysis cycle and chi-square test was used with for qualita ve data.P value was calculated and less than 0.05 was considered to be sta s cally significant.

RESULT
Out of total 100 pa ents enrolled in the study, 59% (n=59) were male and 41% (n=41) were female.The mean age (years) of the pa ents was 55.81±17.94,youngest being 18 and oldest being 88.The dura on of chronic kidney disease varied from 1 month and several years and the mean of dialysis cycles done was 11.43 ± 16.11; with the minimum cycle being 2 and maximum cycle being 106.The causes leading to chronic kidney disease were found to be hypertension in 58%; among them 38% were male and 20% were female; diabetes mellitus 49%; among them, male were 30% and female were 19%; IgA nephropathy 7%, systemic lupus erythematosus 7%; among them females were 6 and male, and glomerulonephri s in 4%, as shown in Table 1.Among the pa ents having chronic kidney disease, 27 were suffering from both hypertension and diabe c mellitus.
Among the total pa ents (n=100), 84 pa ents presented with complain of skin manifesta on but on detail examina on 97 pa ents had at least one skin disease.Xerosis was the most common skin disease seen in these pa ents, and this was seen in 71% of the pa ents among which 43 were hypertensive and 34 were diabe c.Xerosis was followed by pruritus seen in 62%, pallor seen in 54%, mucosal changes seen in 39%, skin infec on seen in 36% (fungal=21%, bacterial 9% and viral=6%), pigmenta on seen in 33% (29 % hyperpigmenta on and 6 % yellow nge), nail changes seen in 29% and hair changes in 34%as shown in Table 1.

TABLE 1:
The causes of chronic kidney disease (stage V) and prevalence of dermatological manifesta on in pa ents undergoing dialysis.

Dermatological manifesta on
Total 100 (100%) Other skin disease observed in our study were alopecia areata in 2 pa ents, followed by ecchymoses in 1, acneform erup ons in 1, seborrhoeic keratosis in 1, eczema in 1 and lichen planus in 1.
The mean serum crea nine was 11.44 ± 5.81mg/dl with minimum of 1.4mg/dl and maximum 28mg/dl.Similarly blood urea was 159.18 ± 51.17mg/dl with minimum of 22mg/dl and maximum of 288mg/dl in our study group.The independent-samples T test was carried out between different dermatological manifesta on and serum crea nine, blood urea, hemoglobin and number of dialysis.There was sta s cally significant associa on of serum crea nine with pruritus (p=0.030) and pigmenta on (p=0.010).Similarly, blood urea shows significant associa on with pruritus (p=0.001).However all other skin, mucosal and nail changes did not show any associa on with serum crea nine and blood urea as shown in Table 2.
In the same way, mean hemoglobin in our study was 6.65 ± 2.03g/dl with minimum of 2g/dl and maximum 10g/dl.On further evalua on, hemoglobin was found to be sta s cally significant with pallor (p=<0.001) and clubbing (p=<0.001)) in pa ent having chronic kidney disease undergoing hemodialysis.In our study, 14% had hemoglobin level less than 5 g/dl; 52% had hemoglobin levels between 5-8 g/dl and 34 % had hemoglobin level more than 8 g/dl.Similarly, number of dialysis cycle shows significant associa on with pigmenta on of skin (p=<0.001) and angular cheili s (p=<0.001).However, in our study there was no significant associa on of hemoglobin and number of dialysis cycle with other skin manifesta on in pa ent of chronic kidney disease as shown in Table 3.
Chi square test illustrated the associa on between pruritus and pa ent with chronic kidney disease with diabe c mellitus (p=0.044).However, there is no associa on of pruritus with chronic kidney disease with hypertension (p=0.145).Similarly xerosis shows no significant associa on with chronic kidney disease with diabe c mellitus and hypertension (p=0.449 and p=0.277 respec vely).
Pradhan M et al      Hemodialysis can ini ate the symptom as well as improve it.It may be due to increased serum histamine levels because of allergic sensi za on to diverse dialyzer membrane components as well as impairing renal excre on of histamine.There is an abnormal pa ern of cutaneous innerva ons in CKD, which occurs due to slowly accumulated pruritogen, the pa ents respec vely.Hyperpigmenata on of the skin in CKD pa ent is a ributed to increasing level beta melanocyte s mula ng hormone due to its decreased excre on in CKD pa ent.A yellowish nge has been a ributed to deposi on of carotenoids and nitrogenous pigments in the dermis or the presence of lipochromes and carotenoids in the epidermis and subcutaneous 13 ssue.There are reports of hypopigmentary skin changes in CKD like vi ligo and pos nflammatoryhypopigmenta on, 4, 5 which was not found in our pa ents.
Perfora ng disorders such as perfora ng folliculi s, Kyrels disease and reac ve perfora ng collagenosis have been 14 described in CKD.In our study perfora ng dermatosis was seen in 2 % of the pa ents.Trauma to the skin secondary to xerosis and pruritus may be the cause for this.Ashokan et al. reported perfora ng disorder in 7.5% of pa ents, Uday kumar Infec on was also seen in major group of study popula on in 36 %.The major type of infec on was fungal infec on (21%) followed by pyodermas (9%) and viral infec on (6% the pa ents.In CKD pa ent skin changes like metasta c calcifica on of the skin, skin cancer, gynaecomas a, uremic frost, 3, Nephrogenicfibrosingdermopathy has also been reported.4 These findings were not observed in our pa ents.There has also a report of skin changes in AV fistula that was not 3, 4,5 observed in our study.Other miscellaneous skin findings were also observed in our pa ents, which may not be a ributed to CKD and dialysis.Other findings observed were alopecia areata, ecchymoses, acneform erup ons, seborrhoeickeratosis, eczema and lichen planus.

