Serum uromodulin is inversely associated with the metabolic syndrome in the KORA F4 study

Abstract

Objective Metabolic syndrome and obesity are risk factors for chronic kidney disease. However, early kidney alterations may escape diagnosis in these conditions due to glomerular hyperfiltration. Uromodulin, a glycoprotein exclusively synthesized in tubular cells of the thick ascending limb of Henle's loop, is a novel tissue-specific biomarker for kidney function. In contrast to the commonly used markers creatinine and cystatin C, serum uromodulin does not primarily depend on glomerular filtration. We hypothesized that serum uromodulin is a marker for metabolic syndrome and related components. Design The analyses included 1088 participants of the population-based KORA F4 study aged 62–81 years. Metabolic syndrome was present in 554 participants. After a mean follow-up time of 6.5 years, 621 participants were reevaluated, of which 92 had developed incident metabolic syndrome. Methods The association of serum uromodulin with metabolic syndrome and its components were assessed using multivariable logistic regression models. Results Serum uromodulin was inversely associated with metabolic syndrome after adjustment for sex, age, estimated glomerular filtration rate, physical activity, smoking, alcohol consumption and high-sensitivity C-reactive protein (OR 0.65; 95% CI 0.56–0.76 per standard deviation uromodulin; P < 0.001). Serum uromodulin was inversely associated with all single components of metabolic syndrome. However, serum uromodulin was not associated with new-onset metabolic syndrome after the follow-up period of 6.5 ± 0.3 years (OR 1.18; 95% CI 0.86–1.60). Conclusions Serum uromodulin is independently associated with prevalent, but not with incident metabolic syndrome. Low serum uromodulin may indicate a decreased renal reserve in the metabolic syndrome.

Serum uromodulin is inversely associated with arterial hypertension and the vasoconstrictive prohormone CT-proET-1 in the population-based KORA F4 study

“…Continuous variables were transformed to a Gaussian distribution by the probability integral transformation followed by an inverse transform sampling and were used as in calculations per one standard deviation. In logistic and linear regression analyses, the association of sUmod with the respective dependent variables was adjusted for covariates in 5 models ( model 1 : sex, age (which are both related to hypertension and have been shown to be associated with sUmod [ 18 ]); model 2 : model 1 plus eGFR (which was decreased in hypertensive participants and is strongly related to sUmod [ 12 ]); model 3 : model 2 plus BMI (which is associated with sUmod [ 20 ]), fasting glucose (associated with sUmod [ 18 ]), current smoking, previous stroke and myocardial infarction; model 4 : model 3 plus arterial hypertension; model 5 : model 4 plus use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, since these medications might influence the renin-aldosterone-angiotensin system). Model 1 and 2 were applied for all analyses, model 3 for the assessment of arterial hypertension, model 4 for CT-proET-1 and model 5 for renin and aldosterone as dependent variables.…”

“…The physiological role of uromodulin in the systemic circulation is still unknown. However, sUmod seems to play an important role beyond renal homeostasis, since it is inversely associated with all-cause and cardiovascular mortality [ 14 – 17 ] and with various cardiovascular risk factors, such as diabetes [ 18 , 19 ], the metabolic syndrome and its single components including elevated blood pressure [ 20 ]. In contrast, genome-wide association studies [ 21 – 24 ] and animal models [ 25 , 26 ] show an increased risk of arterial hypertension in uromodulin-increasing UMOD loci variants, and uromodulin has even been suggested to be a possible target for blood pressure control [ 26 ].…”

Serum Level of Uromodulin as an Early Predictor Marker of Kidney Disorders

“…However, creatinine and urea levels that related to filtration capacity of the kidney showed minor improvement. In this text, the mean value of the creatinine/uromodulin ratio decreased after intervention in both groups and reached significant difference for participants who consumed Barley Talbina supplement, Then et al [12] said that metabolic factors may negatively influence sUMOD levels, indicating that the metabolic syndrome may impair tubular integrity and protein synthesis. Recently, Scheurlen et al described an increment of sUMOD concentration in patients with extreme obesity after Roux-en-Y-gastric bypass, demonstrating improved "kidney functions" or renal reserve after bariatric surgery, which was not distinguishable by conventional kidney function markers [38].…”

“…Uromodulin Tamm-Horsfall protein, a glycoprotein only blended in cylindrical cells of the thick rising appendage of Henle's circle, is a novel tissue-explicit biomarker for kidney work. As opposed to the normally utilized markers creatinine and cystatin C, sUMOD does not fundamentally rely upon glomerular filtration [12]. sUMOD is a novel delicate kidney-explicit biomarker connected to the auxiliary respectability of the distal nephron and to renal capacity [13].…”

Association of uromodulin with acute kidney injury in patients undergoing cardiac surgery

“…Despite the fact that clinical use in particular types of kidney dysfunction still requires further and more accurate development, the current state of knowledge shows THP to be a very valuable tool that could complement traditional renal parameters. Associations between protein concentration and individual metabolic syndrome parameters were also described, as well as the use in estimating the risk of mortality among patients with cardiovascular diseases [ 9 , 10 ].…”