Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression

Waikar, Sushrut S.; Srivastava, Anand; Pálsson, Ragnar; Shafi, Tariq; Hsu, Chi-yuan; Sharma, Kumar; Lash, James P.; Chen, Jing; He, Jiang; Lieske, John C.; Xie, Dawei; Zhang, Xiaoming; Feldman, Harold I.; Curhan, Gary C.

doi:10.1001/jamainternmed.2018.7980

Cited by 97 publications

(98 citation statements)

References 44 publications

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“…To the best of our knowledge, there have not been any previous studies investigating the association of urinary oxalate with GF, PTDM and (cause-specific) mortality in stable KTR. However, a recent study of Waikar et al with CKD patients stage 2 to 4 found 24-h urinary oxalate excretion to be positively associated with all-cause mortality [14]. With regards to the study of Waikar et al, their first four quintiles can be considered to be below the range of hyperoxaluria of 455µmol/24-h, whereas in our population, only the first tertile can be considered normal with regard to urinary oxalate excretion.…”

Section: Discussioncontrasting

confidence: 64%

“…In addition, we also looked for lactate dehydrogenase (LDH) because of its importance in the conversion of glyoxylate (Model 4) [34], for 24-h urinary pH because of its influence on the reaction of oxalate with calcium (Model 5) [35], for fibroblast growth factor 23 (FGF23) because of the relationship with gastrointestinal calcium absorption and oxalate bioavailability [36,37] (Model 6), and for fruits and vegetables as main dietary sources of oxalate [38][39][40] (Model 7). To allow for detection of a potential threshold effect, which was found in an earlier study on urinary oxalate excretion and CKD [14], Cox regression analyses were also performed according to sex-stratified tertiles with the first tertile as reference.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…Although different mechanisms underlying these long-term complications of kidney transplantation have been found, substantial unknown mechanisms particular to the post-kidney transplantation setting remain to be identified in order to provide rationale for the markedly high risk of premature mortality in KTR [13]. A recent prospective cohort study in 3123 patients with chronic kidney disease (CKD) stages 2 to 4, found urinary oxalate as a potential risk factor for progression of CKD [14]. In the post-kidney transplantation setting, the study of oxalate remains overlooked.…”

Section: Introductionmentioning

confidence: 99%

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Urinary Oxalate Excretion and Long-Term Outcomes in Kidney Transplant Recipients

Tubben

Sotomayor

Post

et al. 2019

JCM

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Epidemiologic studies have linked urinary oxalate excretion to risk of chronic kidney disease (CKD) progression and end-stage renal disease. We aimed to investigate whether urinary oxalate, in stable kidney transplant recipients (KTR), is prospectively associated with risk of graft failure. In secondary analyses we evaluated the association with post-transplantation diabetes mellitus, all-cause mortality and specific causes of death. Oxalate excretion was measured in 24-h urine collection samples in a cohort of 683 KTR with a functioning allograft ≥1 year. Mean eGFR was 52 ± 20 mL/min/1.73 m2. Median (interquartile range) urinary oxalate excretion was 505 (347–732) µmol/24-h in women and 519 (396–736) µmol/24-h in men (p = 0.08), with 302 patients (44% of the study population) above normal limits (hyperoxaluria). A consistent and independent inverse association was found with all-cause mortality (HR 0.77, 95% CI 0.63–0.94, p = 0.01). Cause-specific survival analyses showed that this association was mainly driven by an inverse association with mortality due to infection (HR 0.56, 95% CI 0.38–0.83, p = 0.004), which remained materially unchanged after performing sensitivity analyses. Twenty-four-hour urinary oxalate excretion did not associate with risk of graft failure, post-transplant diabetes mellitus, cardiovascular mortality, mortality due to malignancies or mortality due to miscellaneous causes. In conclusion, in KTR, 24-h urinary oxalate excretion is elevated in 44% of KTR and inversely associated with mortality due to infectious causes.

