Utility of Spot Urine Specimens to Assess Tubular Secretion

Garimella, Pranav S.; Li, Kefeng; Naviaux, Jane C.; Shlipak, Michael G.; Abdelmalek, Joseph A.; Castro, E. Díez de; Capparelli, Edmund V.; Naviaux, Robert K.; Ix, Joachim H.

doi:10.1053/j.ajkd.2016.12.016

Cited by 9 publications

(10 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

Section: Discussionmentioning

confidence: 99%

Tubular secretion of creatinine and kidney function: an observational study

et al. 2020

View full text Add to dashboard Cite

show abstract

“…For example, isovalerylglycine and tiglylglycine are glycine conjugates that are metabolites of fatty acids. These 2 solutes have been shown to be not only filtered but also highly secreted, and spot blood and urine measurements perform well to estimate tubular secretion correlate compared with 24-hour tubular clearances ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Assessment of kidney proximal tubular secretion in critical illness

Bhatraju¹,

Chai²,

Sathe³

et al. 2021

JCI Insight

View full text Add to dashboard Cite

Background: Serum creatinine concentrations (SCr) are used to determine the presence and severity of acute kidney injury (AKI). SCr is primarily eliminated by glomerular filtration; however, most mechanisms of AKI in critical illness involve kidney proximal tubules, where tubular secretion occurs. Proximal tubular secretory clearance is not currently estimated in the ICU. Our objective was to estimate the kidney clearance of secretory solutes in critically ill adults. Methods:We collected matched blood and spot urine samples from 170 ICU patients and from a comparison group of 70 adults with normal kidney function. We measured seven endogenously produced secretory solutes using liquid chromatography-tandem mass spectrometry. We computed a composite secretion score incorporating all seven solutes, and evaluated associations with 28-day major adverse kidney events (MAKE28), defined as doubling of SCr, dialysis dependence, or death. Results:The urine/plasma ratio of six of seven secretory solutes were lower in critically ill patients compared with normal individuals after adjustment for SCr. The composite secretion score was moderately correlated with SCr and cystatin C (r = -0.51 and r = -0.53, respectively).Each standard deviation higher composite secretion score was associated with a 25% lower risk of MAKE28 (95% CI 9% -38% lower) independent of severity of illness, SCr and tubular injury markers. Higher urine to plasma ratios of individual secretory solutes isovalerylglycine and tiglylglycine were associated with MAKE28 after accounting for multiple testing.Conclusions: Among critically ill adults, tubular secretory clearance is associated with adverse outcomes and measurement could improve assessment of kidney function and dosing of essential ICU medications.

show abstract

“…Urea, the only other organic waste solute routinely measured, is passively reabsorbed by the kidney tubules. Thus, in relying on creatinine and urea, we may fail to detect impairment of the tubular secretory mechanisms by which the kidney removes a wide variety of waste solutes (1)(2)(3)(4).…”

Section: Discussionmentioning

confidence: 99%

“…The severity of kidney injury is most often assessed by measuring the plasma creatinine level, which serves as a surrogate for the GFR. Many waste solutes, however, are removed from the body through proximal tubular secretion (1)(2)(3)(4). This study tested whether renal clearances of secreted solutes decline in proportion to the GFR in AKI.…”

Section: Introductionmentioning

confidence: 99%

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury

et al. 2020

View full text Add to dashboard Cite

BackgroundImpairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI.MethodsFour endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls. Fractional clearance relative to creatinine was calculated to assess tubular secretion. Fractional clearance values were calculated in terms of the free, unbound levels of HIPP, IS, and PCS that bind to plasma proteins.ResultsFractional clearance values for PAG, HIPP, IS, and PCS were >1.0 in patients with AKI as well as controls, indicating that these solutes were still secreted by the tubules of the injured kidneys. Fractional clearance values were, however, significantly lower in patients with AKI than controls, indicating that kidney injury reduced tubular secretion more than glomerular filtration (AKI versus control: PAG, 2.1±0.7 versus 4.6±1.4, P<0.001; HIPP, 10±5 versus 15±7, P=0.02; IS, 10±6 versus 28±7, P<0.001; PCS, 3.3±1.8 versus 10±3, P<0.001). Free plasma levels rose out of proportion to total plasma levels for each of the bound solutes in AKI, so that calculating their fractional clearance in terms of their total plasma levels failed to reveal their impaired secretion.ConclusionsTubular secretion of organic solutes can be reduced out of proportion to glomerular filtration in AKI. Impaired secretion of protein-bound solutes may be more reliably detected when clearances are expressed in terms of their free, unbound levels in the plasma.

show abstract

Utility of Spot Urine Specimens to Assess Tubular Secretion

Cited by 9 publications

References 8 publications

Tubular secretion of creatinine and kidney function: an observational study

Tubular secretion of creatinine and kidney function: an observational study

Assessment of kidney proximal tubular secretion in critical illness

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury

Contact Info

Product

Resources

About