Lapierre-Nguyen S, You Z, Gitomer B
… +8 more, Abebe KZ, Chapman AB, Harris PC, Perrone RD, Rahbari-Oskoui FF, Torres VE, Chonchol M, Nowak KL
J Am Soc Nephrol
· 2026 May · PMID 42149684
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BACKGROUND: Data are conflicting regarding whether pregnancy influences disease progression in women with autosomal dominant polycystic kidney disease (ADPKD). This study examined whether pregnancy or number of pregnanci...BACKGROUND: Data are conflicting regarding whether pregnancy influences disease progression in women with autosomal dominant polycystic kidney disease (ADPKD). This study examined whether pregnancy or number of pregnancies were associated with kidney disease progression in women with ADPKD. METHODS: Women with early- (Study A) and late-stage (Study B) ADPKD from the Halt the Progression of Polycystic Kidney Disease (HALT-PKD) trials were included to examine the association between self-reported number of pregnancies (categorical predictor: no pregnancy vs. 1-2 pregnancies and ≥3 pregnancies), annual slope of estimated glomerular filtration rate (eGFR), annual percent change in total kidney volume (%ΔTKV) and a composite outcome (kidney failure, 50% decline in eGFR, or death) using multivariable linear regression and Cox proportional hazard models. Additionally, women who became pregnant, had full-term pregnancies, and available data during study participation (n=13) were propensity matched (1:4) to women who were not pregnant during study participation, and a mixed model was applied to determine the association of pregnancy with eGFR slope and %ΔTKV. RESULTS: Across all analyses, 455 women with a median age of 45 (IQR: 38-50) years and eGFR of 69+25 ml/min/1.73m2 at baseline were included. 199 women had 1-2 pregnancies and 165 women had ≥3 pregnancies. There was no association of 1-2 pregnancies or ≥3 pregnancies (vs. no pregnancies) with eGFR slope (Beta-estimate [95% Confidence interval]; 1-2 pregnancies: 0.22 [-0.44,0.89]; ≥3 pregnancies: -0.46 [-1.16, 0.25]), %ΔTKV (Beta-estimate [95% CI]; 1-2 pregnancies: 0.92 [-0.34, 2.17]; ≥3 pregnancies: 0.69 [-0.67, 2.04]), or time to composite outcome (Hazard ratio [95% CI]; 1-2 pregnancies: 1.04 [0.56, 1.93]; ≥3 pregnancies: 1.48 [0.78, 2.77]) in adjusted models. Moreover, there was no difference in annual eGFR slope (Beta-estimate:-0.14 [95% CI: -2.72, 2.44]) and %ΔTKV (Beta-estimate:0.04 [95% CI: -3.74, 3.82]) in women who became pregnant during HALT matched to women who did not became pregnant during HALT. CONCLUSIONS: Pregnancy was not associated with ADPKD progression among women with early and late-stage ADPKD enrolled in the HALT-PKD trials.
Bunda P, Tian X, Nagata S
… +8 more, Lerner G, Medina-Rangel P, Gu J, Zhao H, Greene L, Ferguson S, Inoue K, Ishibe S
J Am Soc Nephrol
· 2026 May · PMID 42149668
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BACKGROUND: Given the post-mitotic nature of podocytes, adapting to both physiological and pathological stress is crucial to prevent podocyte loss. An important component of maintaining cellular homeostasis are lysosomes...BACKGROUND: Given the post-mitotic nature of podocytes, adapting to both physiological and pathological stress is crucial to prevent podocyte loss. An important component of maintaining cellular homeostasis are lysosomes, which are membrane-bound organelles responsible for degradation and recycling of damaged organelles and other macromolecules. Lysosome impairment has been shown to cause cellular and organ dysfunction, highlighting its crucial role in homeostasis. METHODS: We previously showed that podocyte-specific loss of cyclin G-associated kinase (Gak-KO) leads to severe proteinuria, podocyte injury, and kidney failure. To interrogate which GAK domains are necessary for its function, we utilized a transgenic mouse expressing a truncated 62-kDa C-terminal GAK protein (GAK C62), which consists of the clathrin-binding and J domains. We evaluated the functional role of GAK C62 in podocytes using immunofluorescence, western blotting, and in vivo transcriptomic analysis. RESULTS: Our findings revealed significant accumulation of autophagic vesicles in Gak-KO podocytes. By systematically probing for potential causes of autophagosome accumulation, we showed that loss of Gak resulted in impaired lysosomal degradation, secondary to mistrafficking of lysosomal hydrolases. Notably, GAK C62 expression completely rescued these phenotypes at the cellular and organismal levels. Moreover, in vivo TRAP-seq and cytokine profiling demonstrated enrichment of immune-related pathways and IL-11 production in Gak-KO podocytes. CONCLUSIONS: GAK, specifically its C-terminal domains, plays an important role in podocyte lysosome homeostasis. Lysosomal dysfunction due to loss of Gak may lead podocytes to adopt immune-like properties characterized by the release of pro-inflammatory cytokine IL-11.
