KEY POINTS: Peritoneal dialysis use in 2009-2010 was concentrated in a few high use communities with a similar demographic profile. From 2011 to 2020, peritoneal dialysis use expanded most in communities where it had pre...KEY POINTS: Peritoneal dialysis use in 2009-2010 was concentrated in a few high use communities with a similar demographic profile. From 2011 to 2020, peritoneal dialysis use expanded most in communities where it had previously been less common. This suggests that the gain in peritoneal dialysis use was broad and not just the result of further increases in high use areas. BACKGROUND: Peritoneal dialysis (PD) use in the United States has historically varied significantly from region to region and community to community. Studies have reported greater PD use in higher income, Western communities compared with lower income, Northeastern communities. We sought to examine the extent to which recent increases in PD use truly resulted in expanded access at the community level (versus increasing in areas that already had high PD use). METHODS: We used the United States Renal Data System to examine PD initiation patterns across health service areas (HSAs) based on pre-expansion PD use. We categorized PD use in each HSA in 2009-2010 as high (≥11% of patients on dialysis using PD), medium (5.5% to <11%), or low (<5.5%). We then identified incident dialysis patients from 2011 to 2020 and used logistic regression to evaluate how the odds of PD initiation among new dialysis patients changed over this period by baseline HSA PD use category. We then recategorized HSAs using 2020 data to determine the number that changed PD use categories over the study period. RESULTS: We included 755 HSAs in the analysis and subsequently examined 1,195,477 patients from those HSAs who initiated dialysis from 2011 to 2020. The odds of a patient initiating PD as their incident dialysis modality increased most in low PD HSAs (adjusted odds ratio [OR], 1.49 per 5 years; 95% confidence interval [CI], 1.45 to 1.52), followed by medium (adjusted OR, 1.37; 95% CI, 1.35 to 1.39) and high PD HSAs (adjusted OR, 1.17; 95% CI, 1.14 to 1.20). More than half (51%) of HSAs previously categorized as low PD had become medium or high PD HSAs in 2020. CONCLUSIONS: Use of PD as the incident dialysis modality increased most in HSAs where it had previously been less common, suggesting that the gain in PD use was broad and not merely the result of further increases in already high use areas.
Amari T, Miyaki T, Kishi M
… +14 more, Xu J, Sugiura M, Kaneda H, Sakai Y, Imura R, Takeuchi Y, Oliva Trejo JA, Kawasaki Y, Omotehara T, Negishi-Koga T, Ishijima M, Yamaguchi J, Kakuta S, Ichimura K
KEY POINTS: Volume electron microscopy enabled the complete 3D reconstruction of podocytes. Structural changes in podocytes of aged rats were precisely analyzed, and a catalog of these changes was compiled. The structura...KEY POINTS: Volume electron microscopy enabled the complete 3D reconstruction of podocytes. Structural changes in podocytes of aged rats were precisely analyzed, and a catalog of these changes was compiled. The structural plasticity contributing to the maintenance of glomerular epithelium by aged podocytes has been elucidated. BACKGROUND: Podocytes are specialized epithelial cells that constitute the glomerular filtration barrier. Because adult kidneys lack podocyte stem cells, the cells produced during development must persist throughout life. However, podocyte numbers decline with aging and disease, suggesting that surviving podocytes may undergo structural adaptations to maintain the glomerular epithelium. The nature of these changes, however, remains poorly understood. METHODS: We used volume electron microscopy to analyze and compare the three-dimensional ultrastructure of podocytes in young adult (1.5-month-old), adult (6-month-old), and aged (24-month-old) male Wistar rats. RESULTS: Aged podocytes exhibited eight characteristic structural alterations: hypertrophy, pseudocystic changes, irregularity of foot processes, fragmentation, pruning of foot processes, autocellular interdigitation, release of lysoendosomal and multivesicular body contents, and an increase in lysosomal volume. Among these, hypertrophy was particularly notable-it resulted in an approximately 4.6-fold increase in podocyte volume and a 3.0-fold increase in total surface area, enabling adequate coverage of the enlarging glomerular surface. Furthermore, in areas where portions of podocytes seemed to be lost because of fragmentation, adjacent podocytes formed de novo autocellular junctions/interdigitation, thereby preventing exposure of the basement membrane. In addition, aged podocytes showed clustering of lysoendosomes and multivesicular bodies, with evidence of their exocytotic release into the urinary space. This process may compensate for the reduced intracellular degradation capacity associated with aging. CONCLUSIONS: Our study demonstrated the remarkable plasticity of podocytes during aging.
