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163. Steppan CM, Bailey ST, Bhat S et al. The hormone resistin links
obesity to diabetes. Nature 2001; 409: 307312
164. Steppan CM, Lazar MA. The current biology of resistin. J Intern
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165. Kielstein JT, Becker B, Graf S et al. Increased resistin blood levels are
not associated with insulin resistance in patients with renal disease.
Am J Kidney Dis 2003; 42: 6266
UCL Center for Nephrology, University College London Medical School, London, UK, 2Division of Applied Cachexia Research,
Department of Cardiology, Charit-Universittsmedizin, Berlin, Germany, 3Department of Anesthesiology and Critical Care Medicine,
Hpital Lariboisire, University Paris 7 Paris Diderot, France. U942 Inserm, Paris, France, 4Department of Internal Medicine and
Metabolic Diseases, Cardiology Section, Le Scotte Hospital, Siena, Italy, 5Department of Internal Medicine, S. Bortolo Hospital,
Vicenza, Italy, 6Department of Intensive Care Medicine, Austin Hospital, Melbourne, Australia, 7Cardiac Department, Faculty of
Public Health, Medical University, Military Hospital, Wroclaw, Poland, 8Department of Cardiology, VA Medical Centre, Minneapolis,
MN, USA, 9Department of Cardiology, Ospedale San Filippo Neri, Rome, Italy, 10Division of Critical Care Medicine, University of
Alberta Hospital, Edmonton, Canada, 11Department of Nephrology, University of Colorado Health Sciences Center, Denver, CO,
USA, 12Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza, Italy, 13Department of Cardiology,
University of Padova, Italy, 14Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland, 15Trial Coordination
Center, Department of Cardiology and Epidemiology, University Medical Center Groningen, Hanzeplein, The Netherlands, 16Division
of Nephrology, London Health Sciences Centre, University Hospital, London, Ontario, Canada, 17Department of Surgery, The George
Washington University, Washington DC, USA, 18Department of Medicine and Cardiology, San Diego VA Medical Center and University
of California, San Diego, CA, USA, 19Department of Cardiology, Mayo Clinic, Rochester, MN, USA, 20Department of Medicine,
Divisions of Cardiology, Nutrition and Preventive Medicine, William Beaumont Hospital, Royal Oak, MI, USA, 21Department of
Anesthesiology, Duke University Medical Center, Durham, NC, USA, 22R. Adams Cowley Shock Trauma Center, University of
Maryland Medical Center, Baltimore, MD, USA, 23Division of Nephrology, Mediciti Hospitals, Hyderabad, India, 24Department of
Intensive Care, San Bortolo Hospital, Vicenza, Italy and 25Department of Nuclear Medicine, San Bortolo Hospital, Vicenza, Italy
Correspondence and offprint requests to: C. Ronco; E-mail: cronco@goldnet.it
Introduction
Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are
prone to cardiac failure. This has led to the concept of
cardio-renal syndromes, which can be an acute or chronic
cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic
The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: journals.permissions@oxfordjournals.org
2078
Table 1. Heart failure is a clinical syndrome based on the combination of symptoms and signs typical of heart failure supported by objective evidence
of a structural or functional abnormality of the heart at rest [1]
Symptoms
Signs
Evidence
Breathlessness at rest
Breathlessness on exertion
Fatigue
Tiredness
Ankle swelling
Tachycardia
Tachypnoea
Pulmonary rales
Pleural effusion
Raised jugular venous pressure
Peripheral oedema
Hepatomegaly
Cardiomegaly
Third heart sound
Cardiac murmurs
Abnormal echocardiogram
Raised natriuretic peptide concentration
Drugs
Toxins
Endocrine
Nutritional
Others
Circulatory failure
Familial/genetic
Myocarditis
Hypertrophic
Dilated cardiomyopathy
Restrictive cardiomyopathy
Arrhythmogenic right
ventricular tachycardia
induced cardiomyopathy
Cytotoxics
Beta-blockers
Calcium channel antagonists
Antiarrhythmics
Alcohol
Cocaine
Heavy metal poisoning
Herbal medications
Diabetes mellitus
Hypo- and/or hyperthyroidism
Cushings syndrome
Acromegaly
Phaeochromocytoma
Thiamine deficiency
Selenium deficiency
Obesity
Cachexia
Amyloid
Sarcoid
Haemochromatosis
Sickle cell disease
Connective tissue diseases
Chagas disease
HIV infection
Peripartum cardiomyopathy
Septicaemia
Anaemia
Shunts
Thyrotoxicosis
Tamponade
Pulmonary embolism
Cardio-Renal syndromes
The cardiorenal syndromes are a heterogenous group of
conditions, comprising both cardiac and renal dysfunction,
typically on a background of chronic disease. Cardiac failure has recently been defined by the European Society of
Cardiology (ESC) (Table 1) [1]. Heart failure can occur
2079
GFR criteria
Urine output
Risk
Injury
Failure
Loss
End-stage kidney disease
GFR, glomerular filtration rate; SCreat, serum creatinine (mg/dL; to convert to mol/l multiply by 0.88). This was modified by the Acute Kidney Injury
Network to define the acute nature of acute kidney injury as a rise in creatinine or fall in urine output within a 48-h time frame [9].