J Am Soc Nephrol
· 2026 May · PMID 42138991
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Tubulointerstitial fibrosis is a defining histopathologic hallmark of CKD and develops in response to diverse acute and chronic insults to the kidney. Converging evidence has established interstitial fibrosis as a direct...Tubulointerstitial fibrosis is a defining histopathologic hallmark of CKD and develops in response to diverse acute and chronic insults to the kidney. Converging evidence has established interstitial fibrosis as a direct causal driver of kidney function decline. After injury, tubular epithelial cells can initiate fibrotic remodeling by promoting immune cell recruitment and myofibroblast activation. Myofibroblasts, predominantly derived from tissue-resident fibroblasts and pericytes to a lesser extent, are the principal effector cells of kidney interstitial fibrosis, producing the majority of extracellular matrix. During their differentiation, perivascular myofibroblast progenitors detach from the microvasculature and invade the interstitium, which destabilizes capillaries and promotes capillary rarefaction. Capillary rarefaction, together with excessive extracellular matrix deposition that impairs oxygen diffusion, induces sustained tubular hypoxia and perpetuates epithelial injury. This establishes a self-reinforcing cycle of fibrotic remodeling that becomes largely independent of the initiating insult. Over the past decade, technological advances have markedly refined our understanding of this pathogenic cascade. Single-cell and spatial transcriptomics have resolved cellular heterogeneity, defined fibroinflammatory niches, and delineated intercellular communication networks that sustain fibrotic remodeling. In parallel, human pluripotent stem cell-derived kidney organoids have emerged as scalable, multicellular model systems that recapitulate key features of tubular injury, inflammation, and myofibroblast activation, enabling functional validation of candidate targets in a human context. In this review, we synthesize current mechanistic insights into kidney fibrotic remodeling and discuss how high-resolution transcriptomics and increasingly mature organoid platforms accelerate antifibrotic drug discovery.
