Urinothorax and pleural fluid creatinine: a retrospective analysis of pleural fluid studies at a tertiary care center and a review of the literature
Kevin E. Shayani1
, Jacob Schwartz1, Nicole Oslance2, Brandon Wilson2, Oki Ishikawa3, Omar Mahmoud4, Viera Lakticova1
Contributions: (I) Conception and design: O Mahmoud, V Lakticova; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: J Schwartz, KE Shayani, N Oslance, B Wilson, O Ishikawa; (V) Data analysis and interpretation: J Schwartz, KE Shayani, N Oslance, B Wilson; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Background: Urinothorax is a somewhat vaguely defined entity in the pulmonary literature. It is believed to be due to obstructive renal failure resulting in translocation of urine into the pleural space, presenting as transudative pleural effusions. The literature is sparse, and much of the reported data revolves around case reports and series, with less than 100 cases reported to date. The hallmark finding defining urinothorax is a pleural fluid to serum creatinine ratio greater than 1, although this ratio has not been verified in the literature. Further, the utility of this ratio beyond identification of urinothorax is unknown. Pleural fluid creatinine values may be useful beyond identification of urinothorax, and may have diagnostic value in identifying pleural effusions from persistent volume overload, although further studies are needed to verify this. More likely however, there is a paucity of data in the current literature to support the use of pleural fluid creatinine routinely in the identification of urinothorax, as we have identified in this study. This study aims to elucidate the normal values of pleural fluid creatinine and its utility in pleural disease.
Methods: Here we report a large retrospective study on pleural fluid analyses at a tertiary care center, correlating pleural fluid to serum creatinine ratios with the etiology of pleural effusion.
Results: We present a retrospective study on the analysis of over 300 pleural fluid studies, with a focus on pleural fluid to serum creatinine ratio and its relation to pleural disease.
Conclusions: A pleural fluid to serum creatinien ratio of 1:1 is not specific for the diagnosis of urinothorax given its nearly universal distribution amongst pleural effusions of all etiologies. Further studies are needed to establish normal values of pleural fluid creatinine and specifically its utility in true urinothorax and challenging cases such as pseudoexudates.
Keywords: Pleural effusions; urinothorax; pleural fluid creatinine
Submitted May 01, 2025. Accepted for publication Aug 01, 2025. Published online Nov 26, 2025.
doi: 10.21037/jtd-2025-879
Highlight box
Key findings
• Pleural fluid creatinine is often in equilibrium with serum creatinine, and normal values are reflected in a 1:1 ratio.
What is known and what is new?
• Urinothorax is a known, albeit, rare cause of pleural effusions. Diagnostic criteria are vague and unverified, and further utility of pleural fluid creatinine is unknown.
• Here we report a study on over 300 pleural fluid samples, with pleural fluid creatinine used as a possible measure of exudate vs. transudate vs. pseudoexudate and to establish normal values of pleural fluid creatinine.
What is the implication, and what should change now?
• Pleural fluid to serum creatinine ratios of 1:1 should not be used to diagnose urinothorax. This more likely reflects the normal level of pleural fluid creatinine, as it is likely in equilibrium with the serum. A higher cutoff as described in the literature (a ratio of 1.7) should be used if there is suspicion for urinothorax.
