Unraveling metabolism during kidney perfusion using tracer studies: a systematic review.

BACKGROUND: Understanding kidney metabolism during perfusion is vital to further develop the technology as a preservation, viability assessment, and resuscitation platform. We reviewed the evidence on the use of labeled metabolites (tracers) to understand "on-pump" kidney behavior. METHODS: PubMed, Embase, Web of Science, and Cochrane databases were systematically searched for studies evaluating metabolism of (non)radioactively labeled endogenous compounds during kidney perfusion. RESULTS: Of 5899 articles, 30 were included. All were animal studies [rat (70%), dog (13%), pig (10%), rabbit (7%)] perfusing but not transplanting kidneys. Perfusion took place at hypothermic (4-12°C) (20%), normothermic (35-40°C) (77%), or undefined temperatures (3%). Hypothermic perfusion used albumin or a clinical kidney preservation solution, mostly in the presence of oxygen. Normothermic perfusion was mostly performed with oxygenated crystalloids often containing glucose and amino acids with unclear partial oxygen tensions. Active metabolism of carbohydrate, amino acid, lipids, and large molecules was shown in hypothermic and normothermic perfusion. Production of macromolecules, such as prostaglandin, thromboxane, and vitamin D, takes place during normothermic perfusion. No experiments compared differences in metabolic activity between hypothermic and normothermic perfusion. One conference abstract showed increased anaerobic metabolism in kidneys donated after circulatory death by adding labeled glucose to hypothermically perfused human kidneys. CONCLUSIONS: Tracer studies during kidney perfusion contribute to unraveling kidney metabolic behavior in pre-clinical models. Whether findings are truly translational needs further investigation in large animal models of human kidneys. Furthermore, it is essential to better understand how ischemia changes this metabolic behavior.

Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction.

INTRODUCTION: Previous research in the field of cardiovascular diseases suggests a relaxing effect of testosterone (T) on smooth muscle cells. Therefore, it was hypothesized that T could play a significant role in erection development. AIM: To investigate the relaxing effect of T and other molecules of the T signaling pathway on human corpus cavernosum (HCC) tissue. METHODS: Samples of the HCC tissue were obtained from men who underwent penile prosthesis implantation (n = 33) for erectile dysfunction. Samples were used for isometric tension measurement in Ex Vivo experiments. Following standardized precontraction with phenylephrine, increasing doses of T or dihydrotestosterone were administered and blocked by NO/H2S synthesis inhibitors, a KATP blocker, and flutamide (androgen receptor inhibitor). MAIN OUTCOME MEASURE: The outcome was relaxation of the HCC tissue, normalized to a maximum precontraction achieved by phenylephrine. RESULTS: A dose-dependent relaxing effect of dihydrotestosterone and T was observed with a relaxation of, respectively, 24.9% ± 23.4% (P < .0001) and 41.7% ± 19.1% (P = .01) compared with 6.8% ± 15.9% for vehicle (dimethylsulfoxide) at 300 µM. The relaxing effect of T was not countered by blocking NO synthesis, H2S synthesis, KATP channels, or the androgen receptor. CLINICAL IMPLICATIONS: By understanding the underlying mechanisms of T-induced HCC relaxation, potential new therapeutic targets can be identified. STRENGTHS & LIMITATIONS: The strength of the study is the use of fresh HCC tissues with reproducible results. The limitation is the need for supraphysiological T levels to induce the observed effect. CONCLUSION: Rapid androgen-induced relaxation of HCC is likely to occur via nongenomic mechanisms. Previously suggested mechanisms of action by which T modulates HCC relaxation have been excluded. Van den Broeck T, Soebadi MA, Falter A, et al. Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction. J Sex Med 2019; 8:114-119.