Presentation
Results: A total of 181 neonates presented with CKD. Their mean age at the time of presentation was 11.1 days (95% confidence interval [CI]: 9.5-12.8) and the mean creatinine level was 106.5 µmol/ (95% CI: 91.3-121.7). [ncbi.nlm.nih.gov]
The higher the stage (G1->G5) and the greater the amount of protein present in the urine (A1->A3) the more “severe” the CKD. [renal.org]
It is present when the glomerular filtration rate (GFR) is less than 60 ml/min/1.73 m 2 for three consecutive months or greater than or equal to this value in patients with a kidney damage that is present for three or more months 1. [radiopaedia.org]
Entire Body System
- Anemia
The thyroid gland function should be assessed both in differential diagnostics of anemia and in case of unsatisfactory treatment with ESA. [ncbi.nlm.nih.gov]
It also suggests that factors causing the anemia, not the anemia itself, have adverse consequences. [content.nejm.org]
The high rates of heart disease and anemia in the patients who died are consistent with the hypothesis that anemia accelerates the progression of heart disease and increases the risk of death. [archinte.ama-assn.org]
- Inflammation
[…] between oxidative stress, inflammation and endothelial dysfunction. [ncbi.nlm.nih.gov]
Most important, we did not have direct measurements of inflammation ( e.g., C-reactive protein, IL-6) available to confirm the presence or absence of MICS. [jasn.asnjournals.org]
This article reviews the recent epidemiologic data linking obesity and the metabolic syndrome to CKD and summarizes the potential mechanisms of renal injury in this setting, with a focus on the role of inflammation, lipotoxicity, and hemodynamic factors [cjasn.asnjournals.org]
- Fatigue
The Vitality and Physical functioning domains of the SF-36 and the FACT-An Total, Fatigue and Anemia subscales were identified as domains relevant to CKD-associated anemia. [ncbi.nlm.nih.gov]
These include fatigue, drowsiness, decrease in urination or inability to urinate, dry skin, itchy skin, headache, weight loss, nausea, bone pain, skin and nail changes and easy bruising. [hopkinsmedicine.org]
Symptoms can include urinating at night, fatigue, nausea, itching, muscle twitching and cramps, loss of sensation, confusion, difficulty breathing, and yellow-brown skin. Diagnosis is by blood and urine tests. [merckmanuals.com]
Symptoms can include urinating at night, fatigue, nausea, itching, muscle twitching and cramps, loss of appetite, confusion, difficulty breathing, and body swelling (most commonly the legs). Diagnosis is by blood and urine tests. [msdmanuals.com]
- Congestive Heart Failure
[…] renal disease stage 5 with congestive heart failure Benign hypertensive heart and chronic renal disease with congestive heart failure Benign hypertensive heart and CKD Benign hypertensive heart and CKD, stage 5 (GFR Benign hypertensive heart and CKD, [icd9data.com]
Death and hospitalization for congestive heart failure accounted for 74.8% of the composite events. [content.nejm.org]
In addition, congestive heart failure, coronary artery disease, diabetes, and anemia were more prevalent in the patients who died but hypertension prevalence was similar across all stages. [archinte.ama-assn.org]
An extensive study evidenced that treatment and prevention of coronary artery disease, congestive heart failure, diabetes mellitus, and anemia should be the target treatment to reduce the mortality of patients with CKD 3. [radiopaedia.org]
[…] and chronic kidney disease Hypertensive heart and chronic kidney disease with congestive heart failure Hypertensive heart and kidney disease Hypertensive heart and kidney disease with chf Hypertensive heart/kidney dis w/ congestive heart fail Hypertensive [icd10data.com]
- Sepsis
Those things can happen when you: Have a traumatic injury with blood loss, such as in a car wreck Are dehydrated or your muscle tissue breaks down, sending too much protein into your bloodstream Go into shock because you have a severe infection called sepsis [webmd.com]
Consider serious causes such as bleeding, cardiac dysfunction, and sepsis. IV fluids should not be administered routinely (as is done for many ED patients). [emedicine.com]
Respiratoric
- Dyspnea
