Influence of the Renal Cortical Interstitium on the Serum Creatinine Concentration and Serum Creatinine Clearance in Different Chronic Sclerosing Interstitial Nephritides

Abstract

54 biopsy cylinders of patients with different chronic sclerosing interstitial nephritides were investigated morphometrically. The point-counting method was used to determine the relative interstitial volume of the renal cortex. In this study, as in earlier investigations on inflammatory and noninflammatory glomerular diseases, as well as in studies on benign nephrosclerosis, significant positive correlations could be found between serum creatinine concentration and enlargement of the interstitium induced by fibrosis. Furthermore, correlations between decreasing serum creatinine clearance and fibrosis-induced interstitial broadening could be established. Enlargement of the interstitium by lymphocytic and plasma cellular infiltrates had no influence on renal function. Only in 1 patient were the findings not congruent with the above-mentioned observations. This could be explained by a severe anorexia nervosa with muscular atrophy and lack of available creatinine. The clearance values, however, showed the expected impairment of renal function. Interstitial fibrosis may lead to a narrowing of the postglomerular vessel network and to an elevated postglomerular flow resistance. In spite of increased glomerular filtration pressure, slowing of the glomerular blood flow could lead to an elevated serum creatinine concentration. A reduced glomerular filtration rate could lead to tubular atrophy as a sign of inactivity. Furthermore, the deficient Na-Cl resorption in atrophic tubules most likely perpetuates the decrease in the glomerular filtration rate. The glomerular filtration rate could be diminished by the so-called Thurau mechanism.

Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3.

“…The animals had free access to food and water. At the end of the study period, the animals were housed separately in metabolic cages for 24 h, during which time food and water intake was monitored and 24-h urine output was collected. Total urinary protein excretion was assayed by the sulfosalicyclic acid method in each animal.…”

Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model

“…It is recognized that tubulointerstitial rather than glomerular scarring is the more representative lesion in patients with progressive renal disease [1][2][3]. Although the pathogenesis of interstitial fibrosis has been studied extensively, many unsolved questions remain about the initial cause of fibrosis, the stimuli responsible for its perpetuation and the identity of profibrogenic cells [4][5][6][7][8][9][10].…”

Tubulointerstitium as Predictor of Progression of Glomerular Diseases

“…Three groups of investigators in London [1], Seattle [2, 3]and Tübingen [4, 5]have shown that in glomerular diseases the impairment of the glomerular filtration rate correlated better with the extent of tubulointerstitial damage than with the degree of the glomerular damage and suggested that the major events which determine the outcome of these diseases probably occur in the interstitium. In these last 15 years, the importance of tubulointerstitial involvement for the progression of renal damage in glomerular diseases has been supported by a continuously increasing amount of clinical and experimental data, emerging mainly from two types of studies: (1) studies of natural history of large cohorts of patients, showing correlations between single clinical or histological features and progression, and (2) studies based on molecular biology and immunohistochemistry of biopsy specimens, showing the expression of the mRNA and/or the protein of single cytokines or growth factors in the epithelial tubular cells, in the leukocytes infiltrating the interstitium and in the resident interstitial fibroblasts.…”