Li LX, Zhou JX, Zhang H
… +3 more, Calvet JP, Huang CL, Li X
J Am Soc Nephrol
· 2026 May · PMID 41563399
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KEY POINTS: α Klotho as an antiaging protein can extend the lifespan of healthy animals; serum α Klotho was lower in patients with autosomal dominant polycystic kidney disease. Transgenic α Klotho and recombinant α Kloth...KEY POINTS: α Klotho as an antiaging protein can extend the lifespan of healthy animals; serum α Klotho was lower in patients with autosomal dominant polycystic kidney disease. Transgenic α Klotho and recombinant α Klotho delayed cyst growth in Pkd1 mutant mouse kidneys. α Klotho exerted its proapoptotic and anti-inflammatory function through interacting with and destabilizing cellular inhibitor of apoptosis protein 1. BACKGROUND: α -Klotho ( α Klotho) is expressed mainly in the kidney, which is encoded by the KL gene, existing in a membrane-bound form and a soluble circulating form. Soluble serum α Klotho was lower in patients with autosomal dominant polycystic kidney disease (ADPKD). However, the role of α Klotho in ADPKD remains unknown. METHODS: To investigate the roles of α Klotho in ADPKD, we generated transgenic α Klotho and Pkd1 mutant Pkd1-HOMO-KLTg mice to evaluate cyst growth and investigated underlying mechanisms with single-cell RNA sequencing analysis. RESULTS: We showed that α Klotho was lower in diverse kidney cell types in Pkd1 mutant kidneys, which was restored by transgenic α Klotho. We identified differential expression genes and pathways mediated by transgenic α Klotho at single-cell resolution and determined the cytokines and their receptors mediated cell-to-cell communication networks in Pkd1 mutant and Pkd1-HOMO-KLTg kidneys by CellChat analysis. We further showed that α Klotho exerted a proapoptotic and anti-inflammatory function through interacting with and destabilizing cellular inhibitor of apoptosis protein 1, which disturbed TNF and its receptor mediated prosurvival complex, leading to ( 1 ) the formation of predeath complex to increase cystic cell death and ( 2 ) the decrease of the activation of NF-κB, the expression of cytokines, and the recruitment of macrophages, resulting in a delay of cyst growth. Treatment with recombinant α Klotho also delayed cyst growth in Pkd1 mutant kidneys. CONCLUSIONS: This study defined an unknown role and mechanism of α Klotho in the regulation of a TNF-dependent cystic cell apoptosis and inflammation in Pkd1 mutant kidneys.
Chen C, Wang Z, Gao Y
… +16 more, Ellis MR, Ji B, Sieben CJ, Haycraft CJ, Croyle M, Aghevli A, Xu Q, Robichaud JH, He K, Chen C, Huang Y, Yoder BK, Hu J, Harris PC, Yu Y, Ling K
J Am Soc Nephrol
· 2026 May · PMID 41563398
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KEY POINTS: Inositol polyphosphate-5-phosphatase E (INPP5E) and type Ig phosphatidylinositol-4-phosphate 5-kinase (PIPKIγ) coordinated the homeostasis of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisp...KEY POINTS: Inositol polyphosphate-5-phosphatase E (INPP5E) and type Ig phosphatidylinositol-4-phosphate 5-kinase (PIPKIγ) coordinated the homeostasis of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate in primary cilia. Modulating INPP5E or PIPKIγ activity changed the level of polycystin-1 and polycystin-2 in primary cilia. INPP5E inhibition increased the hypomorphic PKD1 variants (PC1-R3277C) in cilia and reduced cystogenesis in the kidney in vitro . BACKGROUND: Autosomal dominant polycystic kidney disease is mainly caused by mutations in PKD1 and PKD2 , which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 and PC2 assemble a cation channel complex enriched in primary cilium, a sensory organelle associated with various developmental diseases, including polycystic kidney disease (PKD). Accumulating evidence supports the necessity of functional polycystin (PC) complex in cilia to prevent cystogenesis in the kidney, indicating that improving their ciliary levels may ameliorate defects underlying PKD pathogenesis. Yet, molecular mechanisms underlying the ciliary targeting and homeostasis of the PC complex are not fully understood. METHODS: Indirect immunofluorescence microscopy was used to monitor ciliary levels of PC1 and PC2 in renal epithelial cells. Electrophysiology analysis in oocytes was used to determine the channel activity of the PC complex. Cystogenesis in the kidney was measured using in vitro 3D-Matrigel cell models and ex vivo mouse embryonic kidney models. RESULTS: Suppressing inositol polyphosphate-5-phosphatase E (INPP5E) or activating type Ig phosphatidylinositol-4-phosphate 5-kinase raised ciliary levels of the PC complex in both normal renal epithelial cells and cells carrying autosomal dominant polycystic kidney disease mutations that interrupt the trafficking of PCs into cilia, including GANAB inactivation and the trafficking PKD1 mutation p.Arg3277Cys (RC). PC1 RC formed a complex with PC2 and exhibited normal channel activity in vitro . An INPP5E that increases PC1 and PC2 in cilia, suppressed in vitro forskolin-induced cystogenesis of inner medullary collecting duct epithelial cell line 3 cells in 3D Matrigel and ex vivo cyst formation in embryonic Pkd1RC/RC mouse kidneys. CONCLUSIONS: Our results demonstrated that increasing the ciliary level of PCs, by manipulating a ciliary phosphoinositide signaling axis, enhanced the functionality of PCs and suppressed cystogenesis of renal epithelial cells in vitro .
