Present diagnostic tests such as serum creatinine determination and creatinine clearance are unable to reflect early tubulointerstitial disease. Because a kidney biopsy cannot be performed in every single patient, tubular epithelial function (namely, the fractional excretion of magnesium; FE Mg) that correlates directly with the degree of tubulointerstitial fibrosis would serve this purpose. FE Mg is normal in acute post-streptococcal glomerulonephritis and mesangial proliferative nephrosis with intact tubulointerstitial structure, and is abnormally elevated in nephrosis with focal segmental glomerulosclerosis (FSGS) and in chronic kidney diseases in which kidney biopsies have been obtained. FE Mg is useful in the screening of tubulointerstitial disease in patients when indication for kidney biopsy in not fulfilled, such as diabetic patients or patients with microscopic proteinuria, hematuria, and hypertension. Altered FE Mg is usually associated with a reduction in peritubular capillary flow. There is a linear correlation between FE Mg and peritubular capillary flow, which supports the chronic ischemic injury inducing altered tubular function and tubulointerstitial fibrosis.