Case Published: December 2018

Case 25 Index

Diagnosis: Type 1 Distal Renal Tubular Acidosis (RTA) due to Sjögren’s syndrome 

Case Summary: Acid and base disorders can be tricky! Let’s break this down step by step. The first step in a patient with an acid-base disturbance is to identify the acid base disorders, and then use the clinical history and additional data to narrow down the differential diagnosis. With a blood gas, we can identify the acid-base disorders using pLACO (click for the step-by-step method). Using pLACO, we find that this woman has a non-gap metabolic acidosis with adequate compensation. The basic labs reveal normal kidney function and hypokalemia.

The next step in the evaluation if a patient with a non-anion gap acidosis is to find out if bicarbonate is being lost from the kidney or through the gastrointestinal tract. The urine anion gap (urine Na + urine K – urine Cl) answers this question. If the sign of this number is positive (i.e 10), we are likely dealing with a renal tubular acidosis (RTA). If the sign is negative (i.e -10), or neGUTive, think about losses from the lower gastrointestinal tract. As chloride is often excreted with ammonium in the urine (NH4+, the primary component of net acid excretion), chloride levels in the urine that exceed the urine Na and urine K combined suggest that the nephron is able to increase ammonium excretion. Thus, if the urine chloride levels are low compared to the net cation excretion (Na + K), a renal tubular acidosis is impairing the ability acidify the urine. In cases in which other anions are excreted with ammonium into the urine (i.e. ketoacidosis, toluene posioning), urine chloride may underestimate ammonium and excretion and thus affect the UAG.  In ketoacidosis and toluene poisoning, negatively charged β-hydroxybutyrate/acetoacetate and hippurate may be excreted with ammonium, respectively.

In this case, the UAG is positive and now we must look for a type 1, 2, or 4 RTA. Now, the serum potassium, clinical history, and urine pH will bring us home. Let’s start with the type 4 RTA, often associated with hyPERkalemia as it associated with true or “pseudo” hypoaldosteronism. We’ll rule this out as the etiology here, as our patient presented with hyPOkalemia and associated symptoms of muscle weakness. We won’t delve into the mechanisms in this case, but causes of type 4 RTAs include diabetes, Addison’s disease, pharmacologic antagonism of aldosterone/ENaC/sodium-potassium ATPase, pseudoaldosteronism II, and obstructive uropathy. 

So now how do we differentiate between type 1 (distal) and type 2 (proximal)? Both the clinical history and urine pH can help us here. In a type 2 RTA, there is urinary wasting of  filtered bicarbonate alone or also wasting of phosphate, AA, glucose, uric acid, citrate, LMW protein. Kidney stone formation is less common given the high concentration of citrate in the urine! The urine pH tends to be lower in the type 2 RTA, as distal urinary acidification remains intact. Etiologies include injury to the proximal tubule (i.e. medications or immunoglobulin light chains), carbonic anhydrase inhibitors, or defects in the basolateral sodium bicarbonate co-transporter (NBCe1)

If a metabolic acidosis is present, a urine pH of higher than 5.5 should raise suspicion for a distal or type 1 RTA!  As distal urinary acidification has been interrupted, the proximal tubule will now try to reabsorb as much bicarbonate as it can…and also reabsorb other molecules including citrate. The low citrate in the urine predisposes these patients to nephrolithiasis and sometimes nephrocalcinosis. In this case, a patient with nephrolithiasis, hypokalemia, a non-gap metabolic acidosis, and urine pH > 5.5 seems like a slam dunk for a type 1 distal RTA. Up to 25% of patient’s with Sjogren’s syndrome (dry eyes, dry mouth, and history of autoimmune disease in our patient) have a type 1 RTA. Causes include mutations or inhibition of the luminal side H+ – ATPase or basolateral AE-1 (bicarbonate-chloride exchanger) as well as problems with carbonic anhydrase II. Another interesting mechanism of a type 1 RTA is H+ “backleak” from the lumen into the tubular cell due to membrane damage caused by amphotericin.

We’ll cover the other RTAs in upcoming cases, but here’s a summary table for now:

For a more in-depth look:

1. Soleimani M, Rastegar A: Pathophysiology of Renal Tubular Acidosis: Core Curriculum 2016. American Journal of Kidney Diseases 68: 488–498, 2016
2. Vallés PG, Batlle D: Hypokalemic Distal Renal Tubular Acidosis. Adv Chronic Kidney Dis 25: 303–320, 2018
3. Yaxley J, Pirrone C: Review of the Diagnostic Evaluation of Renal Tubular Acidosis. Ochsner J 16: 525–530, 2016

Case 25 Index
Case 25 Introduction
Case 25 Physical Exam
Case 25 Diagnostic Testing
Case 25 Diagnostic Testing Continued
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