Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and chronic kidney disease. Two promising preconditioning methods for the kidney, intermittent arterial clamping (IC) and treatment with the hypoxia mimetic cobalt chloride, have never been directly compared. Furthermore, the protective efficacy of the chemically related transition metal Zn²⁺ against renal IRI is unclear. Although Co²⁺ ions have been shown to protect the kidney via hypoxia inducible factor (HIF), the effect of Zn²⁺ ions on the induction of HIF1α, HIF2α and HIF3α has not been investigated previously. The efficacy of different preconditioning techniques was assessed using a Sprague-Dawley rat model of renal IRI. Induction of HIF proteins following Zn²⁺ treatment of the human kidney cell lines HK-2 (immortalized normal tubular cells) and ACHN (renal cancer) was measured using Western Blot. Following 40 minutes of renal ischemia in rats, cobalt preconditioning offered greater protection against renal IRI than IC as evidenced by lower peak serum creatinine and urea concentrations. ZnCl₂ (10 mg/kg) significantly lowered the creatinine and urea concentrations compared to saline-treated control rats following a clinically relevant 60 minutes of ischemia. Zn²⁺ induced expression of HIF1α and HIF2α but not HIF3α in HK-2 and ACHN cells. ZnCl₂ preconditioning protects against renal IRI in a dose-dependent manner. Further studies are warranted to determine the possible mechanisms involved, and to assess the benefit of ZnCl₂ preconditioning for clinical applications.

Partial nephrectomy (open or minimally invasive) usually requires temporary renal arterial occlusion to limit intraoperative bleeding and improve access to intrarenal structures. This is a time-critical step due to the critical ischemia period of renal tissue. Prolonged renal ischemia may lead to irreversible nephron damage in the remaining tissue and, ultimately, chronic kidney disease. This is potentiated by the incompletely understood ischemia-reperfusion injury (IRI). A key mechanism in IRI prevention appears to be the upregulation of an intracellular transcription protein, Hypoxia-Inducible Factor (HIF). HIF mediates metabolic adaptation, angiogenesis, erythropoiesis, cell growth, survival, and apoptosis. Upregulating HIF-1 α via ischemic preconditioning (IPC) or drugs that simulate hypoxia (hypoxia-mimetics) has been investigated as a method to reduce IRI. While many promising chemical agents have been trialed for the prevention of IRI in small animal studies, all have failed in human trials. The aim of this review is to highlight the techniques and drugs that target HIF-1 α and ameliorate IRI associated with renal ischemia. Developing a technique or drug that could reduce the risk of acute kidney injury associated with renal IRI would have an immediate worldwide impact on multisystem surgeries that would otherwise risk ischemic tissue injury.

Sethi K, et al. Investig Clin Urol. 2017 Nov;58(6):447-452. https://doi.org/10.4111/icu.2017.58.6.447

Hemiballism and hemichorea are recognized manifestations of cerebral infarction. Paroxysmal dyskinesias are less well recognized symptoms of transient cerebral ischemia. We describe a 41-year-old man with distal internal carotid artery occlusion and poor intracranial collaterization who developed repetitive stereotyped involuntary arm movements and subsequent cerebral infarction. This peculiar manifestation of transient cerebral ischemia may indicate poor intracranial collateralization with reliance upon leptomeningeal collaterals. Earlier recognition may help avert cerebral infarction.