European Journal of Cardiovascular Medicine

Chronic kidney disease (CKD) is a global public health challenge marked by progressive and irreversible loss of renal function. It affects approximately 10–15% of the adult population worldwide and is associated with numerous systemic complications including cardiovascular, hematological, and dermatological disorders [1]. Among these, cutaneous manifestations are frequently encountered but often underrecognized, despite their diagnostic and prognostic relevance.

The skin serves as an important clinical indicator of systemic health, and in CKD, multiple metabolic and vascular disturbances—such as abnormalities in calcium-phosphorus metabolism, retention of uremic toxins, anemia, and hypoalbuminemia—contribute to a variety of dermatological findings [2,3]. Common manifestations include xerosis, pruritus, hyperpigmentation, pallor, ecchymosis, nail changes, and hair abnormalities. These skin changes may not only impair quality of life but can also reflect the severity of renal dysfunction or signal disease progression [2,4].

Pruritus, in particular, remains one of the most distressing and prevalent dermatological symptoms in patients undergoing dialysis, and its etiology is multifactorial—linked to biochemical imbalances, immune dysregulation, and neuronal hypersensitivity [4]. Similarly, xerosis and pigmentary changes have been widely reported in maintenance hemodialysis patients [5].

Although clinical evaluation is essential, correlating skin findings with biochemical parameters such as serum urea, creatinine, phosphorus, and albumin can enhance understanding of underlying pathophysiology. Furthermore, histopathological analysis of skin lesions provides additional insights, revealing microvascular and dermal alterations associated with chronic inflammation and uremia, which remain underutilized in clinical practice [1].

Despite the high prevalence of cutaneous changes in CKD, there is limited data, particularly from resource-limited settings, that comprehensively assess their clinical, biochemical, and histological correlations. This study was conducted to evaluate the spectrum of skin manifestations in CKD patients and to correlate these changes with biochemical parameters and histopathological features, thereby highlighting their diagnostic and prognostic relevance.

This hospital-based observational study was conducted in the Department of Dermatology in collaboration with the Department of Nephrology at Government Medical College, Kamareddy, a tertiary care teaching hospital in Telangana, India. The study was carried out over a period of nine months, from May 2024 to January 2025, after obtaining approval from the Institutional Ethics Committee.

Study Population:

A total of 100 patients diagnosed with chronic kidney disease (CKD), irrespective of age and gender, attending the nephrology outpatient department or admitted in the inpatient wards were included. CKD was defined and staged as per the KDIGO 2021 guidelines based on estimated glomerular filtration rate (eGFR) and duration of renal impairment (≥3 months).

Inclusion Criteria:

• Patients aged ≥18 years.
• Diagnosed with CKD Stage 3 to 5.
• Willing to provide informed written consent.

Exclusion Criteria:

• Patients with acute kidney injury.
• Those with pre-existing primary dermatological disorders unrelated to CKD.
• Individuals on immunosuppressive therapy or with concurrent malignancies.

Data Collection:

A detailed clinical history was recorded, including demographic data, duration of CKD, comorbidities, and current medications. All patients underwent a comprehensive dermatological examination to identify cutaneous manifestations.

Biochemical Investigations:

Laboratory parameters including serum urea, creatinine, phosphorus, calcium, albumin, and hemoglobin were assessed using standard automated techniques.

Histopathological Evaluation:

Skin biopsies were performed in 40 patients with moderate to severe cutaneous findings under aseptic precautions. Tissue specimens were stained using hematoxylin and eosin and examined for epidermal, dermal, and vascular changes.

Statistical Analysis:

Data were entered into Microsoft Excel and analyzed using SPSS version 26.0. Descriptive statistics were used to express frequencies and percentages. Chi-square test, Student’s t-test, and Pearson correlation coefficient were applied to evaluate the association between skin changes and biochemical/histological parameters. A p-value < 0.05 was considered statistically significant.

A total of 100 patients with chronic kidney disease (CKD) were enrolled in this observational study. The mean age of participants was 51.4 ± 13.6 years, with a male predominance (68%). The majority of patients were in Stage 5 CKD (65%), and the most common comorbidity was hypertension (72%), followed by diabetes mellitus (38%). The mean duration of CKD was 3.6 ± 1.9 years. The detailed demographic and clinical characteristics are presented in Table 1.

Table 1: Demographic and Clinical Profile of Study Participants (N = 100)

Cutaneous manifestations were present in all participants. The most frequently observed dermatological findings included xerosis (78%), pruritus (65%), hyperpigmentation (48%), and pallor (46%). Nail changes such as Lindsay’s nails were seen in 40% of patients, while ecchymosis, hair changes, and uremic frost were less common (Table 2).

