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Abstract
Cardiorenal syndromes (CRS) involve disorders of the heart or kidney whereby one organ dysfunction leads to the
dysfunction of another. Five types of CRS are defined. While the first 4 types describe acute/chronic cardiorenal
or renocardiac syndromes, type-5 CRS refers to secondary CRS or cardiorenal involvement in systemic conditions
and describes the concomitant presence of renal and cardiovascular dysfunction. Type-5 CRS is a recently defined
clinical syndrome and complete epidemiological data on this entity are still lacking. In the following review, epi-
demiological, pathophysiological, clinical, and therapeutic approaches to type-5 CRS will be discussed according
to more recent findings.
Keywords: Cardiorenal syndromes, Fabry disease, Hepato-renal syndrome, Sepsis, Type-5CRS
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e24 Type-5 CRS
TABLE I - C
onditions causing acute and chronic type-5 cardiorenal
syndrome
endothelial dysfunction (37). Experimental studies also suggest involvement in 60%-100% of all cases (42-45). Cardiac involve-
deleterious effects of RAAS activation on renal function during ment is less frequent and varies from 0% to 39.5% (42-45).
sepsis (38). The administration of ACE inhibitors improves cre- In amyloidosis, the heart demonstrates thickening of all
atinine clearance and urine output during experimental bac- 4 chambers, with biatrial dilation, mild dilation of the right
teremia; the application of the selective angiotensin II type 1 ventricle with a normal or small left ventricular cavity. Myo-
receptor antagonist improves renal blood flow and oxygen- cardial cells are separated by amyloid deposits with the in-
ation during experimental endotoxemia (38) (Fig. 2). filtration of intramyocardial vessels. Occasionally epicardial
Finally, sepsis causes complex alterations of HPA and glu- coronary vessels are also involved leading to myocardial
cocorticoid signaling, leading to severe adrenal insufficiency ischemia (46). The conduction system is frequently involved.
in some patients. As a consequence, an increased production The predominant manifestation of amyloid heart disease is
of pro-inflammatory cytokines, free radicals, and prostaglan- congestive heart failure. In patients with small vessel involve-
dins, as well as the inhibition of chemotaxis and the expres- ment and minimal or no myocardial infiltration, the present-
sion of adhesion molecules occurs. The administration of ing complaint may be angina. In addition, atrial arrhythmias
moderate-dose glucocorticoids for 7 days can exert positive are frequently seen (40).
effects, reducing the need for vasopressors and intensive care Renal amyloid is characterized by deposits in the glo-
unit (ICU) assistance (39). merular basement membrane, the subendothelial area, and
the extracellular mesangial system. Occasionally, tubular
CRS-5 and amyloidosis deposits are seen. The majority of patients with renal amyloi-
dosis present with proteinuria, which can vary from minimal
The systemic amyloidoses are an uncommon group of asymptomatic proteinuria to nephrotic syndrome. Hematuria
disorders characterized by the extracellular deposition of is present in about one-third of patients. Chronic renal insuf-
amyloid in 1 or more organs. Cardiac and renal deposition ficiency with little proteinuria can also be seen in patients
leading to restrictive cardiomyopathy and proteinuric renal with extensive vascular deposits (47). In patients with tubular
disease is a common feature of amyloidosis. Importantly, the deposits, tubular dysfunction can be seen.
presence and severity of CRS drives the prognosis of systemic
amyloidosis. CRS-5 and systemic lupus erythematosus
Among many types of amyloidoses, AL (primary) and AA
(secondary) amyloidosis are the most frequently encoun- Heart is very commonly involved in systemic lupus ery-
tered types in clinical practice. AL amyloidosis, in which am- thematosus (SLE). Any cardiac structure, including the peri-
yloid is derived from monoclonal light chains, is associated cardium, myocardium, endocardium, conduction tissue, and
with clinical cardiac involvement in about 50% of all cases even coronary arteries, are involved in SLE.
(40). Subclinical cardiac involvement at autopsy or on en- The spectrum of cardiac complications in SLE is shown in
domyocardial biopsy may be detected in almost all patients. Figure 3. Pericarditis is the most frequent cardiac manifesta-
Renal involvement occurs in 30%-40% of all AL cases (41). In tion of SLE, and pericardial involvement is seen in 11%-54%
contrast, the AA type is characterized by predominant renal of patients on echocardiographic studies (48). Pericarditis
is also included in the American Rheumatolgy Association/ vulvular insufficiencies, most commonly of the mitral or aor-
American College of Reumathology (ARA/ACR) classification tic valves. Although complications are rare, embolic events
criteria of SLE (49). Direct immunofluorescence shows the do occur, and stroke and peripheral embolism have been
granular deposition of immunoglobulin and C3. It indicates reported in 13% of cases. Infectious endocarditis has been
the role of immune complexes in the pathogenesis. Acute reported in 7% of cases, and the risk of endocarditis is in-
or chronic inflammatory changes are seen in the pericar- creased by dental treatments. Antibiotic therapy should be
dium. Acute pericarditis can be fibrinous or serofibrinous, considered for patients with vulvular abnormalities, as SLE
and chronic pericarditis can be fibrous or fibrofibrinous. patients may receive immunosuppressant therapy for their
Pericarditis generally manifests at the start of the disease or primary disease.
