Point‐of‐care ultrasound differentiated the cause of proteinuria in a patient with lung cancer

Point-of-care ultrasound (POCUS) is a bedside ultrasound examination method performed directly by clinicians, focusing on specific concerns to provide a rapid assessment based on the patient's medical history and physical examination findings. It enhances diagnostic accuracy, enables timely diagnoses, serves as a guide for procedures, and notably, can be used to evaluate the effectiveness of treatment over time, making it a powerful tool.1 In recent years, POCUS has evolved to be considered the fifth pillar of physical examination, complementing the traditional methods of inspection, palpation, percussion, and auscultation, thereby elevating its status within the realm of standard physical examination techniques.2 In nephrology, POCUS could serve as a powerful tool to evaluate patients' volume status, urinary system obstructions, assessment of vascular access for dialysis, and cardiac function.3 We believe that nephrologists should be proficient in both performing and interpreting POCUS results. The present report illustrates the utility of POCUS in assessing kidney dysfunction and proteinuria in a patient with lung cancer, eventually leading to a diagnosis of proteinuria due to congestive kidney injury secondary to obstructive heart failure by metastatic pericardial effusion. A man in his sixties diagnosed with lung adenocarcinoma (Stage 4B, T1aN3M1c) and treated with lorlatinib for the past 2 years was referred to the nephrology department owing to systemic edema, dyspnea persisting for a week, mild kidney dysfunction with a 0.22 mg/dL increase in serum creatinine (sCr), 3.75 g/gCr of urinary protein, and 2.33 g/gCr of albuminuria. He took several medications including levetiracetam, rosuvastatin, lorlatinib, and ethyl icosapentate. He also had metastatic brain cancer without any central nerve system manifestations. No urinary protein was confirmed during urine testing 2 weeks prior and kidney function was within normal limits (sCr 0.73 mg/dL). Table 1 shows laboratory data and all vital signs were within normal ranges, such as blood pressure: 132/86 mmHg, heart rate: 103 bpm with regular rhythm, respiratory rate: 18 per minute, and oxygen saturation: 96% (room air). The heart and lung sounds were nothing particular. Physical examination revealed jugular venous distension in the sitting position and expiration phase, as well as systemic edema. POCUS revealed prominent pericardial effusion and inferior vena cava (IVC) dilation to 20 mm without respiratory variation (Figure 1). The pulmonary physician consulted a cardiologist regarding the pericardial effusion and consulted us (nephrologists) regarding mild kidney dysfunction and sudden onset of proteinuria. The pulmonary physician was concerned about the potential association between lorlatinib and new-onset proteinuria. We analyzed the urine biochemistry results to calculate the fractional excretion of sodium (FENa) and urea (FEurea) to differentiate kidney dysfunction; the values were 0.04% and 20.4%, respectively. Rapid ultrasonography did not reveal hydronephrosis and the serum albumin level was above 3.0 g/dL, indicating neither post-renal insufficiency nor nephrotic syndrome (Table 1). Therefore, we further focused on the cause of sudden-onset proteinuria. Based on the physical signs, echocardiography findings, and an IVC diameter exceeding 20 mm, we evaluated the congestive state using POCUS with the venous excess ultrasound score (VExUS) grading system.4, 5 This system evaluates the degree of kidney congestion and risk of acute kidney injury by measuring not only the IVC diameter but also pulse waves of the hepatic, portal, and intra-kidney veins.4 Figure 2A,B shows a severe abnormality pattern in the hepatic vein and a moderate abnormality pattern in the portal vein, respectively, indicating VExUS grading system grade 2, which means moderate kidney congestion. Consequently, we provisionally diagnosed the patient with urinary protein due to congestive kidney injury secondary to obstructive heart failure. The patient was promptly treated with pericardial drainage by a cardiologist to prevent obstruction of the venous return. Three days later, systemic edema decreased, and sCr and urinary protein levels decreased to 0.72 mg/dL and 0.4 g/gCr, respectively (Table 1). Subsequent VExUS revealed normal pulse waves in the hepatic and portal veins (Figure 2C,D). Based on POCUS findings and treatment course, we diagnosed the patient with acute kidney dysfunction and proteinuria due to congestive kidney injury secondary to obstructive heart failure by pericardial effusion. Slightly elevated liver enzymes also decreased to the baseline level after pericardial drainage. Retrospectively, this change was consistent with congestive liver injury. Chemotherapy was continued during the clinical course; however, cytological examination of the pericardial effusion revealed metastatic adenocarcinoma. Thus, the patient was administered alternative chemotherapy. The present case highlights several educational points regarding the utility of POCUS in nephrology. First, POCUS provides rapid bedside diagnosis. Second, congestive kidney injury can cause both acute kidney injury and proteinuria. Third, POCUS offers insights into treatment efficacy and course. In this case, the use of POCUS enabled us to promptly diagnose the patient with congestive kidney injury, with pericardial effusion identified as the primary cause of