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Section: Discussioncontrasting

confidence: 64%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Urinary Oxalate Excretion and Long-Term Outcomes in Kidney Transplant Recipients

Tubben

Sotomayor

Post

et al. 2019

JCM

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“…Nephrolithiasis affect 8% of the US population [6,7] with an ~20% 5year recurrence rate [8,9], and most kidney stones (85-90%) are composed of calcium oxalate [10]. Oxalate also has been implicated in inflammation and CKD progression, suggesting broad impact [11][12][13][14].…”

Section: Mainmentioning

confidence: 99%

Microbial contributions to oxalate metabolism in health and disease

Liu

Devlin

et al. 2020

Preprint

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Over-accumulation of oxalate in humans may lead to nephrolithiasis and nephrocalcinosis. Humans lack endogenous oxalate degradation pathways (ODP), but intestinal microbiota can degrade oxalate and protect against its absorption. However, the particular microbes that actively degrade oxalate in vivo are ill-defined, which restricts our ability to disentangle the underlying taxonomic contributions. Here we leverage large-scale multi-omics data (>3000 samples from >1000 subjects) to show that the human microbiota in health harbors diverse ODP-encoding microbial species, but an oxalate autotroph-Oxalobacter formigenes- dominates this function transcriptionally. Patients with Inflammatory Bowel Disease (IBD) are at significantly increased risk for disrupted oxalate homeostasis and calcium-oxalate nephrolithiasis. Here, by analyzing multi-omics data from the iHMP-IBD study, we demonstrate that the oxalate degradation function conferred by the intestinal microbiota is severely impaired in IBD patients. In parallel, the enteric oxalate levels of IBD patients are significantly elevated and associated with intestinal disease severity, which is consistent with the clinically known nephrolithiasis risk. The specific changes in ODP expression by several important taxa suggest that they play different roles in the IBD-induced nephrolithiasis risk.

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“…Although a serious of studies have found the critical cellular and molecular mediators that lead to brosis, they have not been clinically veri ed. At present, 13% to 16% of patients with CKD need hemodialysis, and they may need kidney transplantation in the long term, and the high risk of cardiovascular disease caused by CKD signi cantly reduces the survival rate of patients [4][5][6]. The rapid development of basic scienti c research provides a platform for the study of new treatments.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-derived exosome miR-21-3p prevents renal fibrosis

Cao

2020

Preprint

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Background: Renal fibrosis is the pathological result of excessive deposition of extracellular matrix (ECM) in the process of chronic kidney disease, but its mechanism is not clear. Mesenchymal stem cells (MSCs) exerts its therapeutic effect mainly through paracrine effects, such as exosome, to change the cellular microenvironment. Here, we explore the function of exosome derived MSCs in renal fibrosis.Methods: UUO model was constructed to simulate renal fibrosis in mice. Heat map and RT-PCR were used to explore the differential expression of miRNAs. RT-PCR and western blot were performed to detect the expression levels of fibrosis-associated genes and proteins in vivo and vitro. Transmission electron microscope and particle size detection were used to confirm the exosome construct. Then we forced expression of miR-21-3p in MSCs and isolated the exosomes. Then the fibrosis-associated genes and proteins were explored after exosomes injection.Results: In this study, we observed that exogenous miR-21-3p, interacted with smad2, the downstream target of miR-21-3p, which prevented renal fibrosis in UUO mice, and alleviate fibrosis in TGF-β1-induced renal tubular epithelium cells (HK-2). The extractive exosome-miR-21-3p treatment blocked renal fibrosis in UUO mice and alleviated fibrosis in TGF-β1-induced HK-2 cells and renal fibrosis mice. Conclusion: Taken together, Overexpression of miR-21-3p prevented CKD-induced renal fibrosis via exosome-mediated miR-21-3p transfer. These results suggest possible therapeutic strategies for using exosome delivery of miR-21-3p to treat complications of CKD.

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Association of Urinary Oxalate Excretion With the Risk of Chronic Kidney Disease Progression

Cited by 97 publications

References 44 publications

Urinary Oxalate Excretion and Long-Term Outcomes in Kidney Transplant Recipients

Urinary Oxalate Excretion and Long-Term Outcomes in Kidney Transplant Recipients

Microbial contributions to oxalate metabolism in health and disease

Mesenchymal stem cell-derived exosome miR-21-3p prevents renal fibrosis

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