during relapses, and rarely leads to cardiac tamponade, con- While patients with SLE live longer, due to improved thera-
strictive pericarditis or purulent pericarditis. pies and preventive measures, death and disability from car-
Myocardial involvement was seen in 40% of SLE cases in diovascular events are increasing. SLE patients are 4-8 times
postmortem examinations (50) and in 20% of cases on echo- more likely to suffer from CAD than non-SLE patients; this is
cardiography (51). However, myocardial involvement is seen seen in 6%-10% of SLE patients (57), and women are 50 times
in only 7%-10% of patients (52). Immune complex and com- more at risk of CAD (58). Atherosclerosis, hypertension, arteri-
plement deposition is seen on direct immunofluorescence, tis, a thrombotic event, an embolism due to endocarditis or va-
whereas an association with anti-Ro/SSA antibodies is also sospasm are the risk factors for the development of CAD (59).
proposed (53). A patient may present with acute illness or Hypertension, sedentary lifestyle, hyperlipidemia and
have a chronic course with the development of cardiomyopa- hyperhomocysteinemia may lead to atherosclerosis in SLE
thy, but left ventricular failure is rarely seen (54). Myocardial patients (60). Steroid therapy in these patients increases
dysfunction in SLE may also be due to renal failure and hy- the lipoprotein and homocysteine levels (61). Inflammation
pertension, coronary artery disease (CAD), vulvular affection, plays an important role in the development of atherosclerotic
or the toxic effects of medications used for treatment of SLE. plaque. Atherosclerotic lesions begin with the recruitment
Libman–Sacks endocarditis (also known as atypical of inflammatory cells, such as monocytes and T cells to the
verrucous endocarditis) is the most typical presentation endothelial wall. Recently, CRP and pentraxines have been
of endocardial involvement in SLE. These vulvular abnor- considered to be inflammatory markers in patients with SLE
malities are detected in 40%-50% of cases with transtho- (62). Autoantibodies and immune complexes also play a
racic echocardiography and 50%-60% with transesophageal major role for atherosclerosis. Circulating antibodies to
echocardiography. Anti-phospholipid antibodies bind to en- oxidized low-density lipoprotein (anti-OxLDL) have been
dothelial cells and activate them. This leads to platelet ag- described, though their relationship to the development and
gregation and thrombus formation (55). Immune-complex progression of atherosclerosis is unclear. Svenungsson et al
and complement deposition also have been reported to (63) have demonstrated that autoantibodies to OxLDL are
have an association with vulvular involvement. more common in SLE patients who have a history of cardio-
Libman–Sacks endocarditis is clinically silent in the ma- vascular disease than in SLE controls or normal subjects.
jority of patients and rarely leads to the development of a Sinus tachycardia is the most frequent rhythm distur-
cardiac murmur. Verrucae develop near the edge of the valve bance observed in SLE patients. Atrioventricular block and
and even if they become large they do not deform the closing bundle branch block are seen in children of mothers with
line of the valves (56). Endocardial involvement may lead to anti-Ro/SSA antibodies, but rarely in adults (64). These
patients are mostly asymptomatic or may have fatigue and TABLE II - International Society of Nephrology/Renal Pathology
palpitations. Syncope is seen in very rare cases (65). Sinus Society (ISN/RPS) 2003 classification of lupus nephritis
tachycardia in SLE patients may be due to pericarditis, myo-
carditis, or chloroquine use (49). Class Histological findings
Renal involvement remains a major cause of morbidity in
Class 1 Minimal mesangial lupus nephritis
patients with SLE. Abnormalities of immune regulation lead to
auto-antibody production in SLE. Antibodies directed against Class 2 Mesangial proliferative lupus nephritis
nuclear antigens and specifically against DNA (anti-dsDNA) Class 3 Focal lupus nephritisa
are considered diagnostic of SLE. Among these, anti-Sm an- Class 4 Diffuse segmental (IV-S) or global (IV-G) lupus nephritisb
tibodies have a significant association with lupus nephritis.