Introduction
Urinothorax is a vaguely defined entity in the pulmonary literature that is believed to be due to obstructive renal failure, resulting in translocation of urine into the pleural space presenting as transudative pleural effusions. It is classified as a pleural effusion of extravascular origin (PEEVO), and diagnosis can be challenging, often requiring a multidisciplinary approach before a definitive diagnosis can be made. Its hallmark finding is a pleural fluid to serum creatinine ratio of >1, with a ratio of >1.7 essentially diagnostic (1). Other common findings include transudative fluid characteristics by Light’s criteria, low pleural fluid protein, similar glucose levels to that of the serum, and low pH (<7.4) given normal urine is typically acidic, although pH can be higher in cases of concomitant urinary tract infection (UTI), especially with urease producing species (2). On the other hand, Light’s criteria for determining an exudative effusion are met or fulfilled if one of the following conditions are met: (I) pleural fluid-to-serum protein ratio greater than 0.5. (II) Pleural fluid-to-serum lactate dehydrogenase (LDH) ratio greater than 0. (III) Pleural fluid LDH greater than 0.67 (i.e., two-thirds) the upper limits of the laboratory’s normal serum LDH (3). In the case of urinothorax, etiologies vary from traumatic to obstructive, but urinothorax has been reported in patients with chronic renal failure, too (Table 1) (4). In cases where there is a fistulous connection between the renal cortices and pleural space, nuclear medicine scans such as renal scintigraphy using Technetium-99 can be diagnostic (5).
Table 1
| Obstructive |
| Prostate disease |
| Hydronephrosis |
| Malignancy |
| Urethral valves |
| Gravid uterus |
| Retroperitoneal fibrosis |
| Renal cystic disease |
| Renal calculi |
| Traumatic |
| Surgical injury |
| Lithotripsy |
| Blunt trauma |
| Renal transplant |
| Radiofrequency ablation |
| Other (proposed) |
| Chronic kidney disease |
| End stage renal disease |
| Congestive heart failure |
The first case of urinothorax was reported in 1968 as a complication of hydronephrosis and was replicated in dog animal models (6). Since this initial report, less than 100 cases exist in the reported literature, mostly in the form of case reports and case series (7). This may not reflect the prevalence of this condition given its rarity and relative obscurity. In addition, underreporting may be caused by lack of testing for this entity. While the pleural fluid to serum creatinine ratio is often diagnostic, depending on the chronicity of the effusion and individual patient characteristics, this ratio may have utility beyond identification of urinothorax although this is unverified (Table 2). Given the lack of normalized values for pleural fluid creatinine, it is possible that elevation of creatinine levels in pleural fluid is more common than previously believed, perhaps more so in cases of transudative effusions and pseudoexudates. Creatinine is a small molecule and may more freely extravasate from serum into pleural space in the setting of elevated hydrostatic pressure (8).
Table 2
| Effusion | Total protein† | LDH† | pH | Creatinine |
|---|---|---|---|---|
| Transudative effusions | Pleural fluid: serum protein <0.5 | Pleural fluid LDH <2/3 upper limit of normal of serum LDH. Pleural fluid: serum LDH typically <0.6 | Typically >7.4 | Unknown |
| Exudative effusions | Pleural fluid: serum protein >0.5 | Pleural fluid LDH >2/3 upper limit of normal of serum LDH | Typically <7.4 | Unknown |
| Pseudo exudative effusions | Pleural fluid: serum protein >0.5; SPPG >3.1; SPAG >1.2 | Pleural fluid LDH >2/3 upper limit of normal of serum LDH | Typically >7.4 | Unknown |
| Urinothorax | Pleural fluid: serum protein typically <0.5 | Pleural fluid: serum LDH typically <0.6. Pleural fluid LDH <2/3 upper limit of normal of serum LDH | Typically <7.4 | Pleural fluid: serum creatinine >1 (supportive); >1.7 (diagnostic) |
†, using Light’s criteria. LDH, lactate dehydrogenase; SPAG, serum to pleural fluid albumin gradient; SPPG, serum to pleural fluid protein gradient.
