Bile Cast Nephropathy: A Comprehensive Review

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Abstract

Bile cast nephropathy (BCN) or cholemic nephropathy (CN) is an acute renal dysfunction, including acute kidney injury (AKI) in the setting of liver injury. It is a common phenomenon in patients with liver disease and is associated with significant morbidity and mortality. CN is characterized by hemodynamic changes in the liver, kidney, systemic circulation, intratubular cast formation, and tubular epithelial cell injury. CN has been overlooked as a differential diagnosis in chronic liver disease patients due to more importance to hepatic injury. However, frequent and considerable reporting of case reports recently has further investigated this topic in the last two decades. This review determines the evidence behind the potential role of bile acids and bilirubin in acute renal dysfunction in liver injury, summarizing the implied pathophysiology risk factors, and incorporating the therapeutic mechanisms and outcomes.

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Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis.

Michael Haase, Rinaldo Bellomo, Prasad Devarajan … (2009)

Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker for the early diagnosis of acute kidney injury (AKI); however, a wide range in its predictive value has been reported. Meta-analysis of diagnostic test studies using custom-made standardized data sheets sent to each author. Different clinical settings of AKI. MEDLINE, EMBASE, and CENTRAL databases and congress abstracts were searched for studies reporting the value of NGAL to predict AKI. Plasma/serum and urine NGAL within 6 hours from the time of insult (if known) or 24-48 hours before the diagnosis of AKI if the time of insult was not known. The primary outcome was AKI, defined as an increase in serum creatinine level > 50% from baseline within 7 days or contrast-induced nephropathy (creatinine increase > 25% or concentration > 0.5 mg/dL in adults or > 50% increase in children within 48 hours). Other outcomes predicted using NGAL were renal replacement therapy initiation and in-hospital mortality. Using a hierarchical bivariate generalized linear model to calculate the diagnostic odds ratio (DOR) and sample size-weighted area under the curve for the receiver-operating characteristic (AUC-ROC), we analyzed data from 19 studies and 8 countries involving 2,538 patients, of whom 487 (19.2%) developed AKI. Overall, the DOR/AUC-ROC of NGAL to predict AKI was 18.6 (95% CI, 9.0-38.1)/0.815 (95% CI, 0.732-0.892). The DOR/AUC-ROC when standardized platforms were used was 25.5 (95% CI, 8.9-72.8)/0.830 (95% CI, 0.741-0.918) with a cutoff value > 150 ng/mL for AKI compared with 16.7 (95% CI, 7.1-39.7)/0.732 (95% CI, 0.656-0.830) for "research-based" NGAL assays. In cardiac surgery patients, the DOR/AUC-ROC of NGAL was 13.1 (95% CI, 5.7-34.8)/0.775 (95% CI, 0.669-0.867); in critically ill patients, 10.0 (95% CI, 3.0-33.1)/0.728 (95% CI, 0.615-0.834); and after contrast infusion, 92.0 (95% CI, 10.7-794.1)/0.894 (95% CI, 0.826-0.950). The diagnostic accuracy of plasma/serum NGAL (17.9 [95% CI, 6.0-53.7]/0.775 [95% CI, 0.679-0.869]) was similar to that of urine NGAL (18.6 [95% CI, 7.2-48.4]/0.837 [95% CI, 0.762-0.906]). We identified age to be an effective modifier of NGAL value with better predictive ability in children (25.4 [95% CI, 8.9-72.2]/0.930 [95% CI, 0.883-0.968]) compared with adults (10.6 [95% CI, 4.8-23.4]/0.782 [95% CI, 0.689-0.872]). NGAL level was a useful prognostic tool with regard to the prediction of renal replacement therapy initiation (12.9 [95% CI, 4.9-33.9]/0.782 [95% CI, 0.648-0.917]) and in-hospital mortality (8.8 [95% CI, 1.9-40.8]/0.706 [95% CI, 0.530-0.747]). Serum creatinine level was used for AKI definition. NGAL level appears to be of diagnostic and prognostic value for AKI.

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KIM-1-mediated phagocytosis reduces acute injury to the kidney.

