Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Kidney histopathology in lethal human sepsis

Authors: Adnan Aslan, Marius C. van den Heuvel, Coen A. Stegeman, Eliane R. Popa, Annemarie M. Leliveld, Grietje Molema, Jan G. Zijlstra, Jill Moser, Matijs van Meurs

Published in: Critical Care | Issue 1/2018

Login to get access

Abstract

Purpose

The histopathology of sepsis-associated acute kidney injury (AKI) in critically ill patients remains an understudied area. Previous studies have identified that acute tubular necrosis (ATN) is not the only driver of sepsis-AKI. The focus of this study was to identify additional candidate processes that may drive sepsis-AKI. To do this we immunohistochemically characterized the histopathological and cellular features in various compartments of human septic kidneys.

Methods

We studied the following histopathological features: leukocyte subsets, fibroblast activation, cellular proliferation, apoptosis, and fibrin deposition in the glomerulus and the tubulointerstitium in human post-mortem kidney biopsy tissue. Biopsy tissue samples from 27 patients with sepsis-AKI were collected 33 min (range 24–150) after death in the ICU. The unaffected part of the kidneys from 12 patients undergoing total nephrectomy as a result of renal carcinoma served as controls.

Results

Immunohistochemical analysis revealed the presence of more neutrophils and macrophages in the glomeruli and more neutrophils in the tubulointerstitium of renal tissue from patients with sepsis compared to control renal tissue. Type II macrophages were predominant, with some macrophages expressing both type I and type II markers. In contrast, there were almost no macrophages found in control kidneys. The number of activated (myo)fibroblasts was low in the glomeruli of sepsis-AKI kidneys, yet this was not observed in the tubulointerstitium. Cell proliferation and fibrin deposition were more pronounced in the glomeruli and tubulointerstitium of sepsis-AKI than in control kidneys.

