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What is chronic kidney disease?

Chronic kidney disease (CKD) develops when there is damage to the kidneys or decreased kidney function for at least three months. Healthy kidneys filter waste products and excess water from the blood so the body can excrete them as urine. Those waste products include urea, oxalic acid, and ammonia.1,2 When diseases such as diabetes and hypertension damage the kidneys, they filter blood more slowly. This can cause harmful wastes and fluids to build up in the body. CKD often develops slowly and irreversibly over a period of months or years.2

Kidney damage is determined by measuring the speed with which your kidneys filter blood. A glomerular filtration rate test (GFR) is the best way to measure this. If your GFR has been low and the protein albumin has been present in your urine (albuminuria) for at least three months, you may be diagnosed with CKD.2,3

Based on the GFR, doctors can determine the stage to which a patient’s CKD has progressed:

  • Stage 1: GFR > 90 mL/min per 1.73 m2
  • Stage 2: GFR 60-89 mL/min per 1.73 m2
  • Stage 3: GFR 30-59 mL/min per 1.73 m2
  • Stage 4: GFR 15-29 mL/min per 1.73 m2
  • Stage 5: GFR < 15 mL/min per 1.73 m2

Kidney functioning at GFR stages 1 and 2 may be considered normal. Albuminuria may be assessed to evaluate for kidney damage. At GFR stages 3 and higher, CKD may be diagnosed. At GFR stage 5, scar tissue (fibrosis) develops and causes kidney failure. A patient at GFR stage 5 has end-stage renal disease (ESRD) and is at high risk of death.2

CKD prevalence worldwide is estimated to be 8-16%, though it varies widely depending on the country. In high-income countries, 11-13% of people have CKD at stage 3-5, though most of those people (90%) have stage 3 CKD.1,4 In the US from 2007-2012, between 12-15% of people had CKD.5

What are common symptoms?

A patient at an early stage of CKD often has no symptoms. Because of this, early detection of CKD usually happens through a routine medical examination and laboratory tests.

As CKD worsens to stage 3 or higher, kidney function gradually decreases. Substances known as ‘uremic retention solutes’ build up in the body and cause complications like inflammation, immune dysfunction, and vascular disease.

These complications are associated with other conditions including (in order of frequency)2,3:

  • Hypertension
  • Anemia
  • Hyperparathyroidism
  • Hyperphosphatemia
  • Acidosis
  • Hypocalcaemia

People with CKD may experience nonspecific symptoms such as2,3:

  • Bone pain
  • Fluid retention
  • Itchiness and muscle cramps
  • Peripheral neuropathy
  • Sleep disturbance
is a condition in which the parathyroid glands overproduce parathyroid hormone (PTH). Normally, PTH helps regulate levels of calcium, vitamin D, and phosphorus in the blood and bones. Too much of the hormone can cause dangerous levels of calcium to build up in the blood.
is an abnormally high concentration of phosphate in the blood.
is a condition in which there is an excess amount of acid in the body’s fluids, especially in the blood. It is normally caused by poor functioning of the lungs and kidneys.
is an abnormally decreased concentration of calcium in the blood.
is a condition in which nerves in the body’s extremities are damaged, causing numbness, pain, and muscle weakness in the affected areas.

What are the causes?

Conditions that contribute to the development of CKD may include (in order of frequency)2:

  • Diabetes
  • Hypertension
  • Obesity
  • Dyslipidemia
  • Smoking

Diabetes and high blood pressure (hypertension) cause almost two thirds of CKD cases, especially in middle and high-income countries.4,5 Diabetes causes high amounts of sugar to build up in the blood, which can damage filters in the kidney. High blood pressure can damage blood vessels in the kidney.6

Infections and immune reactions such as glomerulonephritis can also lead to CKD. Glomerulonephritis can be caused by diabetes, high blood pressure, infections, immune diseases, or medication side effects.4,7

In a small number of cases, genetic disorders can cause kidney and urinary tract abnormalities, such as polycystic kidney disease. These disorders can contribute to CKD.2

is an inflammation of the filtering structures (glomeruli) of the kidney.
refers to elevated concentrations of lipids or fats in your blood.

How does this topic relate to my microbiome?

Patients with CKD have an imbalanced gut microbiome, even at early stages. CKD creates a vicious cycle in which the microbial imbalance in the gut both results from CKD and contributes to it. CKD is also associated with slower movement of food through the intestines and a decreased ability to digest food. Both of these can negatively affect gut microbes.8

In CKD, waste products that can no longer be filtered by the damaged kidneys accumulate in the blood and can end up in the gut, where they are processed by the gut microbiota. For example, when urea accumulates in the gut, some gut microbes manufacture urease and other enzymes which convert the urea into the toxin ‘ammonia.’ Ammonia raises the pH of the gut, negatively affecting the growth of other gut bacteria. Other waste products – such as creatinine, indoles, and phenols – can inhibit or promote the growth of certain gut bacteria. They can also be converted into more toxic compounds.9 These toxins contribute to the progression of CKD and the development of renal fibrosis, which further reduce kidney function.9,10

A common treatment for end-stage CKD is hemodialysis, which uses a dialysis machine to manually filter a patient’s blood. Compared to healthy individuals, the guts of patients undergoing hemodialysis have an increased number of Enterobacteria, Enterococci, Clostridium perfringens, Firmicutes, Actinobacteria, and Proteobacteria, and a decreased number of Bifidobacteria and Lactobacilli.8,10

Which diseases/topics are related to CKD?

