Quantitative Comparison of Skin Colors in Patients With ESRD Undergoing Different Dialysis Modalities
2006; Elsevier BV; Volume: 48; Issue: 2 Linguagem: Inglês
10.1053/j.ajkd.2006.04.087
ISSN1523-6838
AutoresChun‐Fu Lai, Tze‐Wah Kao, Tsen‐Fang Tsai, Hung‐Yuan Chen, Kuo-Chiang Huang, Ming‐Shiou Wu, Kwan‐Dun Wu,
Tópico(s)melanin and skin pigmentation
ResumoBackground: Little is known about the alterations in skin pigmentation in patients with end-stage renal disease (ESRD) in the modern dialysis era. Aims of this study are to quantitatively investigate the skin color of patients with ESRD undergoing different dialysis modalities and determine factors associated with skin color changes. Methods: One hundred twenty-four patients with ESRD undergoing either hemodialysis (HD; n = 51) or peritoneal dialysis (PD; n = 73) were enrolled, and 59 subjects with normal renal function served as controls. Skin colors of the abdomen (non–sun-exposed site) and forearm (sun-exposed site) were measured by using a reflected-light colorimeter and recorded by using the Commission Internationale de l'Eclairage recommended L*a*b* system, in which a higher L* value represents brighter skin. Results: For sun-exposed skin, brightness was not different between patients with ESRD and controls. However, patients with ESRD had a lower L* value in the non–sun-exposed skin area (P < 0.001). HD and PD patients had similar L* values in both sun-exposed and non–sun-exposed skin areas. PD patients with adequate weekly creatinine clearance or residual urine greater than 100 mL/d had brighter skin in the non–sun-exposed area (P = 0.001 and P = 0.035, respectively). Conclusion: Patients with ESRD in Taiwan have significantly darker skin in the non–sun-exposed area, but not the sun-exposed area, than subjects with normal renal function. However, there is no difference in skin darkness between HD and PD patients. Efforts to increase weekly creatinine clearance and preserve residual urine may alleviate hyperpigmentation in PD patients. Background: Little is known about the alterations in skin pigmentation in patients with end-stage renal disease (ESRD) in the modern dialysis era. Aims of this study are to quantitatively investigate the skin color of patients with ESRD undergoing different dialysis modalities and determine factors associated with skin color changes. Methods: One hundred twenty-four patients with ESRD undergoing either hemodialysis (HD; n = 51) or peritoneal dialysis (PD; n = 73) were enrolled, and 59 subjects with normal renal function served as controls. Skin colors of the abdomen (non–sun-exposed site) and forearm (sun-exposed site) were measured by using a reflected-light colorimeter and recorded by using the Commission Internationale de l'Eclairage recommended L*a*b* system, in which a higher L* value represents brighter skin. Results: For sun-exposed skin, brightness was not different between patients with ESRD and controls. However, patients with ESRD had a lower L* value in the non–sun-exposed skin area (P < 0.001). HD and PD patients had similar L* values in both sun-exposed and non–sun-exposed skin areas. PD patients with adequate weekly creatinine clearance or residual urine greater than 100 mL/d had brighter skin in the non–sun-exposed area (P = 0.001 and P = 0.035, respectively). Conclusion: Patients with ESRD in Taiwan have significantly darker skin in the non–sun-exposed area, but not the sun-exposed area, than subjects with normal renal function. However, there is no difference in skin darkness between HD and PD patients. Efforts to increase weekly creatinine clearance and preserve residual urine may alleviate hyperpigmentation in PD patients. ALTERATIONS IN SKIN pigmentation commonly are observed in patients with end-stage renal disease (ESRD).1Picó M.R. Lugo-Somolions A. Sánchez J.L. Burgos-Calderon R. Cutaneous alterations in patients with chronic renal failure.Int J Dermatol. 