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This Month's Highlights
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This Month's Highlights

JASN March 2021, 32 (3) i; DOI: https://doi.org/10.1681/ASN.2021010073
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Mutated PRDM15 in Galloway-Mowat, Nephrotic Syndromes

Proteinuric kidney disease, a leading cause of ESRD in children, is part of Galloway-Mowat syndrome, a rare condition that includes a severe form of progressive nephropathy as well as prominent central nervous system features. The most common renal manifestation is steroid-resistant nephrotic syndrome. Mann et al. found that mutations in the transcriptional regulator PRDM15 are a novel monogenic cause of both isolated early-onset nephrotic syndrome and Galloway-Mowat syndrome. Identifying PRDM15 provides insight into the molecular pathogenesis of nephrotic syndrome and implicates the gene as an important regulator of renal development. See Mann et al., pages 580–596.

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Single-Cell Profiling of Urinary Cells

Microscopic analysis of urinary sediment is one of the most fundamental tests in nephrology. Urinary cells, however, have not been characterized in a standardized unbiased manner. Abedini et al. used single-cell transcriptomics of urine from five individuals with diabetic kidney disease and five controls to characterize 23,082 urinary cells in an unbiased way. Combined analysis of urinary, kidney, and bladder cells indicated that the technique can detect almost all kidney cell types and a variety of bladder cell types in human urine. This pilot study provides a reference dataset for urinary single-cell characterization. See Abedini et al., pages 614–627.

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Effect of Lifestyle Behaviors on Kidney Function

Healthy lifestyle behaviors reduce death and cardiovascular disease among individuals with preserved kidney function, but the benefits of these behaviors among those with reduced kidney function, a group at higher risk for cardiovascular disease, have not been established. In this pooled analysis of three community-based cohort studies that included 27,271 adults, healthy lifestyle behaviors (not smoking, maintaining body mass index in recommended range, engaging in regular physical activity, and consuming a healthy diet and no more than a moderate intake of alcohol), analyzed individually and in combination, were associated with significantly reduced risks of death and cardiovascular disease events among individuals with or without reduced kidney function. These findings highlight the importance of lifestyle behaviors as potentially modifiable risk factors for people with kidney disease. See Schrauben et al., pages 663–675.

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Race and Preemptive Waitlisting

Under current United States national policy, determining a patient’s eligibility for kidney transplantation waitlist registration requires the patient’s GFR to be ≤20 mL/min per 173 m2. Because disease progression is faster for Black versus White patients, this policy may contribute to racial disparities in accruable time on the waitlist before dialysis initiation. Ku et al. used models to determine the association between race and time to ESKD from an eGFR of ≤20 mL/min per 173 m2, finding that this time was shorter for Black versus White patients. They then estimated that allowing registration of Black patients on the transplant waitlist at higher levels of kidney function (as early as an eGFR of 24-25 mL/min per 1.73 m2) had potential to reduce the observed disparities in accruable wait time. See Ku et al., pages 677–685.

Exostosin in Membranous Lupus Nephritis

Approximately 20% of patients with lupus nephritis show membranous lupus nephritis on kidney biopsy. Recently, two proteins, exostosin 1/exostosin 2 (EXT1/EXT2), were shown to be present in a subset of membranous lupus nephritis kidney biopsies. Ravindran et al. found 32.6% of membranous lupus nephritis kidney biopsies to be EXT1/EXT2-positive. Such biopsies showed less chronicity features (glomerulosclerosis and tubular atrophy and interstitial fibrosis) compared with kidney biopsies from EXT1/EXT2-negative patients, who were also more likely than EXT1/EXT2-positive patients to reach ESKD. These findings suggest that EXT1/EXT2-positive patients have better renal outcomes compared with EXT1/EXT2-negative patients. See Ravindran et al., pages 695–706. Also see related editorial by Hilhorst and Anders, pages 525–526.

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SLC12A3 Role in Serum Potassium

Renal potassium handling is important for external potassium homeostasis. The heritability of serum potassium concentrations suggests genetic influences on potassium levels, but the genetic determinants for serum potassium levels are not generally known. Heterozygosity for a pathogenic variant of SLC12A3, causing Gitelman syndrome, is significantly associated with lower potassium levels and lower chloride levels, but not with sodium levels. Notably, this variant shows a novel role in modulating serum BUN levels. This work provides novel insights into SLC12A3 biology and the effects of heterozygosity on electrolyte homeostasis and related subclinical phenotypes that may have implications for personalized medicine. See Wan et al., pages 756–765.

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Journal of the American Society of Nephrology: 32 (3)
Journal of the American Society of Nephrology
Vol. 32, Issue 3
March 2021
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