Pseudoexudate is defined as an effusion with transudative etiology which is falsely identified as exudate by Light’s criteria. The characterization of pseudo exudate often occurs in the context of a transudative effusion that has undergone volume contraction resulting in a slight increase in concentration of fluid. This subsequent volume contraction leads to a protein or LDH value that falls slightly above the cut off value for an exudate, leading the effusion to be misclassified (9). Pseudoexudates are typically seen in a clinical context of heart failure or hepatic hydrothorax as 30% of heart failure effusions may be misclassified as an exudate and 18% of hepatic hydrothorax may be misclassified as exudate (10). These shortcoming of Light’s criteria have lead to a search for other biomarkers such as the use of cholesterol in Heffner’s criteria or the use serum to pleural fluid protein gradient (SPPG) and brain natriuretic peptide (BNP) (11,12). Additionally, the clinical conundrum of effusion characterization has continued to pose a clinical problem such that, some have proposed the development of an ultrasound score (Duet score) to predict effusion characteristics (13). Etiologies for pseudoexudate include concurrent diuretic therapy in heart failure patients, traumatic pleural sampling, and a history of coronary artery bypass grafting (14). In the case of concurrent diuretic use, the pathophysiology is believed to be due to the relative increase in the concentration of proteins in the pleural fluid secondary to decrease in free water as a consequence of diuresis. With chronic pleural effusions, sterile lymphocytic inflammation may contribute to changes transforming previously transudative effusions to exudate. It has been suggested that the use of a serum to pleural fluid albumin gradient (SPAG) as well as an SPPG can be of additional value in assisting with the diagnosis of pseudoexudate, combined with the clinical scenario (15). Pleural fluid NT-pro-BNP has also been reported in the literature, but this is not routinely available at all institutions (16). It is unclear if pleural fluid creatinine has utility in the diagnosis of pleural disease. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-879/rc).
Methods
We analyzed pleural effusion samples collected between 2019 and 2023 at a tertiary care center in New York City. A total of 303 samples were analyzed. All samples that had pleural fluid creatinine measured were selected in this retrospective study—this information was collected as part of an order set that was submitted with any pleural fluid studies during this period. The clinical suspicion for urinothorax was low in these cases. Baseline demographic data were analyzed (Table 3). Acute kidney injury (AKI), chronic kidney disease (CKD), and AKI on CKD were categorized according to the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria and Acute Kidney Injury Network (AKIN) criteria (17). Pleural fluid characteristics including pH, LDH, total protein, albumin, and cell counts with differential were analyzed (Table 4). Pleural effusions were defined as transudate or exudate using Light’s criteria. Pseudoexudate was defined as a pleural effusion that was exudative by Light’s criteria but had elevated serum-pleural effusion albumin gradients or elevated serum-pleural effusion protein gradients in combination with the clinical picture as was best available from patient records (Table 2). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was IRB exempt by the Northwell Health institutional review board. Informed consent was not required for this study given IRB exemption status, as data analysis for this study was performed in a retrospective manner on pleural fluid studies obtained using a pre determined order set, and the nature of this project did not meet criteria for research involving human subjects as it was determined to not be beyond minimal risk.
Table 3
| Characteristic | Exudate (n=201) | Transudate (n=76) | Pseudoexudate (n=26) |
|---|---|---|---|
| Gender, n [%] | |||
| Male | 111 [55] | 34 [44] | 15 [58] |
| Female | 90 [45] | 42 [56] | 11 [42] |
| BMI (kg/m2), mean | 24.64 | 23.97 | 25.05 |
| Comorbidities, n [%] | |||
| DM | 26 [13] | 15 [20] | 5 [20] |
| HTN | 94 [47] | 41 [54] | 13 [50] |
| CHF | 35 [17] | 20 [26] | 12 [46] |
| ILD | 2 [1] | 0 [0] | 0 [0] |
| COPD | 16 [8] | 11 [14] | 1 [4] |
| Malignancy | 84 [42] | 32 [42] | 10 [38] |
| Renal function, n [%] | |||
| Normal baseline function | 163 [81] | 41 [54] | 17 [65] |
| CKD | 14 [7] | 11 [14] | 5 [19] |
| AKI | 27 [13] | 8 [11] | 5 [19] |
| AKI on CKD | 17 [8] | 14 [18] | 3 [16] |
| ESRD on HD | 4 [2] | 10 [13] | 1 [4] |
AKI, acute kidney injury; BMI, body mass index; CHF, congestive heart failure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; ESRD, end stage renal disease; HD, hemodialysis; HTN, hypertension; ILD, interstitial lung disease.
