Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression

Hsu, Chi-yuan; Xie, Dawei; Waikar, Sushrut S.; Bonventre, Joseph V.; Zhang, Xiaoming; Sabbisetti, Venkata; Mifflin, Theodore E.; Coresh, Josef; Diamantidis, Clarissa J.; He, Jiang; Lora, Claudia M.; Miller, Edgar R.; Nelson, Robert G.; Ojo, Akinlolu; Rahman, Mahboob; Schelling, Jeffrey R.; Wilson, F. Perry; Kimmel, Paul L.; Feldman, Harold I.; Vasan, Ramachandran S.; Liu, Kathleen D.; Appel, Lawrence J.; Go, Alan S.; Kusek, John W.; Lash, James P.; Townsend, Raymond R.

doi:10.1016/j.kint.2016.09.003

Cited by 85 publications

(80 citation statements)

References 73 publications

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“…1,2 Although a variety of novel urinary biomarkers of tubular injury, including neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and renal liver-type fatty acid binding protein, have been proposed to improve the accuracy of predicting the development of CKD, they have not been found to improve predictive models of CKD based on traditional laboratory tests in adults. 8,9 …”

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confidence: 99%

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

et al. 2017

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Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

et al. 2017

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“…7 Previous studies have shown associations between biomarkers of tubular injury, such as NGAL and kidney injury molecule-1, and loss of kidney function in patients with CKD, but their clinical usefulness has been challenged. [26][27][28] In the prospective Chronic Renal Insufficiency Cohort Study of 2466 patients with CKD with various etiologies and at different CKD stages, neither kidney injury molecule-1 nor NGAL were independently associated with the rate of disease progression, and none of the biomarkers tested improved the risk prediction in comparison with a clinical model that included eGFR and the urinary albumin-to-creatinine ratio. 26 Additionally, suPAR, which has been recently shown to be associated with eGFR loss during a longer time period (i.e., 1337 days), did not predict short-term decline of eGFR in our study.…”

Section: Discussionmentioning

confidence: 99%

Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss

Zewinger

Rauen

Rudnicki

et al. 2018

JASN

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Background The individual course of CKD may vary, and improved methods for identifying which patients will experience short-term eGFR loss are needed. Assessing urinary Dickkopf-3 (DKK3), a stress-induced tubular epithelia-derived profibrotic glycoprotein, may provide information about ongoing tubulointerstitial fibrosis and short-term eGFR loss.Methods To investigate urinary DKK3's potential as a biomarker of short-term eGFR loss (over 12 months), we prospectively assessed eGFR and urinary DKK3 levels in patients with CKD of various etiologies at baseline and annual follow-ups. We also measured urinary DKK3 in a general population sample and patients with diagnostic kidney biopsies or IgA nephropathy under treatment.Results Median urinary DKK3-to-creatinine concentration at baseline was significantly higher in patients with CKD than the general population sample (431 versus 33 pg/mg). In the CKD cohort, having a urinary DKK3-to-creatinine level .4000 pg/mg was independently and significantly associated after multiple adjustments with mean annual decline in eGFR of 7.6% over 12 months. Urinary DKK3 significantly improved prediction of kidney function decline compared with eGFR or albuminuria alone. Urinary DKK3-tocreatinine levels were related to the extent of tubulointerstitial fibrosis in kidney biopsies. In patients with IgA nephropathy, a rise in urinary DKK3 was associated with significant eGFR decline within 6 months, whereas stable or decreasing urinary DKK3 indicated a more favorable course.Conclusions Urinary DKK3 levels identify patients at high risk for eGFR decline over the next 12 months regardless of the cause of kidney injury and beyond established biomarkers, potentially providing a tool to monitor CKD progression and assess effects of interventions.

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“…Several reports of both blood and urine biomarkers have shown correlations with acute or chronic kidney injury in the general population . Proteins such as albumin, kidney injury molecule‐1, neutrophil gelatinase‐associated lipocalin, and β‐2 microglobulin, are associated with future GFR deterioration, but mainly in patients with abnormal baseline renal function.…”

Section: Discussionmentioning

confidence: 99%

Discovery and Validation of a Biomarker Model (PRESERVE) Predictive of Renal Outcomes After Liver Transplantation

Levitsky¹,

Asrani

Klintmalm

et al. 2020

Hepatology

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BaCKgRoUND aND aIMS:A high proportion of patients develop chronic kidney disease (CKD) after liver transplantation (LT). We aimed to develop clinical/protein models to predict future glomerular filtration rate (GFR) deterioration in this population. appRoaCH aND ReSUltS: In independent multicenter discovery (CTOT14) and single-center validation (BUMC) cohorts, we analyzed kidney injury proteins in serum/plasma samples at month 3 after LT in recipients with preserved GFR who demonstrated subsequent GFR deterioration versus preservation by year 1 and year 5 in the BUMC cohort. In CTOT14, we also examined correlations between serial protein levels and GFR over the first year. A month 3 predictive model was constructed from clinical and protein level variables using the CTOT14 cohort (n = 60). Levels of β-2 microglobulin and CD40 antigen and presence of hepatitis C virus (HCV) infection predicted early (year 1) GFR deterioration (area under the curve [AUC], 0.814). We observed excellent validation of this model (AUC, 0.801) in the BUMC cohort (n = 50) who had both early and late (year 5) GFR deterioration. At an optimal threshold, the model had the following performance characteristics in CTOT14 and BUMC, respectively: accuracy (0.75, 0.8), sensitivity (0.71, 0.67), specificity (0.78, 0.88), positive predictive value (0.74, 0.75), and negative predictive value (0.76, 0.82). In the serial CTOT14 analysis, several proteins, including β-2 microglobulin and CD40, correlated with GFR changes over the first year. CoNClUSIoNS:We have validated a clinical/protein model (PRESERVE) that early after LT can predict future renal deterioration versus preservation with high accuracy. This model may help select recipients at higher risk for subsequent CKD for early, proactive renal sparing strategies. (Hepatology

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Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression

Cited by 85 publications

References 73 publications

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss

Discovery and Validation of a Biomarker Model (PRESERVE) Predictive of Renal Outcomes After Liver Transplantation

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