A 57-year-old man was admitted to our hospital due to presyncope and dyspnea during exercise with a history of CKD-HD. [ncbi.nlm.nih.gov]
| N Engl J Med 2017; 376:2470 A 69-year-old woman with chronic kidney disease and myelofibrosis presented with dyspnea and weakness. Imaging revealed lesions in both perirenal spaces, and extramedullary hematopoiesis was detected on biopsy. [nejm.org]
Symptoms and historical issues associated with CKD should also be elicited such as dyspnea, changes in weight, edema, rashes, arthralgias, hematuria, osteoporosis, anemia, confusion, nausea, bruising, and other signs of uremia. [clinicaladvisor.com]
Heart failure caused by hypertension or coronary artery disease and renal retention of sodium and water may lead to dependent edema and/or dyspnea. [merckmanuals.com]
- Hyperpnea
Acidosis may present as shortness of breath due to the work of breathing from compensatory hyperpnea. [emedicine.com]
Gastrointestinal
- Nausea
The symptoms of hypercalcemia include: Feeling tired Difficulty thinking clearly Loss of appetite Nausea Vomiting Constipation Increased thirst Increased urination Weight loss Other side effects of Vitamin D include: Diarrhea Nausea Swelling Allergic [emedicinehealth.com]
A 69-year-old male was admitted to the hospital with a chief complaint of abdominal pain, nausea, and vomiting. He had an extensive past medical history, including diabetes mellitus type 2 and chronic kidney disease stage III. [ncbi.nlm.nih.gov]
Diet may also help alleviate symptoms of nausea. Salt intake must be carefully regulated to control hypertension. Potassium and phosphorus consumption, over time, may also need to be restricted. [medicalnewstoday.com]
Adults can have non-specific symptoms like nausea, vomiting, weight loss, and easy fatigability. Hypertension is common in adults with chronic kidney disease. [radiopaedia.org]
- Vomiting
While admitted for diagnostic evaluation of frequent falls, transient ischaemic attacks and pain management, she developed vomiting, diarrhoea, melena and hypotension. [ncbi.nlm.nih.gov]
Adults can have non-specific symptoms like nausea, vomiting, weight loss, and easy fatigability. Hypertension is common in adults with chronic kidney disease. [radiopaedia.org]
Feeling of nausea or vomiting. Muscle cramps. Darkness of skin. Cleveland Clinic News & More Cleveland Clinic News & More [my.clevelandclinic.org]
- Hiccup
[…] skin, called uremic frost drowsiness mental cloudiness numbness in your hands and feet restless leg syndrome brittle hair and nails itching weight loss a loss of muscle mass muscle twitching and cramps easy bruising and bleeding blood in your stools hiccups [healthline.com]
Hiccups, pericarditis, coma and seizures are only seen in very severe CKD. [patient.info]
- Polydipsia
[…] intake to prevent disease such as nephrolithiasis; ( 2 ) those who need a high fluid intake to compensate for a underlying disease, such as renal or central diabetes insipidus or salt-wasting nephropathy; and ( 3 ) those who have conditions such as polydipsia [cjasn.asnjournals.org]
Cardiovascular
- Hypertension
AND chronic kidney disease Hypertensive heart AND chronic kidney disease with congestive heart failure Hypertensive heart and CKD Hypertensive heart and CKD, w CHF Hypertensive heart and kidney disease Hypertensive heart and kidney disease with chf Hypertensive [icd9data.com]
Author information 1 Department of Nephrology, Hypertension and Family Medicine, WAM Teaching Hospital, 90-549 Lodz, Poland. [email protected]. 2 Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland [ncbi.nlm.nih.gov]
- Heart Failure
The war against heart failure: the Lancet lecture. The Lancet. 2015; 385: 812–24. [astrazeneca.com]
[…] renal disease stage 5 with congestive heart failure Benign hypertensive heart and chronic renal disease with congestive heart failure Benign hypertensive heart and CKD Benign hypertensive heart and CKD, stage 5 (GFR Benign hypertensive heart and CKD, [icd9data.com]
Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286421- 426 PubMed Google Scholar Crossref [archinte.ama-assn.org]
Death and hospitalization for congestive heart failure accounted for 74.8% of the composite events. [content.nejm.org]
Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. [jasn.asnjournals.org]
- Hypotension
While admitted for diagnostic evaluation of frequent falls, transient ischaemic attacks and pain management, she developed vomiting, diarrhoea, melena and hypotension. [ncbi.nlm.nih.gov]
The most common modality of RRT utilised in the diabetic patient remains HD but this method is associated with many clinical problems, in particular the managment of vascular access and frequent intradialytic hypotension. [doi.org]
[…] values often readily available in the electronic health record (EHR), we are not only able to identify and stage AKI, but can also utilize additional information in the EHR to understand confounding factors like comorbidities, medication administration, hypotension [ndt.oxfordjournals.org]
[…] and Shock Hypotension in dialysis patients may be due to any of the causes encountered in any other patient. [emedicine.com]
- Thrombosis
OBJECTIVE: Introduction: One of the major complications of stage V chronic kidney disease (CKD), treated by program hemodialysis, are hemostatic system disturbances resulting in thrombosis development. [ncbi.nlm.nih.gov]
To summarize, vascular (large- and small-vessel) causes of intrinsic AKI include the following: Renal artery obstruction - Thrombosis, emboli, dissection, vasculitis Renal vein obstruction - Thrombosis Microangiopathy - TTP, HUS, disseminated intravascular [emedicine.com]
[…] of Clinical Outcomes Management May 25, 2018 Neurology Board Review: Multiple Sclerosis May 25, 2018 May 25, 2018 Journal of Clinical Outcomes Management More Quality Improvement Case Studies February 1, 2019 Reducing Rates of Perioperative Deep Vein Thrombosis [jcomjournal.com]
First, uremia-induced platelet dysfunction may protect against thrombosis. Second, competing comorbid risks may attenuate the opportunity for benefit. [onlinejacc.org]
Venous thromboembolism Patients with CKD have an increased risk of deep venous thrombosis (DVT) and require appropriate pharmacologic prophylaxis. [clinicaladvisor.com]
Skin
- Ulcer
We present the case of a non-dialyzed patient with chronic kidney disease and biopsy-proven calciphylaxis who presented with painful cutaneous ulcers on both legs. [ncbi.nlm.nih.gov]
Small sores or breaks in the skin may become deeper skin sores (ulcers). The affected limb may need to be amputated if these skin ulcers do not heal or become larger, deeper, or infected. [nlm.nih.gov]
- Pruritus
The prevalence of CKD-associated pruritus for mean dialysis duration [ncbi.nlm.nih.gov]
Pruritus Common, Bothersome in Non-Dialysis CKD In a study of patients with non-dialysis CKD, pruritus was associated with poor health-related quality-of-life. [renalandurologynews.com]
Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia, nocturia, lassitude, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, water retention, undernutrition, peripheral neuropathies [msdmanuals.com]
Pruritus may respond to dietary phosphate restriction and phosphate binders if serum phosphate is elevated. Severe protein restriction in renal disease is controversial. [merckmanuals.com]
- Skin Ulcer
The skin ulcers drastically improved within 6 months after the initiation of hemodialysis, aggressive wound care, the control of a mineral and bone disorder, and the administration of sodium thiosulfate and hyperbaric oxygen therapy. [ncbi.nlm.nih.gov]
You may not notice a foot injury until you have severe damage to the skin and tissue below, or you get a severe infection. Diabetes can also damage blood vessels. Small sores or breaks in the skin may become deeper skin sores (ulcers). [nlm.nih.gov]
- Purpura
Signs and symptoms Skin Skin examination may reveal the following in patients with AKI: Livedo reticularis, digital ischemia, butterfly rash Palpable purpura: systemic vasculitis Maculopapular rash: Allergic interstitial nephritis Track marks (ie, intravenous [emedicine.com]
Disease for Kidney Transplantation Introduction Cardiovascular Disease Malignancy Infections Recurrent Kidney Disease Renal-Limited Disease Recurrence Systemic Disease Recurrences Primary Oxalosis Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura [elsevier.com]
- Petechiae