1992; 31: 860-863Crossref PubMed Scopus (89) Google Scholar, 2Gupta A.K. Gupta M.A. Cardella C.J. Haberman H.F. Cutaneous associations of chronic renal failure and dialysis.Int J Dermatol. 1986; 25: 498-504Crossref PubMed Scopus (45) Google Scholar, 3Choi H.K. Thome F.S. Orlandini T. Haberman H.F. Increased skin pigmentation in patients with chronic renal failure undergoing hemodialysis infected with the hepatitis C virus [Portuguese].Rev Assoc Med Bras. 2003; 49: 24-28Crossref PubMed Google Scholar Changes in skin color have been related to self-esteem and other psychological characteristics in patients with other diseases.4Ezeilo B.N. Psychological aspects of albinism An exploratory study with Nigerian (Igbo) albino subjects.Soc Sci Med. 1989; 29: 1129-1131Crossref PubMed Scopus (21) Google Scholar, 5Troilius A. Wrangsjo B. Ljunggren B. Potential psychological benefits from early treatment of port-wine stains in children.Br J Dermatol. 1998; 139: 59-65Crossref PubMed Scopus (74) Google Scholar The mechanisms of skin hyperpigmentation in patients with ESRD or those who undergo long-term dialysis treatment remain unclear, but accumulation of such middle-molecular-weight substances as urochromic pigments and β-melanocyte–stimulating hormone has been proposed to have a role.6Smith A.G. Shuster S. Thody A.J. Alvarez-Ude F. Kerr D.N. Role of the kidney in regulating plasma immunoreactive beta-melanocyte-stimulating hormone.Br Med J. 1976; 1: 874-876Crossref PubMed Scopus (34) Google Scholar, 7Gilkes J.J.H. Eady R.A.J. Rees L.H. Munro D.D. Moorhead J.F. Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis.Br Med J. 1975; 1: 656-658Crossref PubMed Scopus (53) Google Scholar, 8Ponticelli C. Bencini P.L. Dermatological disorders.in: Davison A.M. Oxford Textbook of Clinical Nephrology. 2. Oxford University, New York, NY1998: 1995-2001Google Scholar, 9Smith A.G. Shuster S. Comaish J.S. et al.Plasma immunoreactive β-melanocyte-stimulating hormone and skin pigmentation in chronic renal failure.Br Med J. 1975; 1: 658-659Crossref PubMed Scopus (33) Google Scholar, 10Scott A.P. Lowry P.J. Adenocorticotrophic and melanocyte-stimulating peptides in the human pituitary.Biochem J. 1974; 139: 593-602Crossref PubMed Scopus (131) Google ScholarToday, many practical guidelines11National Kidney FoundationK/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy Update.Am J Kidney Dis. 2000; 37: S7-S64Google Scholar, 12National Kidney FoundationK/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy Update.Am J Kidney Dis. 2000; 37: S65-S136Google Scholar, 13European Best Practice Guidelines Expert Group on Hemodialysis: European Renal Association: Section II. Haemodialysis adequacy.Nephrol Dial Transplant. 2002; 17: S16-S31Google Scholar address the issues of dialysis adequacy that most physicians aim to achieve. Nevertheless, little is known about the change in skin pigmentation in the modern dialysis era. Most previous studies of skin hyperpigmentation in patients with ESRD were performed more than 10 years ago in patients treated with low-flux hemodialysis (HD).6Smith A.G. Shuster S. Thody A.J. Alvarez-Ude F. Kerr D.N. Role of the kidney in regulating plasma immunoreactive beta-melanocyte-stimulating hormone.Br Med J. 1976; 1: 874-876Crossref PubMed Scopus (34) Google Scholar, 7Gilkes J.J.H. Eady R.A.J. Rees L.H. Munro D.D. Moorhead J.F. Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis.Br Med J. 1975; 1: 656-658Crossref PubMed Scopus (53) Google Scholar, 14Deleixhe-Mauhin F. Krezinski J.M. Rorive G. Pierard G.E. Quantification of skin color in patients undergoing maintenance hemodialysis.J Am Acad Dermatol. 