by wayne persky |
RSS Feed A recent article published in JAMA, describing research conducted at Brigham and Women's Hospital discusses the association between cardiovascular health and kidney function (Ostrominski, et al., 2024).1 Focusing on heart failure, particularly, the article discussed how the function of the two organs are linked by shared risk factors, hemodynamic effects, and complex biochemical interactions. Statistically, compromised function of both organs frequently coexists, and when it does, the functional issues of one organ tends to negatively affect the function of the other in a self-perpetuating, mutually compromising cycle in which the deteriorating condition of one tends to exacerbate the dysfunction of the other.
This condition is frequently seen in older adults who are hospitalized because of heart failure, and it's referred to as a cardiorenal syndrome. The study found that a significant portion of these patients developed acute kidney injury, or progressed to end-stage kidney disease (requiring dialysis) within a year of their hospitalization. The cycle appears to be driven by the following issues:
This condition is frequently seen in older adults who are hospitalized because of heart failure, and it's referred to as a cardiorenal syndrome. The study found that a significant portion of these patients developed acute kidney injury, or progressed to end-stage kidney disease (requiring dialysis) within a year of their hospitalization. The cycle appears to be driven by the following issues:
- Hemodynamic changes associated with heart failure lead to reduced cardiac output, and this results in reduced blood circulation within the kidneys. This reduced perfusion tends to cause ischemic injury and reduced filtration capabilities needed to acute kidney injury and chronic kidney disease.
- Neurohormonal activation associated with heart failure triggers the activation of the renin angiotensin aldosterone system, and the sympathetic nervous system. While these processes initially help to maintain blood pressure and cardiac output, their chronic activation needs to vasoconstriction, sodium retention, and deteriorating heart and kidney function.
- Inflammatory pathways resulting from the promotion of pro-inflammatory cytokines are a result of both heart failure and kidney disease. These cytokines contribute to the fibrosis and dysfunction of tissues in both the heart and the kidneys.
- Metabolic dysregulation is often seen in patients with chronic kidney disease. Imbalances in calcium, phosphate, and vitamin D metabolism often lead to increased vascular stiffness and calcification, classic symptoms of cardiovascular disease and heart failure.
- Integrated care should be used to simultaneously address both heart and kidney health including the establishment of clinics that specialize in the combined management of the two conditions.
- Early detection and monitoring of kidney function in heart failure patients should be emphasized, including the measurement of estimated glomerular filtration rate (eGFR), and checking for albumin in the urine.
- Therapeutic interventions should be made if deemed to be beneficial after weighing the potential side effects and contraindications.
- Policy and reimbursement changes should be made to allow broader healthcare policy changes such as expanding Medicare reimbursement for interdisciplinary chronic care management in order to support better outcomes for patients with both heart and kidney disease.
But which came first — the chicken or the egg?
This was a one-sided study, that assumed that heart failure causes kidney disease. Based on the interdependencies of these two health issues, the reverse might possibly be true — chronic kidney disease might well be a primary cause of heart failure.
A study published in Kidney Medicine, explores this relationship in depth, focusing on patients with incident chronic kidney disease (CKD) within a large integrated health care system (Yu, et al., 2023).2 The findings illustrate why compromised kidney function may lead to heart failure and other cardiovascular issues.
Yu et al. conducted a retrospective cohort study involving 76,688 patients with incident CKD. They found that 18.6% of these patients had prevalent heart failure. Among those with heart failure, 59.2% had heart failure with preserved ejection fraction (HFpEF), and 23.3% had heart failure with reduced ejection fraction (HFrEF).
A study published in Kidney Medicine, explores this relationship in depth, focusing on patients with incident chronic kidney disease (CKD) within a large integrated health care system (Yu, et al., 2023).2 The findings illustrate why compromised kidney function may lead to heart failure and other cardiovascular issues.
Yu et al. conducted a retrospective cohort study involving 76,688 patients with incident CKD. They found that 18.6% of these patients had prevalent heart failure. Among those with heart failure, 59.2% had heart failure with preserved ejection fraction (HFpEF), and 23.3% had heart failure with reduced ejection fraction (HFrEF).
When the researchers looked at all cause mortality,
The hazard ratio (HR) for 1-year all-cause mortality was significantly higher for CKD patients with heart failure (HR, 1.70) compared to those without heart failure. Specifically, the HRs were 1.59 for HFpEF and 2.43 for HfrEF.