eGFR mL/min/1.73 m2
90
6089
4559
3045
1529
<15 (or dialysis)
Chronic
Cocaine
CCB selfpoisoning
Leptospirosis
Malaria
SLE
Scleroderma renal crisis
HUS
Liver failure
Systemic sepsis
Acute sickle cell disease
Phaeochromoctoma
Burkitts lymphoma
Amyloid
Sarcoid
TB
HIV
Hypertension
Diabetes
Liver failure
Sickle cell disease
Post bone marrow transplant
Fabrys disease
2080
Table 6. Pharmacological agents used in the management of or under investigation for the treatment of acute and chronic heart failure in patients with
the cardiorenal syndrome (CRS) and/or Reno-Cardiac syndrome (RCS)
Drug classes
Indication
Acute RCS
Chronic RCS
Nephroprotection
Chronic CRS
RAAS antagonism
Decrease proteinuria
Beta-blockers
Acute CRS
Chronic RCS
Prevent remodelling
Cardioprotection and prevention
of tachyarrhythmias
Hypotension, bradyarrhythmias
Deterioration in heart failure
symptoms (transient)
Asthma
As above
Aldosterone antagonists
Chronic CRS
Chronic RCS
Diuretics
Acute CRS
Chronic CRS
Acute RCS
Chronic RCS
Secondary CRS
Digoxin
Chronic CRS and
chronic RCS
Reduce HF hospitalizations
Improve symptoms
Mortality unchanged
Acute CRS
Chronic CRS
Continued
Chronic CRS
2081
Table 6. Continued
Drug classes
Inotropic agents
Dopamine
Dobutamine
Levosimendan
Milrinone
Enoximone
Vasopressors
Norepinephrine
Indication
Acute CRS
Arrhythmias
Acute CRS
Acute CRS
Epinephrine
Vasodilators
Nitroprusside
Nitrates
Nesiritide
Hypotension especially in
hypovolaemic patients
Cyanide intoxication for nitroprusside
Hypotension
Can worsen kidney function,
but the data uncertain
Acute CRS
Acute CRS
Respiratory depression
No changes in mortality
Currently licenced only for
pulmonary hypertension
Weight loss?
Vasopressin antagonists
Morphine
Endothelin antagonists
Chronic RCS
As above
Parenteral iron
Chronic CRS
Chronic RCS
Risk of bleeding
Potential risk of vascular calcification
Allopurinol
Chronic CRS
Chronic RCS
Warfarin/antiplatelets
Chronic CRS
Chronic RCS
As above
CO, cardiac output; Na, sodium; K, potassium; H2O, water; ACEIs, angiotensin converting enzyme inhibitors; ARBs, angiotensin II receptor antagonist; EPO, recombinant human erythropoietin; statins, HMG CoA 3 reductase inhibitors; RRT, renal replacement therapy.
Results
The following questions were considered:
Q 1: What are the key management goals in the treatment of patients with cardio-renal syndromes?
Acute CRS
2082
Q 4: What is the best clinical management for renal failure patients who develop acute Reno-Cardiac syndrome?
Q 5: What is the best clinical management for renal
failure patients who develop chronic Reno-Cardiac
syndrome?
Q 6: What clinical research agenda is required to evaluate these management strategies?
A literature search was made concentrating on core management areas, both from the patients perspective in terms
of relief of symptoms, morbidity, quality of life and survival (clinical effectiveness) and for the clinician treating
the patient to improve cardiac output and renal function.
Discussion
2083
vasodilator
nitrate, nesiritide
levosimendan
vasodilator inotrope
dobutamine
Phospho-diesterase inhibitor
levosimendan
consider preload
reduction
fluids, inotrope,
dopamine
Poor Response
Inotrope,
vasopressor
mechanical support
Fig. 1. Algorithm for the management of acute heart failure. ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker;
nitrate, nitroglycerin or nitroprusside; phosphodiesterase inhibitor: milrinone, enoximone.