1992; 27: 950-953Abstract Full Text PDF PubMed Scopus (32) Google Scholar, 15Vahlquist A. Berne B. Berne C. Skin content and plasma transport of vitamin A and β-carotene in chronic renal failure.Eur J Clin Invest. 1982; 12: 63-67Crossref PubMed Scopus (40) Google Scholar Skin color changes in patients treated with more biocompatible and high-flux dialyzers or newer dialysis modalities, such as hemodiafiltration, have not been studied. Peritoneal dialysis (PD), believed to be more effective in middle-molecular-weight waste clearance, also was not investigated with regard to its influence on skin color. Only 1 previous study measured the skin color of HD patients by using an objective method.14Deleixhe-Mauhin F. Krezinski J.M. Rorive G. Pierard G.E. Quantification of skin color in patients undergoing maintenance hemodialysis.J Am Acad Dermatol. 1992; 27: 950-953Abstract Full Text PDF PubMed Scopus (32) Google Scholar As we know, visual evaluation of skin color is highly subjective and influenced by the type and intensity of ambient light. Therefore, it is important to measure skin color by using more reliable instruments, such as a color-reflectance meter.16Porges S.B. Kaidbey K.H. Grove G.L. Quantification of light-induced melanogenesis in human skin.Photodermatology. 1988; 5: 197-200PubMed Google Scholar, 17Takiwaki H. Measurement of skin color Practical application and theoretical considerations.J Med Invest. 1998; 44: 121-126PubMed Google ScholarTo evaluate the skin color of patients with ESRD in the present dialysis era, a reflected-light colorimeter was used in this cross-sectional study to quantify skin color objectively. Comparisons were made among healthy controls and patients with ESRD undergoing different dialysis modalities. Factors associated with skin colors of dialysis patients were determined. The results should be helpful in designing specific treatment for skin-color disorder in patients with ESRD.MethodsDesign and SubjectsThis study included patients with ESRD who were undergoing maintenance dialysis at National Taiwan University Hospital (a tertiary medical center) and Da-Zan Hospital (a local dialysis center) in northern Taiwan. Study patients were restricted to those aged 18 to 80 years and who had received maintenance dialysis therapy for at least 6 months. Written informed consent was obtained from every patient involved. Dialysis modalities for patients at National Taiwan University Hospital included HD and PD. All patients at Da-Zan Hospital received HD only. High-flux polysulfone dialyzers were used according to clinical conditions and vascular access flow. Some patients who had received hemodiafiltration once during their 3 weekly HD sessions also were considered for inclusion. They used high-flux dialyzers and the predilution method for replacement fluid infusion. Non–high-flux dialyzers used in this study had a urea clearance of 185 mL/min or greater with a blood flow of 200 mL/min and were made of cellulose diacetate, polymethylmethacrylate, polyethersulfone/polyarylate, or polysulfone.Patients were excluded if they had any of the following conditions: (1) use of potentially depigmenting or hyperpigmenting drugs18Briganti S. Camera E. Picardo M. Chemical and instrumental approaches to treat hyperpigmentation.Pigment Cell Res. 2003; 16: 101-110Crossref PubMed Scopus (669) Google Scholar, 19Dereure O. Drug-induced skin pigmentation Epidemiology, diagnosis and treatment.Am J Clin Dermatol. 