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Introduction: A Quick Tutorial On Kidney Function
In 2017, the Global Burden of Disease or GBD reported a whopping 700 million cases of chronic kidney disease (CKD) worldwide, making up 9.1% of the total population. In fact, over 4.6% of global deaths in 2017 were attributed to CKD and cardiovascular complications due to CKD.  With a disease that is quite literally sweeping the world, the saliency of this particular of health problem is surprisingly low – because its signs and symptoms can be difficult to notice.
Kidneys as sensor: Your kidneys are two bean-shaped organs found just below your ribs, on either side of your spine. Their main job is to remove wastes and excess fluid from your body, much like a filter. The complex part of their job is not found in filtering, but in maintaining a homeostatic balance in the body – by regulating our fluids and electrolytes (like sodium, potassium, magnesium). An imbalance involving any of these electrolytes can cause problems with other tissues and organs in the body and can even affect your heart (because the heart is a muscle!) Your kidneys maintain this balance by acting as a sensor that continuously monitors your blood. 
Kidneys and pH: As with other bodily fluids, your blood also has a healthy pH level. If the pH level goes up (basic/alkaline) or goes down (acidic), your kidneys will act accordingly to try and restore the level to around 7 (neutral). This is an important balance; derangement in your pH level can signify problems with your lungs (too much carbon dioxide in Chronic Obstructive Pulmonary Disease or COPD can cause respiratory acidosis) or your gastrointestinal tract (excessive vomiting can cause metabolic alkalosis). 
Hormone production in the kidneys: An important hormone produced by the kidney is erythropoietin. This hormone is made by the peritubular cells and is responsible for regulating the production of red blood cells. In kidney disease, especially among patients needing hemodialysis, erythropoietin is given as supplemental injections to help prevent anemia. 
Reabsorption of electrolytes: We previously mentioned that the kidneys sense imbalances in the body, after which they filter and reabsorb fluids, electrolytes, and minerals accordingly. A healthy kidney will reabsorb the following electrolytes at their respective percentages:
– Sodium at 99%: Out of the approximately 24,000 milliequivalents (meqs) of sodium excreted by the kidney, about 23,900 meqs is reabsorbed. 
– Potassium at around 90%: Dr. Ekberg mentions that potassium reabsorption is at 88% but Palmer (2014) reports that the numbers are closer to 90%, with only 10% of potassium reaching the distal parts of the kidney during filtration. 
– Amino acids and glucose are 100 reabsorbed by the body – for good reason. Glucose powers our cells and amino acids help with repairing our tissues. 
Blood creatinine and kidney health: If your get blood work done regularly, the word creatinine may be familiar to you. Creatinine in your blood or urine is an important marker of kidney health. It is a byproduct of the kidneys during filtration and is typically excreted in the urine. However, in chronic kidney disease ,where the kidneys are not filtering out wastes properly, creatinine stays circulating in your blood, causing very elevated levels. Other things can also affect your creatinine levels, such as muscle mass, activity, and muscular breakdown (muscle damage and wasting, like when you get injured or loss muscle mass during chronic disease), as well as age, race, and gender. 
In CKD, your creatinine levels are usually inversely proportional to your eGFR, or estimated glomerular filtration rate. eGFR is the gold standard for diagnosing or staging kidney disease.  The lower the value, the lower your kidneys’ filtration rate is.
The Five Stages of Chronic Kidney Disease
• In stage 1, you may still have normal eGFR (90 and above) but the stage 1 categorization will typically be based on a clinical diagnosis based on the presence other symptoms – such as infection (blood infections, UTI) and/or even the presence of blood and protein in the urine (which signifies kidney damage ) – all while your eGFR is in the normal range.
• Stage 2 is characterized by reduced eGFR (60-89). The signs and symptoms are typically the same with stage 1 or, according to Dr. Ekberg’s experience, sometimes no signs and symptoms at all. In fact, the more symptomatic you are, the likelier your CKD is in the late stages already. 