Class 5 Membranous lupus nephritisc
The initiating event may be the local binding of nuclear or
other antigens to glomerular sites followed by in situ immune Class 6 Advanced sclerosing lupus nephritis
complex deposition. Immune complexes made up of DNA- a
The proportion of glomeruli with active and sclerotic lesions.
anti-DNA along with some other aggregates (nucleosomes, b
The proportion of glomeruli with fibrinoid necrosis and cellular crescents.
ribosomes, chromatin, C1q, laminin, Sm, La [SS-B], Ro [SS-A], c
Class V may occur in combination with class III or IV, in which case both will
and ubiquitin) cause glomerular injury. Previously, T cells were be diagnosed.
considered only as a helping factor for B cells to produce auto-
antibodies, but recent studies support the significant role of
T cells for the progression of renal disease in SLE. Addition- syndrome features. Out of these, 40% of patients will have less
ally, deposition of the immune complex leads to the release of than 3 g/day proteinuria and up to 60% of patients will have
chemokines, such as MCP 1 and RANTES in glomeruli. These elevated anti-DNA antibody titers and low serum complement
chemokines cause a proliferation of mesangium, which results levels. Usually these patients present with hypertension and
in acute glomerular nephritis characterized by mesangial ex- renal dysfunction. Patients of this class are likely to develop
pansion and cellular infiltration. With the progress of disease, thrombotic complications as seen in idiopathic membranous
acute glomerulonephritis turns into chronic glomerulonephri- nephropathy.
tis characterized by glomerulosclerosis, interstitial fibrosis, Patients end up in class VI after long periods of disease’s
and tubular atrophy. Recent studies have been done on toll- flares alternating with periods of inactivity. Patients will
like receptors (TLR), and TLR expression on renal cells causes have inactive sclerotic and fibrotic lesions. Almost all pa-
the activation of end-organ response and renal injury. tients have hypertension and renal dysfunction. But anti-
Females are more commonly affected by SLE, but clinical DNA antibody titers and serum complement levels may be
manifestations are similar in both genders whether adults or normalized by the time patients reaches this stage (67).
children. SLE is a multisystem disease, and any organ system
can be involved in SLE. Kidneys are affected from the start CRS-5 and Fabry disease
of SLE, or at any stage, and follow a protracted course of
remissions and exacerbations. Clinical renal involvement cor- Fabry disease is responsible for CRS-5 with insidious onset
relates well with a degree of glomerular involvement (66). where the kidney and cardiac dysfunction may develop slow-
The clinical features of renal involvement may be correlated ly until a “point of decompensation.” It can also be chronic,
with histologic findings seen on renal biopsy and were classi- acute, or acute-on-chronic CRS-5. Mechanisms in acute and
fied by the International Society of Nephrology/Renal Pathol- chronic CRS-5 are different; the nature, severity, and dura-
ogy Society (ISN/RPS) in 2003 (Tab. II) (67). tion of organ dysfunction are also influenced by the manage-
Patients of class I SLE, having only mesangial involvement, ment interventions. In most cases of CRS-5 there is usually a
often have no or at the most, mild evidence of clinical re- precipitating event that brings the condition to attention; for
nal disease. Patients of class II have proteinuria of less than example, Fabry crises, precipitated by fever, exercise, fatigue,
1 g/day. But these patients have high anti-DNA antibody titer stress, and rapid changes in temperature (68, 69).
and low serum complement. Hypertension is infrequently Being a systemic disease, Fabry disease starts with a spe-
seen and serum creatinine, glomerular filtration rate (GFR) cific effect(s) involving the kidney and/or the heart, contrib-
remains in the normal range. uting to the bilateral organ crosstalk for the development of
In class III patients, proteinuria is often more than 1 g/day CRS-5.
and many patients present with nephrotic range proteinuria.
Most of the patients suffer from hypertension and have Pathology of renal involvement
elevated creatinine at the presentation. Serologic tests usu-
ally indicate active lupus disease at this stage. The natural course of Fabry nephropathy in children
Patients of diffuse lupus nephritis (class IV) present with or adolescent patients is still largely not understood. Like
extensive clinical features. Almost all patients have protein- most aspects of the disease, renal pathology increases in
uria and half of these patients fall in the nephritic range. severity with age. In classically affected Fabry patients,
Hypertension is very common and renal dysfunction is typi- renal lesions result from Gb3 deposition in the glomerular
cal. These patients have very high titers of anti-DNA antibody endothelial, mesangial, intersticial cells, and in podocytes,
and low complement levels. which are terminally-differentiated epithelial cells that accu-
Patients with membranous lupus nephritis (class V) usually mulate numerous myelin-like inclusions in their lysosomes.