CONCLUSION
Skin manifesta ons are common in pa ent with CKD.This increases morbidity in this pa ent with impairment in quality of life and they are resistant to treatment.In developing country like Nepal where dialysis facili es are available only in limited hospital proper evalua on and mely management of this condi on can cause improvement in quality of life of these pa ents.

RECOMMENDATIONS
We recommend the pa ent with chronic kidney disease for early evalua on of skin disease and early interven on.

LIMITATION OF STUDY
The study could have been be er if pa ent of CKD on medical treatment and pa ents with peritoneal dialysis were also included along with pa ent on hemodialysis.

Figure 1 :Figure 3 :
Figure 1: Pigmentary changes in pa ent with CKD on hemodialysis

Figure 4 :
Figure 4: Eczema in pa ent with CKD on hemodialysis

Figure 2 :
Figure 2: Acquired Perfora ng Dermatosis in pa ent with CKD on hemodialysis

TABLE 2 :
Rela on of various dermatological manifesta on in chronic kidney disease with serum crea nine and blood urea using independent-samples t-Test.

TABLE 3 :
Rela on of various dermatological manifesta ons in chronic kidney disease with hemoglobin and number of hemodialysis using independent-samples t-Test.
Pigmentary changes were seen in 33 % of pa ents and there was significant rela onship between pigmentary changes with serum crea nine level and number of dialysis cycles.Hyperpigmenta on was seen in 29 % of the pa ent and yellow nge on the skin was seen in 5 % of the pa ents.Result of pigmentary changes in CKD are variable.Udaykumar et al. reported pigmentary changes in 43% of pa ents and Baghel et al. reported in 13.75 % of pa ents whereas Hajheydari et al. reported in 66.3% pa ents, Dyanchenko et al. in 75.7% pa ents, and Pico et al reported Nail changes was seen in 29 % of the pa ents.Halfand half nail, leuconychia, longitudinal ridges, onychomycosis and clubbing were seen.Nail changes were reported by Ashokan et al. in 21.67 % and Udaykumar et al. reported in 21% 3, 4 pa ents, of the pa ents like our relsult.Contradic ng with our result Shrestha P et al. reported in 62 % and Amatya Bet 2, 10 al. in 82 % which was high compare to our result.Mucosal changes were seen in 39% of the pa ents.Xerostomia, macroglossia, fissured tongue, ulcera ve stoma s and angular cheili s was seen.Shrestha P et al. reported mucosal changes in 22 % pa ents, Ashokan et al. 2, 3,5 7.5% and Baghel et al. in 19 % and of the pa ents.Hair changes were seen in 34 % of the pa ents.Sparse scalp hair and bri le lusterless hair was the hair changes observed.Shrestha P et al. reported hair changes in 12 % pa ents, Ashokan et al. in 15% and Baghel et al. in 19 % of ).Udaykumar et al. reported fungal infec on in (30%), 4 bacterial in (13%) and viral in (12%).Ashokan et al. reported infec on in 17.5% of the pa ents and Amatya B et al. 3,10 reported infec on in only 5%.