Nephrology Month in Review: June 2024

HCPLive Nephrology Month in Review: June 2024

Coming off of a busy month of May with a plethora of renal news and research from the National Kidney Foundation’s (NKF) Spring Clinical Meetings and the 61st European Renal Association (ERA) Congress, June was yet another exciting month in nephrology. Characterized by new studies shining light on the potential of different therapeutic approaches in IgA nephropathy (IgAN), differences in IgAN care, and important associations in renal diseases, the past couple of weeks have served as further evidence of the dawn of a new era of nephrology, as spotlighted in this June 2024 month in review.

IgAN Prognosis, Therapeutics

Atacicept Shows Disease-Modifying Potential in IgAN, Linked to Hematuria Resolution

A post hoc analysis of the phase 2b ORIGIN study of atacicept in patients with IgAN found a substantially greater percentage of patients treated with atacicept achieved hematuria resolution at 36 weeks compared with placebo, with improvements observed as early as 4 weeks. Results add to the growing body of evidence supporting the dual anti-B-cell activation factor (BAFF)–a proliferation-inducing ligand (APRIL) fusion protein’s potential as a disease-modifying treatment for IgAN.

Dapagliflozin’s Association with LCN2, AGER Suggest Therapeutic Effect in IgA Nephropathy

A Mendelian randomization analysis identified instances of co-localization between the target genes of SGLT2 inhibitors and the pathogenesis genes of membranous nephropathy and IgAN. Specifically, investigators identified 8 drug targets causally linked to the occurrence of IgAN (AGER; ATF6; CASP7; JAK2; LCN2; MPO; CAT; and ELF2) and, through conducted comprehensive colocalization analyses, found LCN2 expression and IgAN shared a causal variant, rs3099844 (pP.H4 = 0.935,308), as did AGER expression and IgAN ( rs3130349, pP.H4 = 0.988,317 and rs3130696, pP.H4 = 0.961,451). Of note, both LCN2 and AGER were found to correspond to dapagliflozin.

Free Thyroxine Shows Protective Effect Against Renal Progression in IgA Nephropathy

Findings from this study, coined as the first to explore the relationship between thyroid hormones and IgAN prognosis, suggest free thyroxine has a protective effect against renal progression in IgAN and may be a useful tool for predicting poor IgAN prognosis in combination with tubular atrophy/interstitial fibrosis.

Kaplan-Meier survival curve analysis showed the renal survival rate of patients with IgAN and free thyroxine <15.18pmol/L was lower than with free thyroxine ≥15.18pmol/L (P <.001), and multivariate Cox regression analysis revealed free thyroxine was a protective factor for patients with IgAN (Hazard ratio [HR], 0.68; 95% CI, 0.51–0.90; P = .007).

Variations in IgAN Care

Study Highlights Global Regional Differences in IgA Nephropathy Perspectives, Care

This study leveraged data from 730 nephrologists in the US, EU5, Japan, and China for more than 1500 of their most recently seen patients and found notable variations in perspectives about and approaches to IgAN treatment.

“The comparison of patient chart data across various regions reveals differences in perspectives and IgAN treatment approaches among nephrologists,” investigators concluded.1 “Prognostic and predictive tools are available and utilized globally, but the reliability and correlation between results, lab values, and disease progression calls for better education and alignment of global treatment guidelines.”

Study Highlights Gaps in Clinical IgA Nephropathy Knowledge Among Nephrologists, PCPs

Beyond regional differences in care, findings from this study call attention to differences in clinical knowledge of IgAN between specialists and generalists. Among the participating nephrologists, the greatest percentage of incorrect responses were observed for questions related to the risk of ESRD correlation to proteinuria (88%), International IgAN Prediction Tool (84%), and KDIGO recommendations for patients with IgAN at high risk of progression (70%). For PCPs, the most frequently incorrectly answered questions pertained to the pathophysiology of IgAN (82%), International IgAN Prediction Tool (79%), and the risk of ESRD correlation to proteinuria (72%).

Important Associations in Nephrology

Peroxiredoxins Linked to Kidney Function Decline in IgA Nephropathy

Building upon findings from a previous pilot study confirming differential changes of peroxiredoxins 1-5 in patients with IgAN, lupus nephritis, and membranous nephropathy, this study found 2-cysteine-peroxiredoxins may be viable prognostic markers for the deterioration of kidney function, particularly in patients with IgAN. Thus, investigators suggested the presence of a complex interaction between renal function and peroxiredoxins in patients with IgAN and membranous nephropathy, highlighting the need for personalized treatment strategies guided by biomarker profiling.

Chronic Kidney Disease Linked to Tooth Loss in Postmenopausal Women

Beyond renal health, oral and bone health are important considerations for patients with chronic kidney disease (CKD), as underscored by findings from this study linking CKD to tooth loss in postmenopausal women. Indeed, findings from the analysis of the Korean National Health and Nutrition Examination Survey 2010-2018 data showed eGFR was linked to having ≥ 20 adult teeth, with postmenopausal women with CKD having greater tooth loss compared to those without CKD.

"This study highlights the known link between chronic kidney disease and bone metabolism. Increased attention to oral and bone health is warranted in postmenopausal women with chronic kidney disease, in addition to meticulous efforts aimed at preserving kidney function. Conversely, oral health is a window to overall health, and good oral hygiene is important for women of all ages," Stephanie Faubion, MD, MBA, chair of the department of medicine at Mayo Clinic in Jacksonville and medical director for The Menopause Society, said in a press release.