Li-Li Yang, Craig Brooks, SHENG-XIANG XIAO … (2015)

Kidney injury molecule 1 (KIM-1, also known as TIM-1) is markedly upregulated in the proximal tubule after injury and is maladaptive when chronically expressed. Here, we determined that early in the injury process, however, KIM-1 expression is antiinflammatory due to its mediation of phagocytic processes in tubule cells. Using various models of acute kidney injury (AKI) and mice expressing mutant forms of KIM-1, we demonstrated a mucin domain-dependent protective effect of epithelial KIM-1 expression that involves downregulation of innate immunity. Deletion of the mucin domain markedly impaired KIM-1-mediated phagocytic function, resulting in increased proinflammatory cytokine production, decreased antiinflammatory growth factor secretion by proximal epithelial cells, and a subsequent increase in tissue macrophages. Mice expressing KIM-1Δmucin had greater functional impairment, inflammatory responses, and mortality in response to ischemia- and cisplatin-induced AKI. Compared with primary renal proximal tubule cells isolated from KIM-1Δmucin mice, those from WT mice had reduced proinflammatory cytokine secretion and impaired macrophage activation. The antiinflammatory effect of KIM-1 expression was due to the interaction of KIM-1 with p85 and subsequent PI3K-dependent downmodulation of NF-κB. Hence, KIM-1-mediated epithelial cell phagocytosis of apoptotic cells protects the kidney after acute injury by downregulating innate immunity and inflammation.

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Bile cast nephropathy is a common pathologic finding for kidney injury associated with severe liver dysfunction.

Charles M van Slambrouck, Fadi Salem, Shane M. Meehan … (2013)

Cholemic nephrosis represents a spectrum of renal injury from proximal tubulopathy to intrarenal bile cast formation found in patients with severe liver dysfunction. However, the contribution of this diagnosis has been largely forgotten in the modern literature. To more precisely define this, we conducted a clinicopathologic study of 44 subjects (41 autopsies and 3 renal biopsies) from jaundiced patients at the University of Chicago. Of these, 24 patients had bile casts with involvement of distal nephron segments in 18 mild cases and extension to proximal tubules for 6 severe cases. Eleven of 13 patients with hepatorenal syndrome and all 10 with cirrhosis (due to alcoholism) had tubular bile casts. These casts significantly correlated with higher serum total and direct bilirubin levels, and a trend toward higher serum creatinine, AST, and ALT levels. Bile casts may contribute to the kidney injury of severely jaundiced patients by direct bile and bilirubin toxicity, and tubular obstruction. Both mechanisms are analogous to the injury by myeloma or myoglobin casts. Accounting for the presence of renal bile casts provides a more complete representation of the renal injury that can occur in this unique clinical setting. Thus, bile cast nephropathy is an appropriate term for the severe form of injury observed in the spectrum of cholemic nephrosis. Additional studies are needed to establish the significance of this parameter for patient management in different clinical settings.

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Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 29 March 2022

Publication date (Electronic, collection): March 2022

Volume: 14

Issue: 3

Electronic Location Identifier: e23606

Affiliations

[1 ] Department of Medicine and Research, Avalon University School of Medicine, Willemstad, CUW

[2 ] Department of Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA

[3 ] Medicine, Saint James School of Medicine, Park Ridge, USA

[4 ] Medicine, Ateneo de Manila School of Medicine and Public Health, Quezon City, PHL

[5 ] Department of Medicine, Atlantic University School of Medicine, Gross Islet, LCA

[6 ] Department of Medicine, Jagadguru Sri Shivarathreeshwara (JSS) University, Mysore, IND

[7 ] Department of Medicine, Academy of Medical Sciences, Trivandrum, IND

[8 ] Department of Family and Community Medicine, Saint George's School of Medicine, St. George's, GRD

[9 ] Department of Medicine, The University of Medicine, Tirana, Tirana, ALB

[10 ] Public Health, Eurasian Cancer Research Council, Mumbai, IND

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Manoj R. Somagutta manojleo.go@ 123456gmail.com

Article

DOI: 10.7759/cureus.23606

PMC ID: 9053373

PubMed ID: 35505725

SO-VID: dcbb811e-0cd8-4cff-8386-0b61ff605d2a

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bile Cast Nephropathy: A Comprehensive Review

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Karger: Nephrology

Most cited references 50

Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis.

KIM-1-mediated phagocytosis reduces acute injury to the kidney.

Bile cast nephropathy is a common pathologic finding for kidney injury associated with severe liver dysfunction.

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