Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy

Nielsen, Stine E.; Andersen, Steen; Zdunek, Dietmar; Heß, Georg; Parving, Hans‐Henrik; Rossing, Peter

doi:10.1038/ki.2010.554

Cited by 94 publications

(79 citation statements)

References 23 publications

(34 reference statements)

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“…Two small studies of 63 and 124 patients evaluated KIM-1 in urine and plasma in regard to DN progression in type 1 diabetes, but the data were contradictory (17,35). Another study in type 2 diabetes showed that KIM-1 predicted the decline of eGFR in unadjusted analysis but not progression to macroalbuminuria, whereas progression to ESRD was not evaluated (16). Therefore, our finding that KIM-1 did not predict progression to ESRD in macroalbuminuric patients with type 1 diabetes independently of AER is important.…”

Section: Discussionmentioning

confidence: 58%

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Kidney Injury Molecule-1 and the Loss of Kidney Function in Diabetic Nephropathy: A Likely Causal Link in Patients With Type 1 Diabetes

et al. 2015

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OBJECTIVEWe evaluated the predictive value and clinical benefit of urinary kidney injury molecule (KIM)-1 for progression of diabetic nephropathy (DN) in type 1 diabetes. We also investigated its causal role for the decrease of estimated glomerular filtration rate (eGFR) by a Mendelian randomization (MR) approach. RESEARCH DESIGN AND METHODSWe followed 1,573 patients with type 1 diabetes for 6 years. KIM-1 was measured at baseline and normalized with urinary creatinine. KIM-1 predictive value was evaluated by Cox regression, while its added predictive benefit was evaluated using a panel of statistical indexes. The causality for the loss of renal function was evaluated with MR, utilizing the top signal from our genome-wide association study (GWAS) as the instrumental variable. RESULTSKIM-1 was not an independent predictor of progression of DN when adjusted for albumin excretion rate (AER) and added no prognostic benefit to AER or eGFR. In multiple regressions, KIM-1 was associated with lower eGFR independently of diabetes duration (b = 24.066; P < 0.0001) but not of AER. In our GWAS, rs2036402 in the KIM1 gene was strongly associated with KIM-1 (b = 20.51; P = 6.5 3 10 238 ). In the MR, KIM-1 was associated with lower eGFR, independently of diabetes duration and AER (b = 25.044; P = 0.040), suggesting a causal relationship. CONCLUSIONSKIM-1 did not predict progression to end-stage renal disease independently of AER and added no prognostic benefit to current biomarkers. Nevertheless, the MR showed that the inverse association of increased KIM-1 levels with lower eGFR is likely to represent a causal link.Diabetic nephropathy (DN) is a serious diabetes complication that may progress to end-stage renal disease (ESRD) and is associated with a high risk of premature death (1,2). DN screening is based on albumin excretion rate (AER) or estimated glomerular filtration rate (eGFR) that mainly reflect the glomerular damage. However, tubular damage may also play an important role in DN, and urinary biomarkers of tubular injury are already available (3-5).

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Section: Discussionmentioning

confidence: 58%

“…Human studies confirmed KIM-1 as a biomarker of acute kidney injury or chronic kidney diseases (CKD) (11,15). Its predictive value for DN was studied, but data are contradictory (16)(17)(18)(19). Furthermore, its potential causality regarding the loss of renal function has not been studied in patients with type 1 diabetes.…”

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confidence: 99%

Kidney Injury Molecule-1 and the Loss of Kidney Function in Diabetic Nephropathy: A Likely Causal Link in Patients With Type 1 Diabetes

et al. 2015

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“…High u-LFABP level was considered a risk factor for the progression of DN (adjusted HR 7.285, 95% CI 2.425 -21.883, P < 0.0001), suggesting its ability as an early screening tool as well as predictor of DN [61]. Although these findings introduce u-LFABP, a urinary marker of tubular inflammation, as a supplement to albuminuria in predicting DN development in both type 1 and type 2 diabetic patients, other studies produced contradicting results [62]. Additional studies are needed to clarify the overall predictive role of combining both tubular and glomerular markers.…”

Section: Urinary Markersmentioning

confidence: 49%

Predictors of diabetic nephropathy

Gaballa

Farag

2013

Open Medicine

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AbstractDiabetic nephropathy (DN) is a leading cause of morbidity and mortality in diabetic patients representing a huge health and economic burden. Alarming recent data described diabetes as an unprecedented worldwide epidemic, with a prevalence of ∼6.4% of the world population in 2010, while the prevalence of CKD among diabetics was approximately 40%. With a clinical field hungry for novel markers predicting DN, several clinical and laboratory markers were identified lately with the promise of reliable DN prediction. Among those are age, gender, hypertension, smoking, sex hormones and anemia. In addition, eccentric left ventricular geometric patterns, detected by echocardiography, and renal hypertrophy, revealed by ultrasonography, are promising new markers predicting DN development. Serum and urinary markers are still invaluable elements, including serum uric acid, microalbuminuria, macroalbuminuria, urinary liver-type fatty acid-binding protein (u-LFABP), and urinary nephrin. Moreover, studies have illustrated a tight relationship between obstructive sleep apnea and the development of DN. The purpose of this review is to present the latest advances in identifying promising predictors to DN, which will help guide the future research questions in this field. Aiming at limiting this paramount threat, further efforts are necessary to identify and control independent modifiable risk factors, while developing an integrative algorithm for utilization in DN future screening programs.

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“…Increased urinary NGAL levels in type II diabetic patients with low glomerular hyperfiltration than the normal GFR and control groups were reported by Fu et al 13 However, some studies have shown conflicting results concerning the correlation between increased tubular markers, including urinary NGAL, and disease progression in diabetic patients. Nielsen et al 29 reported a lack of an independent correlation between these biomarkers and GFR in type I diabetic patients with overt nephropathy.…”

Section: Discussionmentioning

confidence: 99%