Tubular ultrastructure in acute renal failure in man: Epithelial necrosis and regeneration

Abstract

It is not clear whether tubular cell necrosis is present or not in acute renal failure (ARF) of ischaemic type ("acute tubular necrosis"). In order to get quantitative data, using precisely defined criteria for tubular cell necrosis, 25 renal biopsies from 24 patients with ARF (11 obtained in the active phase, 14 in the early recovery period) were compared with 12 control biopsies. In all 1959 proximal cells and 1603 distal cells were analysed by electron microscopy. Cellular disintegration was very rare in all groups. Shrinkage necrosis (apoptosis) was not present in the proximal tubules of the controls and was rare in ARF (1.6-2.1%). In the distal tubules of controls 2.7% of all cells showed shrinkage necrosis. The incidence in ARF was not significantly increased. "Non-replacement sites" in distal tubules (probably loci where cells have recently been desquamated) were significantly increased in number (5.2%) in the active phase in ARF compared to controls and recovery. The relative number of regenerating cells was not increased. These data show that there is no widespread necrosis of tubular cells in ARF. The increased incidence in distal tubules of focal, denuded areas of the basement membrane in the active phase of ARF indicates a slightly increased desquamation of cells and/or a failure to cover such sites by adjacent cells. This process is not restricted to the brief induction phase of ARF but continues during the whole active phase.

Urea handling in acute renal failure

“…Only one patient with worsening renal function was reported to manifest hyperkalemia (46 mmol/l). Thus, although published after our review was submitted, these newer results of Rossignol et al 3 are consistent with and support the conclusions of our review.…”

“…Actually, in the normal kidney, the fractional excretion of urea (FE urea ) depends largely on a combination of influences exerted independently on the proximal and the distal nephron. As already well known since several decades, as shown in Figure 5 of our article, 2 and as re-emphasized by Carvounis et al, 3 a strong urea reabsorption occurs in the distal nephron at low urine flow rates, resulting in a dramatic fall in FE urea .…”

The Authors Reply

“…In a subset of 5792 patients, with mean age 64 years, baseline eGFR 70 ± 21 ml/min per 1.73 m 2 (33% o60 ml/min per 1.73 m 2 ), and mean blood pressure 119/72 mm Hg, they noted that in patients with left ventricular systolic dysfunction with or at high risk of heart failure in the post-infarction setting, there was an early change in eGFR, and after 24 months follow-up they noted a gradual deterioration in eGFR ranging from the baseline value of À4.6±0.9 ml/min for those on eplerenone (Po0.0001) to À2.7±0.9 ml/min for those in the placebo group (P ¼ 0.02), giving a mean difference of À1.4 ± 0.3 ml/min (Po0.0001). The difference occurred early within the first month of treatment and persisted, and was independent of blood pressure changes, but may relate to changes in hemodynamics based on plasma volume changes, perhaps similar to the findings of Pisoni et al 3 in patients with resistant hypertension given aldosterone blockade.…”

“…The Authors Reply: We appreciate the positive interest of Professor Bhandari 1 in our recently published comprehensive review on ' Aldosterone blockade in the management of patients with CKD'. 2 The study of Rossignol et al 3 constitutes a post hoc analysis of the EPHESUS study 4 and evaluated the effect of eplerenone on renal function and the interaction between changes in renal function, and subsequent cardiovascular outcomes, in patients with heart failure after an acute myocardial infarction. Even though the average estimated glomerular filtration rate (eGFR) of these patients was 70 ± 21 ml/min per 1.73 m 2 , a large subset of these patients had no established chronic kidney disease (CKD), and data on proteinuria was not available.…”

Pathological Study on Beagles after Long-term Oral Administration of Cadmium

“…Recently, the inhibitory effect of Cd on in Electron microscopic studies revealed an increased number of shrinkage necrosis of the proximal tubular epithelial cells consistent with "apoptosis," which has been recently described as programmed cell death (21). On the other hand, even in the 100 mg group, there were few ordinary necroses as commonly seen in acute tubular necrosis with the destruction of the membrane system (19).…”