Distal renal tubular acidosis in Sjögren Syndrome and postmenopausal osteoporosis

Primary Sjögren syndrome (pSS) is associated with distal renal tubular acidosis
(dRTA). However, the prevalence of dRTA in patients with pSS is unclear. DRTA
is associated with disorders in calcium metabolism, osteoporosis and kidney
stone formation and a poor well-being of the patient. Osteoporosis is diagnosed
in 7% of the population, but numbers about dRTA being the underlying cause is
lacking.
As there is an effective treatment for dRTA, screening for dRTA in patients
with pSS and postmenopausal osteoporosis seems warranted.

The aims of the present study are 1) to confirm the high prevalence of dRTA in
Sjögren using the urinary acidification test with ammonium chloride, 2) to
determine the prevalence of disorders in calcium metabolism in pSS patients
with dRTA, 3) to investigate the association of dRTA with auto-antibodies
against carbonic anhydrase type II (CA II) and the M3-receptor, 4) to assess
the association of altered expression of acid-base expression in urinary
exosomes, 5) to evaluate whether dRTA is more prevalent than currently thought
in postmenopausal osteoporosis using a new screening test with furosemide and
fludrocortisone and compare this against the gold standard test with ammonium
chloride and 6) to assess the effects of alkali treatment with special
attention to the BMD, serum calcium and potassium levels and bone markers and
urinary excretion of calcium and citrate

The study is an observational study. In all 33 subjects with an abnormal
screening test using fludrocortisone and furosemide we will repeat this test
and additionally perform an acidification test using ammonium chloride.
Furthermore, if not performed within the preceding year, all 33 subjects will
undergo an ultrasound examination of the kidneys and a DEXA-scan.
The 105 subjects in the control group will undergo an ultrasound examination
and a DEXA-scan. They will also undergo the screenings test for dRTA by using
the furosemide/fludrocortisone acidification test, to rule out dRTA as the
underlying cause of osteoporosis in our control group.
All 38 cases of postmenopausal osteoporosis will first undergo the screening
test by using the furosemide/fludrocortisone test. Patients with an abnormal
screening test will undergo the follow-up as described above.

All 33 subjects will be seen twice, with minimal one week in between. The 105
control subjects will undergo both radiographic examinations and the screenings
test on one day. Urine and blood will be collected from all 33 subjects. Mild
adverse effects (nausea, vomiting) are described after ammonium chloride
loading. DEXA scanning leads to a negligible radiation load.
All 38 patients with postmenopausal osteoporosis will be seen once to evaluate
the presence of dRTA. Patients with an abnormal test, will be seen twice more
to confirm dRTA.