Diurnal and Long-term Variation in Plasma Concentrations and Renal Clearances of Circulating Markers of Kidney Proximal Tubular Secretion

Rivara, Matthew B.; Zelnick, Leila R.; Hoofnagle, Andrew N.; Newitt, Rick; Tracy, Russell P.; Kratz, Mario; Weigle, David S.; Kestenbaum, Bryan

doi:10.1373/clinchem.2016.260117

Cited by 18 publications

(25 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the adjustment for kidney function in regression models using estimated GFR as a proxy an effect of altered kidney function could not be ruled out entirely. Diminished tubular secretion in obese subjects, which is not necessarily directly related to the GFR 48,49 , of hippurate and cinnamoylglycine might have accounted for our findings independent of gut microbial metabolism 49 . Figure 3.…”

Section: Scientific Reports |mentioning

confidence: 74%

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population

Otto

Budde

Kastenmüller

et al. 2020

Sci Rep

View full text Add to dashboard Cite

obesity is one of the major risk factor for cardiovascular and metabolic diseases. A disproportional accumulation of fat at visceral (VAt) compared to subcutaneous sites (SAt) has been suspected as a key detrimental event. We used non-targeted metabolomics profiling to reveal metabolic pathways associated with higher VAt or SAt amount among subjects free of metabolic diseases to identify possible contributing metabolic pathways. The study population comprised 491 subjects [mean (standard deviation): age 44.6 yrs (13.0), body mass index 25.4 kg/m² (3.6), 60.1% females] without diabetes, hypertension, dyslipidemia, the metabolic syndrome or impaired renal function. We associated MRi-derived fat amounts with mass spectrometry-derived metabolites in plasma and urine using linear regression models adjusting for major confounders. We tested for sex-specific effects using interactions terms and performed sensitivity analyses for the influence of insulin resistance on the results. VAT and SAT were significantly associated with 155 (101 urine) and 49 (29 urine) metabolites, respectively, of which 45 (27 urine) were common to both. Major metabolic pathways were branched-chain amino acid metabolism (partially independent of insulin resistance), surrogate markers of oxidative stress and gut microbial diversity, and cortisol metabolism. We observed a novel positive association between VAt and plasma levels of the potential pharmacological agent piperine. Sex-specific effects were only a few, e.g. the female-specific association between VAT and O-methylascorbate. In brief, higher VAT was associated with an unfavorable metabolite profile in a sample of healthy, mostly non-obese individuals from the general population and only few sex-specific associations became apparent. equal amount of unknown compounds showed significant associations with VAT, including those related to either cortisol or piperine in the derived metabolic network (Fig. 3).Plasma and urine metabolites associated with SAT. Almost all association between SAT and metabolites were already described for VAT. Within each fluid, only two significant observations were unique to SAT (Figs. 1 and 2). Cortisol (inversely) and N1-methyl-2-pyridone-5-carboxamide (positively) levels in plasma as well as 3′-sialyllactose and the unknown compound X-12840 (both positively) levels in urine associated with SAT.

show abstract

Section: Scientific Reports |mentioning

confidence: 74%

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population

Otto

Budde

Kastenmüller

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Is it possible that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger at lower GFR among patients with CKD? These questions are pertinent in the context of renewed recent interest in renal tubular function [27][28][29]. Better understanding of tubular secretion as an independent marker of kidney function may provide insight into kidney disease pathophysiology and improve prediction of adverse outcomes [27].…”

Section: Discussionmentioning

confidence: 99%

Tubular secretion of creatinine and kidney function: an observational study

et al. 2020

View full text Add to dashboard Cite

Background: Prior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). A recent cross-sectional study suggested that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger when GFR is lower among patients with chronic kidney disease (CKD); but there have been no validation of this in other cohorts. Methods: To fill these gaps in knowledge regarding the relation between CrCl and GFR, we conducted crosssectional and longitudinal analysis of the Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK); and cross-sectional analysis of a clinical dataset from the Mayo Clinic of four different patient populations (CKD patients, kidney transplant recipients, post kidney donation subgroup and potential kidney donors). In the cross-sectional analyses (MDRD, AASK and Mayo Clinic cohort), we examined the relation between the CrCl/iothalamate GFR (iGFR) ratio at different categories of iGFR or different levels of CrCl. In the MDRD and AASK longitudinal analyses, we studied how the CrCl/iGFR ratio changed with those who had improvement in iGFR (CrCl) over time versus those who had worsening of iGFR (CrCl) over time. Results: Observed CrCl/iGFR ratios were generally on the lower end of the range reported in the literature for CKD (median 1.24 in MDRD, 1.13 in AASK and 1.25 in Mayo Clinic cohort). Among CKD patients in whom CrCl and iGFR were measured using different timed urine collections, CrCl/iGFR ratio were higher with lower iGFR categories but lower with lower CrCl categories. However, among CKD patients in whom CrCl and iGFR were measured using the same timed urine collections (which reduces dis-concordant measurement error), CrCl/iGFR ratio were higher with both lower iGFR categories and lower CrCl categories. Conclusions: These data refute the recent suggestion that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio increases as GFR decreases in CKD patients. They also highlight the lack of certainty in our knowledge with regard to how much CrCl actually overestimates GFR.

show abstract

“…Diurnal variation in solute levels, which may be occasioned by food intake, has been observed for several of the secreted solutes. 38 Such variation would cause error in residual clearance values calculated from the solute recovery in interdialytic urine collections and post-and pre-treatment plasma concentrations, with the magnitude of the error potentially greater with higher residual solute clearances.…”

Section: Discussionmentioning

confidence: 99%

Residual Function Effectively Controls Plasma Concentrations of Secreted Solutes in Patients on Twice Weekly Hemodialysis

Leong

Sao

Taussig

et al. 2018

JASN

View full text Add to dashboard Cite

Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis. We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and -cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis. Compared with anuric patients on thrice weekly dialysis with the same standard Kt/V, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and -cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations. Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.

show abstract

Diurnal and Long-term Variation in Plasma Concentrations and Renal Clearances of Circulating Markers of Kidney Proximal Tubular Secretion

Cited by 18 publications

References 36 publications

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population

Associations between adipose tissue volume and small molecules in plasma and urine among asymptomatic subjects from the general population

Tubular secretion of creatinine and kidney function: an observational study

Residual Function Effectively Controls Plasma Concentrations of Secreted Solutes in Patients on Twice Weekly Hemodialysis

Contact Info

Product

Resources

About