Bernard Fischbach

Cell-Free DNA and Active Rejection in Kidney Allografts

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.

Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience

Ruiz R, Jennings LW, Kim P, Tomiyama K, Chinnakotla S, Fischbach BV, Goldstein RM, Levy MF, McKenna GJ, Melton LB, Onaca N, Randall HB, Sanchez EQ, Susskind BM, Klintmalm GB. Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience. 
Clin Transplant 2010: 24: 807–811.

Indications for combined liver and kidney transplantation

Ruiz R, Jennings LW, Kim P, Tomiyama K, Chinnakotla S, Fischbach BV, Goldstein RM, Levy MF, McKenna GJ, Melton LB, Onaca N, Randall HB, Sanchez EQ, Susskind BM, Klintmalm GB. Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience. 
Clin Transplant 2010: 24: 807–811.

Routine Ultrasonography Surveillance of Native Kidneys for Renal Cell Carcinoma in Kidney Transplant Candidates

Renal cell carcinoma (RCC) has a high incidence in the kidney transplant population and annual surveillance detects these tumors early in their natural history. Minimal guidelines exist regarding RCC surveillance in ESRD patients awaiting transplant. A retrospective review of our kidney transplant database examined the outcomes of annual ultrasonographic surveillance during initial kidney transplant evaluation and upon annual reassessment. Of 2642 patients listed for transplant, 145 patients were found to have masses during initial kidney transplant evaluation or annual imaging consistent with new complex cystic disease or RCC. A total of 71 patients had RCC identified, with 52 found on initial kidney transplant evaluation and 19 identified on annual surveillance. Male gender and African‐American race were independently associated with RCC (P<.05). RCC was detected a median of 2.0 years after listing (two annual ultrasonography studies). Patients with complex cysts were more likely to undergo transplantation (48.7%) compared to patients with RCC (21.1%; P<.001). There was no significant difference in survival between RCC patients and those found to have complex cystic disease, suggesting incidental RCC can be diagnosed early in the natural history and at a curable stage through implementation of a biennial surveillance program.

Late presentation of adenovirus-induced hemorrhagic cystitis and ureteral obstruction in a kidney-pancreas transplant recipient.

We report a late presentation of adenovirus-induced renal allograft and bladder infection causing azotemia and hemorrhagic cystitis in a patient 5 years after simultaneous kidney-pancreas transplantation. Adenovirus has been increasingly recognized as a cause of morbidity and mortality in both solid organ and stem cell transplant recipients. We wish to emphasize the importance of early detection, as treatment options involve reduction of immunosuppression, followed by the addition of antiviral agents and supportive care.

Whole-organ pancreas transplantation at Baylor Regional Transplant Institute: a chance to cure diabetes.

The success of pancreas transplantation has improved over the past several decades with advancements in surgical technique, immunosuppressive medicines, and immunologic testing. We retrospectively reviewed our experience with pancreas transplantation from 1995 to 2008. At the Baylor Regional Transplant Program, 151 pancreas transplants were performed in 147 patients: 135 were simultaneous pancreas-kidney transplants, 10 were pancreas transplants after kidney transplants, and 6 were pancreas transplants alone. Follow-up information was available for 138 patients. The 1-year acute cellular rejection rate was 31.6%; the 30-day surgical reexploration rate was 10%; and the technical failure rate was 5.3%. Five-year pancreas graft survival rates were 67% for simultaneous pancreas and kidney transplants and 50% for pancreas transplants after kidney transplants. These outcomes exceed expected results as calculated by the Scientific Registry of Transplant Recipients. In addition, the median time to transplant was 3.8 months, compared with a US median of 14.1 months. Pancreas transplantation is currently the closest thing to a cure for diabetes and should be given as an option for diabetic patients with or without end-stage renal disease.

A model for Glomerular filtration Rate Assessment In Liver disease (GRAIL) in the presence of renal dysfunction

Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction ( www.bswh.md/grail ). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985‐2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and Modification of Diet in Renal Disease (MDRD‐4, MDRD‐6) equations for mGFR < 30 mL/min/1.73 m2. Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m2, initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001‐2015). GRAIL had less bias and was more accurate and precise as compared with CKD‐EPI, MDRD‐4, and MDRD‐6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m2, the median difference (eGFR–mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m2 as compared with CKD‐EPI: 8.70 (18.24) mL/min/1.73 m2, MDRD‐4: 8.82 (17.38) mL/min/1.73 m2, and MDRD‐6: 6.53 (14.42) mL/min/1.73 m2. Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m2 versus 36.1% (CKD‐EPI), 36.1% (MDRD‐4), and 52.8% (MDRD‐6) (P < 0.01). An eGFR < 30 mL/min/1.73 m2 by GRAIL predicted development of CKD (26.9% versus 4.6% CKD‐EPI, 5.9% MDRD‐4, and 10.5% MDRD‐6) in center data and needing kidney after LT (48.3% versus 22.0% CKD‐EPI versus 23.1% MDRD‐4 versus 48.3% MDRD‐6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

Use of two expanded-criteria-donor renal allografts in a single patient

The disparity between the number of available renal donors and the number of patients on the transplant waiting list has prompted the use of expanded-criteria-donor (ECD) renal allografts to expand the donor pool. ECD allografts have shown good results in appropriately selected recipients, yet a number of renal allografts are still discarded. The use of dual renal transplantation may lower the discard rate. Additionally, the use of perfusion systems may improve acute tubular necrosis rates with these allografts. We report a successful case of a dual transplant with ECD allografts using a perfusion system. The biopsy appearance and the pump characteristics were suboptimal for these kidneys, making them unsuitable for single transplantation; however, the pair of transplanted kidneys provided increased nephron mass and functioned well. We recommend that ECD kidneys that are individually nontransplantable be evaluated for potential dual renal transplantation. Biopsy criteria and perfusion data guidelines must be developed to improve the success rates with ECD dual renal allografts. Finally, recipient selection is of utmost importance.