When the researchers looked at cardiovascular -related mortality,
The risk was even more pronounced for cardiovascular-related mortality. CKD patients with heart failure had an HR of 6.69 for cardiovascular-related death. For those with HFrEF, this risk was substantially higher (HR, 11.47).
These statistics highlight the severe impact of heart failure on CKD patients, particularly those with reduced ejection fraction, underscoring the need for integrated management strategies.
These statistics highlight the severe impact of heart failure on CKD patients, particularly those with reduced ejection fraction, underscoring the need for integrated management strategies.
The findings showed these mechanisms linking CKD to heart failure:
- Volume Overload — CKD often leads to fluid retention due to impaired renal excretion, increasing the volume load on the heart and leading to heart failure.
- Uremic Toxins — Accumulation of uremic toxins in CKD can cause direct myocardial injury and contribute to cardiac dysfunction.
- Hypertension — CKD frequently results in uncontrolled hypertension, a significant risk factor for the development and progression of HF.
- Anemia — Reduced erythropoietin production in CKD leads to anemia, which increases cardiac workload and exacerbates HF.
- Mineral Bone Disorder — Disturbances in calcium and phosphate metabolism inCKD can lead to vascular calcification, increasing cardiovascular morbidity and mortality.
A recent news article described a real-world example of this connection.
Lisa Pisano became the second person in the world to receive a kidney transplant from a genetically modified pig on April 12, 2024, and this was after she had received an artificial heart pump on April 4. Unfortunately, her doctors decided to remove the genetically engineered pig kidney 47 days after it had been transplanted, and placed her back on dialysis.
The removal wasn't done because her body was rejecting the pig kidney — it was done because the artificial heart pump was unable to supply enough blood in order to keep the pig kidney functioning properly, and the kidney was beginning to lose functional capacity, because of the tissue damage done by the limited blood flow.
Lisa's case clearly illustrates the complexity of treating patients who suffer from both heart failure and end-stage kidney disease, and mirrors the JAMA article's discussion of the interconnectedness of heart and kidney health, often referred to as cardiorenal syndrome. The JAMA article points out that reduced cardiac output in heart failure patients can lead to reduced blood circulation in the kidneys, thereby increasing kidney damage, and intensifying kidney dysfunction, in a self-perpetuating cycle of escalating damage.
The removal wasn't done because her body was rejecting the pig kidney — it was done because the artificial heart pump was unable to supply enough blood in order to keep the pig kidney functioning properly, and the kidney was beginning to lose functional capacity, because of the tissue damage done by the limited blood flow.
Lisa's case clearly illustrates the complexity of treating patients who suffer from both heart failure and end-stage kidney disease, and mirrors the JAMA article's discussion of the interconnectedness of heart and kidney health, often referred to as cardiorenal syndrome. The JAMA article points out that reduced cardiac output in heart failure patients can lead to reduced blood circulation in the kidneys, thereby increasing kidney damage, and intensifying kidney dysfunction, in a self-perpetuating cycle of escalating damage.
And A recent Medical Xpress article
discusses the significant impact of CKD and the challenges associated with its early detection (Hanbury, 2024, July 10).3 Amber Paulus, Ph.D., R.N., an affiliate researcher with Virginia Commonwealth University's School of Nursing, emphasizes that CKD is a major health issue affecting nearly 37 million people in the United States, with 90% of those affected being unaware of their condition. Paulus identifies high blood pressure, diabetes, and obesity as primary risk factors, alongside smoking, heart disease, age, family history, and personal history of acute kidney injury. But similar to almost everyone else in the medical healthcare field, she completely overlooks the risk of compromised kidney function due to magnesium deficiency.
As the article points out, CKD often progresses silently without symptoms until it is advanced, making early detection difficult. Paulus advocates for community-based screenings, especially in high-risk areas like Richmond's East End, to improve awareness and early diagnosis. These screenings involve simple blood and urine tests to measure kidney function and detect damage.
The article highlights barriers to early detection, including lack of awareness, financial hardships, limited healthcare access, and systemic issues like inadequate laboratory supplies and poor medical record-keeping. Early detection and intervention, including lifestyle changes and medications, are crucial for managing CKD and preventing its progression.
As the article points out, CKD often progresses silently without symptoms until it is advanced, making early detection difficult. Paulus advocates for community-based screenings, especially in high-risk areas like Richmond's East End, to improve awareness and early diagnosis. These screenings involve simple blood and urine tests to measure kidney function and detect damage.
