Correspondence

Renal Tubular Acidosis with Autoantibody Directed to Renal Collecting-Duct Cells

N Engl J Med 1994; 331:1593-1594December 8, 1994

Article

To the Editor:

Although distal renal tubular acidosis is often associated with immune-mediated diseases, autoantibodies against renal tubular cells have been detected only sporadically.1-3 We report the case of a 34-year-old woman with Graves' hyperthyroidism and distal renal tubular acidosis whose serum contained antibodies to renal collecting-duct cells.

In August 1989 weight loss and palpitation occurred in the patient. She had exophthalmos, diffuse goiter, and elevated serum thyroid hormone concentrations. She was treated with methimazole and became euthyroid. In June 1991 progressive weakness of the extremities developed over a period of several days. The patient was taking 2.5 mg of methimazole daily and was euthyroid. The serum sodium concentration was 142 mmol per liter, the potassium concentration 2.6 mmol per liter, the chloride concentration 112 mmol per liter, and the creatinine concentration 0.9 mg per deciliter (80 μmol per liter). The arterial blood pH was 7.39, the partial pressure of oxygen 93 mm Hg, the partial pressure of carbon dioxide 26 mm Hg, and the plasma bicarbonate concentration 16.9 mmol per liter. The urine pH was 7.0.

She was given ammonium chloride (0.1 g per kilogram of body weight administered orally over a period of 30 minutes), after which the arterial-blood pH dropped to 7.29 and the plasma bicarbonate concentration dropped to 13 mmol per liter; the urine pH remained above 6.9. Muscle weakness and metabolic acidosis disappeared with oral sodium bicarbonate and potassium therapy. She remained euthyroid after the discontinuation of methimazole in April 1994. As of August 1994, she was asymptomatic while taking alkali and potassium orally.

Antibodies to renal tubular cells were detected by indirect immunofluorescence with the use of cryostat sections of normal human and rabbit renal tissue. Serum from the patient reacted with tubular cells from human and rabbit kidneys in an identical way; the positively stained cells extended from the cortex to the outer medulla and appeared to be collecting-duct cells (Figure 1Figure 1Cryostat Section of Rabbit Kidney Showing Staining of Collecting-Duct Cells after a Reaction with Serum from the Patient and Subsequent Application of Fluorescein Isothiocyanate-Conjugated Goat Antihuman IgG (x575).). Serum samples from normal subjects did not react with human or rabbit renal tissue.

In rabbit kidneys the intercalated cells of the collecting duct are either lectin-binding or band-3-positive.4 Rabbit renal-tissue sections were double-reacted with tetramethylrhodamine isothiocyanate-conjugated peanut lectin and serum from the patient and then with fluorescein isothiocyanate-conjugated goat antihuman IgG. The results indicated that the patient's autoantibodies were reactive with both types of intercalated cells.

A variety of autoimmune diseases can be associated with Graves' disease. Moreover, an association between methimazole therapy and the appearance of autoantibody to insulin has been reported, mostly in Japanese patients.5 Although the exact causal disorder of immunoregulation remains undetermined, the appearance of anti-renal-tubular-cell autoantibodies in our patient probably has a causal relation to the defective distal tubular acidification.

Konosuke Konishi, M.D.
Matsuhiko Hayashi, M.D.
Takao Saruta, M.D.
Keio University School of Medicine, Tokyo 160, Japan

5 References

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   Daniel Batlle, Guillermo Flores. (1996) Underlying defects in distal renal tubular acidosis: New understandings. American Journal of Kidney Diseases 27:6, 896-915
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