2001; 2: 253-262Crossref PubMed Scopus (200) Google Scholar within the last 3 months before the study, except for oral ascorbic acid at a daily dose of 150 mg or less as a dialysis supplement; (2) changes in dialysis modality within the last 6 months before the study; (3) presence of jaundice; (4) average hematocrit less than 26%; (5) serum ferritin level greater than 800 ng/mL (>800 μg/L); (6) preexisting skin disorder; or (7) recent hospitalization for any morbidity within the last 3 months before the study. In addition, PD patients who had not returned to the outpatient clinic in the past 3 months before the study and HD patients who had frequent clotting of dialyzers (ie, clotting of at least one fourth of the dialyzer surface area > 4 times within a month), had not received HD 3 times a week, were using nontunneled dual-lumen catheters for dialysis, or had missed dialysis for any reason for at least 5 times in the 3 months before the study were not included.Biochemical and hematologic data were obtained within 1 month of the start of the study. Serum levels of intact parathyroid hormone, iron, total iron-binding capacity, and ferritin measured within the previous 3 months were used for analysis. Viral hepatitis markers measured within 1 year before the study were recorded. A positive hepatitis B virus (HBV) surface antigen test result is defined as being an HBV carrier, whereas a positive hepatitis C virus (HCV) antibody test result is defined as having infection caused by HCV. For HD patients, delivered single-pool Kt/V in the study month was recorded. Ultrafiltration amount in these patients was recorded as mean ultrafiltration volume for the previous 10 dialysis sessions before skin-color measurement. Dialysis parameters of PD patients consisted of weekly Kt/V, weekly creatinine clearance (CCr), drainage volume, peritoneal equilibrium test, and residual renal function from the last collection. Adequate Kt/V is defined as delivered single-pool Kt/V of 1.2 or greater in HD patients11National Kidney FoundationK/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy Update.Am J Kidney Dis. 2000; 37: S7-S64Google Scholar and weekly Kt/V of 2.0 or greater in continuous ambulatory PD patients, 2.1 or greater in continuous cyclic PD patients, and 2.2 or greater in nocturnal intermittent PD patients.12National Kidney FoundationK/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy Update.Am J Kidney Dis. 2000; 37: S65-S136Google Scholar For PD patients, adequate weekly CCr was 60 L/wk for those with high transporter or high average and 50 L/wk for those with low average or low transporter results in a peritoneal equilibrium test.12National Kidney FoundationK/DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy Update.Am J Kidney Dis. 2000; 37: S65-S136Google ScholarSubjects who were scheduled to receive an adult health checkup from the general community in northern Taiwan during the same period and with an estimated CCr (by Cockcroft-Gault formula) greater than 60 mL/min (>1.0 mL/s) and a normal urinalysis result were invited to serve as healthy controls for the study.Measurements of Skin ColorSkin color was measured with a handheld reflected-light colorimeter (NR-3000; Nippon Denshoku Ind Co, Ltd, Tokyo, Japan). The colorimeter was recalibrated against a standard white tile before each measurement. Measurements were performed just before the midweek session for HD patients, during the outpatient clinic visit for PD patients, and during the health checkup for healthy controls. To minimize the influence of natural solar irradiation, all measurements were carried out indoors in winter or early spring.Skin color was recorded by using the Commission Internationale de l'Eclairage–recommended L*a*b* system.20Robertson A.R. The CIE 1976 color difference formulas.Col Res Appl. 1977; 2: 7-11Google Scholar It is the most commonly used system for quantification of skin color and has been used in patients with many skin disorders,16Porges S.B. Kaidbey K.H. Grove G.L. Quantification of light-induced melanogenesis in human skin.Photodermatology. 