Tamm-Horsfall protein excretion to predict the onset of renal insufficiency

Romero, María Cristina; Zanaro, Noemí Luján; González, Liliana Pernía; Trigo, Pedro; Imventarza, Oscar; Nesse, Alcira

doi:10.1016/s0009-9120(02)00274-6

Cited by 17 publications

(17 citation statements)

References 14 publications

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“…Decreased UMOD concentrations have predicted development of renal failure in diabetes mellitus type 1 [14] and onset of renal insufficiency after liver transplantation [15], whereas other studies have shown that elevated UMOD levels are associated with development of CKD in the general population [16]. The discrepancies between the above studies and our current data might well be due to differences in the extent of renal damage in the different populations and in differences in modifying factors.…”

Section: Discussioncontrasting

confidence: 74%

“…Our data, however, suggest the possibility of a different explanation for the discrepancies, namely a bimodal association that can mimic a positive or a negative association, as well as the lack of an association when the study population is relatively small or contains only a limited range of renal function or UMOD excretion. Our study provides the largest population so far with data on the prognostic impact of UMOD; the number of subjects in other studies have ranged between 34 [15] and 200 [16,23], usually in a case-control design. Thus, it may have been the larger power and the prospective cohort design that allow the identification of the bimodal association pattern.…”

Section: Discussionmentioning

confidence: 99%

“…Decreased UMOD concentrations predict development of renal failure within 20 years in diabetes mellitus type I [14] and onset of renal insufficiency immediately after liver transplantation [15]. In contrast, recent data showed elevated urinary UMOD levels are associated with progressive renal function decline and increased risk for CKD in the general population [16].…”

Section: Introductionmentioning

confidence: 99%

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Uromodulin in Renal Transplant Recipients: Elevated Urinary Levels and Bimodal Association with Graft Failure

Reznichenko¹,

Dijk²,

Heide

et al. 2011

Am J Nephrol

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Background: Urinary uromodulin (UMOD) predicts renal prognosis in native kidneys, but data are conflicting. We investigated its prognostic impact for graft failure (GF) in renal transplant recipients (RTR; n = 600). Methods: UMOD concentration was measured cross-sectionally in RTR at 6.0 years [2.6–11.4] post-transplant, in matched patients with native chronic kidney disease (CKD) and healthy subjects. In 59 cases, RTR allograft biopsies were reviewed. Results: During a follow-up of 5.3 years [4.5–5.7], GF had occurred in 7% of RTR. Median UMOD excretion (mg/24 h) was 20.4 in RTR, 11.6 in CKD and 5.7 in controls (p < 0.001). There was a curvilinear association between UMOD excretion and baseline renal function (p < 0.003) and death-censored GF, with 5.5, 11.5 and 4.0% of the cases in subsequent UMOD excretion tertiles, respectively (p = 0.002). On multivariate Cox regression analysis, hazard ratios for GF for the 1st and 3rd tertiles were 0.37 (p = 0.01) and 0.21 (p = 0.001), respectively. Interstitial fibrosis and tubular atrophy were more severe in the middle tertile (p = 0.007). Conclusions: Urinary UMOD is elevated in RTR and associated with graft function, morphology and outcome in a bimodal fashion. Dissection of the disparate mechanisms of GF prediction by urinary UMOD might provide new clues for its alleged pathogenetic significance in progressive renal function loss.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Uromodulin in Renal Transplant Recipients: Elevated Urinary Levels and Bimodal Association with Graft Failure

Reznichenko¹,

Dijk²,

Heide

et al. 2011

Am J Nephrol

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“…If the par ticles size attained 1 µm and higher, this was an evi dence of high USD probability. The THP concentra tion in urine was also determined by affinity chroma tography [48,49] as well as by HPLC with fluorescence detection [50]. It was found that the ratio The main current trends in the determination of USD markers are summarized in Table 2.…”

Section: (5)mentioning

confidence: 99%

Determination of markers of the urinary stone disease

Yaroshenko

Карцова

2015

J Anal Chem

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546Urinary stone disease (USD) is a metabolic disor der characterized by the formation of concrements (from Latin concrementum, aggregate, union), i.e., heavy masses in kidney and organs of urinary system [1]. The history of the study of USD markers is very long [2], and the interest to this problem keeps steadily growing (Fig. 1). The major publications dealing with various aspects of USD fall to the highly specialized medical journals, such as Journal of Urology, Urology, and European Urology Supplements. The variety of scientific editions on the given problem underlines its urgency (Fig. 2).Almost 40% of urological diseases belong to USD and a trend to its growth is observed [1, 2]. The mech anism of the stone formation process was discussed in [3]. For quite a long time USD can proceed asymp tomatically. The emergence of USD at the early stage can be revealed using biochemical urine analysis [3][4][5]. Urine is a solution of a complex composition because of the elevated salt background and the pres Abstract-The capabilities of physicochemical methods (chromatographic, electrophoretic, potentiometric, and voltammetric) and also field test methods for the determination of the main markers of the urinary stone disease have been considered. The effect of various factors on the processes of stone formation has been dis cussed.

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“…[27] In liver transplant patients, patients with the lowest pre-surgical urinary THP concentrations were the ones who developed renal insufficiency post-surgically. [28] In renal transplant patients, THP urinary concentrations were significantly lower in patients that developed acute renal rejections compared to individuals with stable kidney grafts. [29]…”

Section: Introductionmentioning

confidence: 99%

Human Tamm-Horsfall protein, a renal specific protein, serves as a cofactor in complement 3b degradation

Rhodes

2017

PLoS ONE

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Tamm-Horsfall protein (THP) is an abundant urinary protein of renal origin. We hypothesize that THP can act as an inhibitor of complement since THP binds complement 1q (C1q) of the classical complement pathway, inhibits activation of this pathway, and is important in decreasing renal ischemia-reperfusion injury (a complement-mediated condition). In this study, we began to investigate whether THP interacted with the alternate complement pathway via complement factor H (CFH). THP was shown to bind CFH using ligand blots and in an ELISA (KD of 1 × 10−6 M). Next, the ability of THP to alter CFH’s normal action as it functioned as a cofactor in complement factor I (CFI)–mediated complement 3b (C3b) degradation was investigated. Unexpectedly, control experiments in these in vitro assays suggested that THP, without added CFH, could act as a cofactor in CFI-mediated C3b degradation. This cofactor activity was present equally in THP isolated from 10 different individuals. While an ELISA demonstrated small amounts of CFH contaminating THP samples, these CFH amounts were insufficient to explain the degree of cofactor activity present in THP. An ELISA demonstrated that THP directly bound C3b (KD ~ 5 × 10−8 m), a prerequisite for a protein acting as a C3b degradation cofactor. The cofactor activity of THP likely resides in the protein portion of THP since partially deglycosylated THP still retained cofactor activity. In conclusion, THP appears to participate directly in complement inactivation by its ability to act as a cofactor for C3b degradation, thus adding support to the hypothesis that THP might act as an endogenous urinary tract inhibitor of complement.

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Tamm-Horsfall protein excretion to predict the onset of renal insufficiency

Cited by 17 publications

References 14 publications

Uromodulin in Renal Transplant Recipients: Elevated Urinary Levels and Bimodal Association with Graft Failure

Uromodulin in Renal Transplant Recipients: Elevated Urinary Levels and Bimodal Association with Graft Failure

Determination of markers of the urinary stone disease

Human Tamm-Horsfall protein, a renal specific protein, serves as a cofactor in complement 3b degradation

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