Jackson EK, Cheng D, Gillespie DG
… +5 more, Mi Z, Tofovic SP, Menshikova EV, Ritov VB, Kim-Campbell NA
J Am Soc Nephrol
· 2026 Jun · PMID 41563396
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KEY POINTS: 2'-AMP is endogenous and causes renal vasoconstriction in part by allosteric modulation of P2X1 receptors that enhances ATP-induced opening of P2X1 receptor channels. Kidney tissue nonspecific alkaline phosph...KEY POINTS: 2'-AMP is endogenous and causes renal vasoconstriction in part by allosteric modulation of P2X1 receptors that enhances ATP-induced opening of P2X1 receptor channels. Kidney tissue nonspecific alkaline phosphatase (TNAP) by metabolizing 2'-AMP protects against 2'-AMP-induced renal vasoconstriction, a protection lost when kidney TNAP activity is reduced. Drugs with off-target effects that reduce kidney TNAP activity should be avoided in patients at risk of kidney injury. BACKGROUND: Knockout of 2',3'-cyclic-nucleotide 3'-phosphodiesterse (an enzyme that converts 2',3'-cAMP to 2'-AMP) reduces 2'-AMP production and improves renal perfusion in renal ischemia-reperfusion injury (R-IRI). These findings motivated our hypothesis, herein tested, that 2'-AMP causes renal vasoconstriction. METHODS: The effect of 2'-AMP on renal vascular resistance (RVR) was investigated in rat kidneys, both in vitro and in vivo . 2'-AMP interactions with P2X1 receptors (P2X1Rs) were investigated in membrane preparations and HEK cells. Urinary 2'-AMP levels were assessed in cardiac surgery/cardiopulmonary bypass (CS-CPB) patients using mass spectrometry. RESULTS: In vitro , intra-renal-artery-infused 2'-AMP was rapidly metabolized to adenosine and did not increase RVR. Coadministration of a tissue nonspecific alkaline phosphatase inhibitor (TNAPI) reduced 2'-AMP metabolism, thus enabling 2'-AMP to trigger renal vasoconstriction. In vivo , kidneys rapidly metabolized intra-renal-artery-infused 2'-AMP to adenosine; this was blocked with a TNAPI. In vivo , intra-renal-artery-infused 2'-AMP decreased RVR, as did adenosine. By contrast, when coadministered with a TNAPI, 2'-AMP increased RVR, and this response was inhibited by NF449 (P2X1R antagonist). In membranes, 2'-AMP enhanced 3 H- αβ -methylene-ATP (P2X1R agonist) binding to P2X1Rs, and in HEK cells, 2'-AMP doubled αβ -methylene-ATP-induced (and P2X1R-mediated) calcium influx. In TNAPI+2'-AMP-pretreated, but not naïve, rats, βγ -methylene-ATP (P2X1R agonist) caused renal vasoconstriction. In rats, R-IRI reduced kidney tissue nonspecific alkaline phosphatase (TNAP) activity, and TNAP inhibition worsened R-IRI. In CS-CPB patients, urinary 2'-AMP levels were elevated 169% during CS-CPB and were associated with a 45% increase in peak 24-hour postprocedure serum creatinine. CONCLUSIONS: 2'-AMP is a renal vasoconstrictor; however, TNAP, by metabolizing 2'-AMP to adenosine, protects against 2'-AMP-induced renal vasoconstriction. This protection is lost when TNAP activity is reduced. 2'-AMP-induced renal vasoconstriction involves positive allosteric modulation of P2X1Rs that enhances ATP-induced opening of P2X1R channels. R-IRI reduces kidney TNAP activity, and TNAP inhibition worsens R-IRI outcomes.
