Donor-Derived Cell Free DNA: Is It All the Same?

Background: Clinical utility of donor-derived, cellfree DNA (dd-cfDNA) in transplantation has been extensively reviewed, supporting its use as a surveillance tool for the early and accurate detection of allograft injury. Yet studies comparing different assay methods have been lacking. Methods: Paired sampling of commercially available dd-cfDNA (AlloSure and Prospera) was compared and examined against histology and manufacturer guidance. A total of 76 patients were prospectively assessed, with 11 biopsy sample-proven rejections (antibody-mediated rejection, n=2; T cell-mediated rejection, n=9). Results: Prospera demonstrated larger measurements of dd-cfDNA in comparison with AlloSure, but this was NS (P=0.12). At current manufacturer recommended diagnostic cutoffs, there was no significant difference in sensitivity, specificity, negative predictive value, or positive predictive value of AlloSure versus Prospera in detecting rejection. AlloSure demonstrated a significantly shorter turnaround time (P=0.01) from blood draw to patient result. Conclusions: Although dd-cfDNAs are similar, they are not the same. Extensive evidence for dd-cfDNA interpretation remains the key to building clinical utility when considering clinical implementation, and remaining consistent to a single platform is important when creating data comparisons.

Bilateral native nephrectomy for refractory hypertension in kidney transplant and kidney pancreas transplant patients.

Hypertension is common in renal transplant patients and sometimes very difficult to control. Refractory hypertension can adversely affect renal graft and patient survival. Many antihypertensive medications are not well tolerated or can have important drug interactions with immunosuppressive medications. These drugs can cause significant side effects including fluid depletion, azotemia, electrolyte imbalance, and anemia. Bilateral native nephrectomy in renal transplant patients has been reported to be beneficial in controlling severe hypertension. We report five patients with severe hypertension despite as many as 9 different antihypertensive medications. All patients had previous kidney or simultaneous kidney pancreas transplantation. Each of our patients underwent laparoscopic bilateral native nephrectomy. Renal function varied from creatinine of 1.4-2.4, and the number of antihypertensive medications from 3 to 9 at the time of nephrectomy surgery. Mean arterial blood pressure improved in all five patients at 3-6 months post nephrectomy, the number of antihypertensive medications decreased in 4, but renal function remained stable at 3-6 months in only 3 patients. We found laparoscopic bilateral native nephrectomy to be beneficial in renal and simultaneous kidney pancreas transplant patients with severe and refractory hypertension. Our patients with better baseline renal allograft function at time of nephrectomy received the most benefit. No decrease in allograft function could be attributed to acute rejection.