Pagliazzi A, Wellekens K, de Loor H
… +11 more, Koshy P, Vaulet T, Vranken A, Vanhoutte T, Kuypers D, Jallah B, Jatsenko T, Kyle P, Woodward R, Coemans M, Naesens M
J Am Soc Nephrol
· 2026 May · PMID 42133430
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BACKGROUND: Over the past 25 years, donor-derived cell-free DNA (dd-cfDNA) has emerged as a noninvasive biomarker for detecting allograft rejection in kidney transplant recipients, yet its clinical interpretability and c...BACKGROUND: Over the past 25 years, donor-derived cell-free DNA (dd-cfDNA) has emerged as a noninvasive biomarker for detecting allograft rejection in kidney transplant recipients, yet its clinical interpretability and context(s) of use in post-transplant monitoring remain largely unexplored. METHODS: In this observational cohort study, we analyzed 472 retrospective and 450 prospective plasma samples as the derivation and validation cohorts, respectively. Samples were collected at the time of either an indication or a protocol kidney biopsy. We evaluated three logistic regression models for rejection discrimination: a clinical model, the dd-cfDNA alone, and their combination. Result-specific likelihood ratios (LR) were derived from the dd-cfDNA-based model probabilities and applied to the clinical model predictions to obtain post-test probabilities of rejection. By comparing pre- and post-test probabilities, we assessed the impact of dd-cfDNA on rejection risk stratification. RESULTS: Dd-cfDNA alone demonstrated strong discriminative ability, with AUCs of 0.79 (95% CI: 0.73-0.84) and 0.80 (95% CI: 0.72-0.87) in the derivation and validation cohorts, respectively. Combining dd-cfDNA with clinical parameters improved the above AUCs to 0.82 and 0.87, respectively. We compared pre- and post-test probabilities to determine how dd-cfDNA testing influenced rejection risk estimation. Incorporating dd-cfDNA-testing results clarified risk stratification by reducing the number of samples categorized as intermediate (10-30%) pre-test risk. Overall, 253/345 pre-test intermediate risk samples were reclassified, with 117/162 (72%) and 33/91 (36%) correctly assigned to low (≤10%) and high (≥30%) post-test risk, respectively. With 10% probability threshold for warranting a kidney biopsy, 482 biopsies would have been safely avoided using post-test probabilities, with 437 (91%) of these being protocol biopsies. CONCLUSIONS: Our study confirmed the strong association between dd-cfDNA% and rejection after kidney transplantation. Using test result-specific likelihood ratio, we evaluated the impact of integrating dd-cfDNA% for estimating time-point-specific rejection risk, demonstrating its potential to reduce the number of unnecessary biopsies in a cohort with a relatively low rejection prevalence.
Li H, Li G, Huang L
… +10 more, Fan T, Zhang Y, Zhang J, Gu L, Wang J, Hu L, Tang H, Song Y, Luo Q, Wang J
J Am Soc Nephrol
· 2026 May · PMID 42113583
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BACKGROUND: Diabetic kidney disease (DKD) is a major complication of diabetes, driven by chronic inflammation throughout its initiation and progression. Developing effective novel therapeutics is urgently needed. Eupalin...BACKGROUND: Diabetic kidney disease (DKD) is a major complication of diabetes, driven by chronic inflammation throughout its initiation and progression. Developing effective novel therapeutics is urgently needed. Eupalinolide B, a natural small compound derived from Eupatorium lindleyanum DC. , has multiple bioactive properties, notably anti-tumor and anti-inflammatory activities. However, the therapeutic potential of Eupalinolide B for DKD remains unclear. This study is to investigate the potential effects, direct targets and pharmacological mechanisms of Eupalinolide B against DKD, and discover novel therapeutic targets in the progression of DKD. METHODS: The therapeutic effects of Eupalinolide B were assessed in high glucose-induced rat mesangial HBZY-1 cells and db/db diabetic mice. Targeting and binding site engagement of Eupalinolide B was validated through activity-based protein profiling technology, pull-down assay, surface plasmon resonance analysis, high-resolution mass spectrometry analysis. The target protein was knocked down to investigate its role in DKD-related inflammation and determine whether Eupalinolide B's renoprotective effects depend on the protein. The impact of Eupalinolide B on protein-protein interactions was examined using immunoblotting, immunohistochemistry, immunofluorescence, and co-immunoprecipitation assays. RESULTS: Eupalinolide B was observed to ameliorate the glomerular filtration dysfunction and histopathological damage in db/db mice, and suppress NF-κB and MAPK pro-inflammatory pathways in both high glucose-induced HBZY-1 cells and db/db mice. Additionally, we found that Eupalinolide B directly bound to cysteine 64 and 234 residues of cell division cycle 37 (CDC37), the essential co-chaperone of heat shock protein 90 (HSP90). Mechanistically, by targeting CDC37, Eupalinolide B disrupted the interaction between CDC37 and HSP90, consequently blocking downstream pro-inflammatory signaling upon high glucose induction in HBZY-1 cells. CONCLUSIONS: Eupalinolide B was identified as a novel CDC37-targeting agent with renoprotective and anti-inflammatory effects against DKD that functions by inhibiting CDC37-HSP90 interaction.