The article highlights barriers to early detection, including lack of awareness, financial hardships, limited healthcare access, and systemic issues like inadequate laboratory supplies and poor medical record-keeping. Early detection and intervention, including lifestyle changes and medications, are crucial for managing CKD and preventing its progression.
Although this is not noted in the article,
if CKD is this widespread, some of the blame has to be placed on clinicians who either fail to properly test for kidney function, or don't properly follow-up on test results that indicate compromised kidney function.
So how important is all this to us in our own lives?
The importance of this is surely defined by our own personal health status as indicated by our test results (and probably by parameters that are not normally tested by our doctors). In retrospect, I can certainly relate, because the findings of studies such as these might have been very useful to me about eight or nine years ago, when my own test results suddenly began showing significant signs of compromised kidney function, and my doctor failed to address them. The association between kidney function and cardiovascular issues wasn't even on my doctors' radar, although there were earlier studies that showed an association.
My case was more complex than this.
In my own case, my situation was so complex that it's not surprising that my doctors overlooked the connection. About a year or so before my symptoms began to show up, I developed a magnesium deficiency because of inadequate supplemental dosing, and the deficiency became critical after three back-to-back antibiotic treatments for a series of dental procedures. I would wake up in the wee hours of the morning sweating like a pig (in the cold of winter), with tachycardia, and shallow, rapid breathing. And one morning, when I decided to check my blood pressure, my systolic pressure was very low, at 85 mmHg, suggesting the symptoms of shock. Yet, after I ate breakfast, my blood pressure tended to become elevated during the day, with the systolic pressure often increasing by about 80 to100 mg of mercury. As severe as my symptoms were, none of my doctors ever seemed to have a clue about what might be wrong.
When I would describe my symptoms to doctors, they would respond with a blank stare as if I were speaking in a foreign language. And I had a very unique symptom that makes severe magnesium deficiency obvious. My perspiration had a very powerful, unique, and noxious odor that would probably gag a buzzard a quarter-mile away. I've never smelled a similar odor before or since, but if I ever smelled it again, I would immediately recognize it as a symptom of a chronic magnesium deficiency, because it was so unique.
Unfortunately, doctors are totally aware of this unique (easy to identify) symptom because there is no well-established evidence that a chronic magnesium deficiency specifically causes a distinctive odor associated with perspiration. Magnesium deficiency can lead to various symptoms, including muscle cramps, fatigue, and irritability, but a characteristic odor is not commonly recognized as one of these symptoms.
When I would describe my symptoms to doctors, they would respond with a blank stare as if I were speaking in a foreign language. And I had a very unique symptom that makes severe magnesium deficiency obvious. My perspiration had a very powerful, unique, and noxious odor that would probably gag a buzzard a quarter-mile away. I've never smelled a similar odor before or since, but if I ever smelled it again, I would immediately recognize it as a symptom of a chronic magnesium deficiency, because it was so unique.
Unfortunately, doctors are totally aware of this unique (easy to identify) symptom because there is no well-established evidence that a chronic magnesium deficiency specifically causes a distinctive odor associated with perspiration. Magnesium deficiency can lead to various symptoms, including muscle cramps, fatigue, and irritability, but a characteristic odor is not commonly recognized as one of these symptoms.
Why is that true?
It's true because no medical research has never been undertaken to verify, dispute, or otherwise investigate an association of a unique odor with a chronic magnesium deficiency. I'm sure I had that odor as I was asking my doctors about my symptoms, because it was a very strong, persistent order that taking a shower didn't remove for long, but none of them ever recognized it. Instead, they almost surely assumed that I just needed a shower.
Looking back now, it's obvious that after I ate breakfast, my magnesium level increased slightly, so the deficiency wasn't nearly as severe. The deficiency only became severe during the wee hours of the morning as my body ran out of magnesium. And I had hypertension during the day, because chronic magnesium deficiency causes hypertension.
Looking back now, it's obvious that after I ate breakfast, my magnesium level increased slightly, so the deficiency wasn't nearly as severe. The deficiency only became severe during the wee hours of the morning as my body ran out of magnesium. And I had hypertension during the day, because chronic magnesium deficiency causes hypertension.
Doctors never detect magnesium deficiency.
