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| Year : 2012 | Volume
: 23
| Issue : 3 | Page : 562-568 |
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| Cardio-renal-anemia syndrome: A report of three cases |
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UH Okafor1, EI Unuigbe2
1 Renal Unit, Department of Medicine, ESUT Teaching Hospital, Parklane Enugu, Nigeria
2 Renal Unit, Department of Medicine, University of Benin Teaching Hospital, Benin City, Nigeria
Click here for correspondence address and email
| Date of Web Publication | 7-May-2012 |
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 Abstract | | |
Patients with chronic kidney diseases (CKDs) and cardiovascular diseases (CVDs) present with various degree of anemia. Anemia has been associated with poor outcome in patients with CKD and CVD. CVD is the commonest cause of morbidity and mortality in patients with CKD. CKD causes anemia and CVD, and this rapidly deteriorates when anemia is not corrected. This triad of CVD, CKD, and anemia has been termed cardio-renal-anemia syndrome. The objective of this study is to highlight the importance of cardio-renal-anemia syndrome, their relationship, and management. Three patients with various stages of CKD who presented with anemia and cardiovascular abnormalities are reported. The patients responded well to various interventional measures, with improvement in their clinical and laboratory parameters. Cardio-renal-anemia syndrome is an entity that should be identified. Early and appropriate intervention leads to better outcome.
How to cite this article:
Okafor U H, Unuigbe E I. Cardio-renal-anemia syndrome: A report of three cases. Saudi J Kidney Dis Transpl 2012;23:562-8 |
| Introduction | |  |
Hematological and cardiovascular abnormalities are common complications seen in patients with chronic kidney diseases (CKDs). The commonest cause of morbidity and mortality in these patients is usually cardiovascular disease as reported by the American Heart Association in 2003. [1] Anemia is a common occurrence in patients with cardiovascular diseases, occurring in about 50% of patients with congestive cardiac failure. [2] Anemia has also been reported to cause and worsen the outcome of patients with cardiovascular diseases (CVDs). Poor tissue perfusion resulting from anemia and CVDs was noted to lead to renal impairment in patients with normal renal function and further deterioration in patients with renal impairment. [3] Therefore, anemia, CVD, and CKD have been noted to occur together frequently. They have been implicated to propagate and worsen each other.
We present these three cases to highlight the importance of this clinical triad of anemia, CVD, and CKD, their relationship, and management.
| Case Reports | | |
Case 1
Mrs. I. M., a 50-year-old lady, presented with recurrent facial and leg swelling of eight months duration, cough for five months, and difficulty in breathing for one week. The facial swelling was worse in the morning. Her urine was frothy, but there was no change in volume. Cough was productive with frothy sputum with no associated hemoptysis or chest pain. She complained of easy fatigability, dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea. There was no nausea, vomiting, or pruritus. She had been diagnosed to be a diabetic for three years and hypertensive for one year, but was not compliant to medications and had defaulted during follow-up. There was no known family history of hypertension, diabetes mellitus, or renal disease.
On examination, she was pale, had facial puffiness and bilateral pitting edema. Jugular venous pulsation was noted to be elevated. Her pulse was 108/min, regular with thickened arterial wall and locomotor brachialis. The blood pressure was 160/108 mm Hg supine. She had left ventricular hypertrophy and cardiomegaly with 1 st , 2 nd , 3 rd , and 4 th heart sounds heard with summation gallop. There were bilateral basal crepitations. The abdomen was distended, with marked epigastric and right hypochondrial tenderness. There was a tender, soft, and smooth hepatomegaly. The spleen was tipped, and there was ascites. Fundoscopy revealed grade 3 hypertensive retinopathy. A diagnosis of congestive heart failure (CHF) from hypertensive heart disease in a patient with background diabetic nephropathy was made.
Results of investigation revealed proteinuria of 3+ and packed cell volume (PCV) of 20%; blood film showed microcytic hypochromic red blood cells, serum urea of 130 mg/dL, and serum creatinine of 4.5 mg/dL. The estimated creatinine clearance was 10.5 mL/min using Cockcroft-Gault formula. Fasting blood glucose was 70 mg/dL; chest X-ray showed cardiomegaly and features of pulmonary edema. Renal ultrasonography showed bilaterally shrunken kidneys measuring 7.81 × 3.84 cm and 8.23 × 3.52 cm left and right, respectively, with poor corticomedullary differentiation. Electrocardiography showed sinus tachycardia and left ventricular hypertrophy.
