THE IMPORTANCE OF TUBULOINTERSTITIAL INJURY IN THE EARLY PHASE OF PRIMARY GLOMERULAR-DISEASE

Objectives. As tubulointerstitial damage is regarded secondary to glom erular injury in primary glomerulopathies, we assessed lesions to rena l tubulointerstitium in recently diagnosed primary glomerular diseases and evaluated their impact on progression of the disease during the f irst 2 years after diagnosis, Design. A nonrandomized prospective stud y assessing tubulointerstitial morphometry at diagnosis, markers of tu bular function within the next 6 months and progression of the disease (creatinine clearance) during 24 months' follow-up. Setting. Single t ertiary referral centre. Subjects, Forty-six patients with primary glo merular disease, the diagnostic oligobiopsy performed within 2 months of the onset of clinical symptoms. Interventions, All patients were su bjected to anti-inflammatory/immunosuppressive treatment. Main outcome measures. Alterations in results of tubulointerstitial morphometry an d tubular function tests, correlations between these variables and par ameters of nephrosis/renal function, selection of the most accurate pr edictor of disease progression within 24 months after diagnostic biops y. Results. Function of proximal tubules, markedly deteriorated at the time of diagnosis, significantly improved 6 months later (urinary bet a(2)-microglobulin: P < 0.0025), along with reduction in proteinuria ( P < 0.00125). No appreciable alterations in function oi distal tubules were noted. Morphometric indices revealing interstitial expansion and tubular atrophy significantly correlated with creatinine clearance at 6 months (P = 0.032) and were the best predictors of deteriorating re nal function at 24 months. Excretion of beta(2)-microglobulin at the t ime of diagnosis was the best marker for impairment of glomerular filt ration 6 months later. Conclusions. Significant damage to cortical tub ulointerstitium occurs concurrently with glomerular injury in primary glomerulopathies and may predict the clinical course of the disease al ready in its initial phase.