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Renal Tubular Acidosis

How do we recognize renal tubular acidosis? Number one, what I said before; first have a blood pH. You’ve got to have acidosis. I can’t tell you how often I have been consulted by some of you out there who will say, "Low CO2, low bicarbonate, we have an acidosis. Please evaluate the acidosis for us." And it turns out, of course, that it’s a compensation because the blood pH, when we got it, was 7.6. So number one, be sure you know the acid-base status. Start stepwise. Start with your first step which is; know the primary disorder. Then these patients are hyperchloremic. They have a normal anion gap.

Now there are different types. We nephrologists have an incredible amount of imagination and wit, so we of course call them type I and type II, with our great creativity. Type I is called distal RTA. It is caused by a problem in the distal tubule with the inability to decrease the urine pH to 5.5 during acidosis. Because the kidney can’t push out hydrogen ions out of the body. There is one of a number of molecular defects that cause the kidney to be unable to kick out hydrogen ions. You eat 3 milliequivalents per kilo of hydrogen ion per day in your phosphates and your sulfates and the things that you eat.

How do you evaluate these patients? They have a hyperchloremic metabolic acidosis and they have a positive urinary anion gap. That’s because these patients don’t make very much ammonia. The urine - a lot of the positives that are over here to balance out the chlorides, etc. - is ammonia and usually the sodium plus potassium minus chloride normally is a negative number. But in distal RTA the sodium plus the potassium minus the chloride is a positive number in distal RTA. We’ll get to proximal RTA in a minute. And in normals, it’s a negative number. The urine pH, for the sake of this discussion here, is always greater than 5.5.

The types; it is associated with many many things, and I’ve listed a number of them here. Genetically transmitted disease, autoimmune diseases and disorders associated with nephrocalcinosis. If you hear nephrocalcinosis and acidosis, think type I RTA, and there are a couple of situations here. Drugs that have tubular toxicity; we talked about hypokalemia with cisplatin and amphotericin. Ampho will also give you a situation of RTA. Ampho also gives you renal failure in very sick patients, but in patients that are not so sick and we are using lower doses of ampho, there is a tubular toxicity, and that’s amphotericin-B I’m talking about. Others include pyelonephritis obstruction and kidney transplant.

Type II RTA is different than type I RTA. It’s not that you can’t excrete hydrogen ions. It’s that the kidneys leak bicarbonate. There is a low threshold in the blood for spilling bicarbonate in the urine. Normally you and I start to spill about 22.

So what is the Fanconi’s syndrome? The Fanconi’s syndrome is a disease of the proximal tubule, that has all of the listed criteria, or many of the listed criteria; proximal RTA, they have amino aciduria, glucosuria, phosphaturia and hypophosphatemia.

What are examples? This is the one they will ask you. Number one, cystinosis. Most frequent cause. Galactosemia, Wilson’s disease are others, and on the slide - because Dr. McCabe is interested in glycogenosis and he’s my boss; I’m vice chairman and he’s the chairman - I put glycogenosis twice. Glycogen storage disease, Wilson’s disease, galactosemia, but cystinosis, nephropathic cystinosis, is the archetypal one. Here are some other selected causes.

How do you evaluate type II RTA? Again, hyperchloremia, metabolic acidosis. But the anion gap is negative. Remember I told you that for distal RTA the anion gap was positive. This one is not a problem with making ammonia. This is a problem just with leaking lots of bicarb. So the anion gap is negative. The urine pH is greater than 5.5 when the plasma bicarb is what is normal to you and me, but when the plasma bicarb falls below the threshold, the urine pH is low.