Are borderline changes real rejection? Current viewpoints.

PURPOSE OF REVIEW: The clinical significance and treatment of borderline changes are controversial. The lowest detectable margin for rejection on histology is unclear. We review recent evidence about borderline changes and related biomarkers. RECENT FINDINGS: Borderline change (Banff ≥ t1i1) is associated with progressive fibrosis, a greater propensity to form de-novo DSA, and reduced graft survival. Isolated tubulitis appears to have similar kidney allograft outcomes with normal controls, but this finding should be validated in a larger, diverse population. When borderline change was treated, a higher chance of kidney function recovery and better clinical outcomes were observed. However, spontaneous borderline changes resolution without treatment was also observed. Various noninvasive diagnostic biomarkers have been developed to diagnose subclinical acute rejection, including borderline changes and ≥ Banff 1A TCMR. Biomarkers using gene expression and donor-derived cell-free DNA, and HLA DR/DQ eplet mismatch show potential to diagnose subclinical acute rejection (borderline change and ≥Banff 1A TCMR), to avoid surveillance biopsy, or to predict poor kidney allograft outcomes. SUMMARY: Borderline changes are associated with poor kidney allograft outcomes, but it remains unclear if all cases of borderline changes should be treated. Novel biomarkers may inform physicians to aid in the diagnosis and treatment.

Passive sweat collection and colorimetric analysis of biomarkers relevant to kidney disorders using a soft microfluidic system.

The rich range of biomarkers in sweat and the ability to collect sweat in a non-invasive manner create interest in the use of this biofluid for assessments of health and physiological status, with potential applications that range from sports and fitness to clinical medicine. This paper introduces two important advances in recently reported classes of soft, skin-interfaced microfluidic systems for sweat capture and analysis: (1) a simple, broadly applicable means for collection of sweat that bypasses requirements for physical/mental exertion or pharmacological stimulation and (2) a set of enzymatic chemistries and colorimetric readout approaches for determining the concentrations of creatinine and urea in sweat, throughout ranges that are physiologically relevant. The results allow for routine, non-pharmacological capture of sweat for patient populations, such as infants and the elderly, that cannot be expected to sweat through exercise, and they create potential opportunities in the use of sweat for kidney disease screening/monitoring. Studies on human subjects demonstrate these essential capabilities, with quantitative comparisons to standard methods. The results expand the range of options available in microfluidic sampling and sensing of sweat for disease diagnostics and health monitoring.