The connective tissue of the kidney parenchyma, called interstitial tissue, surrounds the nephrons, ducts, and blood and lymphatic vessels. This tissue increases considerably in amount from the cortex (where it constitutes approximately 7% of the volume) to the inner region of the medulla and papilla (where it may constitute more than 20% of the volume).
In the cortex, two types of interstitial cells are recognized: cells that resemble fbroblasts, found between the basement membrane of the tubules and the adjacent peritubular capillaries, and occasional macrophages. In their intimate relationship with the base of the tubular epithelial cells, the fibroblasts resemble the subepithelial fibroblasts of the intestine. These cells synthesize and secrete the collagen and glycosaminoglycans of the extracellular matrix of the interstitium.
In the medulla, the principal interstitial cells resemble myofbroblasts. They are oriented to the long axes of the tubular structures and may have a role in compressing these structures. The cells contain prominent bundles of actin filaments, abundant rough endoplasmic reticulum (rER), a well-developed Golgi complex, and lysosomes. Prominent lipid droplets in the cytoplasm appear to increase and decrease in relation to the diuretic state.
Most fibroblasts originate within the interstitial tissue through a mechanism called epithelial–mesenchymal transition. The conversion of tubular epithelial cells into a mesenchymal phenotype is initiated by an alteration in the balance of local cytokine concentrations. During persistent injury and chronic inflammation of the kidney parenchyma, fibroblasts increase their numbers and, by secreting excess extracellular matrix, destroy normal interstitial architecture of the kidney. Research studies suggest that in renal fbrosis, more than one third of all disease-related fibroblasts originate from tubular epithelial cells at the site of injury. Proliferation of fibroblasts in response to local mitogens usually leads to irreversible renal failure characterized by tubulointerstitial nephritis. Recent therapeutic interventions in renal fibrosis are directed toward inhibiting fibroblast formation by shifting local cytokine balance in favor of reversal mesenchymal– epithelial transition.
The countercurrent multiplier system creates hyperosmotic urine.
The term countercurrent indicates a flow of fluid in adjacent structures in opposite directions. The ability to excrete hyper-osmotic urine depends on the countercurrent multiplier system that involves three structures:  Loop of Henle, which acts as a countercurrent multiplier. The ultrafiltrate moves within the descending limb of the thin segment of the loop toward the renal papilla and moves back toward the corticomedullary junction within the ascending limb of the thin segment. The osmotic gradients of the medulla are established along the axis of the loop of Henle.
 Vasa recta, form loops parallel to the loop of Henle. They act as countercurrent exchangers of water and solutes between the descending part (arteriolae rectae) and ascending part (venulae rectae) of the vasa recta. The vasa recta help to maintain the osmotic gradient of the medulla.
 Collecting duct in the medulla acts as an osmotic equilibrating device. Modified ultrafiltrate in the collecting ducts can be further equilibrated with the hyperosmotic medullary interstitium. The level of equilibration  depends on activation of ADH-dependent water channels (AQP-2).
A standing gradient of ion concentration produces hyper-osmotic urine by a countercurrent multiplier effect.
The loop of Henle creates and maintains a gradient of ion concentration in the medullary interstitium that increases from the corticomedullary junction to the renal papilla. As noted above, the thin descending limb of the loop of Henle is freely permeable to water, whereas the ascending limb of the loop of Henle is impermeable to water. Further, the thin ascending limb cells add Na and Cl to the interstitium.