Huang H, Tattersfield C, Jacas S
… +12 more, Karreci ES, Rumde A, Kelly J, Francey L, Subramanian B, Huang M, Ryback B, Schumacher V, Alper SL, Zsengellér ZK, Pollak MR, Friedman DJ
J Am Soc Nephrol
· 2026 May · PMID 42101909
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BACKGROUND: 13% of African Americans have a high risk APOL1 genotype, carrying two risk alleles (G1/G1, G1/G2 or G2/G2). The mechanisms underlying nephropathy caused by these APOL1 risk variant genotypes are not fully un...BACKGROUND: 13% of African Americans have a high risk APOL1 genotype, carrying two risk alleles (G1/G1, G1/G2 or G2/G2). The mechanisms underlying nephropathy caused by these APOL1 risk variant genotypes are not fully understood. Downstream of gene function, homeostatic maintenance of a complex and interconnected network of metabolites is essential for normal kidney function. However, this metabolic network can be rerouted by genetic changes or environmental insults, both of which can contribute to development and/or progression of kidney diseases. APOL1 nephropathy exhibits both genetic and environmental triggers, but how APOL1 might alter metabolic homeostasis and how such changes may contribute to disease progression remains unclear. METHODS: APOL1 nephropathy was induced in human BAC transgenic APOL1 mice by IFN-γ adenovirus. Non-targeted metabolomics was performed on glomeruli from risk variant (G1/G1 and G2/G2) and non-risk variant (G0/G0) mice as well as on tetracycline-inducible cell lines expressing risk or non-risk variants. Metabolic signaling pathways in risk or non-risk groups were compared and transcriptional changes driving these metabolic differences were identified. Metabolic interventions were performed in both APOL1 risk and non-risk variant-expressing cells and in mice. The effect of metabolic intervention was evaluated by cytotoxicity assays and urine albumin-to-creatinine ratios for cellular and in vivo responses, respectively. RESULTS: Perturbed purine metabolism was the strongest metabolite differentiator between high- and low-risk APOL1 genotypes in cultured cells and in whole glomeruli. Expression of APOL1 G2/G2 downregulated the rate-limiting enzymes of purine biosynthesis and induced ATP depletion. In APOL1 G2/G2-expressing cells, supplementation with the purine biosynthesis precursor AICAr rescued purine biosynthesis, reduced cytotoxicity and boosted ATP. In interferon-γ treated APOL1 G2/G2 transgenic mice, AICAr administration boosted purine biosynthesis, decreased kidney pAMPK, and reduced albuminuria levels. AICAr treatment rescued G2 mouse podocyte death induced by the inflammatory stimuli of combined interferon-γ and Toll-like receptor 1/2 agonist. CONCLUSIONS: Increasing purine biosynthesis mitigated APOL1 risk-variant induced injury in cell and transgenic mouse models of APOL1 kidney disease.
Wong ETY, Balshaw R, Gibson IW
… +11 more, Ho J, Shaw J, Karpinski M, Trachtenberg A, Pochinco D, Goldberg A, Birk P, Pinsk M, Rush DN, Nickerson PW, Wiebe C
J Am Soc Nephrol
· 2026 May · PMID 42096292
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KEY POINTS: De novo donor-specific anti-HLA antibody, microvascular inflammation, and T-cell-mediated rejection events frequently occurred concomitantly or serially, and their interconnectedness and complexity are undera...KEY POINTS: De novo donor-specific anti-HLA antibody, microvascular inflammation, and T-cell-mediated rejection events frequently occurred concomitantly or serially, and their interconnectedness and complexity are underappreciated. Microvascular inflammation without donor-specific anti-HLA antibody did not independently worsen prognosis after adjustment for serial or concomitant T-cell-mediated rejection and de novo donor-specific anti-HLA antibody events in time-dependent models. HLA-DR/DQ alloimmune