present with proteinuria, edema, and other typical nephrotic Podocyte foot process effacement has been described and
Since inflammation and immune disorders play an impor- 4. Calvin JE, Driedger AA, Sibbald WJ. An assessment of myocar-
tant role in the pathogenesis of sepsis, the removal of cyto- dial function in human sepsis utilizing ECG gated cardiac scin-
kines and immunomodulation are 2 approaches based on tigraphy. Chest. 1981;80(5):579-586.
extracorporeal techniques utilizing convection, high-volume 5. Merx MW, Weber C. Sepsis and the heart. Circulation. 2007;
116(7):793-802.
hemofiltration, and high-permeability membranes (89). The
6. Jafri SM, Lavine S, Field BE, Bahorozian MT, Carlson RW.
best results were obtained with high-permeability mem- Left ventricular diastolic function in sepsis. Crit Care Med.
branes and absorption (89). 1990;18(7):709-714.
A therapeutic alternative is provided by hit cellular 7. Poelaert J, Declerck C, Vogelaers D, Colardyn F, Visser CA. Left
elements accountable for apoptosis and neutrophil activa- ventricular systolic and diastolic function in septic shock. Inten-
tion and removed by polymyxin filters or a citrate anticoag- sive Care Med. 1997;23(5):553-560.
ulant-based selective cytopheretic device (90, 91). 8. Virzì GM, Clementi A, de Cal M, et al. Oxidative stress: dual
To manage heart complications, especially in the hyper- pathway induction in cardiorenal syndrome type 1 pathogen-
acute stage, a multipronged approach is required to maintain esis. Oxid Med Cell Longev. 2015;2015: Article ID 391790.
filling pressures with fluid therapy, together with vasopres- 9. Natanson C, Fink MP, Ballantyne HK, MacVittie TJ, Conklin JJ,
Parrillo JE. Gram-negative bacteremia produces both severe
sors, vasodilators, and inotropes. The vasopressors should
systolic and diastolic cardiac dysfunction in a canine model
be carefully employed because of depressive effects on car- that simulates human septic shock. J Clin Invest. 1986;78(1):
diac output (increased afterload) especially with concomitant 259-270.
hypovolemia. Vasodilators increase cardiac output, especial- 10. Merx MW, Liehn EA, Janssens U, et al. HMG-CoA reductase in-
ly in ischemic patients, while phosphodiesterase inhibitors hibitor simvastatin profoundly improves survival in a murine
have inotropic and vasodilatory effects, but they provide less model of sepsis. Circulation. 2004;109(21):2560-2565.
increase of myocardial oxygen requirements. 11. Stahl TJ, Alden PB, Ring WS, Madoff RC, Cerra FB. Sepsis-induced
Vasopressin increases arterial pressure, but it has negative diastolic dysfunction in chronic canine peritonitis. Am J Physiol.
effects on cardiac output. More recently levosimendan has 1990;258(3 Pt 2):H625-H633.
been proven to provide benefits in decompensated heart fail- 12. Cunnion RE, Schaer GL, Parker MM, Natanson C, Parrillo JE.
The coronary circulation in human septic shock. Circulation.
ure to increase ejection fraction and diuresis. Levosimendan ef-
1986;73(4):637-644.
ficacy is still to be proven in the prevention of type-5 CRS (92). 13. Levy RJ, Piel DA, Acton PD, et al. Evidence of myocardial
Renal support includes the removal of any nephrotoxic hibernation in the septic heart. Crit Care Med. 2005;33(12):
drug and media, the maintenance of adequate perfusion 2752-2756.
pressure and, if indicated, early intervention with dialysis 14. Hinshaw LB. Sepsis/septic shock: participation of the micro-
therapy (92, 93). circulation: an abbreviated review. Crit Care Med. 1996;24(6):
There is no role for dopamine for improving renal hemo- 1072-1078.
dynamics (94) and there are limited studies with fenoldopam 15. Horton JW, Maass D, White J, Sanders B. Nitric oxide modu-
(95). Norepinephrine decreases renal perfusion in normal lation of TNF-alpha-induced cardiac contractile dysfunction
conditions, but increases systemic blood pressure in septic is concentration dependent. Am J Physiol Heart Circ Physiol.
2000;278(6):H1955-H1965.
patients (89), while vasopressin increases diuresis and the
16. Francis SE, Holden H, Holt CM, Duff GW. Interleukin-1 in myo-
GFR in septic patients (96). cardium and coronary arteries of patients with dilated cardio-
Diuretics have a limited role in managing heart and kidney myopathy. J Mol Cell Cardiol. 1998;30(2):215-223.
involvement in septic patients (97). Renal replacement ther- 17. Reines HD, Halushka PV, Cook JA, Wise WC, Rambo W. Plasma
apy with continuous renal replacement therapy should be thromboxane concentrations are raised in patients dying with
promptly started (94). Early ultrafiltration seems to improve septic shock. Lancet. 1982;2(8291):174-175.
renal outcomes in septic shock patients. However, all of these 18. Kelm M, Schäfer S, Dahmann R, et al. Nitric oxide induced
data need to be confirmed in further clinical trials. contractile dysfunction is related to a reduction in myocardial
energy generation. Cardiovasc Res. 1997;36(2):185-194.
