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 cellmediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types $IB versus controls). Thus, ddcfDNA 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.

Reduction in immunosuppression alone resulted in the successful resolution of viremia with preservation of renal function and prevention of clinical BKV nephritis and graft loss.

Background Previous studies have demonstrated that donor-derived cell-free DNA (dd-cfDNA) found in circulating blood of transplant recipients may serve as a noninvasive biomarker of allograft rejection. To better interpret the clinical meaning of dd-cfDNA, it is essential to understand the biological variation of this biomarker in stable healthy recipients. This report establishes the biological variation and clinical reference intervals of dd-cfDNA in renal transplant recipients by using an analytically validated assay that has a CV of 6.8%. Methods We sampled venous blood at patient surveillance visits (typically at posttransplant months 1–4, 6, 9, and 12) in a 14-center observational study. Patients with stable renal allograft function spanning ≥3 serial visits were selected. We used AlloSure®, a targeted next-generation sequencing-based approach, to measure dd-cfDNA in the plasma and computed the intraindividual CV (CVI) and interindividual CV (CVG), the index of individuality (II), and reference change value (RCV). Results Of 93 patients, 61% were men, 56% were Caucasian, mean age was 49 years, and 63% were deceased donor kidney recipients. Of 380 blood samples, the dd-cfDNA median value was 0.21% (interquartile range 0.12%–0.39%) and the 97.5th percentile was 1.20%. In 18 patients with an average of 4.1 tests, the CVI was 21%, CVG was 37%, II was 0.57, and RCV was 61%. Conclusions In a renal transplant recipient, a dd-cfDNA level above 1.2% is out of range and potentially abnormal. A serial increase of up to 61% in level of dd-cfDNA in a patient may be attributable to biological variation. Clinicaltrials.gov Identifier: NCT02424227

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BKV serostatus can be used to risk stratify patients for posttransplantation infection.

Background: The outcome of gastrointestinal bleeding in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients is difficult to discern from the literature. Many publications are small, single-center series or are from an era prior to advanced interventional endoscopy, widespread use of proton pump inhibitors or treatment for Helicobacter pylori infections. In this study, we quantify the role of CKD and ESRD as independent predictors of mortality in patients admitted to the hospital with a principal diagnosis of primary upper gastrointestinal bleeding (UGIB). Methods: We used the Nationwide Inpatient Sample that contains data on approximately 8 million admissions in 1,000 hospitals chosen to approximate a 20% stratified sample of all US facilities. Patients discharged with the principal diagnosis of primary UGIB, CKD or ESRD were identified through the ninth revision of the International Classification of Diseases, clinical modification (ICD-9-CM) codes. The outcome variables included frequency and in-hospital mortality of UGIB in CKD and ESRD patients as compared to non-CKD patients and were analyzed using logistic regression modeling. Results: In 2007, out of a total of 398,213 admissions with a diagnosis of primary UGIB, 35,985 were in CKD, 14,983 in ESRD, and 347,245 in non-renal disease groups. The OR for primary UGIB hospitalization in CKD and ESRD was 1.30 (95% CI 1.17–1.46) and 1.84 (95% CI 1.61–2.09), respectively. The corresponding all-cause mortality OR was 1.47 (95% CI 1.21–1.78) and 3.02 (95% CI 2.23–4.1), respectively. Conclusion: Patients with CKD or ESRD admitted with primary UGIB have up to three times higher risk of all-cause in-hospital mortality, warranting heightened vigilance by their clinicians.

The impact of subclinical inflammation (SCI) noted on early kidney allograft biopsies remains unclear. This study evaluated the outcome of SCI noted on 3-month biopsy. A total of 273/363 (75%) kidney transplant recipients with a functioning kidney underwent allograft biopsies 3-months posttransplant. Among those with stable allograft function at 3 months, 200 biopsies that did not meet the Banff criteria for acute rejection were identified. These were Group I: No Inflammation (NI, n = 71) and Group II: Subclinical Inflammation (SCI, n = 129). We evaluated differences in kidney function at 24-months and allograft histology score at 12-month biopsy. SCI patients had a higher serum creatinine (1.6 ± 0.7 vs 1.38 ± 0.45; P = .02) at 24-months posttransplant, and at last follow-up at a mean of 42.5 months (1.69 ± 0.9 vs 1.46 ± 0.5 mg/dL; P = .027). The allograft chronicity score (ci + ct + cg + cv) at 12-months posttransplant was higher in the SCI group (2.4 ± 1.35 vs 1.9 ± 1.2; P = .02). The incidence of subsequent rejections within the first year in SCI and NI groups was 24% vs 10%, respectively (P = .015). De novo donor-specific antibody within 12 months was more prevalent in the SCI group (12/129 vs 1/71, P = .03). SCI is likely not a benign finding and may have long-term implications for kidney allograft function.