• Stage 3 is when things get pretty serious, with your eGFR at 30 to 59, which is around 50 percent reduction of your normal kidney function.
• Stage 4 is the penultimate stage before you hit the end of the road, with your eGFR at 15-29. Your kidneys are barely functioning at this point, with the filtration rate as low as it is. The symptoms (see the list below) are likely of the same nature as the previous stage, but are more severe in nature, and often, with the previous symptoms present all at once. Here, your doctor may start preparing you for hemodialysis or a kidney transplant. 
• The last stage, stage 5, is called ESRD or End Stage Renal Disease. Your eGFR is now less than 15 and you would now need several sessions of dialysis monthly, if not weekly, to help filter out your blood. You may also be a candidate for a kidney transplant – which is very often based on a waiting list.
10 Signs And Symptoms Chronic Kidney Disease
Dr. Ekberg lists 10 signs your kidneys are toxic in one of his popular videos. Here are the signs from the video, together with our notes and references:
1. Urinary changes
Kidney damage can happen when you have an infection, which is reflected in blood work and urine tests. You may notice changes in your urine, specifically with the color, smell, and frequency, as well as abnormal test results with bacteria and protein – all signs of infection. 
Hypertension can reflect kidney damage as fluid buildup occurs and raises blood pressure. However, this is a double-edged sword as kidney disease can also stem from uncontrolled hypertension, because persistently high blood pressure can damage the delicate blood vessels and tissues of the kidney. 
As previously mentioned, the kidneys are responsible for the production of erythropoietin (EPO), the hormone that helps regulate the production of red blood cells. When your kidneys are damaged and not producing enough EPO, your hemoglobin levels can drop and cause anemia. 
4. Bone Disease
You might be thinking, “What do bones have to do with the kidneys?”. It gets a little technical with this portion, but basically, the kidneys are responsible for clearing phosphate, a mineral, from the blood. Equal levels of phosphate and calcium are part of the body’s natural homeostasis. As your kidney becomes damaged is unable to remove phosphate from your system, your thyroid tries to balance out the elevated phosphate by causing bone breakdown (via production of the parathyroid hormone) and the release of calcium in your bones. 
Edema, or swelling, happens due to the excess fluid circulating in the system. This can be typically seen in the distal extremities like the hands and feet, as too much fluid is pushed out into the space in between the cells (called third spacing). This can also happen because of disruptions in the cell wall due to deranged albumin levels (responsible for cell wall permeability). You may also see puffiness under the eyes. Edema or swelling can also happen in the lungs, a dangerous condition called pulmonary edema. 
6. Back Pain
Or more specifically, flank pain. This symptom is typically non-specific and can be caused by a variety of reasons including muscle pain, but if it is accompanied by other symptoms on this list, your kidneys may be the cause. Kidney stones can also cause back pain, which is usually sharp in nature.  A recurrent urinary tract infection (UTI) that travels up the ureters and causes a kidney infection can also present as flank pain. 
7. Pulmonary Edema and COPD
People at this stage of kidney disease often present with breathing problems, this again is due to the excess fluid in the body which can end up in the lungs. Dr. Ekberg mentions COPD as something that is caused by CKD. Alternately, a study in 2016 found that people who already had COPD were 1.6 times more likely to develop CKD. 
Trouble sleeping can occur as a you start to experience more and more of the symptoms on the list. Difficulty breathing, swelling of your extremities, pain, and the building toxicity in your blood can all affect your sleep. Psychologically, depression and anxiety can also contribute to insomnia. 
9. Ammonia Breath
This classic symptom is usually accompanied by a metallic taste in your mouth. This is a sign of uremia, where the excess urea in the blood reacts with saliva, creating ammonia. 