Table 2: Prevalence of Cutaneous Manifestations in CKD Patients

Biochemical parameters showed significant associations with certain cutaneous findings. Patients with pruritus had significantly higher mean serum urea (98.2 ± 14.6 mg/dL) and serum phosphorus levels (5.8 ± 0.9 mg/dL) (p < 0.01). Hyperpigmentation was associated with elevated serum creatinine (9.2 ± 2.1 mg/dL, p = 0.003). Xerosis was significantly associated with hypoalbuminemia, with a mean albumin level of 3.1 ± 0.4 g/dL (p = 0.02). These correlations are summarized in Table 3.

Table 3: Biochemical Correlates of Selected Skin Manifestations

Skin biopsies were performed in 40 patients exhibiting moderate to severe cutaneous changes. Histopathological evaluation revealed epidermal atrophy in 70%, dermal fibrosis in 45%, and fragmentation of elastic fibers in 30%. Microvascular changes, such as vessel wall thickening and basement membrane alterations, were present in 32.5%, and calcification was seen in 15% of samples (Table 4).

Table 4: Histopathological Features Observed in Skin Biopsies (n = 40)

A significant association was observed between the severity of CKD and the presence of microvascular histological changes. Stage 5 CKD patients exhibited the highest proportion (37.5%) of microvascular abnormalities compared to Stage 4 (30%) and Stage 3 (16.7%) patients, and this difference was statistically significant (p < 0.01) (Table 5).

Table 5: Association Between Histological Changes and CKD Severity (n = 40)

The present study highlights the wide spectrum of cutaneous manifestations in patients with chronic kidney disease (CKD) and their significant correlation with biochemical and histological parameters. Dermatological changes were observed in all 100 patients, reaffirming that skin involvement is a common and clinically relevant aspect of CKD, particularly in advanced stages [6].

Xerosis (78%) was the most frequently noted manifestation, aligning with findings in previous studies that report its prevalence ranging from 50% to 90% in CKD patients [7]. The high incidence of xerosis is attributed to reduced sebaceous and sweat gland function, impaired epidermal hydration, and altered skin barrier integrity. In our study, xerosis showed a statistically significant association with hypoalbuminemia, suggesting a possible link with malnutrition and systemic inflammation—a finding supported by earlier reviews emphasizing the nutritional-dermatological interplay in CKD [11].

Pruritus, reported in 65% of patients, significantly correlated with elevated serum urea and phosphorus levels (p < 0.01). These findings support the hypothesis that uremic toxins, calcium-phosphate imbalance, and systemic inflammation contribute to neuropathic and histamine-independent itch mechanisms [8,11]. Uremic pruritus has a well-established impact on quality of life and sleep, further underscoring its clinical importance in CKD care [11].

Hyperpigmentation (48%) and pallor (46%) were also prevalent. Hyperpigmentation significantly correlated with elevated serum creatinine (p = 0.003), likely due to retained chromogenic substances such as urochromes and increased melanin deposition stimulated by chronic inflammation and UV exposure [7]. Pallor, on the other hand, is a direct consequence of renal anemia, frequently seen in CKD due to erythropoietin deficiency and chronic disease state.

Histopathological examination performed in 40 patients revealed epidermal atrophy (70%), dermal fibrosis (45%), and microvascular changes (32.5%), which were significantly more frequent in patients with Stage 5 CKD (p < 0.01). These findings are consistent with earlier literature describing the histopathological hallmarks of advanced CKD-related skin changes, including microangiopathy, basement membrane alterations, and dermal sclerosis [6,9,10]. The presence of microvascular damage may reflect chronic endothelial dysfunction associated with prolonged uremia and oxidative stress [12].

Moreover, the role of structural proteins such as CD151, essential for proper assembly of the dermal-epidermal junction and glomerular basement membrane, has been implicated in the pathogenesis of skin and renal involvement, suggesting a shared molecular pathway in certain CKD subtypes [10]. These insights further reinforce the value of skin biopsies as a diagnostic adjunct in evaluating the extent and systemic nature of CKD-related pathology.

Overall, the present study contributes to the growing body of evidence that cutaneous manifestations are not merely cosmetic concerns but integral components of systemic disease monitoring and management in CKD [11].

This study highlights the high prevalence and diverse spectrum of cutaneous manifestations in patients with chronic kidney disease. Xerosis, pruritus, hyperpigmentation, and nail changes were the most common findings, significantly associated with biochemical abnormalities such as elevated urea, creatinine, phosphorus, and low albumin levels. Histopathological evaluation revealed epidermal and microvascular alterations correlating with disease severity, particularly in advanced CKD stages. These results emphasize the clinical relevance of dermatological assessment in CKD patients as an adjunct to systemic evaluation. Early identification of skin changes can guide timely interventions, improve patient quality of life, and potentially serve as non-invasive markers for disease monitoring and prognosis.

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