Acute renal failure: the glomerular and tubular connection

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Abstract
Acute renal failure (ARF) is a common clinical entity which results from multiple causes. Experimental models in animals have duplicated many of the clinical syndromes which can be classified into (1) ARF due to increased filtered load of endogenous and exogenous materials, (2) ARF associated with exogenous nephrotoxins and (3) ischemic forms of renal failure secondary to hypoperfusion and hypotension. The mechanisms leading to the reduction in GFR are multiple and the alterations in determinants of nephron filtration rate and degree of tubular backleak and obstruction are described for each of these subtypes of experimental ARF. The specific mechanisms whereby tubular damage translates into a reduction in GFR in ARF are discussed for each sub-type of ARF. Tubular damage can often be dissociated from the reduction in GFR, possibly by inhibiting tubuloglomerular feedback responses, but such increases in GFR and nephron filtration rate are not necessarily beneficial to the organism because of potential volume depletion and the risk of magnifying further tubular damage. Information on the physiologic role of tubuloglomerular feedback activity in ARF is provided and supports the concept that feedback induced reductions in GFR after tubular injury may preserve extracellular volume and minimize further tubular damage. Reductions in tubular metabolic work appears to prevent and ameliorate further tubular injury after the initial insult. The mechanisms which associate changes in GFR and tubular damage can now be described, and therapies which improve GFR without correcting the tubular damage may compound the clinical problem and increase renal damage.