Liu M, Zhang T, Cao W
… +4 more, Tan TJ, Yin D, Wang H, Xia Y
J Am Soc Nephrol
· 2026 Jun · PMID 41563390
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The tissue microenvironment plays a pivotal role in polycystic kidney disease (PKD) progression, orchestrating cyst initiation and expansion through dynamic interactions among kidney epithelial, stromal, and immune cells...The tissue microenvironment plays a pivotal role in polycystic kidney disease (PKD) progression, orchestrating cyst initiation and expansion through dynamic interactions among kidney epithelial, stromal, and immune cells, alongside systemic factors. Accurately reconstructing this complex in vivo milieu is essential to elucidate the mechanisms of PKD pathogenesis and to develop effective therapeutics. Human pluripotent stem cell-derived kidney organoids and patient-specific tubuloids have emerged as powerful platforms for modeling PKD within defined genetic contexts, faithfully recapitulating key pathological features of tubular cystogenesis. However, current organoid culture systems remain limited in their ability to replicate the full complexities of the native disease niche. Integrating bioengineering with developmental and biological insights will be essential to recreating physiologically relevant microenvironments. Such innovations will enhance the fidelity, predictive power, and translational utility of PKD organoid models, ultimately enabling more accurate drug testing and personalized therapeutics.
Kucirka LM, Boggess KA, Wood ME
… +8 more, Quist-Nelson J, Derebail VK, Flythe JE, Chalem A, Manuck TA, Meyer ML, Stuebe AM, Reynolds ML
J Am Soc Nephrol
· 2026 May · PMID 41563389
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KEY POINTS: In the United States, one in three pregnant women receiving maintenance dialysis experienced severe maternal morbidity from 2000 to 2020. History of severe maternal morbidity was associated with higher mortal...KEY POINTS: In the United States, one in three pregnant women receiving maintenance dialysis experienced severe maternal morbidity from 2000 to 2020. History of severe maternal morbidity was associated with higher mortality and a longer time to kidney transplantation in the years following delivery. BACKGROUND: Pregnant women receiving maintenance dialysis are at high risk for adverse pregnancy outcomes. Little is known about their rates of severe maternal morbidity and the association of severe maternal morbidity with future kidney transplant wait times and mortality. METHODS: This is a cohort study of women who gave birth while receiving maintenance dialysis from January 1, 2000, to December 31, 2019, as captured in the United States Renal Data System. Nonkidney severe maternal morbidity, defined by the US Centers for Disease Control and Prevention, was assessed from 4 weeks before birth to 6 weeks postpartum. Multivariable regression models examined risk factors independently associated with severe maternal morbidity. Multivariable Cox proportional hazards were stratified by the presence or absence of severe maternal morbidity to examine time to mortality, and, separately, the receipt of a kidney transplant. RESULTS: We identified 1082 births among 986 women who were receiving dialysis at the time of birth. In total, 332 women (34%) and 342 births (32%) experienced at least one nonkidney severe maternal morbidity. The most common severe maternal morbidity events were blood transfusion (16% of all births), pulmonary edema/acute heart failure (10%), sepsis (6%), and acute respiratory distress syndrome (5%). In multivariable analyses, risk factors independently associated with severe maternal morbidity included Black or other/unknown race, body mass index >35 kg/m 2 , and dialysis initiation within 1 year before giving birth. Patients who experienced severe maternal morbidity had a higher risk of mortality than those who did not (adjusted hazard ratio, 1.69; 95% confidence interval, 1.30 to 2.19) and were less likely to receive a kidney transplant than those who did not (adjusted subhazard ratio, 0.76; 95% confidence interval, 0.59 to 0.97). CONCLUSIONS: In the United States, one in three pregnant women receiving maintenance dialysis experienced severe maternal morbidity with risk factors that included recent dialysis initiation. In the following years, the history of severe maternal morbidity was associated with higher mortality and a longer time to kidney transplantation.
