Pleural Effusion Types in Chronic Kidney Disease

Chronic kidney disease (CKD) is a major global health burden. As CKD progresses through stages III-V, systemic complications become increasingly prevalent, with pleural effusion identified in 20-40% of CKD patients at autopsy. Pleural effusion in CKD arises from diverse mechanisms. Transudative effusions are predominantly associated with fluid overload and heart failure. Exudative effusions are most commonly caused by tuberculosis, uremic pleuritis, and parapneumonic processes.

The cornerstone of differentiating transudative from exudative pleural effusions remains Light's Criteria. However, the criteria carry an acknowledged risk of misclassification in CKD patients, where altered protein metabolism, reduced serum albumin, and dialysis-related biochemical shifts may distort pleural fluid-serum ratios. Given the diagnostic complexity posed by coexisting comorbidities, there is a clear need for a dedicated prospective study that systematically evaluates the incidence, etiology, and biochemical classification of pleural effusions in CKD Stage 3-5 patients.

Eligible participants will undergo a comprehensive clinical evaluation, which includes a structured clinical history form to capture demographic data, presenting symptoms, CKD history, dialysis status, and comorbidities. A physical examination will assess signs of fluid overload and pleural effusion findings.

Imaging studies will be utilized to confirm and grade the effusion. This includes a Chest X-ray (PA view) as an initial screening tool and Thoracic Ultrasound to assess effusion volume, echogenicity, and loculation. A CT Chest may be performed if ultrasound or X-ray findings are inconclusive, or if malignancy or complicated effusion is suspected.

A diagnostic thoracentesis will be performed under full aseptic conditions and ultrasound guidance to minimize complications. Approximately 30-60 mL of pleural fluid will be aspirated for diagnostic analysis, which includes gross appearance, total protein, LDH, glucose, pH, albumin, cell count, Gram stain, AFB smear, and cytology. Simultaneous serum laboratory tests will be collected at the same time as the thoracentesis for ratio calculations.

To evaluate diagnostic accuracy in the CKD population, four classification methods will be applied to each patient's samples:

• Standard Light's Criteria: An effusion is exudative if the pleural fluid/serum protein ratio is >0.5, pleural fluid/serum LDH ratio is >0.6, or pleural fluid LDH is >2/3 of the upper normal limit of serum LDH.
• Abbreviated Light's Criteria: Uses only the protein (>0.5) or LDH (>0.6) ratios.
• Modified Light's Criteria: Requires at least two of the three original criteria to be positive.
• Serum-Pleural Effusion Albumin Gradient (SPAG): Calculated as Serum Albumin minus Pleural Fluid Albumin. A SPAG > 1.2 g/dL indicates a transudative effusion, while a SPAG ≤ 1.2 g/dL indicates an exudative effusion. SPAG is particularly valuable in CKD patients to prevent misclassifying a true transudate as an exudate.

Inclusion criteria

• Adults aged ≥18 years of either sex
• Confirmed diagnosis of CKD Stage 3-5 based on eGFR < 60 mL/min/1.73 m² for ≥3 months, as per KDIGO 2012 guidelines
• Radiologically confirmed pleural effusion on chest X-ray (CXR) or thoracic ultrasound
• Patients on hemodialysis or peritoneal dialysis, as well as those not yet on dialysis (CKD Stage 3-5 pre-dialysis)
• Willingness to provide written informed consent

Exclusion criteria

• Patients with Acute Kidney Injury (AKI) or acute-on-chronic kidney disease without prior CKD diagnosis
• Trauma-related pleural effusion (hemothorax, chylothorax)
• Known active malignancy with suspected malignant effusion
• Patients with post-surgical or iatrogenic pleural effusion
• Patients who refuse consent or are unable to undergo thoracentesis due to coagulopathy or other contraindications
• Pregnancy