Table 4
| Characteristic | Exudate | Transudate | Pseudoexudate | P value |
|---|---|---|---|---|
| Pleural fluid pH | 7.52 (7.49, 7.55) | 7.63 (7.59, 7.67) | 7.58 (7.52, 7.64) | 0.004 |
| Pleural fluid LDH | 588 (486, 690) | 106 (93, 113) | 324 (148, 500) | <0.001 |
| Pleural fluid total protein | 3.78 (3.65, 3.91) | 2.27 (2.05, 2.49) | 2.95 (2.57, 3.33) | <0.001 |
| Pleural fluid creatinine | 1.06 (0.95, 1.17) | 1.75 (1.42, 2.08) | 1.61 (1.28, 1.94) | <0.001 |
| Pleural fluid creatinine ratio | 0.97 (0.95, 0.99) | 1.00 (0.98, 1.02) | 0.96 (0.91, 1.01) | 0.34 |
The data have been indicated to be reflective of the mean of these values with the range in parenthesis. LDH, lactate dehydrogenase.
Statistical analysis
Subsequent subgroup analysis was performed using analysis of variance. Means of pleural fluid creatinine along with serum to pleural fluid creatinine ratio was analyzed between three major categories of pleural disease: exudative pleural effusions, transudative pleural effusions, and pseudoexudative pleural effusions. P values were obtained between groups, with values <0.05 signifying statistical significance.
Results
Our data was notable for 201 exudates, 76 transudates and 26 pseudoexudates, summarized in Table 2. No urinothorax was identified in our cohort. One hundred and sixty samples were collected from male patients, with the remaining 143 from female patients. Baseline demographic information and comorbidities can be seen in Table 3. Mean pleural fluid to creatinine ratio was 0.97 (range, 0.95, 0.99) for exudates, 1.00 (range, 0.98, 1.02) for transudates and 0.97 (range, 0.96, 1.01) for pseudoexudates, with no statistically significant difference between the groups (P=0.34). The Forest plot of pleural fluid to serum creatinine ratio was created and can be seen in Figure 1. Additional fluid analysis can be seen in Table 4.
Discussion
Urinothorax is an obscure entity in the pulmonary literature, and diagnosis requires pleural fluid creatinine measurement with calculation of pleural to serum creatinine ratio. The accepted specific cut off for pleural creatinine to serum ratio in urinothorax is 1.7, whilst a ratio greater than 1 is suggestive in the correct clinical context, however, based on this analysis a ratio of more than 1 may be more common than previously thought. Most of the literature focuses on obstructive or traumatic insults to the urinary tract, resulting in accumulation of urine in the pleural space. However, in theory any condition with reduced urine output or poor renal perfusion can result in accumulation of creatinine in the pleural space. Given the findings of this study, we suspect that this is due to creatinine’s ability to freely traverse the pleural space, and thus any increase in serum creatinine should reflect in increases in pleural fluid creatinine. This can commonly be seen in patients with chronic or end stage kidney disease, as well as patients with congestive heart failure. Patients with these chronic conditions will often develop pleural effusion. The effusions often display similar pleural fluid characteristics as reported in urinothorax, with exceptions of low pH. Pleural fluid creatinine is not routinely measured, and this may account for why this process is under-reported in the literature. Based on the results of our database, the classically used pleural fluid to creatinine ratio of more than 1 appears to be not very specific for diagnosis of urinothorax. It is very possible that the levels of creatinine in the pleural fluid reflect similar values as to what is in level of creatinine in the serum generally. In our cohort, across all three categories of pleural effusion (exudate, transudate, and pseudoexudate), this ratio remained near 1 regardless of etiology to the pleural effusion.