Tolerico M, Molina J, Insenga A
… +12 more, Carrazco A, Njeim R, Sloan A, Griswold A, Kurano M, Mendez A, Nathans R, Bolek R, Ettou S, Berasi S, Fornoni A, Merscher S
J Am Soc Nephrol
· 2026 Jul · PMID 41563385
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KEY POINTS: We identified dysregulation of the apolipoprotein M/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 4 (S1PR4) axis in the glomeruli and podocytes of a mouse model of Alport syndrome. Exogenous apolip...KEY POINTS: We identified dysregulation of the apolipoprotein M/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 4 (S1PR4) axis in the glomeruli and podocytes of a mouse model of Alport syndrome. Exogenous apolipoprotein M or antagonism of S1PR4 was sufficient to prevent kidney failure, podocyte injury, and lipid accumulation. Apolipoprotein M reduced lipid accumulation in podocytes via cholesterol efflux, while S1PR4 antagonism promoted autophagy of lipid droplets. BACKGROUND: Renal lipid dysmetabolism contributes to glomerular disease progression, including Alport syndrome. We recently identified alterations in the apolipoprotein M (APOM)/sphingosine-1-phosphate (S1P)/S1P receptor 4 signaling axis in glomeruli from patients with glomerular disease. METHODS: We used Col4a3 knockout mice and immortalized podocytes derived from these mice as a mouse model of Alport syndrome. Mice and podocytes were treated with recombinant APOM or the S1P receptor 4-specific antagonist, CYM50358. RESULTS: Col4a3-/- glomeruli and podocytes exhibited reduced APOM and increased S1P receptor 4 expression and increased sphingosoine-1-phosphate levels, mirroring findings in patients with glomerular disease. Treatment with APOM or CYM50358 reduced albuminuria, BUN, and plasma creatinine and ameliorated glomerulosclerosis, tubulointerstitial fibrosis, podocyte loss, and foot process effacement. Both treatments reduced triglyceride and cholesterol accumulation in glomeruli and podocytes. RNA-seq analysis of Col4a3-/- revealed that S1P receptor 4 antagonism upregulated lysosomal and autophagy-related genes. Western blot analysis confirmed increased LC3-II/LC3-I ratios and decreased p62, indicating enhanced autophagic flux. Treated podocytes showed increased lysosome numbers and colocalization with lipid droplets. By contrast, APOM had no effect on autophagy but promoted cholesterol efflux. Furthermore, knockdown of APOM or overexpression of sphingosine-1-phosphate receptor 4 was sufficient to cause podocyte cell death. CONCLUSIONS: We found that the APOM/S1P axis was dysregulated in Col4a3-/- podocytes. Targeting this pathway through APOM supplementation or S1P receptor 4 antagonism improved kidney function and reduced lipid accumulation by enhancing either cholesterol efflux or autophagy, respectively.
Chebib FT, Wang X, Udani SM
… +19 more, Westemeyer M, Clark D, Zhang Z, Bloom MS, Milo Rasouly H, Kolupaeva V, Mizani MR, Dossabhoy NR, Faravardeh A, Demko ZP, Kotte S, Punj S, Chapman SL, Rabinowitz M, Schneider R, Tabriziani H, Bhorade S, Gharavi AG, Dahl NK
J Am Soc Nephrol
· 2026 Apr · PMID 41563380
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KEY POINTS: Genetic testing in CKD showed diagnostic and clinical utility in the year following reporting of test results. Genetic testing was helpful for or changed management in 86% of patients with a positive finding...KEY POINTS: Genetic testing in CKD showed diagnostic and clinical utility in the year following reporting of test results. Genetic testing was helpful for or changed management in 86% of patients with a positive finding and 42% with a negative finding. Clinical utility was seen across 12 clinical cohorts, including CKD of unknown etiology and hypertension or diabetes-related nephropathy. BACKGROUND: CKD is a significant public health burden, affecting >800 million people worldwide with significant cost to the health care system. CKD is a disease process with substantial genetic and phenotypic heterogeneity that can obscure a definitive diagnosis, resulting in suboptimal management. Recent guidelines support greater adoption of genetic testing in CKD. We assessed the diagnostic and clinical utility in the year following broad-panel CKD genetic testing. METHODS: The Renasight Clinical Application, Review, and Evaluation (RenaCARE) study ( NCT05846113 ) was a single-arm, interventional, prospective, multicenter study evaluating the utility of genetic testing with a 385-gene panel on the diagnosis and management of CKD. Clinical history was collected before testing, and nephrologists responded to questionnaires at both 1 month and 1 year after testing. The impact of genetic testing on CKD diagnosis and management were assessed in active study patients at the 1-year time point. RESULTS: In a cohort of 1388 CKD patients with 13 pretest clinical categories of CKD, 335 (24%) patients had a positive genetic finding; 1174 had a questionnaire completed at 1 year and were included in the analysis. Genetic testing was reported helpful for clinical management and/or led to a change in management in 86% of patients with a positive test finding and 42% of patients with a negative test finding. In addition, genetic testing resulted in a change in the physician estimation of the 5-year prognosis for 55% of patients with a positive test finding and 18% of those with a negative test finding. CONCLUSIONS: Supporting the previous results of the RenaCARE study at 1 month, this report demonstrated that genetic testing was helpful in the clinical management and estimated prognosis of patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT05846113 .