19. Preiser JC, Zhang H, Vray B, Hrabak A, Vincent JL. Time course
Disclosures of inducible nitric oxide synthase activity following endotoxin
Financial support: No grants or funding have been received for this administration in dogs. Nitric Oxide. 2001;5(2):208-211.
study. 20. Khadour FH, Panas D, Ferdinandy P, et al. Enhanced NO and
Conflicts of interest: None of the authors has financial interest related superoxide generation in dysfunctional hearts from endo-
to this study to disclose. toxemic rats. Am J Physiol Heart Circ Physiol. 2002;283(3):
H1108-H1115.
21. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS,
References Wenzel RP. The natural history of the systemic inflamma-
tory response syndrome (SIRS). A prospective study. JAMA.
1. Ronco C, McCullough P, Anker SD, et al. Acute Dialysis Qual- 1995;273(2):117-123.
ity Initiative (ADQI) consensus group. Cardio-renal syndromes: 22. Ympa YP, Sakr Y, Reinhart K, Vincent JL. Has mortality from
report from the consensus conference of the acute dialysis acute renal failure decreased? A systematic review of the lit-
quality initiative. Eur Heart J. 2010;31(6):703-711. erature. Am J Med. 2005;118(8):827-832.
2. Li X, Hassoun HT, Santora R, Rabb H. Organ crosstalk: the role 23. Jörres A, Gahl GM, Dobis C, et al. International Multicentre
of the kidney. Curr Opin Crit Care. 2009;15(6):481-487. Study Group. Haemodialysis-membrane biocompatibility and
3. Virzì GM, Clementi A, Brocca A, et al. Molecular and genetic mortality of patients with dialysis-dependent acute renal
mechanisms involved in the pathogenesis of cardiorenal cross failure: a prospective randomised multicentre trial. Lancet.
talk. Pathobiology. 2016;83(4):201-210. 1999;354(9187):1337-1341.
24. Brocca A, Virzì GM, Pasqualin C, et al. Cardiorenal syndrome 46. Shirahama T, Cohen AS. High-resolution electron micro-
type 5: in vitro cytotoxicity effects on renal tubular cells and in- scopic analysis of the amyloid fibril. J Cell Biol. 1967;33(3):
flammatory profile. Anal Cell Pathol (Amst). 2015;2015: Article 679-708.
ID 469461. 47. Falck HM, Törnroth T, Wegelius O. Predominantly vascular amy-
25. Cohen J. The immunopathogenesis of sepsis. Nature. loid deposition in the kidney in patients with minimal or no pro-
2002;420(6917):885-891. teinuria. Clin Nephrol. 1983;19(3):137-142.
26. Hotchkiss RS, Karl IE. The pathophysiology and treatment of 48. Omdal R, Lunde P, Rasmussen K, Mellgren SI, Husby G. Trans-
sepsis. N Engl J Med. 2003;348(2):138-150. esophageal and transthoracic echocardiography and Doppler-ex-
27. Ricci Z, Ronco C. Pathogenesis of acute kidney injury during aminations in systemic lupus erythematosus. Scand J Rheumatol.
sepsis. Curr Drug Targets. 2009;10(12):1179-1183. 2001;30(5):275-281.
28. Badr KF, Kelley VE, Rennke HG, Brenner BM. Roles for throm- 49. Doria A, Iaccarino L, Sarzi-Puttini P, Atzeni F, Turriel M, Petri M.
boxane A2 and leukotrienes in endotoxin-induced acute renal Cardiac involvement in systemic lupus erythematosus. Lupus.
failure. Kidney Int. 1986;30(4):474-480. 2005;14(9):683-686.
29. Kikeri D, Pennell JP, Hwang KH, Jacob AI, Richman AV, 50. Doherty NE, Siegel RJ. Cardiovascular manifestations of
Bourgoignie JJ. Endotoxemic acute renal failure in awake rats. systemic lupus erythematosus. Am Heart J. 1985;110(6):
Am J Physiol. 1986;250(6 Pt 2):F1098-F1106. 1257-1265.