risk categories were multivariable correlates of microvascular inflammation-free survival, suggesting an association with HLA mismatch. BACKGROUND: Microvascular inflammation (sum of glomerulitis [g] and peritubular capillaritis [ptc] scores ≥2) frequently occurs without donor-specific anti-HLA antibodies (DSAs), often alongside T-cell-mediated rejection (TCMR), yet its independent prognostic significance remains uncertain. METHODS: In a consecutive single-center cohort of 689 kidney transplant recipients (2004-2021), we examined the impact of first g+ptc≥2, TCMR, and de novo DSA (dnDSA) events on death-censored allograft loss using Cox models with time-dependent covariates to account for event timing and overlap. RESULTS: A first g+ptc≥2 occurred in 106/689 (15%) recipients, and 88% had concomitant or sequential TCMR and/or dnDSA. Most g+ptc≥2 biopsies were associated with TCMR (76%), including those with g=0. When assessed individually, the first g+ptc≥2 (hazard ratio [HR], 4.33; 95% confidence interval [CI], 2.5 to 7.5), TCMR (HR, 4.07; 95% CI, 2.3 to 7.1), and dnDSA (HR, 4.26; 95% CI, 2.2 to 8.3) events were each associated with death-censored allograft loss. However, in a combined time-dependent model, first TCMR (HR, 2.74; 95% CI, 1.4 to 5.4) and dnDSA (HR, 2.32; 95% CI, 1.1 to 5.1) remained independently associated with death-censored allograft loss, whereas g+ptc≥2 did not (HR, 1.77; 95% CI, 0.84 to 3.73). CONCLUSIONS: In a modern tacrolimus-based cohort, g+ptc≥2 without DSA was not associated with worse outcomes after adjustment for serial or concomitant TCMR and dnDSA events.
Amleh A, Makayes Y, Abergel E
… +5 more, Varshavsky DB, Benyamini H, Plaschkes I, Nechama M, Volovelsky O
J Am Soc Nephrol
· 2026 May · PMID 42090211
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BACKGROUND: The increasing popularity of ketogenic diets raises concerns regarding their safety during pregnancy. While mild ketosis is a common metabolic adaptation in gestation, the impact of diet-induced, supraphysiol...BACKGROUND: The increasing popularity of ketogenic diets raises concerns regarding their safety during pregnancy. While mild ketosis is a common metabolic adaptation in gestation, the impact of diet-induced, supraphysiological ketosis on fetal kidney development remains unknown. We aimed to investigate the effects of maternal ketosis on offspring nephrogenesis and long-term kidney outcomes. METHODS: Two complementary murine models were employed: maternal exposure to a ketogenic diet or β-hydroxybutyrate supplementation throughout gestation. Offspring were evaluated at birth and during postnatal development. Kidney structure and function were assessed by nephron counts, kidney size, and serum markers of kidney function and injury. Nephron progenitor cell (NPC) dynamics were examined using RNA sequencing, gene set enrichment analysis, immunostaining, and qPCR to assess proliferation and inflammation-related markers. RESULTS: Both the ketogenic diet and the β-hydroxybutyrate supplementation models induced maternal ketosis and reduced offspring nephron number. Offspring exhibited impaired kidney function, more pronounced in the ketogenic diet group. Transcriptomic analysis of NPCs revealed downregulation of cell-cycle and Myc signaling pathways, alongside upregulation of inflammatory pathways, including TNFα/NFκB signaling. Immunostaining confirmed reduced NPC proliferation and c-Myc expression, alongside increased TNFα expression. Although postnatal NPC proliferation partially recovered after reversion to a standard diet, it was insufficient to rescue the nephron endowment deficit. CONCLUSIONS: Maternal ketosis disrupted nephrogenesis by suppressing c-Myc signaling and activating inflammatory pathways in NPCs, leading to a congenital nephron deficit and compromised adult kidney function.