[…] indicate renal artery stenosis (a systolic bruit is of limited diagnostic value but the presence of a systolic and diastolic bruit is highly correlated with renal artery stenosis), edema, pulse deficits (especially in the lower extremities), rashes, petechia [clinicaladvisor.com]
Urogenital
- Kidney Failure
failure syndrome kidney failure, chronic CRF - Chronic Renal Failure Chronic Renal Failure Disease Chronic Renal Failure edit Language Label Description Also known as English chronic kidney disease progressive loss in kidney function over a period of [wikidata.org]
Chronic kidney failure, as opposed to acute kidney failure, is a slow and gradually progressive disease. Even if one kidney stops functioning, the other can carry out normal functions. [medicalnewstoday.com]
Booklets What I need to know about Kidney Failure and How it’s Treated Treatment Methods for Kidney Failure: Hemodialysis Treatment Methods for Kidney Failure: Peritoneal Dialysis Treatment Methods for Kidney Failure: Kidney Transplantation Kidney Failure [niddk.nih.gov]
People with permanent kidney failure need dialysis or a transplanted kidney to do the work of their failed kidneys. Chronic renal failure is in contrast to acute renal failure. It may also be referred to as chronic kidney failure. [medicinenet.com]
Ckd may lead to kidney failure. [icd9data.com]
- Renal Insufficiency
The first task confronting the physician caring for a patient with renal disease is to decide whether the renal insufficiency is acute or chronic. [ncbi.nlm.nih.gov]
[…] failure Chronic progressive renal insufficiency Chronic renal failure Chronic renal failure syndrome Chronic renal impairment Chronic renal impairment associated with Type 2 diabetes mellitus Chronic renal insufficiency CKD (chronic kidney disease) Diabetes [icd9data.com]
The end-stage of chronic renal insufficiency. [icd10data.com]
- Uremia
Improved understanding of the pathogenic mechanisms underlying IR in CKD may lead to more effective therapeutic strategies to reduce uremia-associated morbidity and mortality. [ncbi.nlm.nih.gov]
2017 2018 2019 Billable/Specific Code Type 1 Excludes acute kidney failure ( N17.- ) chronic kidney disease ( N18.- ) chronic uremia ( N18.9 ) extrarenal uremia ( R39.2 ) prerenal uremia ( R39.2 ) renal insufficiency (acute) ( N28.9 ) uremia of newborn [icd10data.com]
As kidney function declines, waste products build up in the blood causing a condition known as uremia. [davita.com]
Some patients may need dialysis or transplantation at GFR 15 mL/min/1.73 m 2 because of symptoms of uremia. [web.archive.org]
- Renal Injury
This article reviews the recent epidemiologic data linking obesity and the metabolic syndrome to CKD and summarizes the potential mechanisms of renal injury in this setting, with a focus on the role of inflammation, lipotoxicity, and hemodynamic factors [cjasn.asnjournals.org]
In the face of renal injury (regardless of the etiology), the kidney has an innate ability to maintain GFR, despite progressive destruction of nephrons, as the remaining healthy nephrons manifest hyperfiltration and compensatory hypertrophy. [emedicine.medscape.com]
- Nocturia
Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia, nocturia, lassitude, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, water retention, undernutrition, peripheral neuropathies [msdmanuals.com]
Mild to moderate loss of kidney function may cause only mild symptoms, such as the need to urinate several times during the night (nocturia). [merckmanuals.com]
Neurologic
- Seizure
Although carbapenem-related neurotoxicity most commonly manifests as seizures, our series indicates that acute and reversible peripheral neuropathy can also develop. [ncbi.nlm.nih.gov]
[…] develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia, nocturia, lassitude, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, water retention, undernutrition, peripheral neuropathies, and seizures [msdmanuals.com]
[…] cramping, and pain Not being able to feel things in some parts of your body Restless legs syndrome, which is when you have pain or other bad feelings in your legs, usually at night, that make you need to move them Problems with thinking, confusion, and seizures [merckmanuals.com]