congestion. It is imperative that this condition be promptly treated, and cytological testing should be performed, particularly in a patient with lung cancer. In the cardiorenal syndrome, heart failure is often complicated by impaired kidney function, leading to a worse prognosis.6 Furthermore, kidney congestion due to congestive heart failure is a more important determinant of kidney dysfunction or proteinuria than kidney hypoperfusion.7 Several reports have indicated the relationship between proteinuria/albuminuria and the severity of congestion.8 Some mechanisms of those relationships have been speculated, such as tubulointerstitial damage and increased levels of atrial natriuretic peptides, which reduce proximal tubular reabsorption of urinary protein, resulting in increasing proteinuria.8 Notably, a clinically relevant report regarding renal pathology in congestive kidney disease was published.9 Renal biopsies performed in cases of albuminuria due to right heart failure with a history of tetralogy of Fallot revealed dilatation of the peritubular capillaries and straight renal cortical arteries. Dilated capillaries may indicate an early sign of kidney congestion.9 However, obtaining direct evidence of renal congestion without a biopsy is challenging. Our patient did not undergo a kidney biopsy to determine the cause of proteinuria; however, the VExUS grade indicated proteinuria caused by congestive nephropathy, which rapidly and dramatically improved after pericardial fluid drainage (Figure 2C,D). Essentially, there are no absolute contraindications to pericardial fluid drainage in the presence of cardiac tamponade and shock vitals. However, certain conditions, such as a small amount of pericardial fluid, aortic dissection, post-infarction-free wall rupture, coagulopathy, and thrombocytopenia, require a high degree of caution.10 Clinical manifestations of congestion include short-term weight gain, jugular vein distention, edema, pleural effusions, and ascites. In addition, imaging findings of right heart failure, elevated brain natriuretic peptide (BNP), and renal dysfunction may lead to suspicion of congestive nephropathy. However, direct evidence of renal congestion is difficult to obtain. Central venous pressure (CVP) is a parameter used to evaluate renal congestion; however, it cannot be easily measured without the central venous catheter. Beaubien-Souligny et al. proposed the VExUS grading system as an assessment tool for quantifying kidney congestion.4 Initially, the IVC diameter is measured; if an elevated right atrial pressure is suggested (IVC ≥20 mm), Doppler evaluation of the hepatic, portal, and renal parenchymal veins is performed, and the degree of congestion is comprehensively determined from the presence of pulse waveform changes in each vein.4, 5 For clinicians, some useful web-based educational materials regarding volume evaluation, including VExUS grading system, are now available (i.e. POCUS101; https://www.pocus101.com/vexus-ultrasound-score-fluid-overload-and-venous-congestion-assessment/). Figure 3 schematically shows the severity of congestion in each hepatic, portal, and intrarenal vein assessed by pulse wave doppler. According to these wave patterns,4 Figure 2A,B show a severe abnormality in the hepatic vein and a moderate abnormality in the portal vein, respectively. Although the intrarenal vein is not shown, it exhibited severe congestion. Thus, an IVC diameter of ≥20 mm coupled with two severe congestion signs may be interpreted as VExUS grade 2, which represents moderate kidney congestion.4 After pericardial fluid drainage, the sCr returned to baseline level. We could detect kidney congestion through the IVC diameter and VExUS grading system, including in the hepatic, portal, and intra-kidney veins. Furthermore, urinary examination findings (FENa and FEurea) in congestive kidney injury are similar to the pre-renal insufficiency, mainly caused by extra-cellular volume depletion or dehydration, even though the congestion and volume depletion are completely opposite status. This case also showed FENa less than 1% and FEurea less than 35% despite the congestive state. In this regard, POCUS can help physicians to make the correct diagnosis. Some chemotherapeutic agents can cause proteinuria or kidney dysfunction.11 Thus, in patients experiencing these kidney-related issues, chemotherapy is often discontinued. However, withdrawing chemotherapy poses a significant risk for patients with malignancies. Therefore, accurately addressing urine protein or kidney dysfunction in congestive patients with cancer is crucial. Recently, POCUS has been highlighted as “NephroPOCUS” (https://nephropocus.com/) or POCUN (Point of Care Ultrasound in Nephrology) (https://www.renalfellow.org/?s=POCUS) in the nephrology field. We believe that nephrologists must familiarize themselves with POCUS, not only in performing but also in interpreting POCUS results, particularly when managing patients with edema, acute kidney injury, or proteinuria. This case report highlights three crucial points: (1) physicians should recognize kidney congestion as a cause of kidney dysfunction and proteinuria; (2) POCUS, especially the VExUS grading system, serves as a valuable tool for physicians to rapidly and easily evaluate kidney congestion; and (3) POCUS can differentiate the cause of proteinuria between congestive kidney injury and chemotherapy-related proteinuria. M. Y. received St. Marianna University Research grant in 2023. The authors declare no conflicts of interest.