The early phase of experimental acute renal failure

Abstract

Experiments were performed to determine whether furosemide, given in doses high enough to induce a strong diuresis and to inhibit the mechanism of tubuloglomerular feedback, offers any protection from acute renal failure induced by a nephrotoxin or ischaemia. Microperfusion of the loop of Henle revealed that a tubular furosemide concentration of 5 x 10(-5) mol x 1(-1) was necessary to fully inhibit the tubuloglomerular feedback response to a raised sodium chloride concentration at the macula densa. The infusion of furosemide systemically to achieve such concentrations in the tubule resulted in an improvement in renal function when given before or after the nephrotoxin but was without effect when given before or after ischaemia. Measurements of furosemide concentrations in the urine, however, confirmed that sufficient amounts were applied to inhibit the feedback mechanism. It is concluded from this and similar studies that furosemide is only beneficial in models of acute renal failure with an obstructive or nephrotoxic pathogenesis, in which it acts by flushing out the noxious material and not by inhibiting the mechanism of tubuloglomerular feedback.

Physiological role for P2X1 receptors in renal microvascular autoregulatory behavior

“…Furosemide (50 µM) was infused into the renal artery to inhibit the TGF response. This approach has been used extensively in the whole kidney and micropuncture models to block TGF-mediated responses (24,32,33,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). In this series of experiments, diameter measurements were made 55 ± 2 µm and 48 ± 3 µm from the glomerulus in WT and KO mice, respectively.…”

“…Inhibition of TGF signals with furosemide has been used by Schnermann et al, in a micropuncture setting, to investigate TGF influences on stop-flow pressure (36,37,40,41,45). Furosemide treatment has also been used by other investigators to assess TGFdependent effects in whole kidney and juxtamedullary nephron preparations (24,32,33,38,39,(42)(43)(44).…”

Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury

“…2,6,7 The relative importance of both segments in the pathogenesis of AKI remains controversial and may depend on the models used. 4 Inhibition of sodium reabsorption and hence oxygen consumption in TALs using furosemide reduced TAL injury in some, 8 -10 but not all experimental settings [11][12][13][14][15] and failed to reduce the incidence of AKI in humans. 16 Hypoxia-inducible transcription factors (HIF) mediate cellular protection against reduced oxygen delivery by regulating cellular pathways and functions, including glycolysis, angiogenesis, erythropoiesis, and cell survival decisions.…”

Mechanisms of intranephronal proteinaceous cast formation by low molecular weight proteins.

“…For BJPs, hemoglobin, and myoglobin (MYG), the tubulointerstitium is the usual site of damage (2)(3)(4)(5). Although proximal tubule injury occurs with reabsorption and catabolism of some LMWPs (6-8), a major morphologic pattern of tubule damage in patients (2,3,(9)(10)(11) and several experimental models of LMWP nephrotoxicity (5,10,(12)(13)(14) consists of casts of LMWPs in the lumen of the distal nephrons.…”