10. Severe Toxicity
Last on the list is the severe toxicity caused by uremia, or the build up urea and other wastes in the blood, which is caused simply by the kidneys’ inability to perform their task.  As this build-up of wastes continues, azotemia also develops, which is the elevation of your BUN or blood urea-nitrogren and creatinine levels – the two markers in blood work that is typically monitored in CKD patients. According to Dr. Ekberg, a person who is uremic can experience itching, nausea and vomiting, poor appetite, and cramps.
Loss of kidney function is a serious matter and be aware that without proper management, CKD can lead to disability if not death. So what to we do? One of the major causes of CKD is diabetes; as hyperglycemia, like hypertension, damages the kidney’s very delicate tissues. If you are diabetic or pre-diabetic, you have to make adjustments in your diet and exercise daily to help keep your weight down and prevent / reduce insulin resistance, which is a major risk factor for diabetes. Remember, prevention is key!
10 Signs Your Kidneys Are Toxic Graphic © healthpowerboost.com. Egg Illustration: Gray’s Anatomy (PD)
 Cockwell, P. (2020). The global burden of kidney disease. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32977-0/fulltext
 National Institute of Diabetes and Digestive and Kidney Diseases. Your Kidneys and How They Work. https://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they-work
 Hamm, L., et. Al. (2015). Acid-Base Homeostasis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670772/
 Schoener, B. & Borger, J. (2021). Erythropoietin Stimulating Agents. https://www.ncbi.nlm.nih.gov/books/NBK536997/
 Wardener, H. (1978). The control of sodium excretion. https://pubmed.ncbi.nlm.nih.gov/358840/
 Palmer, B. (2014). Regulation of Potassium Homeostasis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455213/
 Alsahli, M. & Gerich, J. (2017). Renal glucose metabolism in normal physiological conditions and in diabetes. https://pubmed.ncbi.nlm.nih.gov/28866383/
 Singh, A. (2016). Nanoparticle Pharmacokinetics and Toxicokinetics. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/kidney-tubule-absorption
 Mayo Clinic. Creatinine tests. https://www.mayoclinic.org/tests-procedures/creatinine-test/about/pac-20384646
 Cleveland Clinic. eGFR. https://my.clevelandclinic.org/health/diagnostics/21593-estimated-glomerular-filtration-rate-egfr
 Fresenius Kidney Care. Stage 1 of Chronic Kidney Disease. https://www.freseniuskidneycare.com/kidney-disease/stages/stage-1
 Fresenius Kidney Care. Stage 2 of Chronic Kidney Disease. https://www.freseniuskidneycare.com/kidney-disease/stages/stage-2
 Hamrahian, S. & Falkner, B. (2017). Hypertension in Chronic Kidney Disease. https://pubmed.ncbi.nlm.nih.gov/27873228/
 Nitta, K., et. al. (2017). Management of Osteoporosis in Chronic Kidney Disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790712/
 Bobkova, I., et. al. (2016). https://journals.sagepub.com/doi/full/10.5301/pocj.5000204
 Mount Sinai. Flank pain. https://www.mountsinai.org/health-library/symptoms/flank-pain
 Cleveland Clinic. Flank pain. https://my.clevelandclinic.org/health/symptoms/21541-flank-pain
 Fresenius Kidney Care. Stage 2 of Chronic Kidney Disease. https://www.freseniuskidneycare.com/kidney-disease/stages/stage-4
 Chen, C. & Liao, K. (2016). Chronic Obstructive Pulmonary Disease is associated with risk of Chronic Kidney Disease: A Nationwide Case-Cohort Study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863146/
 Ancoli-Israel, S. (2006). The Impact and Prevalence of Chronic Insomnia and Other Sleep Disturbances Associated With Chronic Illness. https://www.ajmc.com/view/may06-2308ps221-s229
 Fresenius Kidney Care. What is Ammonia Breath and Is It a Symptom of CKD? https://www.freseniuskidneycare.com/thrive-central/ammonia-breath
 Meyer, T. & Hostetter, T. (2007). Uremia. https://www.nejm.org/doi/10.1056/NEJMra071313
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