When my PCP ordered a series of tests to try to locate the problem, they showed that my kidney function was quite low (an eGFR value in the mid-30s), but my doctor chose to ignore that, and focused instead on my TSH value (which was below the normal level), and cut my thyroid treatment in half. In retrospect, the thyroid test results were probably skewed because of my magnesium deficiency.
Emergency department doctors make the same mistake.
One morning my symptoms were so bad that I couldn't force myself to eat breakfast, so I went to the emergency department. Although the doctors there officially ruled my test results as "fine", and sent me home, a day or so later, when I looked at the online test results, I immediately spotted the problem. My magnesium level was flagged by the lab at significantly below the normal level. Tripling my magnesium dose resolved my early morning symptoms in one day, including the unique perspiration order, which totally disappeared.
At any rate, te damage done by the combination of the magnesium deficiency, and the inadequate thyroid treatment led up to an arrhythmia one day, and although that faded away on its own, later in the day, three weeks later, I had a stroke.
About a year and a half later, another arrhythmia caused me to wake up and smell the coffee. It dawned on me that unless I found the problem, and resolved it, I was probably about to have another stroke. So I did some serious online research and discovered that undertreated hypothyroidism can lead to compromised kidney function, and compromised kidney function can cause cardiac issues. When I pointed this research out to my doctor, he immediately restored my thyroid treatment to its original dose, and I haven't had any health problems since. Prior to this, every time some little health issue, or unusual symptom came up, my eGFR would plummet. Now (at least for the past six years), my eGFR stays consistently in the normal range, and I have no cardiac issues.
At any rate, te damage done by the combination of the magnesium deficiency, and the inadequate thyroid treatment led up to an arrhythmia one day, and although that faded away on its own, later in the day, three weeks later, I had a stroke.
About a year and a half later, another arrhythmia caused me to wake up and smell the coffee. It dawned on me that unless I found the problem, and resolved it, I was probably about to have another stroke. So I did some serious online research and discovered that undertreated hypothyroidism can lead to compromised kidney function, and compromised kidney function can cause cardiac issues. When I pointed this research out to my doctor, he immediately restored my thyroid treatment to its original dose, and I haven't had any health problems since. Prior to this, every time some little health issue, or unusual symptom came up, my eGFR would plummet. Now (at least for the past six years), my eGFR stays consistently in the normal range, and I have no cardiac issues.
So the moral of this story is:
We can't rely on our doctors to diagnose, or even suspect, complex health issues that involve multiple organs. They're trained in med school to diagnose health problems by looking at test results based on the functioning of individual organs. Complex issues that involve multiple organs are almost never on their radar. It's painfully obvious that if we want to safeguard our own health, it's up to us to learn how to analyze our medical test results, and when anything looks suspicious, we have to do the research ourselves, because far too often, if we ask our doctor about suspicious test results, they'll simply shrug them off as nothing to worry about, or return a blank stare, because they don't have a clue. And spotting out of range test results is easy, because the lab even flags them to make them easier to notice.
If this research had existed a decade ago, and I or my doctors had been aware of it, could I have been able to avoid going through a stroke, and then having to recover from it? Probably not, because there were too many complicating factors. But that doesn't mean that this information can't be useful for anyone else who happens to find themselves in a similar situation. Always ask questions about suspicious test results.
If this research had existed a decade ago, and I or my doctors had been aware of it, could I have been able to avoid going through a stroke, and then having to recover from it? Probably not, because there were too many complicating factors. But that doesn't mean that this information can't be useful for anyone else who happens to find themselves in a similar situation. Always ask questions about suspicious test results.
References
1. Ostrominski, J. W., Greene, S. J., Patel, R. B., Solomon, N. C., Chiswell, K., DeVore, A. D., . . . Vaduganathan, M. (2024). Kidney Outcomes Among Medicare Beneficiaries After Hospitalization for Heart Failure. JAMA Cardiology, Retrieved from https://jamanetwork.com/journals/jamacardiology/article-abstract/2819215
2. Yu, A. S., Pak, K. J., Zhou, H., Shaw, S. F., Shi, J., Broder, B. I., and Sim, J. J. (2023).All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California. Kidney Medicine, 5(5), 100624. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151415/
3. Hanbury, C. (2024, July 10). Researcher details risk factors for chronic kidney disease and barriers for early detection. Medical Xpress, Retrieved from https://medicalxpress.com/news/2024-07-factors-chronic-kidney-disease-barriers.html?utm_source=nwletter&utm_medium=email&utm_campaign=daily-nwletter
