The importance of tubulointerstitial injury in the early phase of primary glomerular disease.

OBJECTIVES

As tubulointerstitial damage is regarded secondary to glomerular injury in primary glomerulopathies, we assessed lesions to renal tubulointerstitium in recently diagnosed primary glomerular diseases and evaluated their impact on progression of the disease during the first 2 years after diagnosis.

DESIGN

A nonrandomized prospective study assessing tubulointerstitial morphometry at diagnosis, markers of tubular function within the next 6 months and progression of the disease (creatinine clearance) during 24 months' follow-up.

SETTING

Single tertiary referral centre.

SUBJECTS

Forty-six patients with primary glomerular disease, the diagnostic oligobiopsy performed within 2 months of the onset of clinical symptoms.

INTERVENTIONS

All patients were subjected to antiinflammatory/immunosuppressive treatment.

MAIN OUTCOME MEASURES

Alterations in results of tubulointerstitial morphometry and tubular function tests, correlations between these variables and parameters of nephrosis/renal function, selection of the most accurate predictor of disease progression within 24 months after diagnostic biopsy.

RESULTS

Function of proximal tubules, markedly deteriorated at the time of diagnosis, significantly improved 6 months later (urinary beta2-microglobulin: P < 0.0025), along with reduction in proteinuria (P < 0.00125). No appreciable alterations in function of 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 renal function at 24 months. Excretion of beta2-microglobulin at the time of diagnosis was the best marker for impairment of glomerular filtration 6 months later.

CONCLUSIONS

Significant damage to cortical tubulointerstitium occurs concurrently with glomerular injury in primary glomerulopathies and may predict the clinical course of the disease already in its initial phase.