Veno-Arterial Index (VAI)—A Promising Tool For Identifying Renal Transplant Rejection

The objective of this study is to evaluate the veno-arterial index (VAI) as a predictor of renal rejection in kidney transplant patients. A diagnostic test study was conducted between January 2014 and May 2018. Renal transplant patients who underwent percutaneous renal biopsy were included. The VAI was obtained by measuring the flow velocity in the renal segmental vein and dividing this value by the peak systolic velocity of the segmental artery in this same location. The records of 77 patients were analyzed. Among these patients, 32 (42%) were positive for transplant rejection and 29 presented with acute rejection. In patients with renal rejection, the median VAI was 0.67 (interquartile range [IQR] = 0.56-0.87), and in kidneys with a negative biopsy for rejection, the median VAI was 0.41 (IQR = 0.27-0.57), with a statistically significant difference ( P = .007) and a value much higher than that obtained for the general population of 0.30 (IQR = 0.18-0.44). Subacute and acute rejected kidneys had an even higher VAI of 0.725 (IQR = 0.57-0.87; P = .0001). Although the resistive index has a good correlation with glomerular filtration, it is not possible by that index to differentiate among the multiple causes that can lead to graft dysfunction. The results of this study show that the VAI might be a useful parameter, which when elevated could predict renal transplant rejection.

Acute renal transplant rejection following nivolumab therapy for metastatic melanoma

Cancers can develop the ability to evade immune recognition and destruction. Immune checkpoint inhibitors (ICIs) are drugs targeting these immune evasion mechanisms. ICIs have significantly improved outcomes in several cancers including metastatic melanoma. However, data on toxicities associated with allograft transplant recipients receiving ICI is limited. We describe a case of a 71-year-old woman who was diagnosed with metastatic melanoma 13 years after renal transplantation. She was commenced on the ICI nivolumab. She developed acute renal transplant rejection 15 days after administration of the first dose. She continues on haemodialysis but has demonstrated complete oncological response. This case demonstrates the risk of acute renal transplant rejection versus improved oncological outcomes. Patients and clinicians must consider this balance when initiating ICI therapy in allograft transplant recipients. Patients should be fully consented of the potential consequences of acute renal transplant rejection including lifelong dialysis.

Urinary nitrate concentration as a marker for kidney transplant rejection

Background Early identification and treatment of kidney transplant rejection episodes is vital to limit loss of function and prolong the life of the transplanted kidney and recipient. Current practice depends on detecting a creatinine rise. A biomarker to diagnose transplant rejection at an earlier time point than current practice, or to inform earlier decision making to biopsy, could be transformative. It has previously been shown that urinary nitrate concentration is elevated in renal transplant rejection. Nitrate is a nitric oxide (NO) oxidation product. Transplant rejection upregulates NO synthesis via inducible nitric oxide synthase leading to elevations in urinary nitrate concentration. We have recently validated a urinary nitrate concentration assay which could provide results in a clinically relevant timeframe. Our aim was to determine whether urinary nitrate concentration is a useful tool to predict renal transplant rejection in the context of contemporary clinical practice. Methods We conducted a prospective observational study, recruiting renal transplant participants over an 18-month period. We made no alterations to the patients’ clinical care including medications, immunosuppression, diet and frequency of visits. We collected urine samples from every clinical attendance. We assessed the urinary nitrate to creatinine ratio (uNCR) between patient groups: routine attendances, biopsy proven rejection, biopsy proven no rejection and other call backs. uNCR was examined over time for those with biopsy proven transplant rejection. These four groups were compared using an ANOVA test. Results A total of 2656 samples were collected. uNCR during biopsy proven rejection, n = 15 (median 49 μmol/mmol, IQR 23–61) was not significantly different from that of routine samples, n = 164 (median 55 μmol/mmol, IQR 37–82) (p = 0.55), or biopsy proven no rejection, n = 12 (median 39 μmol/mmol, IQR 21–89) (P = 0.77). Overall uNCR was highly variable with no diagnostic threshold for kidney transplant rejection. Furthermore, within-patient uNCR was highly variable over time, and thus it was not possible to produce individualised patient thresholds to identify rejection. The total taking Tacrolimus was 204 patients, with no statistical difference between the uNCR of all those on Tacrolimus, against those not, p = 0.18. Conclusion The urinary nitrate to creatinine ratio is not a useful biomarker for renal transplant rejection.

P1612CAN THE URINARY NITRATE TO CREATININE RATIO BE USED AS A MARKER FOR KIDNEY TRANSPLANT REJECTION?

Background and Aims Early identification and treatment of kidney transplant rejection episodes is vital to limit loss of function and prolong the life of the transplanted kidney and recipient. Current practice depends on detecting a creatinine rise. A biomarker to diagnose transplant rejection, either at an earlier time point, or to inform earlier decision making to biopsy, could be transformative. Urinary nitrate concentration is elevated in renal transplant rejection. Nitrate is a nitric oxide (NO) oxidation product. Transplant rejection upregulates NO synthesis via inducible nitric oxide synthase leading to elevations in urinary nitrate concentration. Historically, assays for measurement of inorganic nitrate in biological fluids have been too time consuming to be useful in a clinical setting. We have recently validated a urinary nitrate concentration assay which could provide results in a clinically relevant timeframe. Our aim was to determine whether urinary nitrate concentration is a useful tool to predict renal transplant rejection in the context of contemporary clinical practice. Method We conducted a prospective observational study, recruiting renal transplant participants over an 18 month period. We made no alterations to the patients’ clinical care including medications, immunosuppression, diet and frequency of visits. We collected urine samples from every clinical attendance including routine attendances, unscheduled attendances for acute clinical indications, and on the day of attendance for biopsy, for those who underwent biopsy. We measured the urinary nitrate to creatinine ratio (uNCR) between patient groups including routine attendances, biopsy proven rejection and biopsy proven “no rejection”. uNCR was examined over time for those with transplant rejection. Groups were compared using a 2 tail t-test of unequal variance, for statistical significance. Results A total of 2656 samples were collected. uNCR during biopsy proven rejection, median 49 µmol/mmol, IQR 23-61, was not significantly different from that of routine samples, median 55 µmol/mmol, IQR 37-82 (p=0.56), or biopsy proven “no rejection”, median 39 µmol/mmol, IQR 21-89, (P=0.77). Overall uNCR was highly variable; median 52 µmol/mmol, IQR 31-81, with no diagnostic threshold for kidney transplant rejection. Furthermore, within-patient uNCR was highly variable over time, and thus it was not possible to produce individualised patient thresholds to identify rejection. Conclusion The urinary nitrate to creatinine ratio is not a useful biomarker for renal transplant rejection.