1988; 5: 197-200PubMed Google Scholar, 17Takiwaki H. Measurement of skin color Practical application and theoretical considerations.J Med Invest. 1998; 44: 121-126PubMed Google Scholar, 21Piérard G.E. EEMCO guidance for the assessment of skin colour.J Eur Acad Dermatol Venereol. 1998; 10: 1-11PubMed Google Scholar as well as patients with ESRD.14Deleixhe-Mauhin F. Krezinski J.M. Rorive G. Pierard G.E. Quantification of skin color in patients undergoing maintenance hemodialysis.J Am Acad Dermatol. 1992; 27: 950-953Abstract Full Text PDF PubMed Scopus (32) Google Scholar In the system, skin color is defined by its reflectance (L*) and chromaticity (a* and b*). The L* value indicates brightness ranging from black (L* = 0) to white (L* = 100). The a* value represents the balance between red (positive value up to +100) and green (negative value up to −100), and the b* value represents the balance between yellow (positive value up to +100) and blue (negative value up to −100).Two skin sites, the forearm and abdomen, representing sun-exposed and non–sun-exposed areas were tested, respectively. The forearm site refers to skin on the dorsal side, 2 cm cephalic to the wrist, of the nonshunted limb (HD patients) or nondominant limb (PD patients and healthy controls) of a subject. The abdomen site refers to the skin 5 cm cephalic to the umbilicus. For each skin site, 5 measurements were carried out. After excluding maximum and minimum values, the mean value of the other 3 measurements was used for analysis.This study was approved by the Research Ethical Committees of both hospitals and monitored by the Institutional Review Board of National Taiwan University Hospital.Statistical AnalysesNoncategorical characteristics of both patients and controls are presented as mean ± SD, and intergroup differences were assessed by using t-test. Associations of possible factors with skin color were analyzed by using chi-square and Pearson test for categorical and continuous variables, respectively. Stepwise multiple linear regression analysis with both backward elimination and forward selection was used to evaluate any association between skin color, the outcome variable, and multiple independent variables. All tests were 2 tailed, with significance defined by P less than 0.05. Statistical Package for Social Sciences, version 12.0 (SPSS 12.0 for Windows; SPSS Inc, Chicago, IL), was used for statistical analysis.ResultsDemographic and Clinical Characteristics of Patients and ControlsOne hundred twenty-four patients with ESRD were enrolled and completed skin-color measurements between November 2004 and March 2005. They were aged 19 to 80 years (mean, 53.0 ± 12.6 years). There were 63 men and 61 women, 51 were HD patients, and 73 were PD patients. Duration of renal replacement therapy ranged from 6 to 199 months (52.7 ± 46.5 months). Seventeen patients (13.7%) had diabetes mellitus, 13 patients (10.5%) were HBV carriers, and 12 patients (9.7%) were HCV infected. The study included 59 control subjects. There were no significant differences in age, sex, and percentage with diabetes mellitus between controls and patients with ESRD. A smaller percentage of controls were HBV carriers, and controls had greater hematocrit and serum albumin values (Table 1).Table 1Demographic and Clinical Characteristics of Healthy Controls and Patients With ESRDHealthy Controls (n = 59)Patients With ESRD (n = 124)PWomen32 (54.2)61 (49.2)0.532Age (y)54.0 ± 8.7 (31-72)53.0 ± 12.6 (19-80)0.537Diabetes mellitus7 (11.9)17 (13.7)0.818HBV