- Headache
In the immediate postoperative period, he developed sudden, severe headache and was found to have bifrontal extradural hemorrhage. He underwent prompt drainage of the hematoma and was discharged on the fifth postoperative day in stable condition. [ncbi.nlm.nih.gov]
These include fatigue, drowsiness, decrease in urination or inability to urinate, dry skin, itchy skin, headache, weight loss, nausea, bone pain, skin and nail changes and easy bruising. [hopkinsmedicine.org]
Kidney Disease Symptoms More frequent urination, especially at night Feeling tired and having less energy Trouble sleeping Nausea Headaches Weight loss and/or loss of appetite Swelling in feet, ankles or around the eyes due to fluid buildup There are [mottchildren.org]
The waste buildup can make you sick and you may have these symptoms: swelling of the ankles, face or belly, vomiting, loss of appetite, fatigue, weakness, confusion and headaches. [heart.org]
- Lethargy
Case study 2 June, 83 years of age, is a female nursing home resident with a 3 month history of lethargy, anorexia and itch. [racgp.org.au]
Symptoms of anaemia include: tiredness lethargy shortness of breath (dyspnoea) palpitations (awareness of heartbeat) Anaemia can occur because of many other conditions and your doctor will investigate to rule out any other possible causes. [hse.ie]
Encephalopathy, a condition in which the brain malfunctions, may ensue and lead to confusion, lethargy, and seizures. Heart failure may cause shortness of breath. Body swelling may develop, particularly in the legs. [msdmanuals.com]
Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). [en.wikipedia.org]
- Convulsions
Convulsions were reported in nine patients in the darbepoetin alfa group and in four patients in the placebo group. No cases of antibody-mediated pure red-cell aplasia were reported in either group. [doi.org]
- Burning Sensation
Then suddenly again I felt pain inthe urinary system now,lot of urination, slight burning sensation. [reakomp.ru]
Workup
Acute Kidney Injury Workup. Medscape Reference. Available online at http://emedicine.medscape.com/article/243492-workup#c13. Accessed May 2016. (April 2014) Seaborg E. New Biomarkers Offer Hope for Identifying Acute Kidney Injury Risk. [labtestsonline.it]
Other benefits of early nephrology referral include proper patient education regarding options for renal replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an arteriovenous fistula in those patients opting for [en.wikipedia.org]
[…] stenosis, renal atheroembolic disease, atherosclerosis with aortorenal occlusion, and certain cases of necrotizing vasculitis (eg, polyarteritis nodosa) Renal biopsy: Can be useful in identifying intrarenal causes of AKI and directing targeted therapy See Workup [emedicine.com]
The increasing sensitivity of cTn assays has had a dramatic impact on the use of cTn testing, which is now an essential component of the diagnostic workup and management of acute coronary syndromes (ACS). [journal.frontiersin.org]
X-Ray
- Nephrolithiasis
J Urol 155 : 839 –843, 1996 ↵ Strauss AL, Coe FL, Deutsch L, Parks JH: Factors that predict relapse of calcium nephrolithiasis during treatment: A prospective study. [cjasn.asnjournals.org]
Nephrolithiasis and Chronic Kidney Disease Introduction Types of Stones Clinical Presentation Differential Diagnosis Diagnosis Nephrolithiasis and CKD Management General Measures to Prevent Stone Recurrence Treatment of Specific Stone Types Conclusion [elsevier.com]
Information regarding other risk factors such as vascular disease, tobacco dependence, dyslipidemia, a history of urological issues (recurrent infections, nephrolithiasis, prostatic or other obstructions), congenital issues such as a solitary kidney, [clinicaladvisor.com]
Control of underlying disorders Possible restriction of dietary protein, phosphate, and potassium Vitamin D supplements Treatment of anemia Treatment of contributing comorbidities (eg, heart failure, diabetes mellitus, nephrolithiasis, prostatic hypertrophy [merckmanuals.com]
[…] nephrotic range proteinuria (UACR greater than 300 mg/g) should be seen by a nephrologist, as should those whose albuminuria is not improved despite addition of an ACEI or ARB or when the etiology is unclear. 7 The presence of hereditary kidney disease, nephrolithiasis [journals.lww.com]
