Experiments were performed on rats to investigate the significance of the medullary hyperemia known to follow renal ischemia. To this end, its frequency was determined, its severity was quantified, and its relation to renal function was examined early (1 to 3 hr) and later (18 hr) after 45 min of warm ischemia. All kidneys were found to have a hyperemic outer medulla early after ischemia, which was shown to develop during the period of ischemia itself, but which was found to be highly variable in its severity. The degree of hyperemia was assessed both subjectively by grading and by histometric determinations of inner stripe capillary volume. One to hours after ischemia, the severity of medullary hyperemia was reflected in all indices of renal function, the least congested kidneys showing the best function. Eighteen hours after ischemia, the degree of medullary hyperemia was reflected in all indices of renal function, except urine flow rate; the non-congested kidneys showed functional recovery and the still-congested kidneys showed worsening function. Glomerular blood flow, known to be preferentially reduced in deep nephrons 1 to 3 hr after ischemia, had normalized 18 hr after ischemia in the non-congested kidneys but was still severely and unevenly depressed in the congested kidneys. It is concluded that congestion of the outer medulla is a key event in ischemic renal failure, its occurrence is coincidental with the reduction in deep nephron perfusion and urinary concentrating power in the early and maintenance phase and its disappearance heralds the restoration of deep nephron perfusion and urinary concentrating ability in the recovery phase.

The literature contains many reports of the use of commercially available anti-IL-1 agents (anakinra/Kineret, canakinumab/Ilaris, or rilonacept/Arcalyst) in treatment-resistant adult-onset Still's disease (AOSD). These have been widely summarized in many review articles, but a full account of all reports with each of the agents used is not available. This literature review includes all reports of treatment outcomes in patients treated for AOSD with any commercially available anti-IL-1 agent (excluding cases of unconfirmed or atypical AOSD or treatments only for rare AOSD complications). The summary makes use of tabular formats, to identify the available reports and to provide data for compiling and comparison to classical therapies. For each anti-IL-1 agent used, a table shows the frequency of remission during treatment and the frequency of stopping or reducing steroid use, which were reported in almost all articles. A brief textual summary is used to describe other relevant but less often described efficacy aspects and any safety information. The compiled data show that treatment with all anti-IL-1 agents is effective in AOSD, indicating that IL-1 has a central role in the pathogenesis of AOSD. Rates of full or partial remission with each agent were similar to each other (91-100%) and superior to the outcomes published for classical therapies. Primary treatment failures were rare, but efficacy was lost over time in some cases. Of note, the newer anti-IL-1 agents with longer half-lives may show prolonged efficacy. An articular involvement seems to be less responsive than systemic features of disease. However, long-term follow-up shows that efficacy may persist for many years. There is substantial evidence that anti-IL-1 agents have a strong steroid-sparing effect and considerable evidence that the use of disease-modifying anti-rheumatic drugs can also be reduced or stopped. Thus, the use of anti-IL-1 agents may reduce the side-effects of co-treatment. The high response rate to anti-IL-1 agents, especially in refractory AOSD cases, suggests that their appropriate use in a timely manner can slow disease progression and reduce treatment side-effects.

Experiments were performed on rats subjected to renal ischemia and various treatment procedures to determine the origin and functional consequences of vascular obstruction. To this end, its occurrence and severity was assessed qualitatively and quantitatively in the outer medulla, where it is particularly prominent. The incidence of medullary hyperemia was not influenced by inhibiting thrombocyte aggregation with 5 or 70 mg/kg of acetyl salicylic acid or preventing fibrin deposition with 100 IE/kg of heparin before ischemia, and these substances produced no improvement renal function. The incidence and degree of hyperemia, however, could be substantially reduced or completely eliminated by acutely raising blood pressure after ischemia or by decreasing the number of circulating erythrocytes before ischemia. These procedures were effective in raising filtration rate and tubular reabsorption from 20% to 60% of normal, in restoring renal blood flow and vascular resistance to completely normal, and in diminishing epithelial damage both three and 18 hours after ischemia. The following conclusions are drawn: first, vascular obstruction, which is not lessened by inhibiting thrombus formation but is easily reversed or prevented by raising perfusion pressure or decreasing hematocrit, is probably caused by erythrocyte aggregation during ischemia. Second, vascular obstruction, which appears to raise renal vascular resistance and lower blood flow and filtration rate, cannot be limited to the medulla but must also be present in the cortex. Finally, reversing or preventing vascular obstruction can fully restore renal perfusion, partially restore glomerular and tubular function, greatly reduce tubular necrosis and thus prevent renal failure.

No abstract