carrier1 (1.7)13 (10.5)0.039HCV infection2 (3.4)12 (9.7)0.232Hematocrit (%)42.9 ± 4.5 (27.6-54.3)31.9 ± 3.5 (26.1-44.0)<0.001Albumin (g/dL)4.7 ± 0.3 (3.80-5.30)4.1 ± 0.3 (3.30-4.90)<0.001NOTE. Values expressed as number (percent), or for continuous values, mean ± SD (range). To convert serum albumin in g/dL to g/L, multiply by 10. Open table in a new tab Comparisons between HD and PD patients are listed in Table 2. HD patients were older, had a longer duration of renal replacement therapy, were more likely to have HCV infection, and had a greater hematocrit than PD patients (P < 0.001). Most HD patients (90.2%) used an arteriovenous fistula as vascular access. All except 1 patient used at least 1 high-flux dialyzer per week. Mean delivered single-pool Kt/V was 1.5, and mean ultrafiltration volume was 2.7 L/session. HD patients generally had no or little urine output. PD modalities used by our patients included continuous ambulatory PD (72.6%), nocturnal intermittent PD (5.5%), and continuous cyclic PD (21.9%). In their latest peritoneal equilibrium test, more than one half of PD patients (53.4%) were low average, 21.9% were high average, 21.9% were low transporter, and 2.7% were high transporter. Mean prescribed daily dialysate amount was 9.4 ± 1.8 L, resulting in a mean daily drainage volume of 10.1 ± 2.2 L. Weekly Kt/V and weekly CCr were 2.2 ± 0.2 and 56.5 ± 13.5 L/1.73 m2 body surface area, respectively. Mean residual renal glomerular filtration rate was 1.7 ± 2.2 mL/min (0.03 ± 0.04 mL/s), and mean residual urine volume was 474.3 ± 598.8 mL/d.Table 2Comparisons Between HD and PD PatientsHD (n = 51)PD (n = 73)PWomen26 (51.2)35 (47.9)0.855Age (y)57.9 ± 10.949.5 ± 12.6<0.001Renal replacement therapy duration (mo)70.6 ± 58.840.5 ± 30.60.001Diabetes mellitus10 (19.6)7 (9.6)0.121HBV carrier5 (9.8)8 (11.0)1.000HCV infection11 (21.6)1 (1.4)<0.001Cause of ESRD0.214 Chronic glomerulonephritis17 (33.3)26 (35.6) Diabetic nephropathy7 (13.7)4 (5.5) Hypertensive nephrosclerosis7 (13.7)6 (8.2) Lupus nephritis3 (5.9)2 (2.7) Polycystic kidney disease1 (2.0)1 (1.4) Chronic interstitial nephritis1 (2.0)5 (6.8) Other causes/cause unknown15 (29.4)29 (39.7)Hematocrit (%)33.7 ± 3.430.6 ± 3.0<0.001Albumin (g/dL)4.1 ± 0.34.1 ± 0.30.896Ferritin (ng/mL)279.9 ± 170.7249.9 ± 154.20.319Transferrin saturation (%)27.6 ± 11.430.3 ± 14.10.234Corrected serum calcium level (mg/dL)9.5 ± 0.89.5 ± 0.70.879Serum phosphate level (mg/dL)5.8 ± 2.05.7 ± 1.40.719Serum intact parathyroid level (pg/mL)283.7 ± 427.7424.0 ± 331.40.052NOTE. Values expressed as number (percent), or for continuous values, mean ± SD (range). To convert serum albumin in g/dL to g/L, multiply by 10; ferritin in ng/mL to μg/L, multiply by 1; corrected calcium in mg/dL to mmol/L, multiply by 0.2495; phosphate in mg/dL to mmol/L, multiply by 0.3229. Open table in a new tab Skin Colors of Patients With ESRD and ControlsTable 3 lists results of skin-color measurement for healthy controls and patients with ESRD. For all subjects, although the L* value was lower, a* and b* values were higher on the forearm than abdomen (P < 0.001). In comparison to controls, L* values for patients with ESRD showed no difference on the forearm, but were significantly lower on the abdomen (P < 0.001); a* values of these patients were significantly lower and b* values were significantly higher on both the forearm and abdomen. There was no difference in L* values in either skin area between HD and PD patients. HD patients had higher a* value and lower b* value on the forearm than PD patients (P < 0.001); both groups of patients had similar a* and b* values on the abdomen.Table 3Skin Colors of Healthy Controls and Patients With ESRDSkin ColorControls (n = 59)ESRD (n = 124)PESRDPHD (n = 51)PD (n = 73)Forearm (sun-exposed area) L*62.7 ± 4.162.2 ± 4.40.44462.0 ± 4.362.3 ± 4.50.714 a*12.0 ± 3.67.6 ± 3.1<0.0018.8 ± 3.26.7 ± 2.8<0.001 b*12.4 ± 1.814.6 ± 2.7<0.00113.6 ± 2.715.3 ± 2.5<0.001Abdomen (non–sun-exposed area) L*71.0 ± 3.067.1 ± 4.0<0.00167.8 ± 3.366.6 ± 4.40.065 a*5.4 ± 4.74.0 ± 3.00.0373.5 ± 2.84.4 ± 3.00.090 b*10.3 ± 2.713.5 ± 3.3<0.00113.1 ± 3.413.8 ± 3.20.279 Open table in a new tab Factors Related to Skin ColorTo examine predictors of skin color, linear regression analysis of ESRD, sex, age, diabetes mellitus, HBV carrier, HCV infection, hematocrit, and albumin level that included all subjects was performed (Table 4). ESRD was an independent factor for lower L* value on the abdomen (P < 0.001), lower a* value on the forearm (P = 0.001), and higher b* value on both sites (P < 0.001). Sex and age, but not ESRD, independently determined L* value on the forearm. Hematocrit independently determined higher a* values on both the forearm (P = 0.015) and abdomen (P = 0.002).Table 4Significant Independent Factors for Skin Color by Multivariate Analysis in All SubjectsIndependent FactorsSkin ColorWith Positive CorrelationWith Negative CorrelationForearm (sun-exposed area) L*Female sex (P < 0.001)Age (P = 0.001) a*Hematocrit (P = 0.015)Female sex (P = 0.001), ESRD (P = 0.001) b*ESRD (P < 0.001)Age (P < 0.001)Abdomen (non–sun-exposed area) L*NoneESRD (P < 0.001) a*Hematocrit (P = 0.002)Age (P = 0.041) b*ESRD (P < 0.001)Age (P = 0.001) Diabetes (P = 0.050)NOTE. N = 183. Open table in a new tab For patients with ESRD, we performed stepwise regression analysis of the following factors: dialysis modality, sex, age, duration of renal replacement therapy, diabetes mellitus, HBV carrier, HCV infection, hematocrit, albumin level, ferritin level, and transferrin saturation (Table 5). Sex (P = 0.005) and age (P = 0.025) independently determined L* value on the forearm. Whereas HD was an independent factor of higher a* value on the forearm (P < 0.001), dialysis modality did not influence L* and b* values in either skin area or a* value on the abdomen. Moreover, duration of renal replacement therapy was not related to any domain of skin color.Table 5Significant Independent Factors for Skin Color by Multivariate Analysis in Patients With ESRDIndependent FactorsSkin ColorWith Positive CorrelationWith Negative CorrelationForearm (sun-exposed area) L*Female sex (P = 0.005)Age (P = 0.025) a*HD (P < 0.001)Female sex (P = 0.002) b*NoneAge (P < 0.001)Abdomen (non–sun-exposed area) L*NoneNone a*NoneAge (P = 0.001) b*NoneAge (P < 0.001)NOTE. N = 124. Open table in a new tab Analysis of only HD patients showed that 11 patients with HCV infection had a significantly lower L* value in sun-exposed skin (P = 0.025) and a marginally lower L* value in non–sun-exposed skin (P = 0.055) than patients without HCV infection. HCV infection remained a significant variable affecting L* values in sun-exposed skin after multiple linear regression analysis. However, HCV infection did not affect a* or b* values. No significant impact of HBV carriage on skin color was found.Effect of Waste Clearance on Skin ColorOf all patients, 107 (86.3%) had an adequate Kt/V. No difference in L* values in eith skin area was found in patients with and without adequate Kt/V (Fig 1A). In PD patients, 43 patients had an adequate weekly CCr and 30 patients had an inadequate weekly CCr. L* value on the abdomen (P = 0.001), but not forearm, was higher in patients with adequate weekly CCr (Fig 1B). This difference remained significant in multiple linear regression analysis.Forty-two PD patients with residual urine volume greater than 100 mL/d had a higher L* value on the abdomen, but not the forearm, than the