This Month’s Highlights

doi:10.1681/ASN.2018121271

BASIC RESEARCH

Whole-Exome Sequencing Can Help Prevent Allograft Failure

Researchers have presented case reports describing previously undiagnosed genetic disorders that led to early allograft failure in kidney transplant recipients. Whole-exome sequencing (WES) has found that about 20% of pediatric patients with CKD have a relevant mutation, but the diagnostic yield of WES in kidney transplant recipients is undetermined. Using WES, Mann et al. arrived at a molecular genetic diagnosis for 34 of 104 (32.7%) kidney transplant recipients at a single center. Such diagnoses had clinical implications for many patients requiring transplant, allowing for tailoring pre- and post-transplant treatment. In some patients, receiving the diagnosis earlier might have curtailed negative consequences. Such potential benefits support considering WES for any child or young adult with CKD. See Mann et al., pages 201–215.

IL-34 Promotes Lupus Nephritis

Macrophages and autoantibodies play key roles in lupus nephritis pathology in humans and in a mouse model for lupus. Wada et al. show that levels of IL-34 (which mediates macrophage proliferation) and IL-34’s two receptors rise in the kidney as nephritis progresses. Deleting IL-34 in the mice suppresses circulating autoantibodies, nephritis, and the systemic illness. Patients with lupus nephritis have elevated IL-34 blood and urine levels, and, like lupus-prone mice, expression of IL-34 and its receptors that correlates with evidence of disease activity. These findings suggest that IL-34 is a promising novel therapeutic target. See Wada et al., pages 244–259.

Inducing Human Podocytes from Pluripotent Stem Cells

Although researchers can induce nephron progenitor cells and kidney organoids from stem cells, directing differentiation toward a specific nephron segment remains a challenge. Yoshimura et al. studied the effects of various growth factors in cultured mouse embryonic nephron progenitor cells, demonstrating phase-specific manipulation of Wnt and Tgf-β signaling is critical for podocyte differentiation. Using this insight into the nephron-patterning process, they were able to selectively induce human pluripotent stem cell–derived podocytes with molecular, morphological, and functional characteristics of human adult podocytes. Because this new protocol will make human podocytes more accessible, these pluripotent stem cell–derived podocytes are expected to serve as a valuable resource in kidney research. See Yoshimura et al., pages 304–321.

CLINICAL EPIDEMIOLOGY

Frailty and Cognition in Kidney Transplant

Cognitive function generally improves as kidney function is restored following transplant. However, given that frailty is a predictor of adverse outcomes among kidney recipients, stressors related to surgery and immunosuppression might curtail short-term cognitive improvement and contribute to subsequent decline among frail patients. Chu et al. found that although both frail and nonfrail patients show cognitive improvement by 3 months post-transplant, cognitive function plateaus for nonfrail recipients between 1–4 years after transplant and declines for frail recipients. Transplant centers are encouraged to apply available evidence-based strategies to reduce risk of cognitive impairment among frail transplant recipients. See Chu et al., pages 336–345.

ESRD and Excess Influenza-Like Illness Deaths

Influenza’s seasonal activity contributes to seasonal patterns in morbidity and mortality, particularly among vulnerable populations such as patients with ESRD, but the relationship between seasonal fluctuations of influenza-like illness (ILI) and seasonal patterns of mortality in patients with ESRD has not been explicitly investigated. Gilbertson et al. found that community ILI activity is associated with seasonal variation in mortality among ESRD patients, and likely contributes to >1000 deaths per year. Heightened surveillance efforts, such as timely reporting of ILI activity within dialysis units to the Centers for Disease Control and Prevention, as well as study of treatment and containment strategies during high-risk periods, may be warranted. See Gilbertson et al., pages 346–353.

CLINICAL RESEARCH

Preventing Bone Loss after Kidney Transplant

In this study of 34 kidney transplant patients randomized to receive zoledronate or no treatment for 12 months, Bacelar Marques et al. found that both groups experienced decreased bone turnover, an occurrence not affected by zoledronate, and neither group experienced bone loss in the central skeleton. However, biopsied bone from both groups showed impaired trabecular connectivity, and high-resolution imaging detected trabecular bone loss at peripheral skeleton sites, partially attenuated by zoledronate. Because fractures in transplant patients are most commonly peripheral fractures, bisphosphonates may be considered for patients with high fracture risk and evidence of bone loss in the peripheral skeleton at the time of transplant. See Bacelar Marques et al., pages 355–365.