In the realm of human health, certain interconnections often go unnoticed until they manifest as significant concerns. One such nexus of health conditions that warrants our attention is the intricate relationship between kidney disease and low hemoglobin levels. While they might seem unrelated at first glance, a closer examination reveals a hidden connection that can have profound implications for individuals’ well-being.
Unveiling the Web of Interdependence
The human body is a complex ecosystem where different systems intricately interact to maintain equilibrium. Kidneys and hemoglobin are two entities seemingly disparate, yet their connection is a testament to the body’s remarkable design. The kidneys play a pivotal role in regulating various physiological processes, including blood filtration, electrolyte balance, and blood pressure. On the other hand, hemoglobin, the iron-rich protein in red blood cells, is responsible for transporting oxygen from the lungs to all body tissues. Despite operating in distinct domains, these systems are interdependent in ways we are only beginning to understand.
The Silent Agitator: Kidney Disease
Kidney disease often earns the moniker of the “silent disease” due to its gradual onset and subtle progression. It can stem from various factors, including diabetes, hypertension, and genetic predispositions. As the kidneys lose their functionality, they struggle to filter waste products and excess fluids from the blood, leading to a buildup of toxins in the body. This scenario sets the stage for a series of cascading health complications, one of which is a decline in hemoglobin levels.
Unraveling the Connection
In the blood, molecular oxygen (O2) is transported by hemoglobin within erythrocytes. The maintenance of normal blood oxygen levels is the result of complex metabolic pathways involving the kidneys, the bone marrow and many molecules (hormones, growth factors, cytokines, vitamins, etc), which act according to a very rigorous “timetable” to regulate erythropoiesis as needed.
Abnormalities in one or more of these factors may induce different kinds of anemia that require different treatments. Anemia is particularly frequent among patients with progressive chronic kidney disease (CKD). The causes are many and include:
- inadequate production of erythropoietin (a hormone that stimulates the bone marrow to produce red blood cells)
- erythropoiesis inhibition due to the accumulation of uremic toxins
- reduced red blood cell survival
- iron deficiency
- malnutrition
- inflammation
- folate and/or vitamin B12 deficiency
- dysregulated iron metabolism
- oxidative stress
- chronic gastrointestinal blood loss
- secondary kidney hyperparathyroidism
- blood losses during hemodialysis sessions in patients with end‐stage kidney disease requiring replacement therapy.
Anemia as a condition seems to accelerate the progression of kidney damage
through different mechanisms –
- Firstly, low hemoglobin levels reduce oxygen delivery to the kidneys with resulting medullary hypoxia that favors interstitial fibrosis.
- Anemia may also stimulate kidney sympathetic nerve activity and then induce an increase in glomerular pressure and proteinuria, which is another factor contributing to CKD progression. 1
Erythropoietin
Erythropoietin is a hormone playing a key role in the production of erythrocytes. The starting point of the erythropoietic process is an oxygen sensing system that is located in the kidney at the level of cells known as renal erythropoietin‐producing (REP) cells which can detect hypoxia (low oxygen environment) with great sensitivity. 2
Hypoxia induces a complex adaptive response that aims at facilitating cellular metabolism and restoring normal oxygen blood levels through a process involving the transcription factor known as hypoxia‐inducible factor‐1 (HIF‐1). The compensatory mechanisms stimulated by hypoxia include erythropoiesis through increased erythropoietin production, angiogenesis, anaerobic glycolysis, glucose transport, and regulation of cell cycle and apoptosis. 3
Anemia: More Than Just Fatigue
Anemia, often associated with low hemoglobin levels, is a condition that extends beyond mere physical weariness. Its effects can permeate various aspects of a person’s life, influencing cognitive function, mood, and overall quality of life. The feeling of perpetual tiredness can hinder productivity and limit one’s ability to engage in daily activities. Moreover, anemia’s effects on cognitive function underscore the urgency of addressing this issue comprehensively.
A Call for Holistic Healthcare
The relationship between kidney disease and low hemoglobin levels underscores the need for a holistic approach to healthcare. A myopic focus on isolated conditions might lead to a failure to recognize these subtle connections that impact health outcomes. Healthcare providers should adopt a comprehensive view, considering how various conditions intersect and influence each other. Addressing kidney disease’s impact on hemoglobin levels should be a crucial aspect of managing both these health concerns effectively.