30. Ravikant T, Lucas CE. Renal blood flow distribution in septic hy- 51. Cervera R, Font J, Paré C, et al. Cardiac disease in systemic
perdynamic pigs. J Surg Res. 1977;22(3):294-298. lupus erythematosus: prospective study of 70 patients. Ann
31. Langenberg C, Wan L, Egi M, May CN, Bellomo R. Renal blood Rheum Dis. 1992;51(2):156-159.
flow in experimental septic acute renal failure. Kidney Int. 52. Roberts WC, High ST. The heart in systemic lupus erythemato-
2006;69(11):1996-2002. sus. Curr Probl Cardiol. 1999;24(1):1-56.
32. Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo 53. Logar D, Kveder T, Rozman B, Dobovisek J. Possible association
R. Pathophysiology of septic acute kidney injury: what do we between anti-Ro antibodies and myocarditis or cardiac con-
really know? Crit Care Med. 2008;36(4)(Suppl):S198-S203. duction defects in adults with systemic lupus erythematosus.
33. Virzì GM, Clementi A, Ronco C. Cellular apoptosis in the cardio- Ann Rheum Dis. 1990;49(8):627-629.
renal axis. Heart Fail Rev. 2016;21(2):177-189. 54. Busteed S, Sparrow P, Molloy C, Molloy MG. Myocarditis as a
34. Cunningham PN, Dyanov HM, Park P, Wang J, Newell KA, prognostic indicator in systemic lupus erythematosus. Post-
Quigg RJ. Acute renal failure in endotoxemia is caused by grad Med J. 2004;80(944):366-367.
TNF acting directly on TNF receptor-1 in kidney. J Immunol. 55. Soltész P, Szekanecz Z, Kiss E, Shoenfeld Y. Cardiac mani-
2002;168(11):5817-5823. festations in antiphospholipid syndrome. Autoimmun Rev.
35. Papaioannou VE, Dragoumanis C, Theodorou V, Gargaretas 2007;6(6):379-386.
C, Pneumatikos I. Relation of heart rate variability to serum 56. Jensen-Urstad K, Svenungsson E, de Faire U, et al. Cardiac
levels of C-reactive protein, interleukin 6, and 10 in patients valvular abnormalities are frequent in systemic lupus ery-
with sepsis and septic shock. J Crit Care. 2009;24(4):625. thematosus patients with manifest arterial disease. Lupus.
e1-625.e7. 2002;11(11):744-752.
36. Ramchandra R, Wan L, Hood SG, Frithiof R, Bellomo R, May CN. 57. Petri M, Perez-Gutthann S, Spence D, Hochberg MC. Risk fac-
Septic shock induces distinct changes in sympathetic nerve ac- tors for coronary artery disease in patients with systemic lupus
tivity to the heart and kidney in conscious sheep. Am J Physiol erythematosus. Am J Med. 1992;93(5):513-519.
Regul Integr Comp Physiol. 2009;297(5):R1247-R1253. 58. Toloza SM, Uribe AG, McGwin G Jr, et al. LUMINA Study Group.
37. Nakada TA, Russell JA, Boyd JH, et al. Association of angio- Systemic lupus erythematosus in a multiethnic US cohort (LU-
tensin II type 1 receptor-associated protein gene polymor- MINA). XXIII. Baseline predictors of vascular events. Arthritis
phism with increased mortality in septic shock. Crit Care Med. Rheum. 2004;50(12):3947-3957.
2011;39(7):1641-1648. 59. Korkmaz C, Cansu DU, Kaşifoğlu T. Myocardial infarction in
38. Hagiwara S, Iwasaka H, Matumoto S, Hidaka S, Noguchi T. Ef- young patients (< or = 35 years of age) with systemic lupus
fects of an angiotensin-converting enzyme inhibitor on the erythematosus: a case report and clinical analysis of the lit-
inflammatory response in in vivo and in vitro models. Crit Care erature. Lupus. 2007;16(4):289-297.
Med. 2009;37(2):626-633. 60. Manger K, Kusus M, Forster C, et al. Factors associated with
39. Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids in the coronary artery calcification in young female patients with SLE.
treatment of severe sepsis and septic shock in adults: a system- Ann Rheum Dis. 2003;62(9):846-850.
atic review. JAMA. 2009;301(22):2362-2375. 61. Petri M, Lakatta C, Magder L, Goldman D. Effect of prednisone
40. Falk RH, Dubrey SW. Amyloid heart disease. Prog Cardiovasc and hydroxychloroquine on coronary artery disease risk factors
Dis. 2010;52(4):347-361. in systemic lupus erythematosus: a longitudinal data analysis.
41. Kyle RA, Bayrd ED. Amyloidosis: review of 236 cases. Medicine Am J Med. 1994;96(3):254-259.
(Baltimore). 1975;54(4):271-299. 62. McMahon M, Hahn BH. Atherosclerosis and systemic lupus
42. Gertz MA, Kyle RA. Secondary systemic amyloidosis: erythematosus: mechanistic basis of the association. Curr Opin
response and survival in 64 patients. Medicine (Baltimore). Immunol. 2007;19(6):633-639.
