You are on page 1of 1

This Months Highlights

BASIC RESEARCH

CLINICAL EPIDEMIOLOGY

Selective Recruitment of
Autoimmune-Induced Neutrophils

Disincentives to Living Donation

Therapeutic strategies to selectively prevent autoimmune-induced neutrophil


inltration are needed to prevent endorgan damage. Disteldorf et al. show
that induction of chemokine (C-X-C
motif) ligand 5 (CXCL5) expression
by the Th17/IL-17 immune response recruits neutrophils that promote kidney tissue injury in a mouse model of crescentic GN, but
CXCL5 is not required for neutrophil recruitment and bacterial
clearance in acute bacterial pyelonephritis. Additionally, renal
CXCL5 expression is higher in patients with ANCA-associated
crescentic GN than in patients with bacterial pyelonephritis,
further supporting the relevance of investigating CXCL5 as a
therapeutic target. See Disteldorf et al., pages 5566.
Kidney Mesenchymal Stem CellLike Cells

The decline in living donor transplantation in the United States after 2005 is
unexplained. In this issue, Gill et al. examined the association between donor
income and longitudinal changes in living kidney donation using zip code and
income data for all living donors in the United States. In adjusted
linear regression models, the rate of living donation from 1999 to
2004 increased in all income quintiles, but from 2005 to 2010,
living donation increased only in the highest income quintile
and declined in the three lowest quintiles. This information should
prompt a discussion regarding policies to reduce nancial barriers
to living kidney donation. See Gill et al., pages 201207.
CLINICAL RESEARCH
Novel Mutation in Atypical
Hemolytic Uremic Syndrome

Mesenchymal stem cell (MSC)-like cells


with a kidney-specic gene expression
signature have been isolated from kidneys of adult mice. Here, Li et al. show
that these cells are enriched in the mature collecting duct epithelium in mice
and, in vitro, undergo a mesenchymalepithelial transition, display characteristics of MSCs, and promote epithelial
wound repair. When microinjected in neonatal mice, these
cells integrate specically into the collecting duct epithelium.
The in vivo function of kidney MSC-like cells in development,
homeostasis, and tissue repair should be determined. See Li
et al., pages 8194.

Genomic rearrangements in the region


encoding complement factor H (CFH)
and ve CFH-related (CFHR) proteins
havebeenidentiedinpatientswithatypical hemolytic uremic syndrome (aHUS)
and associate with post-transplant recurrence. In this issue, Valoti et al. report that
4.5% of 154 patients with aHUS studied
had genomic rearrangements in this region, including a novel mutation producing a CFHR1/CFH hybrid protein that causes complement dysregulation. The authors propose genetic screening that
includes analysis of CFH/CFHR rearrangements to identify the patients most likely to benet from eculizumab after a kidney transplant. See Valoti et al., pages 209219.

Determinants of Podocyte Injury


Phenotype

Genetic Alterations in SteroidResistant Nephrotic Syndrome

Sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) and soluble urokinase plasminogen activator receptor


(suPAR) have been linked individually
to podocyte aVb3 integrin activation.
Here, Yoo et al. report that high circulating suPAR levels, as detected in patients with FSGS or diabetic kidney disease (DKD), are
necessary but not sufcient to induce podocyte injury in both
diseases. Notably, podocyte SMPDL3b levels are low in patients
with FSGS but high in patients with DKD, and results of functional studies suggest SMPDL3b levels control the phenotype of
the suPAR-induced podocyte injury. These results may inform the
development of treatments for specic glomerular diseases. See
Yoo et al., pages 133147.

The genetic alterations underlying steroidsensitive nephrotic syndrome (SSNS) and


steroid-resistant NS (SRNS) are unknown. Here, Giglio et al. performed
next-generation sequencing analysis of
19 genes previously reported as possible
causes of NS. The authors identied
pathogenic alterations in 32% of the children with sporadic SRNS, but in none of the children with clinically
indistinguishable sporadic SSNS. Furthermore, these alterations associated with lack of response to immunosuppressive drugs. The
data from this retrospective analysis suggest that extended genetic
screening of children with SRNS may inform genetic counseling
and disease management. See Giglio et al., pages 230236.