What is renal tubular acidosis (RTA)?

Renal tubular acidosis is a condition or disease in which the kidney does not take acid out of blood and put it into urine like it should. Protein is broken down to yield energy and amino acids, and the amino acids are used to make new proteins. Acid is generated as a waste product in this process, and the part of the kidney called the tubule takes the hydrogen ions, the acid molecules, out of the blood and puts them into the tubular fluid, which ultimately becomes urine. The kidney defect is limited to this, although along with it comes some decrease in the ability to concentrate the urine, meaning the ability to put a large amount of waste products into a small amount of urine. This ability is crucial in times of decreased fluid intake, or during increased fluid losses, like during episodes of diarrhea and vomiting. So the child with RTA becomes more easily dehydrated under these circumstances. Sometimes parents or doctors will be fooled about the dehydration, because lack of urinary concentrating ability means that the child keeps urinating fairly frequently. Frequency and amount of urination cannot be used as a marker of hydration.

What are the types of RTA?

There are three kinds of RTA. Two of them involve the distal part of the renal tubule and the third involves the proximal part. Proximal RTA (also called type II RTA) is most usually part of a systemic disease, often part of a metabolic disease, ie one involving the chemical processes inside the cells, such as cystinosis, tyrosinemia, Lowe's syndrome, Wilson's disease, all rare diseases. Once in a while type II RTA is a primary disorder, ie; not associated with anything else. In proximal RTA bicarbonate (alkali, the opposite of acid) is lost into the tubular fluid (the precursor fluid of urine) at the level of the proximal part of the tubule. Large amounts of bicarbonate can be lost here, so that the doses of bicarbonate needed to replace the bicarbonate lost are large in children with this disease.

Much more common are the two types of distal RTA, types I and IV RTA. Distal RTA and proximal RTA result in acidosis (high blood acid levels) by different mechanisms. In distal RTA the distal part of the tubule fails to secrete acid (hydrogen ions) into the urine, so acid is left in blood and acidosis results. In the normally functioning distal tubule, hydrogen ion (acid) is pulled out of blood and secreted into the tubular fluid, the fluid that will soon be urine. Potassium handling by the distal tubule is also affected in type IV RTA. The difference between type I RTA and type IV RTA is the way potassium is handled. In type I RTA potassium tends to be lost into urine in abnormally high amounts and so blood potassium level is on the low to low normal side. In type IV RTA the opposite is true and urinary potassium levels are low, resulting in potassium levels that are high in blood. Both types I and IV can occur as a primary defect and stand alone as the only thing wrong with the kidney, or they may be associated with renal diseases, most often renal diseases involving the tubules, which include many of the renal diseases considered birth defects like obstructive uropathy (ex posterior urethral valves), renal dysplasia, and reflux nephropathy. (Reflux nephropathy is the situation when reflux has led to damage and scarring in the kidney; reflux without this damage will not cause RTA.) Because of this fact, I suggest doing a renal ultrasound in any child newly diagnosed with RTA.

Do you wonder what happened to type III? It was eliminated as a separate type. Type III was formerly type I with a component of type II, and now that is just called type I. Some infants and small children with type I RTA also lose some bicarbonate into the urine at the level of the proximal tubule. This usually improves or stops with advancing age. So what used to be type III is now just called type I (with the recognition that there can be proximal losses in type I) or is called type I with bicarbonate wasting.

How is RTA discovered? What are the tests for RTA?

Children with RTA often present in infancy or as toddlers with feeding problems, growth failure, vomiting, and/or recurrent episodes of dehydration. It can be a somewhat difficult diagnosis, since there are several situations that lead to false blood test results. To look for acidosis (excess acid in blood, meaning inadequate alkali) most often blood electrolytes are checked, ie the levels of sodium, potassium, chloride and CO2 (carbon dioxide). Carbon dioxide is measured in lieu of measuring bicarbonate, the main form of alkali in blood, since the measurement of carbon dioxide is easier than the measurement of bicarbonate. So in the lab the bicarbonate in blood is converted to carbon dioxide, then the carbon dioxide measured. In the process, carbon dioxide, which is a gas, can evaporate off, making the measurement falsely low. This evaporation can also happen when blood is drawn by heel stick or finger stick, where the blood smears on the heel or finger and the CO2 has an opportunity to evaporate. It can also happen when only a small amount of blood is drawn, particularly if it goes into a big tube so that the surface area on top of the blood is high, when the blood sits for a long time before the test is run.