She was admitted and commenced on intravenous frusemide 80 mg twice daily, lisinopril tablets 5 mg daily, and astefer capsule 1 daily. She was commenced on maintenance hemodialysis and transfused with two units of packed red blood cells. She had intravenous iron dextran infusion 750 mg to correct the iron deficit, and thereafter commenced on subcutaneous erythropoietin 4000 units twice weekly. She improved remarkably and was discharged six weeks after admission to continue maintenance hemodialysis and other medications including erythropoietin. Her biochemical indices on discharge were serum urea of 14 mg/dL, serum creatinine of 2.8 μg/dL, and PCV of 30%. She has being on regular follow-up, but not dialysing adequately because of financial limitations. She was clinically stable as seen at her last out-patient visit.
Case 2
Miss S. J., a 28-year-old tailor, was diagnosed to be hypertensive six years prior to presentation to us. She was not regular for her follow-up and also was not compliant to the prescribed anti-hypertensives. She presented with abdominal pain of nine weeks, leg swelling and cough of six weeks duration. She denied any history of facial and abdominal swelling. Abdominal pain was dull, maximal at the epigastrium, aggravated by meals, occasionally associated with vomiting of recently ingested food, but there was no hematemesis or passage of melena stool. She had productive cough with frothy sputum associated with exertional dyspnea, orthopnea, but no hemoptysis. Past medical history, and social and drug history were not contributory. Mother was hypertensive, but there was no family history of diabetes mellitus or renal disease.
Clinical examination revealed a young lady who was pale with bilateral pitting pedal and sacral edema. The pulse was 116/min regular, small volume with thickened arterial wall and locomotor brachialis. Blood pressure was 230/160 mmHg supine, jugular venous pulsation was elevated. Examination of the heart showed left ventricular hypertrophy, cardiomegaly and gallop rhythm. There were bilateral basal crepitations and marked epigastric tenderness, and tender, soft hepatomegaly and splenomegaly of 2 cm below left costal margin.
She was admitted with a diagnosis hypertensive heart disease in CHF. The results of investigations revealed proteinuria 3+, PCV of 20%, normocytic normochromic red blood cells, serum urea and creatinine of 100 mg/dL and 3.2 mg/dL, respectively, with estimated glomerular filtration rate (GFR) of 19.6 mg/dL and 24-h protein excretion of 1.5 g. Chest X-ray showed cardiomegaly and unfolding aorta, electrocardiography revealed left ventricular hypertrophy, and echocardiography showed marked left ventricular hypertrophy and low ejection fraction. Renal ultrasonography showed bilaterally shrunken kidneys.
She was treated with intravenous frusemide 80 mg twice daily, alpha-methyldopa tablets 500 mg thrice daily, lisinopril 10 mg daily, atenolol 100 mg daily, and subcutaneous erythropoietin 4000 IU twice weekly. She was advised low salt and low protein uremic diet.
She was discharged home 29 days after admission with marked improvement. Since then, she has been regular for follow-up and compliant to medications. She has returned to her work and has had arterio-venous (A-V) fistula created in preparation for hemodialysis in the future.
Case 3
Mr. I. T., a 55-year-old businessman being managed by the hematologist as a case of refractory anemia from hypocellular bone marrow, was referred to us on account of deranged serum electrolytes, elevated urea, and creatinine with a diagnosis of renal impairment. He had been on analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) for left hip osteoarthritis for ten years. He was also diagnosed to be hypertensive eight years before presentation and claimed compliance to medications.
He complained of facial swelling of six months duration and weakness of three months duration with associated leg swelling but no abdominal swelling. He had recently noticed a reduction in his urine volume, with no associated dysuria, hematuria, or nocturia; the urine was not frothy. He also complained of dizziness, easy fatigability, generalized body weakness, anorexia, and dyspnea on mild exertion.