1991;70(4):246-256. 63. Svenungsson E, Jensen-Urstad K, Heimbürger M, et al. Risk fac-
43. Janssen S, Van Rijswijk MH, Meijer S, Ruinen L, Van der Hem tors for cardiovascular disease in systemic lupus erythemato-
GK. Systemic amyloidosis: a clinical survey of 144 cases. Neth J sus. Circulation. 2001;104(16):1887-1893.
Med. 1986;29(11):376-385. 64. Brucato A, Doria A, Frassi M, et al. Pregnancy outcome in 100
44. David J, Vouyiouka O, Ansell BM, Hall A, Woo P. Amyloidosis in women with autoimmune diseases and anti-Ro/SSA antibodies:
juvenile chronic arthritis: a morbidity and mortality study. Clin a prospective controlled study. Lupus. 2002;11(11):716-721.
Exp Rheumatol. 1993;11(1):85-90. 65. Comín-Colet J, Sánchez-Corral MA, Alegre-Sancho JJ, et al.
45. Okuda Y, Takasugi K, Oyama T, Onuma M, Oyama H. [Amyloi- Complete heart block in an adult with systemic lupus erythe-
dosis in rheumatoid arthritisclinical study of 124 histologically matosus and recent onset of hydroxychloroquine therapy.
proven cases]. Ryumachi. 1994;34(6):939-946. Lupus. 2001;10(1):59-62.
66. Cameron JS. Lupus nephritis. J Am Soc Nephrol. 1999;10(2): 83. Reinhart K, Bauer M, Riedemann NC, Hartog CS. New
413-424. approaches to sepsis: molecular diagnostics and biomarkers.
67. Weening JJ, DAgati VD, Schwartz MM, et al. The classification Clin Microbiol Rev. 2012;25(4):609-634.
of glomerulonephritis in systemic lupus erythematosus revis- 84. Dellinger RP, Levy MM, Carlet JM, et al. International Surviving
ited. J Am Soc Nephrol. 2004;15(2):241-250. Sepsis Campaign Guidelines Committee; American Associa-
68. Hilz MJ, Stemper B, Kolodny EH. Lower limb cold exposure tion of Critical-Care Nurses; American College of Chest Physi-
induces pain and prolonged small fiber dysfunction in Fabry cians; American College of Emergency Physicians; Canadian
patients. Pain. 2000;84(2-3):361-365. Critical Care Society; European Society of Clinical Microbiol-
69. Gubler MC, Lenoir G, Grünfeld JP, et al. Early renal changes in ogy and Infectious Diseases; European Society of Intensive
hemizygous and heterozygous patients with Fabrys disease. Care Medicine; European Respiratory Society; International
Kidney Int. 1978;13(3):223-235. Sepsis Forum; Japanese Association for Acute Medicine;
70. Fogo AB, Bostad L, Svarstad E, et al. All members of the Inter- Japanese Society of Intensive Care Medicine; Society of Criti-
national Study Group of Fabry Nephropathy (ISGFN). Scoring cal Care Medicine; Society of Hospital Medicine; Surgical In-
system for renal pathology in Fabry disease: report of the Inter- fection Society; World Federation of Societies of Intensive
national Study Group of Fabry Nephropathy (ISGFN). Nephrol and Critical Care Medicine. Surviving Sepsis Campaign: in-
Dial Transplant. 2010;25(7):2168-2177. ternational guidelines for management of severe sepsis and
71. Tøndel C, Bostad L, Hirth A, Svarstad E. Renal biopsy findings in septic shock: 2008. Crit Care Med. 2008;36(1):296-327.
children and adolescents with Fabry disease and minimal albu- 85. Vignon P, Frank MB, Lesage J, et al. Hand-held echocardiog-
minuria. Am J Kidney Dis. 2008;51(5):767-776. raphy with Doppler capability for the assessment of critical-
72. Fervenza FC, Torra R, Lager DJ. Fabry disease: an under- ly-ill patients: is it reliable? Intensive Care Med. 2004;30(4):
recognized cause of proteinuria. Kidney Int. 2008;73(10): 718-723.