Conclusions

The extensive heterogeneity of observations among and within patients emphasizes the need to thoroughly characterize patients with sepsis-AKI in a large sample of renal biopsy tissue from patients with sepsis.
Appendix
Available only for authorised users
Literature
1.
Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005;365:63–78.CrossRef
2.
Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA. 1995;273:117–23.CrossRef
3.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.CrossRef
4.
Moeckel GW. Pathologic perspectives on acute tubular injury assessment in the kidney biopsy. Semin Nephrol. 2018;38:21–30.CrossRef
5.
Forni LG, Joannidis M. Blood pressure deficits in acute kidney injury: not all about the mean arterial pressure? Crit Care. 2017;21:102.CrossRef
6.
Su F, Wang Z, Cai Y, Rogiers P, Vincent JL. Fluid resuscitation in severe sepsis and septic shock: albumin, hydroxyethyl starch, gelatin or Ringer’s lactate-does it really make a difference? Shock. 2007;27:520–6.CrossRef
7.
Payen D, Lukaszewicz AC, Legrand M, Gayat E, Faivre V, Megarbane B, et al. A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. PLoS ONE. 2012;7:e35838.CrossRef
8.
Dewitte A, Coquin J, Meyssignac B, Joannes-Boyau O, Fleureau C, Roze H, et al. Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury. Crit Care. 2012;16:R165.CrossRef
9.
Zarbock A, Kellum JA, Schmidt C, Van AH, Wempe C, Pavenstadt H, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA. 2016;315:2190–9.CrossRef
10.
Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351:159–69.CrossRef
11.
Maiden MJ, Otto S, Brealey JK, Finnis ME, Chapman MJ, Kuchel TR, et al. Structure and function of the kidney in septic shock. A prospective controlled experimental study. Am J Respir Crit Care Med. 2016;194:692–700.CrossRef
12.
Langenberg C, Bagshaw SM, May CN, Bellomo R. The histopathology of septic acute kidney injury: a systematic review. Crit Care. 2008;12:R38.CrossRef
13.
Waikar SS, McMahon GM. Expanding the role for kidney biopsies in acute kidney injury. Semin Nephrol. 2018;38:12–20.CrossRef
14.
Takasu O, Gaut JP, Watanabe E, To K, Fagley RE, Sato B et al.: Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med 2013, 187: 509–517.
15.
Lerolle N, Nochy D, Guerot E, Bruneval P, Fagon JY, Diehl JL, et al. Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration. Intensive Care Med. 2010;36:471–8.CrossRef
16.
de Caestecker M., Humphreys BD, Liu KD, Fissell WH, Cerda J, Nolin TD, et al. Bridging translation by improving preclinical study design in AKI. J Am Soc Nephrol. 2015;26:2905–2916.
17.
Rabb H, Griffin MD, McKay DB, Swaminathan S, Pickkers P, Rosner MH, et al. Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps. J Am Soc Nephrol. 2016;27:371–9.
18.
de Caestecker M, Harris R. Translating knowledge into therapy for acute kidney injury. Semin Nephrol. 2018;38:88–97.CrossRef
19.
Kiryluk K, Bomback AS, Cheng YL, Xu K, Camara PG, Rabadan R, et al. Precision medicine for acute kidney injury (AKI): redefining AKI by agnostic kidney tissue interrogation and genetics. Semin Nephrol. 2018;38:40–51.CrossRef
20.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med. 2003;29:530–8.CrossRef
21.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–12.CrossRef
22.
Aslan A, Jongman RM, Moser J, Stegeman CA, van Goor H, Diepstra A, et al. The renal angiopoietin/Tie2 system in lethal human sepsis. Crit Care. 2014;18:423.CrossRef
23.
Aslan A, van Meurs M, Moser J, Popa ER, Jongman RM, Zwiers PJ, et al. Organ-specific differences in endothelial permeability-regulating molecular responses in mouse and human sepsis. Shock. 2017;48:69–77.CrossRef
24.
Tavares MB, Chagas de Almeida MC, Martins RT, de Sousa AC, Martinelli R, dos Santos WL. Acute tubular necrosis and renal failure in patients with glomerular disease. Ren Fail. 2012;34:1252–7.CrossRef
25.
Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014;6:13.CrossRef
26.
Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS, et al. Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol. 2011;22:317–26.CrossRef
27.
Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496:445–55.CrossRef
28.
Rogers NM, Ferenbach DA, Isenberg JS, Thomson AW, Hughes J. Dendritic cells and macrophages in the kidney: a spectrum of good and evil. Nat Rev Nephrol. 2014;10:625–43.CrossRef
29.
Huen SC, Cantley LG. Macrophage-mediated injury and repair after ischemic kidney injury. Pediatr Nephrol. 2015;30:199–209.CrossRef