other 31 PD patients with residual urine volume less than 100 mL/d (P = 0.035; Fig 1C). The effect of residual urine remained significant when multiple linear regression analysis was performed. Patients receiving continuous cyclic PD or nocturnal intermittent PD used automated PD machines. PD modalities (continuous ambulatory PD, 53 patients, versus automated PD, 20 patients) had no effect on L* values (Fig 1D). Five HD patients received hemodiafiltration in 1 of their 3 sessions per week. Their L* values on the forearm and abdomen were not different from those of 46 patients who received only HD (data not shown).In evaluating the impact of Kt/V adequacy, weekly CCr adequacy, residual urine volume, different PD modalities, and hemodiafiltration on skin color, none of these factors was found to be an independent variable affecting either a* or b* value on both the forearm and abdomen.DiscussionAlterations in cutaneous pigmentation in patients with ESRD have been described for a long time. Generalized skin darkness was reported as the most common skin disorder in patients with uremia, with a prevalence of 22% to 36%.1Picó M.R. Lugo-Somolions A. Sánchez J.L. Burgos-Calderon R. Cutaneous alterations in patients with chronic renal failure.Int J Dermatol. 1992; 31: 860-863Crossref PubMed Scopus (89) Google Scholar, 3Choi H.K. Thome F.S. Orlandini T. Haberman H.F. Increased skin pigmentation in patients with chronic renal failure undergoing hemodialysis infected with the hepatitis C virus [Portuguese].Rev Assoc Med Bras. 2003; 49: 24-28Crossref PubMed Google Scholar The cause of skin hyperpigmentation is not completely understood. The yellowish or light-brown color was suggested to be related to accumulation of such middle-molecular-weight pigments as lipochromes and carotenoid.8Ponticelli C. Bencini P.L. Dermatological disorders.in: Davison A.M. Oxford Textbook of Clinical Nephrology. 2. Oxford University, New York, NY1998: 1995-2001Google Scholar However, 1 study showed that serum and tissue β-carotene levels were not elevated in patients with ESRD.15Vahlquist A. Berne B. Berne C. Skin content and plasma transport of vitamin A and β-carotene in chronic renal failure.Eur J Clin Invest. 1982; 12: 63-67Crossref PubMed Scopus (40) Google Scholar Increased melanogenesis caused by accumulation of the weakly dialyzable β-melanocyte–stimulating hormone in patients with ESRD also was proposed,6Smith A.G. Shuster S. Thody A.J. Alvarez-Ude F. Kerr D.N. Role of the kidney in regulating plasma immunoreactive beta-melanocyte-stimulating hormone.Br Med J. 1976; 1: 874-876Crossref PubMed Scopus (34) Google Scholar, 7Gilkes J.J.H. Eady R.A.J. Rees L.H. Munro D.D. Moorhead J.F. Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis.Br Med J. 1975; 1: 656-658Crossref PubMed Scopus (53) Google Scholar, 10Scott A.P. Lowry P.J. Adenocorticotrophic and melanocyte-stimulating peptides in the human pituitary.Biochem J. 1974; 139: 593-602Crossref PubMed Scopus (131) Google Scholar but has been argued against by others because of the absence of correlation between degree of skin darkness and plasma β-melanocyte–stimulating hormone level.9Smith A.G. Shuster S. Comaish J.S. et al.Plasma immunoreactive β-melanocyte-stimulating hormone and skin pigmentation in chronic renal failure.Br Med J. 1975; 1: 658-659Crossref PubMed Scopus (33) Google Scholar A third possible explanation is that peroxidase, in addition to tyrosinase, leads to melanogenesis in pigment cells.22Kasraee B. Peroxidase-mediated mechanisms are involved in the melanocytotoxic and melanogenesis-inhibiting effects of chemical agents.Dermatology. 2002; 205: 329-339Crossref PubMed Scopus (59) Goog
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