1193-1199. 86. KDIGO Clinical Practice Guideline for Acute Kidney Injury:
73. Ortiz A, Oliveira JP, Waldek S, Warnock DG, Cianciaruso B, Wan- Summary of recommendation statements. Kidney Int Suppl.
ner C; Fabry Registry. Nephropathy in males and females with 2012;2(1):8-12. http://kdigo.org/clinical_practice_guidelines/
Fabry disease: cross-sectional description of patients before pdf/KDIGO%20AKI%20Guideline.pdf. Accessed October 7, 2017.
treatment with enzyme replacement therapy. Nephrol Dial 87. Calvin JE, Driedger AA, Sibbald WJ. An assessment of myo-
Transplant. 2008;23(5):1600-1607. cardial function in human sepsis utilizing ECG gated cardiac
74. Hůlková H, Ledvinová J, Poupĕtová H, Bultas J, Zeman J, Elleder M. scintigraphy. Chest. 1981;80(5):579-586.
[Postmortem diagnosis of Fabry disease in a female heterozy- 88. Bellomo R, Prowle JR, Echeverri JE, Ligabo V, Ronco C. Fluid
gote leading to the detection of undiagnosed manifest disease management in septic acute kidney injury and cardiorenal
in the family]. Cas Lek Cesk. 1999;138(21):660-664. syndromes. Contrib Nephrol. 2010;165:206-218.
75. Ashrafian H, Redwood C, Blair E, Watkins H. Hypertrophic 89. Tapia P, Chinchón E, Morales D, et al. Effectiveness of short-
cardiomyopathy:a paradigm for myocardial energy depletion. term 6-hour high-volume hemofiltration during refrac-
Trends Genet. 2003;19(5):263-268. tory severe septic shock. J Trauma Acute Care Surg. 2012.
76. Jung WI, Sieverding L, Breuer J, et al. 31P NMR spectroscopy 72(5):1228-1237; discussion 1237-1238.
detects metabolic abnormalities in asymptomatic patients 90. Nakamura M, Oda S, Sadahiro T, et al. Treatment of severe
with hypertrophic cardiomyopathy. Circulation. 1998;97(25): sepsis and septic shock by CHDF using a PMMA membrane
2536-2542. hemofilter as a cytokine modulator. Contrib Nephrol. 2010;166:
77. Linhart A, Palecek T, Bultas J, et al. New insights in cardiac 73-82.
structural changes in patients with Fabrys disease. Am Heart J. 91. Humes HD, Sobota JT, Ding F, Song JH; RAD Investigator
2000;139(6):1101-1108. Group. A selective cytopheretic inhibitory device to treat the
78. Elliott PM, Kindler H, Shah JS, et al. Coronary microvascular immunological dysregulation of acute and chronic renal fail-
dysfunction in male patients with Anderson-Fabry disease and ure. Blood Purif. 2010;29(2):183-190.
the effect of treatment with alpha galactosidase A. Heart. 92. Hou ZQ, et al. Effect of Levosimendan on Estimated Glomerular
2006;92(3):357-360. Filtration Rate in Hospitalized Patients with Decompensated
79. Hasegawa H, Takano H, Shindo S, et al. Images in cardiovascu- Heart Failure and Renal Dysfunction. Cardiovasc Ther. 2012.
lar medicine. Transition from left ventricular hypertrophy to 93. Chou YH, Huang TM, Wu VC, et al. NSARF Study Group. Impact
massive fibrosis in the cardiac variant of Fabry disease. Circu- of timing of renal replacement therapy initiation on outcome
lation. 2006;113(16):e720-e721. of septic acute kidney injury. Crit Care. 2011;15(3):R134.
80. Takenaka T, Teraguchi H, Yoshida A, et al. Terminal stage car- 94. Bellomo R, Wan L, May C. Vasoactive drugs and acute kidney
diac findings in patients with cardiac Fabry disease: an elec- injury. Crit Care Med. 2008;36(4)(Suppl):S179-S186.
trocardiographic, echocardiographic, and autopsy study. J 95. Landoni G, Bignami E, Gonfalini M, Mizzi A, Zangrillo A.
Cardiol. 2008;51(1):50-59. Fenoldopam in cardiac surgery-associated acute kidney injury.
81. Sharma A, Sartori M, Zaragoza JJ, et al. Fabrys disease: an Int J Artif Organs. 2008;31(6):561.
example of cardiorenal syndrome type 5. Heart Fail Rev. 96. Guzman JA, Rosado AE, Kruse JA. Vasopressin vs norepineph-
2015;20(6):689-708. rine in endotoxic shock: systemic, renal, and splanchnic hemo-
82. Germain DP. Aortic root dilatation is highly prevalent in male dynamic and oxygen transport effects. J Appl Physiol (1985).
patients affected with Fabry disease and correlates with the 2003;95(2):803-809.
presence of a megadolicho-ectatic basilar artery. Am J Hum 97. Nigwekar SU, Waikar SS. Diuretics in acute kidney injury. Semin
Genet. 2007;81:300. Nephrol. 2011;31(6):523-534.