Good Response
stabilize
initiate diuretic
ACEI/ARB
-blocker
2084
yes
no
yes
yes
persisting symptoms
QRS> 120 ms
no
yes
consider
ICD
no
no further
treatment
indicated
consider digoxin
hydralazine/nitrate
LVAD and cardiac transplantation
Fig. 2. Algorithm for the management of chronic heart failure (CHF). ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor
blocker; LVEF, left ventricular ejection fraction; CRT-D, resynchronization therapy defibrillator; CRT-P, cardiac resynchronization therapy
pacemaker; LVAD, left ventricular assist device.
Type 2
Type 3
Type 4
Type 5
Etiologies
AV, arterio-venous; LV, left ventricule; COPD, chronic obstructive pulmonary disease.
consider
CRT-P or CRT-D
LVEF <35%
Repeated studies have shown that only a small proportion of CKD patients are prescribed cardioprotective
ACEIs and beta-blockers, despite these drugs having
been shown to reduce cardiovascular morbidity and mortality [25,133,134]. Although many patients with CKD
were excluded from the major trials, smaller prospective
studies reported a benefit for carvedilol [135]. The prescription of cardioprotective medications has not been
shown to increase the incidence of intradialytic hypotension [128]. However, hypotension can occur following
bradykinin generation, which may be exacerbated by
ACEIs [18].
Additional management strategies include correcting
anaemia, controlling calcium and phosphate product and
parathyroid hormone to minimize vascular calcification
[136,137] and providing adequate dialysis [138].
Pericardial tamponade occasionally occurs in uraemia
and typically responds to intensive dialysis and biochemical control but may require drainage [139].
Although arterio-venous fistulae (AVF) are the preferred access for haemodialysis [140]; high-flow fistulae
or grafts may cause significant cardiac shunting leading
to pulmonary hypertension and high output CHF [141].
Patent AVF in renal transplant patients predispose to
CHF [142]. However, central venous access catheters predispose to infections including bacterial endocarditis.
Although there is strong evidence for treatment strategies using ACEIs, beta-blockers, ARBs and aldosterone
antagonists from well-designed randomized clinical trials
in CHF, there is a paucity of equivalent evidence for patients with CKD and dialysis [143]. The limited trials
available for review are in keeping with previous results
for beta-blockers and ACEIs [134], although combinations of ACEIs, ARBs and statins have not always shown
benefit [101]. Thus, randomized clinical trials of management of CHF are required in both CKD and dialysis
patients.
Unfortunately, there is limited evidence for the management of acute heart failure, let alone for patients with
abnormal renal function. This is one area where the development of biomarkers for both acute renal and cardiac
dysfunction could aid the development of clinical trials
for patients with an acute cardio-renal syndrome to allow
clinical-goal-directed therapies to be studied.
Conflict of interest statement. None declared.
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Received for publication: 18.11.09; Accepted in revised form: 15.4.10
Transplantation Institute, Department of Immunology, Transplantology and Internal Medicine, Warsaw Medical University, Warsaw,
Poland, 2Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland, 3Department of Pathology, Warsaw
Medical University, Warsaw, Poland, 4Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw,
Poland and 5Unit of Abdominal Transplantation, Department of Abdominal and Transplantation Surgery, Universit catholique de
Louvain-UCL, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Correspondence and offprint requests to: Krzysztof Mucha; E-mail: kjmucha@gmail.com
Abstract
Post-transplant lymphoproliferative disorders (PTLDs) are
serious, life-threatening complications of solid-organ
transplantation (SOT) and bone marrow transplantation
leading to a high mortality (3060%). PTLD represents a
heterogeneous group of lymphoproliferative diseases.
They become clinically relevant because of the expansion
of transplantation medicine together with the development
of potent immunosuppressive drugs. Although the diagnostic morphological criteria of different forms of PTLD
are commonly known, rapid and correct diagnosis is not
always easy. Because of the limited number of clinical
trials, a consensus is lacking on the optimal treatment of
PTLD. This review focuses on incidence, risk factors, clin-
Introduction
The term post-transplant lymphoproliferative disorder or
disease (PTLD) was first introduced in 1984 by Starzl [1].
Today, it represents a heterogeneous group of lymphoproli-
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and reproduction in any medium, provided the original work is properly cited.