Potassium levels are also important to measure in children with RTA, and there is room for lab error here, too. The normal concentration of potassium in liquid part of the blood is about 3.5 to 5.2 meq/liter. Yet the concentration of potassium inside cells, including red blood cells, is 160 meq/liter, more than 30 times higher. So if any red cells break apart in the process of drawing the blood or handling the blood, then the potassium level comes back as falsely high. Often the lab technologists can tell this since when they spin the blood down and take the serum, the liquid part of the blood, away from the cells, the serum is reddish if red cells have broken, whereas it should be a clear very pale yellowish color. However, platelets can also break in the process and the tech will not be able to tell this, resulting in a falsely high level that is not appreciated. Platelets are small cells in blood, also high in potassium as are all body cells; their job is to promote clotting when it is needed.

I tell you all this technical stuff so that you will be prepared for some difficulty with the blood tests needed in children with RTA, since checking electrolytes is needed both for diagnosis and follow-up. With all the technical possibilities for error in the test, many of which are difficult to prevent, it is not unusual to have to repeat the tests, especially in babies and small children where blood drawing can be difficult.

At the time of diagnosis, urine testing is also needed to make the
determination that the acidosis (high level of acid in blood) is the fault of the kidney. Acidosis can also result from overproduction of acid, and the kidney can be working fine and getting rid of acid very well, but the amount produced can overwhelm the ability of the kidney to get rid of it. In this case the problem is not RTA, and other causes for the acidosis need to be pursued.

What is the treatment for RTA?

The treatment for RTA consists of the administration of alkali, either as bicarbonate or as something that is turned into bicarbonate rapidly in the body. Since the normal kidney is getting rid of acid continuously, the alkali needs to be given in frequent doses, usually in 3-4 doses a day. Once or twice a day dosing will generally leave the child acidotic (ie with high blood levels of acid) for a significant portion of the day, and the symptoms of the disease will continue, especially the problem of growth failure.

The options for treatment are sodium bicarbonate pills, sodium bicarbonate liquid, sodium citrate liquid, mixed sodium citrate and potassium citrate liquid. In the USA the bicarbonate pills come as 325 mg and 650 mg (doctors often talk of acid and alkali amounts in terms of meq which are milliequivalents, and the 650 mg pills are 7.7 meq each). Sodium bicarbonate liquid does not come commercially, since it is not stable as a liquid for long enough to be practical to market it that way, but a pharmacist can make it up, and it will be stable for at least a month. Sodium citrate comes commercially as Bicitra, which contains one meq of alkali per milliliter (abbreviation ml; ml is the same as cc). Mixed sodium and potassium citrate comes commercially as Polycitra, which is 2 meq/ml, one of sodium and one of potassium. (There is also Polycitra K, which is
all potassium.)

In checking the blood for its acid/alkali level (bicarbonate level) to check how the child is doing with treatment, it is best to check the blood right before a dose of alkali is due. What you see after each dose is given is that within an hour after the dose the blood acid level is maximally low, so the alkali (bicarbonate) level is maximally high. Then over the next few hours the acid level rises, ie the alkali (bicarbonate) level decreases, until another medication dose is given and the cycle repeated. What the medication should do is to keep the acid level in the blood normal all the time. Right before a dose is due the alkali level should be no lower than the lower limit of normal and right after a dose it will be high. If the alkali level gets too high, ie the blood acid level gets too high, then growth may not be what it could be, since high acid levels interfere with growth. Besides poor growth, inadequate treatment can result in decreased energy, nausea, and other nonspecific symptoms.

What is the long-term outlook for a child with isolated RTA (RTA not linked to another kidney disease)?

Some of the children, in my experience about half, who have type I and type IV RTA will outgrow it before they get to kindergarten with no traces of the disease. The others will go on with the disease for life. As long as they take their medication regularly, they remain healthy. If children with types I or IV do not take their medication, then growth is often a problem and frequently a condition called nephrocalcinosis, will intervene. Nephrocalcinosis is calcification of the kidney, which if it gets to be severe enough, can further interfere with the functioning of the kidney and even lead to kidney failure. The nephrocalcinosis does not occur if the condition is adequately treated and blood acid levels are kept in reasonable range. With treatment, the child with isolated (primary) RTA should continue to have good kidney function and be healthy, except for the urinary concentrating defect, on a lifelong basis.