Petzl AM, Ren Y, Norby FL
… +18 more, Wang J, Dubin RF, Antanavicius I, Segal MR, Chen LY, Alonso A, Rhee EP, Bansal N, Kimmel PL, Vasan RS, Surapaneni A, Grams ME, Feldman H, Marchlinski FE, Go AS, Lee H, Ganz P, Deo R
J Am Soc Nephrol
· 2026 May · PMID 42065929
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KEY POINTS: Using proteomics and Mendelian randomization, we identified causal proteins for the development of atrial fibrillation in patients with CKD. Immunologic function, cell growth, and neural development were comm...KEY POINTS: Using proteomics and Mendelian randomization, we identified causal proteins for the development of atrial fibrillation in patients with CKD. Immunologic function, cell growth, and neural development were common biologic pathways underlying atrial fibrillation and left atrial enlargement. Machine learning led to a nine-protein risk model that had a similar predictive performance for incident atrial fibrillation as clinical risk scores. BACKGROUND: CKD is strongly associated with atrial fibrillation. Understanding the biologic pathways for this association and creating predictive models have been challenging. Left atrial enlargement is a substrate for atrial fibrillation, but any overlap between biomarkers of atrial fibrillation and left atrial enlargement in patients with CKD is unknown. METHODS: We evaluated 4590 plasma proteins with SomaScan in two cohorts of adult patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC; n =2654) and the Atherosclerosis Risk in Communities cohort (ARIC; n =1326). Using Mendelian randomization, we identified proteins along the causal pathway to atrial fibrillation. We also identified proteins and corresponding pathways associated with larger echocardiographic left atrial size, a recognized substrate for atrial fibrillation. Finally, we developed and validated a multiprotein risk score for incident atrial fibrillation in the CKD population. RESULTS: Over 5 years, incident atrial fibrillation occurred among 150 patients in the CRIC and 140 in the ARIC cohort. We identified three proteins causally linked to incident atrial fibrillation: neural EGF like‑like protein 1, cartilage intermediate layer protein 2, and matrix metallopeptidase 12. Pathway analysis revealed an overlap in eight of the top ten canonical pathways for incident atrial fibrillation and left atrial enlargement. A risk model for incident atrial fibrillation composed of proteins had annualized areas under the receiver-operating characteristic curve over 5 years ranging from 0.65 to 0.76, a performance similar to the Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation (CHARGE-AF) clinical risk score. CONCLUSIONS: This study identified causal proteins and biologic mechanisms underlying incident atrial fibrillation in CKD. A proteomic risk score for incident atrial fibrillation in CKD performed similarly to the CHARGE-AF clinical risk score.
Piedrafita A, Sablik M, Preka E
… +32 more, Goutaudier V, Demir Z, Mezine F, Divard G, Dagobert J, Robin B, Truchot A, Thalamas T, Sannier A, Rabant M, Aubert O, Maanaoui M, Le Quintrec M, Couzi L, Chauveau B, Bestard O, Elias M, Louis K, Rosales IA, Smith RN, Anglicheau D, Del Bello A, Budde K, Halleck F, Huang E, Adam B, Villard J, Kamar N, Lefaucheur C, Colvin RB, Mengel M, Loupy A
KEY POINTS: Normalization methods affected the performance of gene-based diagnostic classifiers for kidney transplant rejection across a large multicenter cohort. Complex normalization reduced classifier performance by o...KEY POINTS: Normalization methods affected the performance of gene-based diagnostic classifiers for kidney transplant rejection across a large multicenter cohort. Complex normalization reduced classifier performance by overcorrecting signal, while simpler methods preserved rejection signature and key robustness. By identifying optimal normalization methods, this work advances a standardized preprocessing framework for molecular diagnostics in transplantation. BACKGROUND: The Banff 2022 classification endorses intragraft gene expression profiling using the Banff Human Organ Transplant (B-HOT) consensus gene panel for rejection diagnosis. However, lack of standardized analytical pipelines, including data normalization, limits clinical implementation, with its effect on diagnostic performance yet to be determined. METHODS: We evaluated ten normalization methods in 868 kidney allograft biopsies