Researchers have found that, melatonin (the sleep hormone) may improve erythropoietin responsiveness through its anti-inflammatory action, thus improving CKD-induced anemia. Moreover, in a recently reported randomized controlled trial of 60 patients with diabetic kidney disease, nighttime melatonin 10 mg led to improved glycemic profile and oxidative stress parameters. 7
Empowering Patients through Awareness
Empowering individuals with knowledge is a fundamental step in the journey toward better health. Patients living with kidney disease need to be aware of the potential consequences it can have on their hemoglobin levels. Regular monitoring of hemoglobin levels should be a standard practice, enabling early intervention if any decline is observed. By fostering a sense of agency and collaboration between healthcare providers and patients, we can proactively manage the impact of kidney disease on hemoglobin levels.
Research and Innovation: Lighting the Path Forward
Advancements in medical research and technology play a pivotal role in unraveling the complexities of health conditions. The connection between kidney disease and low hemoglobin levels is a prime example of how research can illuminate hidden relationships. As we delve deeper into understanding the molecular and physiological underpinnings of this connection, new avenues for treatment and management may emerge. Innovations such as synthetic erythropoietin and targeted therapies offer hope for individuals grappling with the dual challenges of kidney disease and anemia.
Until the marketing of recombinant human erythropoietin in the 1980s, anemia caused by progressive chronic kidney failure required frequent blood transfusions. This implied a high risk of infectious complications, sensitization, transfusion‐induced iron overload, and other adverse effects, in addition to the difficulty of finding enough blood units. 4 The chance to use recombinant human erythropoietin (injecting DNA fragments responsible for a protein, to a suitable host cell for scaled production of the protein) has meant a real revolution for renal patients, inducing a marked improvement of anemia correction and quality of life.
Epoetin alpha/beta, Darbepoetin alpha, methoxy polyethylene glycol‐epoetin beta – are known as erythropoiesis‐stimulating agents (ESAs), can be administered both subcutaneously and intravenously for increasing erythropoietin production. The first way is preferred in patients with CKD not on dialysis, while the second one is basically used in hemodialysis patients.
However, ESAs have some dark sides. In the last decades, several studies have been performed identifying pros and cons of ESA therapy, and the hemoglobin range to be reached in CKD‐related anemia has been often resized according to the progressive discovery of the potential side effects of these drugs, primarily represented by the greater risk of cancer progression and cardio‐ and cerebrovascular events observed in patients treated with higher dose ESAs. 4-6
Breaking Barriers: Collaborative Care Approach
The synergy between nephrologists, hematologists, and other healthcare specialists is crucial in providing comprehensive care to individuals with kidney disease and low hemoglobin levels. A collaborative approach that transcends traditional medical silos can lead to more effective diagnosis, treatment, and management strategies. By fostering interdisciplinary dialogue and knowledge exchange, we can optimize patient care and improve their overall quality of life.
Conclusion: Bridging the Gap
The intricate connection between kidney disease and low hemoglobin levels serves as a poignant reminder of the multifaceted nature of human health. As we navigate the intricate web of physiological interdependencies, it becomes evident that isolated approaches to healthcare fall short of the mark. Embracing a holistic perspective, advancing medical research, and fostering collaborative care are all essential steps in addressing the challenges posed by these interwoven conditions. By bridging the gap between kidney function and hemoglobin levels, we can pave the way for a healthier, more vibrant future for individuals worldwide.
References
- Mehdi U, Toto RD. Anemia, diabetes, and chronic kidney disease. Diabetes Care. 2009;32(7):1320‐1326.
- Suzuki N, Yamamoto M. Roles of renal erythropoietin‐producing (REP) cells in the maintenance of systemic oxygen
homeostasis. Pflugers Arch. 2016;468(1):3‐12. - Buemi M, Lacquaniti A, Maricchiolo G, et al. Regenerative medicine: does Erythropoietin have a role? Curr Pharm Des. 2009;15(17):2026‐2036.
- Cernaro V, Lacquaniti A, Buemi A, Lupica R, Buemi M. Does erythropoietin always win? Curr Med Chem. 2014;21(7): 849‐854.
- Pfeffer MA, Burdmann EA, Chen CY, et al. TREAT investigators. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361(21):2019‐2032.
- Singh AK, Szczech L, Tang KL, et al. CHOIR Investigators. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355(20):2085‐2098.
- Satari M, Bahmani F, Reiner Z, Soleimani A, Aghadavod E, Kheiripour N, Metabolic and anti-inflammatory response to melatonin administration in patients with diabetic nephropathy. Iran J Kidney Dis. 2021 Jan;1(1):22–30.