Tubular function and tubulointerstitial disease.

Tubular transport determined by the fractional excretion (FE) of filtered solutes was studied in 129 nephrotic patients; 72 patients with mesangial proliferation (MesP-NS) and intact tubulointerstitium (group 1), 13 patients with MesP-NS and superimposed tubulointerstitial fibrosis (TIF; group 2), 27 patients with mild focal segmental glomerulosclerosis (FSGS; group 3), and 17 patients with severe FSGS (group 4). In the 72 nephrotic patients with MesP-NS and normal tubulointerstitium (no TIF), tubular transport was intact (FE of sodium [FENa], 0.5 +/- 0.5; FE of calcium [FECa], 0.3 +/- 0.3; FE of phosphate [FEPO4], 14 +/- 13; FE of uric acid [FEUA], 9.8 +/- 5; FE of magnesium [FEMg], 1.3 +/- 0.5). In the 13 nephrotic patients with MesP-NS and superimposed TIF (4.9% +/- 2%), there was no difference in FE solutes from those in group 1 except for FEMg (3.3 +/- 0.9; P < 0.001). In the 27 nephrotic patients with mild FSGS (TIF, 28% +/- 9%), four of five variables of FE solutes (FENa, 1.2 +/- 0.7; P < 0.001; FECa, 0.9 +/- 0.8; P < 0.001; FEPO4, 17 +/- 12; P, not significant; FEUA, 16.5 +/- 8; P < 0.001; FEMg, 4. 1 +/-1; P < 0.001) were significantly different from those of patients with MesP-NS without TIF, and two of five variables (FECa, FEMg) were statistically different from those of patients with MesP-NS with TIF. In the severe category of FSGS (TIF, 69% +/-19%), all FE solutes were statistically different from the other groups (FENa, 4.8 +/- 3; FECa, 2 +/- 1; FEPO4, 47 +/- 24; FEUA, 37 +/- 18; FEMg, 12 +/- 6). Thus, the results imply that (1) normal tubular transport reflects an underlying intact tubulointerstitial structure, whereas tubular dysfunction indicates an underlying tubulointerstitial disease, and (2) FEMg is the most sensitive index to detect an early abnormality of tubular structure and function.

Renal dysfunction in glomerulonephropathy associated with rapid onset renal failure.

Eight patients between the ages of 5 and 26 years developed a rapid decline of renal function with a period of oliguria or anuria which ranged between 1 and 21 days. The initial assessment of renal function revealed a severe degree of glomerular, tubular, and vascular abnormalities. The magnitude of the renal dysfunction was quantified and expressed in terms of a clinical score. The degree of glomerular and tubular dysfunction was inversely proportional to the renal plasma flow and peritubular capillary blood flow, respectively. Similar findings have been observed in a variety of other glomerulonephropathies where a relationship exists between the reduction of peritubular capillary blood flow and the severity of the tubulointerstitial disease. Evidence to support the position that the reduction of peritubular capillary blood flow plays a primary role in inducing tubulointerstitial disease is as follows: (i) A reduction of peritubular capillary blood flow has been documented in mesangial proliferative nephrosis with steroid resistance prior to the detection of tubulointerstitial disease. (ii) Ischemic insults are capable of inducing tubulointerstitial disease in the experimental setting of renal artery occlusion in animals. (iii) As demonstrated in the present report, an improvement of tubular function can be achieved following an increase in peritubular capillary blood flow with therapy designed to enhance renal perfusion.

Renal dysfunctions in glomerulonephropathy with rapidly declined renal failure.

Eight patients aged between 5 and 26 years developed rapid deterioration of renal function and became oliguric/anuric with duration ranging from 1 to 21 days. The initial functional assessment revealed severe degree of glomerular, tubular, and vascular dysfunctions. The magnitude of renal dysfunction was quantified and expressed in terms of a clinical score. The degree of glomerular and tubular dysfunctions were inversely proportional to the renal plasma flow and peritubular capillary blood flow (PTCB), respectively. Similar findings have been observed in a variety of severe glomerulonephropathies. In this aspect, it is likely that the reduction of peritubular capillary blood flow and tubulointerstitial disease are interrelated. Further evidence to support the primary role of reduction of PTCB in inducing tubulointerstitial disease is provided by the following: (a) Reduction of PTCB is documented in mesangial proliferative nephrosis with steroid resistance prior to the detection of tubulointerstitial disease. (b) Ischemic insult can induce tubulointerstitial disease in experimental setting of renal artery occlusion in animal, (c) Improved tubular function can be achieved following the increase in PTCB with the enhanced renal perfusion therapy.