To identify clinical and immunological risk factors underlying the development of renal involvement in primary Sjögren's syndrome (pSS).
Seventy-eight patients (75 females, 3 males) with pSS were carefully interviewed and clinical and laboratory data from the time of diagnosis recorded. The baseline data on patients shown to have either latent or overt distal renal tubular acidosis (dRTA), mild proteinuria or increased urinary excretion of alpha-1 microglobulin (alpha1m) after a mean disease duration of 9 +/- 4 years, were compared to the baseline data on those who did not have these manifestations at follow-up.
Patients with subsequent latent or overt dRTA were found to have significantly higher baseline levels of serum total gamma-globulin (24 +/- 7 vs. 19 +/- 6 g/l, p = 0.011) and serum protein (84 +/- 7 vs. 79 +/- 7 g/l, p = 0.024) compared to those with normal renal acidification capacity. The baseline levels of serum beta-2 microglobulin (beta2m) were higher in patients with an acidification defect than in those with normal acidification capacity (3.1 +/- 1.1 vs. 2.6 +/- 0.8 mg/l, p = 0.072). In those with subsequent proteinuria the levels of serum beta2m were almost significantly higher at baseline as compared to those with normal urinary protein excretion (3.1 +/- 1.4 vs. 2.5 +/- 0.8 mg/l, p = 0.052). The subgroup of pSS patients who had increased urinary alpha1m excretion as a sign of tubular proteinuria, had higher baseline levels of ESR (55 +/- 27 mm/h vs. 40 +/- 23 mm/h, p = 0.076) and significantly higher baseline levels of serum beta2m (4.6 +/- 1 .8 vs. 2.6 +/- 0.8 mg/l, p = 0.029) as compared to those with normal urinary alpha1m excretion.
High levels of serum total gamma-globulin, serum protein and serum beta2m were the best predictors of the development of dRTA in pSS patients. High baseline levels of serum beta2m were also associated with the subsequent occurrence of mild proteinuria and increased urinary alpha1m excretion in patients with pSS.