As opposed to a vast majority of serum proteins, creatinine is a significantly smaller molecule with a molecular weight of 113 Da (18). For comparison, albumin has a molecular weight of 66.5 kDa with nearly 10 times the diameter of creatinine (19). The diffusion of molecules into the pleural space is directly correlated with size of the diffusing molecule, with smaller molecules able to diffuse more freely compared to larger ones (20). Owing to its smaller size, it may be that creatinine can freely diffuse into the pleural space as opposed to much larger serum proteins and counterparts. This may explain why the value of creatinine in the pleural fluid is similar to the level of creatinine in the serum, regardless of the etiology of pleural effusion, as seen in our study.
In cases of chronic pleural effusions, suspected transudative effusions may appear as exudative for a variety of reasons: concurrent diuretic usage resulting in relative concentration of pleural fluid protein and LDH, traumatic pleural taps, a history of coronary artery bypass surgery, or chronic inflammatory changes in the pleural space. Even effusions that typically present as transudative, such as those associated with congestive heart failure (CHF), can eventually develop exudative properties with increases in pleural fluid total protein and LDH. SPAG and SPPG have been suggested to assist in differentiating true exudates from these suspected pseudoexudates, along with the clinical scenario. Based on the results of this study, it is unclear whether pleural fluid creatinine can assist in this distinction.
While in theory, states of chronic volume overload related pleural effusions frequently identified as pseudoexudate may have higher absolute values of creatinine, the ratio of pleural fluid creatinine to the serum does not significantly change when compared to exudates. It appears that serum to pleural fluid creatinine ratios are relatively universal irrespective of etiology and composition of the effusion. Given that the absolute values of pleural fluid creatinine were highest in both the transudate and pseudoexudate groups, and the level of renal dysfunction was also highest in these groups (19% in the exudate group vs. 46% and 35% in the transudate and pseudoexudate groups respectively), this suggests that any state of decreased renal function will reflect in pleural fluid creatinine level and ratio of fluid to serum creatinine will not differ between the groups. There appears to be a mild trend of elevated ratio in transudate and pseudoexudate compared to exudate noted on Forest plot, suggesting larger sample analysis may be of value to confirm or revoke the theory this ratio may serve as additional tool for identification of pseudoexudate.
Certain limitations of this analysis exist, mainly that there are no established normal values for pleural fluid creatinine. While there are no normal values established for pleural fluid creatinine, the findings from this retrospective chart review suggest that the normal ranges likely reflect serum values of individual patients given its uniformity across a diverse pathogenesis for pleural effusions. Additionally, none of the patients in this study were diagnosed with a true urinothorax, which may impact the validity of these findings. Further, pleural fluid creatinine is not a routine test that is performed, and all institutions may not have the capability to measure this from pleural fluid. Lastly, this was a database generated from a retrospective chart review and not a prospectively designed trial powered to detect differences in pleural fluid creatinine.
Conclusions
Pleural fluid creatinine has long been thought to be the diagnostic answer to urinothorax, with pleural fluid and serum ratio of more than 1 believed to be strongly supportive and a ratio >1.7 to be nearly diagnostic. Based on the results of this database, ratio of >1 is commonly seen in pleural fluid analysis and likely reflects the ability of creatinine to freely traverse between serum and pleural fluid, in stark contrast to other serum proteins and LDH. Given this finding, we suggest that a ratio of 1:1 is not specific for the diagnosis of urinothorax given its nearly universal distribution amongst pleural effusions of all etiologies. A higher ratio such as >1.7 (combined with the clinical history) is likely to be of further diagnostic benefit. Whether elevated ratio of fluid to serum creatinine has utility beyond this is still to be determined. Further studies are needed to establish normal values of pleural fluid creatinine and specifically its utility in true urinothorax and challenging cases such as pseudoexudates.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-879/rc
Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-879/dss
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-879/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-879/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was IRB exempt by the Northwell Health institutional review board. Informed consent was not required for this study given IRB exemption status, as data analysis for this study was performed in a retrospective manner on pleural fluid studies obtained using a pre determined order set, and the nature of this project did not meet criteria for research involving human subjects as it was determined to not be beyond minimal risk.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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