Kidney health is strongly related to cardiovascular health. Patients who suffer from CKD are at high risk of developing cardiovascular disease (CVD). In fact, the heart and kidneys generally fail together, so deaths associated with CKD are often related to increased atherosclerosis (hardening of the arteries) and heart failure.4 Unfortunately, drug treatments for atherosclerosis and heart failure put CKD patients at an increased risk of acute kidney injury (AKI).3,4 Because of this, CKD must be considered when prescribing drugs to these patients. Additionally, both CVD and AKI are considered risk factors for CKD since these conditions may lead to kidney failure.4

Other diseases that often occur at the same time as CKD include (in order of frequency)5,11:

  • Diabetes
  • Hypertension
  • Obesity
  • High cholesterol
  • Renal artery stenosis
  • Anemia
  • Bone disease
  • Secondary hyperparathyroidism
occurs when the blood vessels narrow in one or both kidneys. It can be caused by an accumulation of plaque in the vessels, which eventually obstructs blood flow. Reduced blood flow causes the blood vessels to harden and decreases kidney function. This can result in high blood pressure.
occurs when the parathyroid glands (small glands located in the neck) become enlarged and overproduce parathyroid hormone. This overproduction can cause bones to become weak and brittle, and can also cause calcium to accumulate in tissues and organs.

How can people take action?

The best treatment for CKD is prevention. Controlling your blood sugar and blood pressure by maintaining a healthy diet and lifestyle can help keep CKD at bay.

Early stages of CKD often are symptomless, so regular medical examinations are critical for detecting and assessing the disease. Screening is especially important for elderly people, those with a family history of CKD, and people with related diseases like diabetes, hypertension, and CVD.4 Early treatment for CKD can keep the disease from developing further and reduce renal and cardiovascular complications. This improves both survival and quality of life.

For patients with CKD, accurate diagnosis and timely care are essential. Treatment often involves proper nutrition, managing blood pressure and blood sugar, quitting smoking, and may include prescription medications.4,5 Consuming certain pre- and probiotics can help reestablish gut balance and reduce the levels of microbes that generate uremic toxins.10

Once CKD has advanced to end-stage renal disease (ESRD), the kidneys are no longer able to remove toxic wastes and fluids from the blood. Hemodialysis, peritoneal dialysis, and eventually kidney transplantation may be necessary.4

Hemodialysis uses a dialysis machine to filter waste products – such as urea, creatinine, and potassium – from the blood. How often hemodialysis is needed depends on the severity of a patient’s ESRD, but this treatment is typically done three times a week at a dialysis center.

A healthcare provider may choose to put a patient on peritoneal dialysis instead. Peritoneal dialysis filters the blood through a tube (also known as catheter) surgically placed inside the abdomen. This catheter is periodically emptied (usually 4-6 times a day) into a collection bag. Peritoneal dialysis gives patients more independence since the catheters can be emptied by the patient, by a caregiver at home, or even while traveling. A healthcare provider will determine whether dialysis is necessary and which type is best for the patient.

References

1. Hill, N. R., Fatoba, S. T., Oke, J. L., Hirst, J. A., Callaghan, A. O., Lasserson, D. S., & Hobbs, F. D. R. (2016). Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis. Plosone, 1–18.

2. Webster, A. C., Nagler, E. V., Morton, R. L., & Masson, P. (2016). Chronic Kidney Disease. The Lancet, 389(10075), 1238–1252.

3. Levey, A. S., & Coresh, J. (2012). Chronic kidney disease. The Lancet, 379(9811), 165–180.

4. Jha, V., Garcia-Garcia, G., Iseki, K., Li, Z., Naicker, S., Plattner, B., … Yang, C. W. (2013). Chronic kidney disease: Global dimension and perspectives. The Lancet, 382(9888), 260–272.

5. Wouters, O. J., O’Donoghue, D. J., Ritchie, J., Kanavos, P. G., & Narva, A. S. (2015). Early chronic kidney disease: diagnosis, management and models of care. Nature Reviews Nephrology, 11(8), 491–502.

6. The National Institute of Diabetes and Digestive and Kidney Diseases (2016). Causes of Chronic Kidney Disease. Retrieved September 25 2018.

7. Stanifer, J. W., Muiru, A., Jafar, T. H., & Patel, U. D. (2016). Chronic kidney disease in low- and middle-income countries. Nephrology Dialysis Transplantation, 31(6), 868–874.

8. Wing, M. R., Patel, S. S., Ramezani, A., & Raj, D. S. (2016). Gut microbiome in chronic kidney disease. Experimental Physiology, 101(4), 471–477.

9. Nallu, A., Sharma, S., Ramezani, A., Muralidharan, J., & Raj, D. (2016). Gut microbiome in chronic kidney disease: challenges and opportunities. Translational Research, 179(May), 24–37.

10. Ramezani, A., Massy, Z. A., Meijers, B., Evenepoel, P., Vanholder, R., & Raj, D. S. (2016). Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target. American Journal of Kidney Diseases, 67(3), 483–498.

11. López-Novoa, J. M., Martínez-Salgado, C., Rodríguez-Peña, A. B., & Hernández, F. J. L. (2010). Common pathophysiological mechanisms of chronic kidney disease: Therapeutic perspectives. Pharmacology and Therapeutics, 128(1), 61–81.