Serum
- Hyperglycemia
CVD risk reduction includes control of hyperglycemia, dyslipidemia, and BP. An LDL cholesterol goal of 70 mg/dl has been suggested for such high-risk patients. [cjasn.asnjournals.org]
This is called hyperglycemia. The body is unable to use the glucose for energy. This leads to the symptoms of type 2 diabetes. Type 2 diabetes usually develops slowly over time. [nlm.nih.gov]
In particular, controlling hyperglycemia in patients with diabetic nephropathy and controlling hypertension in all patients substantially slows deterioration of GFR. [merckmanuals.com]
- Glomerular Filtration Rate Decreased
Her estimated glomerular filtration rate decreased from an admission value of 34 mL/min/1.73 m2 to 13 mL/min/1.73 m2. CT scan showed retroperitoneal haematoma. [ncbi.nlm.nih.gov]
Treatment
An extensive study evidenced that treatment and prevention of coronary artery disease, congestive heart failure, diabetes mellitus, and anemia should be the target treatment to reduce the mortality of patients with CKD 3. [radiopaedia.org]
Since there are limited treatments for CKD, others with CKD may benefit from acupuncture and herbal treatments. [ncbi.nlm.nih.gov]
Few studies have examined the safety and efficacy of pharmacotherapy for treatment of dyslipidemia in the CKD population, and ongoing studies such as the Study of Heart and Renal Protection (SHARP) should help clarify the current treatment guidelines. [doi.org]
Prognosis
The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. [ncbi.nlm.nih.gov]
Chronic Kidney Disease Prognosis Consortium (CKD-PC) is a research group composed of investigators representing cohorts from around the world. Investigators share data for the purpose of collaborative meta-analyses to study prognosis in CKD. [jhsph.edu]
[…] irregularities papillary calcifications cysts (see also: acquired cystic kidney disease ) Abnormal Doppler findings in these patients are 2 : reduced renal vascularity increased resistance index (RI) values (segmental and interlobular arteries) Treatment and prognosis [radiopaedia.org]
Etiology
Clinical presentation depends a lot on etiology. Children with chronic kidney disease can have growth disorder, edema and cola colored urine (due to RBC casts). [radiopaedia.org]
CONCLUSION: Congenital anomalies of the kidneys and urinary tract is the most common etiology in neonates with CKD. Chronic kidney disease in neonates is associated with high morbidity and mortality rates. [ncbi.nlm.nih.gov]
Epidemiology
Long Beach, the Department of Epidemiology, University of California, Los Angeles (UCLA), and the Los Angeles Biomedical Research Institute at Harbor–UCLA, Torrance — all in California (K.K. [doi.org]
Several recent epidemiologic studies have shown that obesity and the metabolic syndrome are independent predictors of CKD. [cjasn.asnjournals.org]
A cross-sectional analytical epidemiological study was conducted based on active screening for chronic kidney disease and risk factors in persons aged ≥18 years during 2009-2011. [ncbi.nlm.nih.gov]
Pathophysiology
Aging and the Kidney: Clinical and Pathophysiological Issues Introduction Pathophysiology Pathogenesis Diagnosis Treatment Summary References Chapter 12. [elsevier.com]
This pathophysiological cascade is still incompletely understood. Patients with advanced CKD and dialysis patients are especially at risk to develop CUA. [ncbi.nlm.nih.gov]
Prevention
Prevention It is not too ambitious to consider CKD prevention. Hypertension and diabetes are the major causes of CKD in developed nations. [jasn.asnjournals.org]
The results of the Diabetes Prevention Program (DPP) funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) show that moderate exercise, a healthier diet, and weight reduction can prevent the development of type 2 diabetes [healthypeople.gov]
Treating the condition that is causing the problem may help prevent or delay CKD. People who have diabetes should control their blood sugar and blood pressure levels and should not smoke. [nlm.nih.gov]
Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA. 1998 ; 279 : 1615–1622. [circ.ahajournals.org]