On examination, he was found to be a middle-aged man, in respiratory distress, pale, and mildly dehydrated. He had facial puffiness and bilateral pitting pedal edema. His pulse was 80/min, had thickened arterial wall, blood pressure was 150/100 mmHg supine, and there was left ventricular hypertrophy and cardiomegaly. Fundoscopy showed grade 2 hypertensive retinopathy. A diagnosis of chronic renal failure secondary to analgesic nephropathy was made with a possible differential diagnosis of hypertensive nephrosclerosis.
Results of investigations revealed proteinuria of 2+ and 24-h protein excretion of 2.9 g. The PCV was 19%, blood film showed microcytosis, hypochromia, and anisocytosis. The other findings were: serum urea 364 mg/dL, serum creatinine 10.8 mg/dL, serum sodium 127 mmol/L, serum potassium 6.0 mmo/L, serum bicarbonate 15 mmol/L, serum calcium 7.8 mg/dL, and serum phosphate 7.9 mg/dL. Creatinine clearance was 6.3 mL/min, urine was negative for Bence Jones protein, and serum electrophoresis was also normal. Renal ultrasonography showed bilaterally shrunken kidneys measuring 7.35 × 3.42 cm, 7.06 × 3.77 cm right and left, respectively, with loss of corticomedullary differentiation. He was rehydrated with intravenous 5% dextrose saline, and hyperkalemia was corrected with 10% calcium gluconate and 50% dextrose. He was transfused with 2 units of packed red blood cells. He was commenced on tablets lisinopril 5 mg daily, and continued tablets moduretic 1 daily and capsule astefer twice daily. Tablets doxazocin 4 mg daily, and later tablets nifedipine were added to achieve optimum blood pressure control. Subsequently, he was given intravenous iron dextran infusion 500 mg and was commenced on subcutaneous erythropoietin 4000 IU twice weekly.
He was initiated on maintenance hemodialysis using initially a femoral vein vascular access and later with an A-V fistula.
He improved and was discharged six weeks after admission, and was advised to continue on maintenance hemodialysis twice weekly. The PCV was 31%, serum creatinine was 3.0 mg/dL (264 μmol/L), and serum urea was 69 mg/dL (11.5 mmol/L) two weeks after discharge. He had a live related kidney transplant five months after discharge. He is regular on follow-up and is now fully compliant to the medications. He is stable and has returned to his normal routine prior to onset of illness.
| Discussion | | |
These three reported cases had in common the clinical entities of CKD, anemia, and CVD. CKD was due to diabetic nephropathy in the first case, chronic glomerulonephritis in the second, and analgesic nephropathy in the third. Anemia was severe in all cases with hematocrit ranging from 18 to 20%. CVD was manifested as florid CHF in two cases, and cardiomegaly and left ventricular hypertrophy was present in all. Thus, all three cases, irrespective of their primary diagnosis, had cardiac decompensation, cardiomegaly, anemia, and CKD.
CKD is a major health problem with its increasing prevalence/morbidity and mortality taking a heavy toll on health care finances. [4] CVD and especially CHF are common medical problems with high morbidity and mortality. [1],[3] Likewise, anemia occurs frequently, is a recognized complication of CKD, and can cause progression of CKD with its prevalence and magnitude increasing with decreasing renal function. [2],[3],[5],[6]
Anemia causes and occurs in a large number of patients with CHF. Its prevalence and severity increases as CHF becomes more severe [7] and it is a strong independent risk factor for mortality in CHF patients. [7],[8] The association among the components in the triad of CKD, CVD, and anemia has been termed the cardio-renal-anemia syndrome, with its components relating to each other in a complex, vicious, and poorly understood manner. [5],[9],[10],[11]
CKD is a risk factor for CVD, particularly coronary heart disease (CHD), left ventricular hypertrophy, and heart failure. The prevalence of CHD and CHF is increased in patients undergoing hemodialysis, and mortality due to CVD in patients on dialysis is higher than that in the general population. [12],[13],[14],[15],[16] Both the traditional and non-traditional cardiovascular risk factors are also present in the uremic patients and play a role in the complex pathogenesis of CVD in CKD patients. These risk factors include diabetes mellitus, hypertension, dyslipidemia, elevated lipoprotein, smoking, inflammation, oxidative stress, hyperhomocysteinemia, and hyperphosphatemia. [17],[18] The increased risk of CVD is not restricted to the stage of endstage real failure alone but is present throughout the spectrum of CKD to the extent that up to 50% of patients commencing dialysis have features of CVD. CVD has been reported in CKD with GFR >60 mL/min. [19],[20],[21] CVD occurs commonly in