Increased urinary osmolyte excretion indicates chronic kidney disease severity and progression rate

Gil, Ryan; Ortíz, Alberto; Markoska, Katerina; Schepers, Eva; Vanholder, Raymond; Glorieux, Griet; Schmitt‐Kopplin, Philippe; Heinzmann, Silke S.

doi:10.1093/ndt/gfy020

Cited by 49 publications

(46 citation statements)

References 47 publications

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“…The bulk of myo-inositol is produced by the kidneys [32]. In CKD, urinary levels of myo-inositol increase due to reduced tubular reabsorption [33]. ADMA is implicated with chronic kidney disease [34,35].…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolites associate with the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease

et al. 2020

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Background The variable course of autosomal dominant polycystic kidney disease (ADPKD), and the advent of renoprotective treatment require early risk stratification. We applied urinary metabolomics to explore differences associated with estimated glomerular filtration rate (eGFR; CKD-EPI equation) and future eGFR decline. Methods Targeted, quantitative metabolic profiling (1 H NMR-spectroscopy) was performed on baseline spot urine samples obtained from 501 patients with ADPKD. The discovery cohort consisted of 338 patients (56% female, median values for age 46 [IQR 38 to 52] years, eGFR 62 [IQR 45 to 85] ml/min/1.73m 2 , follow-up time 2.5 [range 1 to 3] years, and annual eGFR slope-3.3 [IQR-5.3 to-1.3] ml/min/1.73m 2 /year). An independent cohort (n = 163) was used for validation. Multivariate modelling and linear regression were used to analyze the associations between urinary metabolites and eGFR, and eGFR decline over time. Results Twenty-nine known urinary metabolites were quantified from the spectra using a semi-automatic quantification routine. The model optimization routine resulted in four metabolites that most strongly associated with actual eGFR in the discovery cohort (F = 128.9, P = 7×10 −54 , R 2 = 0.724). A model using the ratio of two other metabolites, urinary alanine/citrate, showed the best association with future annual change in eGFR (F = 51.07, P = 7.26×10 −12 , R 2 = 0.150). This association remained significant after adjustment for clinical risk markers

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Section: Discussionmentioning

confidence: 99%

Urinary metabolites associate with the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease

et al. 2020

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“…In contrast, in Clock-mutant mice, Atp1b1 expression was low and blood pressure high [44]. The expression of both NCC and ATP1B1 is altered in kidney injury, potentially linking kidney injury to an altered expression of kidney circadian genes regulating blood pressure [45,46].…”

Section: Chronodisruption In Ckdmentioning

confidence: 99%

Chronodisruption: A Poorly Recognized Feature of CKD

Carriazo

Ramos

Sanz

et al. 2020

Toxins

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Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic.

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“…Inhibition of myo-inositol transport has been shown to cause acute renal failure in rats [62]. Furthermore, it has recently been shown through urine metabolomics profiling of humans that increased levels of myo-inositol are significantly associated with kidney disease and inversely proportional to eGFR [63]. It has also been shown to be elevated in the plasma metabolomic profiles of patients with end-stage renal disease [50,61].…”

Section: Discussionmentioning

confidence: 99%

“…In looking at known perturbations in gene expression levels in AR [14] we observed that the sodium-myo-inositol transporter (SMIT), encoded by SLC5A3, is located in the thick ascending limb and functions to reabsorb myo-inositol into the renal medullary cells under conditions of hypertonicity [64]. Thus, perturbations of this transporter may be a key mechanism for acute rejection related tissue injury, mediated by hyperosmolar stress [63]. Given that patients with AR may have preserved kidney graft function and stable serum creatinine levels, the utility of this biomarker may be confounded given its correlation with eGFR.…”

Section: Discussionmentioning

confidence: 99%

Targeted Urine Metabolomics for Monitoring Renal Allograft Injury and Immunosuppression in Pediatric Patients

Sigdel

Schroeder

Yang

et al. 2020

JCM

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Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related to non-immune and immune injuries can cause slow deterioration and premature failure of organ transplants. Diagnosis of these injuries by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially in pediatric cohorts. We investigated the metabolomic profiles of biopsy matched urine samples from 310 unique kidney transplant recipients using gas chromatography–mass spectrometry (GC-MS). Focused metabolite panels were identified that could detect biopsy confirmed acute rejection with 92.9% sensitivity and 96.3% specificity (11 metabolites) and could differentiate BK viral nephritis (BKVN) from acute rejection with 88.9% sensitivity and 94.8% specificity (4 metabolites). Overall, targeted metabolomic analyses of biopsy-matched urine samples enabled the generation of refined metabolite panels that non-invasively detect graft injury phenotypes with high confidence. These urine biomarkers can be rapidly assessed for non-invasive diagnosis of specific transplant injuries, opening the window for precision transplant medicine.

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Increased urinary osmolyte excretion indicates chronic kidney disease severity and progression rate

Cited by 49 publications

References 47 publications

Urinary metabolites associate with the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease

Urinary metabolites associate with the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease

Chronodisruption: A Poorly Recognized Feature of CKD

Targeted Urine Metabolomics for Monitoring Renal Allograft Injury and Immunosuppression in Pediatric Patients

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