Renal interstitium

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Wang et al. injected a Texas-red-labelled phosphorothioated AS-ODN into the dopamine lA receptor in the rat renal interstitium. Fluorescence was detected after 24 h in both tubular epithelium and intra-renal vasculature. Treatment resulted in a 35% decrease in the dopamine lA receptor protein, causing a reduction in urinary sodium excretion and urine output [131],... 

Direct tubular toxicity of proteinuria or interaction of tubular cells (or renal interstitium) with some specific components of the proteinuric urine, for example, albumin, transferrin, immunoglobulins and their fragments, components of complement, and chemotactic or growth factors, has been suggested (R7). 

Re-absorption is a two-step process beginning with the active or passive extraction of substances from the mbule fluid into the renal interstitium (the connective tissue that surrounds the nephrons), followed by their transport from the interstitium into the bloodstream. These transport processes are driven by hydrostatic, oncotic, diffusion and active transport. Some key regulatory hormones for re-absorption include aldosterone, which stimulates active sodium re-absorption (and water as a result), and antidiuretic hormone, which stimulates passive water re-absorption. Both hormones exert their effects principally on the collecting ducts. 

Fillastre JP, Moulin B, and Josse S. Aetiology of nephrotoxic damage to the renal interstitium and tubuli.Toxicology Letters 46 45-54,1989. 

This particular form of chronic tubulo-interstitial nephritis is characterized by an important cellular infiltration of the interstitium with macrophages, T-cells but also B-cells. Furthermore, after arrest of the drug, there is improvement of the renal function in some cases [26,93]. In those in which there is a delayed diagnosis of renal damage, recovery of renal function does not occur. Instead, several of those patients needed one or another form of renal replacement therapy. An important aspect of this type of toxic nephropathy is the documented persistence of the inflammation of the renal interstitium even several months after arrest of drug intake [28]. 

First attempts to experimentally reproduce CHN failed two groups of seven Wistar rats were orally administered either pure aristolochic adds (10 mg/kg for 5 days a week during 3 months) or herbs powders (containing AA) mixed with fenfluramine. At sacrifice animals in both groups had developed the expected tumors but not fibrosis of the renal interstitium [61]. However, when 12 female New Zeeland whife rabbits were injected intraperitoneaUy with 0.1 mg aristolochic acids per kg, 5 days a week, for 17 to 21 months, they developed a severe hypocellular interstitial fibrosis, urothelial atypias and, in 3 of them, tumors of the urinary tract [62]. 

Morphine also increased the accumulation of types 1 and 3 collagen in the renal interstitium [52]. Mor-... 

Type V collagen along with Type VI collagen has been found in the mesangium, glomerular basement membrane, and renal interstitium. Type VI collagen is a ubiquitous protein present in many types of extra-... 

Normally, the renal filtrate is concentrated as it moves down the descending loop of Henle, due to the osmotic gradient in the renal interstitium. As the interstitium becomes saturated with water, the concentration gradient disappears and the filtrate becomes less concentrated, due to the retention of water normally reabsorbed into the interstitium. This results in an increase in urine volume and decreased filtrate osmolality. 

The mannitol molecule is not transported across the thin limb of the loop of Henle. Thus, the associated water molecules also cannot pass into the renal interstitium. The countercurrent mechanism is thus disrupted, and. to some extent, results in the dehydration of the renal interstitium. 

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