from nine European and North American centers, all Banff-graded and B-HOT-profiled on nCounter, comprising derivation ( n =441), internal ( n =186), and external ( n =241) validation cohorts. Each method was assessed through its downstream impact on ( 1 ) gene count stability, ( 2 ) differential expression and cross-platform concordance with RNA sequencing (RNA-seq) data, and ( 3 ) discrimination and calibration of predictive models for antibody-mediated rejection (AMR) and T -cell-mediated rejection (TCMR). RESULTS: Most methods improved count stability and showed high concordance with RNA-seq for overall gene expression. They also produced robust differential expression signatures consistent with those detected by RNA-seq, except for RUVSeq and RCRNorm , which identified fewer differentially expressed genes and showed lower concordance. In the overall validation cohort ( n =427), diagnostic performance was consistently high across nSolver -based approaches, nanostringr , NanoStringDiff , MetaNorm , and RCRNormFast (AMR, area under the ROC curve [AUROC], 0.88-0.91; area under precision-recall curves [AUPRC], 0.86-0.89; TCMR AUROC, 0.90-0.92; AUPRC, 0.78-0.83). Performance declined with RCRNorm (AMR AUROC/AUPRC, 0.55/0.41; TCMR, 0.53/0.18) and, for TCMR, with RUVSeq (AUROC, 0.84-0.85; AUPRC, 0.64-0.65). Calibration was satisfactory for most methods, except for RCRNorm and for TCMR models after RUVSeq . CONCLUSIONS: Normalization choice significantly impacted gene expression profiles and diagnostic classifier performance. Most methods, including nSolver-based pipelines, achieved robust discrimination for both AMR and TCMR. Complex methods, including RCRNorm, and RUVSeq for TCMR, reduced performance, with simpler approaches consistently outperforming them for B-HOT-based molecular diagnostics.
KEY POINTS: eGFR discordance was associated with higher risk of AKI in allogeneic hematopoietic stem cell transplantation and adoptive T-cell therapies. Among hematopoietic stem cell transplantation recipients, eGFR disc...KEY POINTS: eGFR discordance was associated with higher risk of AKI in allogeneic hematopoietic stem cell transplantation and adoptive T-cell therapies. Among hematopoietic stem cell transplantation recipients, eGFR discordance was associated with slower time-to-platelet engraftment. Among adoptive T-cell recipients, eGFR discordance was associated with prolonged cytopenia. BACKGROUND: Discordance between eGFR on the basis of serum creatinine (eGFR cr ) versus cystatin C (eGFR cys ) is associated with adverse outcomes in patients with and without cancer. We hypothesized that eGFR discordance is associated with AKI and death after hematopoietic stem cell transplantation (HSCT) or receipt of adoptive T-cell therapies. METHODS: We conducted a multicenter study of adults receiving allogeneic HSCT and adoptive T-cell therapies who had paired serum creatinine and cystatin C values obtained in the 30 days preceding conditioning or lymphodepleting chemotherapy. The primary exposure was eGFR discordance, defined as eGFR cys ≥30% lower than eGFR cr . The primary outcome was a composite outcome of AKI (≥50% increase in serum creatinine or receipt of KRT) or death within 90 days after HSCT or adoptive T-cell infusion. Secondary outcomes included time-to-platelet engraftment in HSCT and prolonged cytopenia in adoptive T-cell recipients. We used multivariable logistic regression and cause-specific Cox regression with inverse probability weighting to adjust for confounders. RESULTS: Of 274 patients receiving HSCT (median age, 65 years; interquartile range, 52-71; 43% female), 86 (31%) had an eGFR discordance. Among 236 adoptive T-cell recipients (median age, 67 years; interquartile range, 60-74; 59% female), 78 (33%) had a discordance in eGFR. eGFR discordance was associated with higher odds of AKI or death in HSCT (odds ratio, 1.75; 95% confidence interval, 1.03 to 3.02) and adoptive T-cell recipients (odds ratio, 2.37; 95% confidence interval, 1.12 to 4.94). However, adjustment for eGFR cr-cys attenuated these associations in both cohorts. eGFR discordance was also associated with slower time-to-platelet engraftment in HSCT recipients and prolonged cytopenia after adoptive T-cell therapy. CONCLUSIONS: A pretreatment eGFR discordance was associated with AKI or death in HSCT and adoptive T-cell recipients; however, this association was attenuated after adjusting for eGFR cr-cys .