30.
Langenberg C, Gobe G, Hood S, May CN, Bellomo R. Renal histopathology during experimental septic acute kidney injury and recovery. Crit Care Med. 2014;42:e58–67.CrossRef
31.
Kosaka J, Lankadeva YR, May CN, Bellomo R. Histopathology of septic acute kidney injury: a systematic review of experimental data. Crit Care Med. 2016;44:897–903.
32.
Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999;27:1230–51.CrossRef
33.
Enestrom S, Druid H, Rammer L. Fibrin deposition in the kidney in post-ischaemic renal damage. Br J Exp Pathol. 1988;69:387–94.PubMedPubMedCentral
34.
Block H, Herter JM, Rossaint J, Stadtmann A, Kliche S, Lowell CA, et al. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med. 2012;209:407–21.CrossRef
35.
Thornton MA, Winn R, Alpers CE, Zager RA. An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury. Am J Pathol. 1989;135:509–15.PubMedPubMedCentral
36.
Wulfert FM, van Meurs M, Kurniati NF, Jongman RM, Houwertjes MC, Heeringa P, et al. Age-dependent role of microvascular endothelial and polymorphonuclear cells in lipopolysaccharide-induced acute kidney injury. Anesthesiology. 2012;117:126–36.CrossRef
37.
Tadagavadi RK, Reeves WB. Renal dendritic cells ameliorate nephrotoxic acute kidney injury. J Am Soc Nephrol. 2010;21:53–63.CrossRef
38.
Rouschop KM, Roelofs JJ, Claessen N, da Costa MP, Zwaginga JJ, Pals ST, et al. Protection against renal ischemia reperfusion injury by CD44 disruption. J Am Soc Nephrol. 2005;16:2034–43.CrossRef
39.
Jang HR, Rabb H. Immune cells in experimental acute kidney injury. Nat Rev Nephrol. 2015;11:88–101.CrossRef
40.
Singbartl K, Bockhorn SG, Zarbock A, Schmolke M, Van Aken H. T cells modulate neutrophil-dependent acute renal failure during endotoxemia: critical role for CD28. J Am Soc Nephrol. 2005;16:720–8.CrossRef
41.
Martina MN, Noel S, Bandapalle S, Hamad AR, Rabb H. T lymphocytes and acute kidney injury: update. Nephron Clin Pract. 2014;127:51–5.CrossRef
42.
Jang HR, Gandolfo MT, Ko GJ, Satpute SR, Racusen L, Rabb H. B cells limit repair after ischemic acute kidney injury. J Am Soc Nephrol. 2010;21:654–65.CrossRef
43.
Burne-Taney MJ, Ascon DB, Daniels F, Racusen L, Baldwin W, Rabb H. B cell deficiency confers protection from renal ischemia reperfusion injury. J Immunol. 2003;171:3210–5.CrossRef
44.
Zhang MZ, Yao B, Yang S, Jiang L, Wang S, Fan X, et al. CSF-1 signaling mediates recovery from acute kidney injury. J Clin Invest. 2012;122:4519–32.
45.
Belliere J, Casemayou A, Ducasse L, Zakaroff-Girard A, Martins F, Iacovoni JS, et al. Specific macrophage subtypes influence the progression of rhabdomyolysis-induced kidney injury. J Am Soc Nephrol. 2015;26:1363–77.CrossRef
46.
Sandbo N, Taurin S, Yau DM, Kregel S, Mitchell R, Dulin NO. Downregulation of smooth muscle alpha-actin expression by bacterial lipopolysaccharide. Cardiovasc Res. 2007;74:262–9.CrossRef
47.
Marx D, Metzger J, Pejchinovski M, Gil RB, Frantzi M, Latosinska A, et al. Proteomics and metabolomics for AKI diagnosis. Semin Nephrol. 2018;38:63–87.CrossRef
48.
Malone AF, Wu H, Humphreys BD. Bringing renal biopsy interpretation into the molecular age with single-cell RNA sequencing. Semin Nephrol. 2018;38:31–9.CrossRef
49.
Li R, Zijlstra JG, Kamps JA, van Meurs M, Molema G. Abrupt reflow enhances cytokine-induced proinflammatory activation of endothelial cells during simulated shock and resuscitation. Shock. 2014;42:356–64.CrossRef
Metadata
Title
Kidney histopathology in lethal human sepsis
Authors
Adnan Aslan
Marius C. van den Heuvel
Coen A. Stegeman
Eliane R. Popa
Annemarie M. Leliveld
Grietje Molema
Jan G. Zijlstra
Jill Moser
Matijs van Meurs
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-2287-3

Other articles of this Issue 1/2018

Critical Care 1/2018 Go to the issue

Research

Comparison of exercise intensity during four early rehabilitation techniques in sedated and ventilated patients in ICU: a randomised cross-over trial

Review

Vitamin D deficiency and supplementation in critical illness—the known knowns and known unknowns

Research

Plasma mitochondrial DNA and metabolomic alterations in severe critical illness

Research

Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome

Review

Antiepileptic drugs in critically ill patients

Viewpoint

Position of draining venous cannula in extracorporeal membrane oxygenation for respiratory and respiratory/circulatory support in adult patients