Hofherr A, Mäki-Petäjä K, Selvarajah V
… +5 more, Grice D, Bartesaghi S, Jimenez E, Pecoits-Filho R, Heerspink HJL
J Am Soc Nephrol
· 2026 May · PMID 41563367
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KEY POINTS: In 558 adults with type 2 diabetes and CKD, inhibition of IL-33 by tozorakimab was well tolerated. IL-33 signaling was blocked at all doses, eosinophil counts decreased, and urinary CC-chemokine ligand 2 decr...KEY POINTS: In 558 adults with type 2 diabetes and CKD, inhibition of IL-33 by tozorakimab was well tolerated. IL-33 signaling was blocked at all doses, eosinophil counts decreased, and urinary CC-chemokine ligand 2 decreased at the high dose versus placebo. No significant differences in urinary albumin-creatinine ratio were observed between placebo and tozorakimab on top of standard of care. BACKGROUND: In patients with type 2 diabetes and CKD, elevated inflammatory biomarkers are associated with adverse kidney outcomes. IL-33 contributes to glomerular endothelial inflammation in diabetic kidney disease (DKD). This study evaluated the therapeutic potential of tozorakimab, an IL-33-neutralizing mAb, in DKD. METHODS: FRONTIER-1 ( NCT04170543 ) was a phase 2b, randomized, double-blind, placebo-controlled trial including adults with type 2 diabetes, an eGFR of 25-75 ml/min per 1.73 m 2 , urinary albumin-creatinine ratio (UACR) of 100-3000 mg/g, and maximally tolerated renin-angiotensin-aldosterone system blocker therapy. Participants received tozorakimab (30, 60, 120, or 300 mg) or placebo every 28 days for 168 days. All participants received dapagliflozin during days 85-168. The primary end point was UACR change on treatment from baseline to day 169 (per-protocol population). Exploratory end points included inflammatory biomarkers linked to IL-33 activity. RESULTS: Among 558 randomized participants (mean [SD] age 67 [10] years, 30% female, mean [SD] eGFR 48 [15] ml/min per 1.73 m 2 , geometric mean UACR 460 mg/g), tozorakimab ( N =425) was well tolerated with no safety concerns identified. In the per-protocol population ( N =465), IL-33 signaling was inhibited by >95% across all doses, eosinophil counts decreased by >19%, and urinary CC-chemokine ligand 2 levels were significantly decreased by 29% with the 300 mg dose (two-sided 90% confidence intervals, 14% to 42%) versus placebo. However, no statistically significant differences in UACR were observed between placebo (-22%) and treatment (-23% to -25%). CONCLUSIONS: Tozorakimab effectively inhibited IL-33 signaling but did not reduce UACR compared with placebo in patients with DKD over 24 weeks. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT04170543.
J Am Soc Nephrol
· 2026 Apr · PMID 41563365
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Hypertension is a global burden and a major contributor to cardiovascular disease and premature death. Public health guidelines for the management of high BP contain numerous dietary recommendations, of which one is a re...Hypertension is a global burden and a major contributor to cardiovascular disease and premature death. Public health guidelines for the management of high BP contain numerous dietary recommendations, of which one is a reduction in salt (NaCl) intake. In addition, the modern diet is also characterized by low potassium (K + ) content and recent guidelines propose increasing K + intake as an alternative or complementary measure to reducing salt intake for lowering of BP. Most beneficial effects of K + supplementation on BP involve a homeostatic response of the kidney to dietary-induced changes in extracellular K + concentrations, particularly decreased reabsorption of NaCl in the distal convoluted tubule. However, the effects of greater K + intake on BP are not linear, and the ideal K + supplementation or intake for management of BP remains unclear. This article covers the mechanisms in the kidney by which changes in K + translate to alterations in BP, the effects of altered K + intake in animal models and human populations, and the importance of concurrent salt intake and what constitutes K + supplementation.