The influence of perfusion solution on renal graft viability assessment

BACKGROUND: Kidneys from donors after cardiac or circulatory death are exposed to extended periods of both warm ischemia and intra-arterial cooling before organ recovery. Marshall’s hypertonic citrate (HOC) and Bretschneider’s histidine-tryptophan-ketoglutarate (HTK) preservation solutions are cheap, low viscosity preservation solutions used clinically for organ flushing. The aim of the present study was to evaluate the effects of these two solutions both on parameters used in clinical practice to assess organ viability prior to transplantation and histological evidence of ischemic injury after reperfusion. METHODS: Rodent kidneys were exposed to post-mortem warm ischemia, extended intra-arterial cooling (IAC) (up to 2 h) with preservation solution and reperfusion with either Krebs-Hensleit or whole blood in a transplant model. Control kidneys were either reperfused directly after retrieval or stored in 0.9% saline. Biochemical, immunological and histological parameters were assessed using glutathione-S-transferase (GST) enzymatic assays, polymerase chain reaction and mitochondrial electron microscopy respectively. Vascular function was assessed by supplementing the Krebs-Hensleit perfusion solution with phenylephrine to stimulate smooth muscle contraction followed by acetylcholine to trigger endothelial dependent relaxation. RESULTS: When compared with kidneys reperfused directly post mortem, 2 h of IAC significantly reduced smooth muscle contractile function, endothelial function and upregulated vascular cellular adhesion molecule type 1 (VCAM-1) independent of the preservation solution. However, GST release, vascular resistance, weight gain and histological mitochondrial injury were dependent on the preservation solution used. CONCLUSIONS: We conclude that initial machine perfusion viability tests, including ischemic vascular resistance and GST, are dependent on the perfusion solution used during in situ cooling. HTK-perfused kidneys will be heavier, have higher GST readings and yet reduced mitochondrial ischemic injury when compared with HOC-perfused kidneys. Clinicians should be aware of this when deciding which kidneys to transplant or discard

Non-heartbeating donation of kidneys for transplantation.

There is a persistent shortage of kidneys available for transplantation. In the early 1980s, therefore, we published the concept of non-heartbeating (NHB) donation; that is, procurement of kidneys from donors whose death has been accompanied by irreversible circulatory arrest. NHB donors are generally categorized using four definitions; category III (awaiting cardiac arrest) and category IV (cardiac arrest while braindead)--or 'controlled'--donors are the most suitable for initiating NHB donation programs. Delayed graft function is associated with use of kidneys from such donors, but has no effect on graft survival in the short or long term. Use of kidneys from category I (dead upon arrival at hospital) and category II (unsuccessfully resuscitated), or 'uncontrolled', donors is likewise associated with delayed graft function, but also with an increased risk of primary nonfunction. Viability testing of donated organs from these sources is a prerequisite for transplantation. Machine preservation parameters and enzyme release measurements help to distinguish viable from nonviable kidneys. The proportion of NHB donor kidneys in the total pool of postmortem kidneys differs considerably between countries. In The Netherlands, the proportion is nearly 50%. This figure is markedly higher than that in the US and Canada, where national programs have now been initiated to increase rates of NHB donation. In the future, warm preservation techniques might facilitate better viability testing, thereby increasing NHB donation from category I and II donors and further reducing the shortage of kidneys available for transplantation

Human papillomavirus genotypes detected in clinician-collected and self-collected specimens from women living in the Mississippi Delta

<p>Abstract</p> <p>Background</p> <p>There are no data available on human papillomavirus (HPV) infections in women living in the Mississippi Delta, where cervical cancer incidence and mortality among African American women is among the highest in the United States. The aim of this analysis was to report the age-specific prevalence of HPV in this population.</p> <p>Methods</p> <p>We recruited 443 women, 26–65 years of age, from the general population of women living in the Mississippi Delta to participate; 252 women had been screened for cervical cancer within the last 3 years while 191 had not. Women underwent a pelvic exam and had clinician-collected Pap sample taken for the routine cervical cancer screening by cytology. Women were asked to collect a self-collected specimen at home and return it to the clinic. Both specimens were tested for HPV genotypes.</p> <p>Results</p> <p>Four hundred and six women (91.6%) had HPV genotyping results for the clinician-collected and self-collected specimens. The prevalence of carcinogenic HPV was 18.0% (95% CI: 14.4%-22.1%) for clinician-collected specimens and 26.8% (95% CI: 22.6%-31.4%) for self-collected specimens. The concordance for the detection of carcinogenic HPV between clinician-collected and self-collected specimens was only fair (kappa = 0.54). While the prevalence of carcinogenic HPV in either sample decreased sharply with increasing age (p_trend< 0.01), the prevalence of non-carcinogenic HPV did not, especially the prevalence of HPV genotypes in the alpha 3/4/15 phylogenetic group.</p> <p>Conclusions</p> <p>The prevalence of carcinogenic HPV in our sample of women living in the Mississippi Delta was greater than the prevalence reported in several other U.S. studies. The high carriage of HPV infection, along with lack of participation in cervical cancer screening by some women, may contribute to the high cervical cancer burden in the region.</p