Transient acute kidney injury after chimeric antigen receptor T-cell therapy in patients with hematological malignancies

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Understanding kidneys

Facts and Functions

Our kidneys ensure that we stay healthy because they clean our blood. Every day, they filter about 1,800 litres of blood and excrete the filtered waste of products and toxins through urine. It takes just five minutes for all the blood in our body to pass through the kidneys; every day this happens about 300 times. The blood flows back into the heart via the renal vein, and the urine is directed via the ureters into the bladder, where it is collected and finally excreted via the urethra.

Our kidneys tirelessly filter toxins from our blood like a sewage treatment plant.

The filtering systems within the kidney are called nephrons. Our kidneys are made up of a million nephrons. The filter in the nephrons, called the glomerulus, is so fine that only water and small substances pass through. This so-called primary urine, containing salts, nutrients and waste products, is collected in the tubule. 125 millilitres per minute, 180 litres per day. Almost all of the fluid and vital substances such as water, sugar, amino acids and salts are returned to the body in the branched tubule system. Finally, only around 1.5 litres of concentrated urine are excreted.

In addition to detoxification, our kidneys ensure that our blood pressure, water, minerals, acids and alkalis in the body remain within the normal range and that our bones do not become weak.

Larger blood components such as blood cells or proteins are not filtered in the glomerulus and instead are retained in the glomerulus and returned into the bloodstream. In this way, the kidneys regulate the body’s water and salt balance as well as the body’s pH and blood pressure.

The kidneys produce various hormones. They regulate the production of red blood cells in the bone marrow, and phosphate and calcium metabolism by activating vitamin D, and thus ensure that the bones remain healthy.

Check-Up

Patients at risk should have their kidney function checked regularly. But even supposedly healthy people can benefit from a regular health check-up by a doctor. In some European countries, health services provide a health check. These check-ups are usually done by general practitioners and are, in some countries, restricted to patients who have risk factors, such as higher age, high blood pressure, the presence of diabetes mellitus and/or cardiovascular disorders.

How do you recognise when your kidneys are not working optimally?

Blood test

In kidney disease, the kidneys can no longer filter the blood adequately and waste products remain in the body. Creatinine and urea accumulate in the blood. The levels of these metabolic end products can be determined with a blood test. Since creatinine is formed in the muscles, the amount of creatinine in the blood depends on muscle mass and muscle work. The normal value is 0.8 – 1.2 mg/dl or 70 – 106 µmol/l, and the normal urea concentration is 20 – 45 mg/dl or 3.3 – 7.5 mmol/l.

Higher levels of creatinine in the blood denote poor levels of kidney function.

Glomerular Filtration Rate (GFR)

The glomerular filtration rate (GFR) can be used to assess the kidney function and the severity of the disease. The GFR is the volume filtered by the glomeruli of the kidneys in a given time. The normal value is 90 to 130 millilitres per minute. Thus, a healthy kidney filters at least 90 millilitres of primary urine from the blood per minute. The GFR measure most commonly used in clinical practice is estimated using the creatinine level in the blood serum and taking into account age and gender.

Chronic kidney disease can be staged, according to the estimated glomerular filtration rate (eGFR). It is an important marker to decide on diagnosis, prognosis and treatment.

Patients with stage 5 CKD have an eGFR of fewer than 15 millilitres per minute and may be dependent on dialysis, filtering the toxins from the blood artificially, or a kidney transplant.

In addition, a sensitive marker for determining the GFR is the level of the metabolic protein cystatin C in serum, which is independent of muscle mass and therefore of age and sex. In declining kidney function, cystatin C is insufficiently filtered out of the blood. The normal value is below 0.96 milligrams/litre.

Urine test

In addition to blood values, urine values are also important for examining kidney function. If the filtering capacity of the glomeruli is impaired, protein may no longer be retained in the body and passes increasingly into the urine (proteinuria).

A healthy person normally excretes little or no protein, at most 200 milligrams of protein per day.

To assess kidney function, the concentration of the protein albumin in the urine should be checked; in a healthy person, it is less than 30 milligrams. A concentration of 30-300 milligrams of albumin is called microalbuminuria. A rapid urine test – urinalysis or urine dipstick testing – for microalbuminuria can provide the first indication of an issue with the kidneys. However, the protein concentration in the urine depends on your fluid uptake. To increase the accuracy of the test, the albumin concentration is therefore related to the concentration of creatinine in the urine in a laboratory test (albumin/creatinine quotient). Diabetics in particular should be tested regularly for microalbuminuria to assess the filtering capacity of the kidneys.

If protein is detected in a rapid urine test, further tests must be undertaken.

Urine dipstick testing is an essential part of check-ups by the general practitioner. It provides quick and easy information about the protein concentration and thus about the health of the kidneys. The less protein in the urine, the healthier the kidneys.

Kidney Replacement

When the kidneys fail, the blood must be purified via dialysis. This is because the accumulation of waste products in the blood can be life-threatening. There are two methods for artificial blood purification: Hemodialysis and peritoneal dialysis.

In hemodialysis, the blood is continuously removed from the body and purified outside the body in an external machine using a dialysis fluid to help remove the toxins. The ‘purified’ blood is then returned and so the cycle continues. Each session lasts for about 4-5 hours and it usually takes place three times a week in a dialysis centre. In some circumstances, it can be done at home.

Peritoneal dialysis can be performed independently at home. In this process, the blood is not filtered through a machine but through the patient’s peritoneum; the membrane inside the stomach. About two litres of dialysis fluid are introduced into the patient’s abdominal cavity via an abdominal catheter, drained after several hours and replaced with new dialysis fluid.

In end stage kidney disease, dialysis and kidney transplantation are the two major treatment options.

However, dialysis cannot replace all renal functions, such as the production of the hormone erythropoietin, which is important for blood synthesis, or vitamin D, which is essential for bone synthesis. Many dialysis patients suffer from anaemia, bone metabolism disorders, high blood pressure, and reduced physical fitness.

If appropriate, kidney transplantation is the optimal form of kidney replacement therapy. However, if there is no living kidney donor then the waiting times for a deceased donor kidney may be long. Additionally, following kidney transplantation patients have to take medication to suppress the immune system for the rest of their lives. Without immunosuppression, their bodies would reject the donor’s kidney.

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Stages of CKD according to KDIGO 2012 Clinical Practice Guideline