Wednesday, September 7, 2022

A kidney ‘punch’ can tell much

renal biopsy is when a small piece of a patient's kidney is removed for analysis, usually by inserting a needle through the skin and into the kidney. Though invasive, the clinical value can be high for helping decide how to treat lupus or transplanted patients.  How to maximize that value? 

In this study, Clark and colleagues applied computer imaging techniques to answer why only about half of lupus patients with inflamed kidneys (nephritis) proceed to kidney failure (end stage renal disease, ESRD) and lose their kidney. They supposed there were subtle differences in the “frequency and organization of principal cellular effectors” between those patients who did, or didn’t, progress. They obtained biopsies from a cohort of 55 well-characterized lupus patients, of which 19 progressed to ESRD. They labeled very thin slices (sections) of kidney with 6 markers (CD3, CD4, CD20, CD11c, BDCA2, and DAPI) and counted several types of immune cells using confocal microscopy and deep learning analysis. 

Figure 2: left panel (H) are CD20+ B cells, right panel (I are CD3+CD4- T cells, (probably CD8+?).

They found a remarkably clear distinction: those with few B cells and many CD4- T cells, probably CD8+, often progress to ESRD (shown in red, panels H and I from figure 2).  Patients with many B cells and few CD4- T cells do not progress to ESRD (blue).  In the discussion, the authors mention that some clinical trials have targeted exactly those cells that this study indicate may be protective (B cells) or innocuous (CD4+ T cells).  A validated "identification, friend or foe" (IFF) system seems a good principle before aiming and firing.  

Abraham R, Durkee MS, Ai J, Veselits M, Casella G, Asano Y, Chang A, Ko K, Oshinsky C, Peninger E, Giger ML, Clark MR. Specific in situ inflammatory states associate with progression to renal failure in lupus nephritis. J Clin Invest. 2022 Jul 1;132(13)

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