Ischemic acute kidney injury (AKI) triggers expression of adaptive (protective) and maladaptive genes. Agents that increase expression of protective genes should provide a therapeutic benefit. We now report that bardoxolone methyl (BARD) ameliorates ischemic murine AKI as assessed by both renal function and pathology. BARD may exert its beneficial effect by increasing expression of genes previously shown to protect against ischemic AKI, NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-γ (PPARγ), and heme oxygenase 1 (HO-1). Although we found that BARD alone or ischemia-reperfusion alone increased expression of these genes, the greatest increase occurred after the combination of both ischemia-reperfusion and BARD. BARD had a different mode of action than other agents that regulate PPARγ and Nrf2. Thus we report that BARD regulates PPARγ, not by acting as a ligand but by increasing the amount of PPARγ mRNA and protein. This should increase ligand-independent effects of PPARγ. Similarly, BARD increased Nrf2 mRNA; this increased Nrf2 protein by mechanisms in addition to the prolongation of Nrf2 protein half-life previously reported. Finally, we localized expression of these protective genes after ischemia and BARD treatment. Using double-immunofluorescence staining for CD31 and Nrf2 or PPARγ, we found increased Nrf2 and PPARγ on glomerular endothelia in the cortex; Nrf2 was also present on cortical peritubular capillaries. In contrast, HO-1 was localized to different cells, i.e., tubules and interstitial leukocytes. Although Nrf2-dependent increases in HO-1 have been described, our data suggest that BARD's effects on tubular and leukocyte HO-1 during ischemic AKI may be Nrf2 independent. We also found that BARD ameliorated cisplatin nephrotoxicity.

The concepts discussed in this review are important for clinical medicine. Drugs and genetic manipulation may ameliorate ischemic kidney injury by regulating the inflammatory response to cell injury.

Renovascular hypertension (RVH) represents a secondary and potentially remediable form of hypertension. Elevated blood pressure is only one of a broad array of pathophysiologic consequences that are associated with decreased renal perfusion. Our ability to accurately and noninvasively detect stenotic lesions within the renal artery is growing. However, functional assessment of renal parenchyma and hemodynamic significance of renal artery lesions is still limited. Advances in endovascular techniques spurred interest in the concept of ischemic nephropathy and the effect of renal artery revascularization on renal function. Despite the relative frequency of atherosclerotic renal artery stenosis (ARAS), there currently is no consensus on the most appropriate therapy. In this article, we focus on the two most common causes of RVH, ARAS and fibromuscular dysplasia. We discuss the therapeutic strategies, disease mechanisms, clinical findings, evolving trends, and developments.

Tl-201 brain SPECT appears unreliable for differentiating primary lymphoma from nonmalignant brain lesions in patients with AIDS. Early brain biopsy is necessary to establish a definitive diagnosis when appropriate.

IntroductionHyperacute rejection may be prevented by avoiding the transplantation of kidneys into patients with pre-existing anti-donor Class I human leukocyte antigen antibodies. However, the role of anti-donor-Class II-human leukocyte antigen-DQ antibodies is not established. The question is ever more relevant as more sensitive cross-matching techniques detect many additional antibodies during the final crossmatch. We now report successful renal transplantation of a patient who had pre-existing antibodies against his donor's human leukocyte antigen-DQ5.Case presentationOur patient, a Caucasian man, was 34 years of age when he received his first deceased donor renal transplant. After 8 years, his first transplant failed from chronic allograft dysfunction and an earlier bout of Banff 1A cellular rejection. The second deceased donor kidney transplant was initially allocated to the patient due to a 0 out of 6 mismatch. The B cell crossmatch was mildly positive, while the T Cell crossmatch was negative. Subsequent assays showed that the patient had preformed antibodies for human leukocyte antigen DQ5 against his second donor. Despite having preformed antibodies against the donor, the patient continues to have excellent allograft function two years after his second renal transplant.ConclusionThe presence of pre-existing antibodies against human leukocyte antigen DQ5 does not preclude transplantation. The relevance of having other antibodies against class II human leukocyte antigens prior to transplantation remains to be studied.