CKD patients; CHF is present in up to 64% of patients with CKD, is implicated in the genesis of CKD, and is a strong predictor of end-stage renal disease (ESRD) and optimum treatment of CHF retards progression of renal impairment. CHF results in reduced cardiac output, causing renal vasoconstriction, renal hypoxia, and eventually renal cell death and fibrosis [22],[23],[24] . Renal function is further compromised through an increase in angiotensin, aldosterone, and norepinephrine, which occurs in CHF. [25],[26] Reciprocally, the CKD produced by the hemodynamic effects of reduced cardiac output is thought to be a major cause of anemia in CHF, and it has been suggested that the effects of CHF and CKD may add together to produce anemia. [5]
Anemia, on its part, is a bog factor in the etiology, worsening, or progression of both CKD and CVD. Although caused by CKD, anemia increases the risk of progression of CKD to end-stage disease. [27],[28] Likewise, anemia, irrespective of its etiology, causes both structural and functional renal and cardiac impairment. There is activation of the sympathetic, renin-angiotensin-aldosterone systems and vasopressin in response to peripheral ischemia, arteriolar vasodilatation, and reduction in blood pressure caused by anemia. Consequently, there is renal hypoperfusion, reduction in GFR, and increased sodium and water reabsorption with resultant increased plasma volume, cardiac dilatation, left ventricular hypertrophy, and eventually CHF. [27],[29]
In cardio-renal-anemia syndrome, just as CKD causes anemia, which worsens cardiac function, the cardiovascular disease and particularly CHF can cause anemia, even in the absence of CKD through production of cytokines. [30],[31] It has been proposed that anemia is contributory to the progression of CHF and CKD and their resistance to treatment. Correction of anemia improves cardiac function, reduces ventricular dilatation and hypertrophy, reduces the need and frequency of hospitalization, and prevents further deterioration of CHF and CKD. [5],[9],[32],[33]
Anemia was a marked feature in all the three case reports and it was either overlooked or poorly managed initially. Although anemia is regarded as a common and moderating or worsening factor in CVD and CKD, earlier reports have also stressed its correction is often neglected. [5] Anemia can be corrected using subcutaneous erythropoietin in addition to oral/intravenous iron where there is evident iron deficiency or depletion of iron stores. Erythropoietin, apart from reducing frequency of blood transfusion, is thought to delay progression of renal disease, and prevent and control CHF and CKD. [5],[34]
As has been suggested by other reports, the patients with the cardio-renal-anemia syndrome should be managed aggressively with a multi-disciplinary approach, particularly co-operation between cardiologists and nephrologists as seen in some centers. [5] Multidisciplinary management of these patients will encourage early referral and avoid late referral as occurred in the cases reported. In these cases, early intervention may have slowed down the progression to ESRD. The attitude of collaboration and early referral is even more pertinent and applicable to our practising scenario where renal replacement therapy is expensive, funds are scarce for patients, and the government is not involved in the renal care funding. The aggressive and prompt use of erythropoietin should be encouraged. Though erythropoietin is expensive, it is still a far cry from total cost of multiple hospital admissions and the treatment of the CKD patient with rapidly declining renal function.
The objectives in the treatment of patients with cardio-renal-anemia syndrome are to relieve the symptoms, correct reversible lesions, improve comorbid state, and treat and prevent modifiable risk factors. The outcome as in our patients is good if prompt, appropriate, and especially early intervention is initiated. Otherwise prognosis will be poor.
In conclusion, cardio-renal-anemia syndrome is a complex self-destructive triad of CKD, CVD, and anemia that improves on prompt and appropriate intervention, especially early correction of anemia with oral/intravenous iron, erythropoietin, multivitamins, and/or blood transfusion depending on the patient's need. Early referral to a nephrologist and involvement of the cardiologist is paramount for early intervention. Two of our patients were referred to us in ESRD and the other in stage 4 CKD. Earlier referral would have delayed the progression of the disease and other comorbidities.
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Correspondence Address:
U H Okafor
Renal Unit, Department of Medicine, ESUT Teaching Hospital, Parklane Enugu
Nigeria
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