Urinary retinol binding protein predicts renal outcome in systemic immunoglobulin light‐chain (AL) amyloidosis

Rezk, Tamer; Salota, Rashim; Gan, Jaslyn; Lachmann, Helen; Fontana, Marianna; Siew, Keith; Martinez‐Naharro, Ana; Guillotte, Christianne; Bass, Paul; Sachchithanantham, Sajitha; Mahmood, Shameem; Petrie, Aviva; Whelan, Carol; Pinney, Jennifer H.; Dockrell, Mark; Foard, Darren; Lane, Thirusha; Wechalekar, Ashutosh; Hawkins, Philip N.; Walsh, Stephen B.; Gillmore, Julian D.

doi:10.1111/bjh.17706

Cited by 3 publications

(2 citation statements)

References 17 publications

(33 reference statements)

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“…In fact the amyloid score correlated well with renal outcome in an independent cohort [ 4 ]. Recently, a large prospective study confirmed that an elevated urinary retinol-binding protein level, indicating proximal tubule cell dysfunction, is a good predictor of renal outcome in LA, independent of estimated glomerular filtration rate (eGFR), urinary protein-to-creatinine ratio (uPCR), and clonal response [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

et al. 2023

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In light chain amyloidosis (LA), the massive glomerular and vascular amyloid deposition leading to interstitial fibrosis/tubular atrophy (IFTA) is thought to be responsible for renal failure. The amyloid deposition in the interstitium and the tubular basement membrane (TBM) has received less attention in the study of LA. We, therefore, collected clinical and laboratory data on patients diagnosed with LA in our Nephrology Department and studied amyloid deposition in the TBM. Twelve LA patients were diagnosed by renal biopsy during a seven-year period. In 4 of the 12, amyloid deposition could also be detected in the TBM. In our first case of a patient with diabetes mellitus, non-amyloid fibrils resembling ‘diabetic fibrillosis’ were also seen by electron microscopy. Despite the double damage, IFTA was negligible, blood vessels were unaffected, and the glomerular deposition was segmental. In the other three cases, significant (>50%) IFTA and a severely reduced estimated glomerular filtration rate were already detected at the time of diagnosis and amyloid deposition was also observed in the blood vessels. These findings indicate the importance of TBM amyloid deposition in the progression of renal disease. This may represent a late-stage presentation of the disease with a heavy LC burden.

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Section: Introductionmentioning

confidence: 99%

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

et al. 2023

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“…Retinol-binding Protein (RBP), discovered by Berggard in 1961 in immunoelectrophoresis, can be filtered through the glomeruli, most of which is reabsorbed by proximal renal tubular epithelial cells, and only a small amount is excreted from the urine. Urinary retinol-binding protein is an indicator of early renal tubular injury in patients with multiple myeloma ( Rezk et al, 2021 ). Meanwhile, URBP excretion was found to be increased in diabetic patients compared with healthy subjects and correlated with 24-hour urinary protein and serum creatinine.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of α1-MG and URBP in early diabetic renal impairment

Zhou,

Zhang,

Chen

et al. 2023

Front. Physiol.

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Aims/Introduction: Diabetic kidney disease (DKD) is defined as diabetes with impaired renal function, elevated urinary albumin excretion, or both. DKD is one of the most common microvascular complications of diabetes and plays an important role in the cause of end-stage renal disease (ESRD). About 5% of people with type 2 diabetes (T2DM) already have kidney damage at the time they are diagnosed, but other triggers of renal insufficiency, such as obesity, hyperlipidemia, glomerular atherosclerosis are often present, making it difficult to define “diabetic kidney disease” or “diabetic nephropathy” precisely in epidemiology or clinical practice. Therefore, the aim of this study is to identify diabetic patients with CKD at an early stage, and evaluate the value of tubular injury markers including α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), N-acetyl-beta-D-glucosaminidase (NAG) and Urinary retinol binding protein (URBP) in the development of diabetes to DKD.Materials and methods: We recruited a total of 182 hospitalized patients with T2DM in the First Affiliated Hospital of Zhengzhou University from February 2018 to April 2023. We collected basic clinical characteristics and laboratory biochemical parameters of the patients. Based on their levels of urinary albumin creatinine ratio (UACR) and glomerular filtration rate (GFR), patients were divided into DM group (UACR≤30 mg/g and eGFR≥90 mL/min/1.73 m2, n = 63) and DKD group (UACR>30 mg/g or eGFR<90 mL/min/1.73 m2, n = 119) excluding other causes of chronic kidney disease. We further developed diagnostic models to improve the ability to predict the risk of developing DKD by screening potential risk factors using univariate and multivariate logistic regression analysis. Calibration plots and curve analysis were used to validate the model and clinical usefulness. Next, we screened patients with relatively normal estimated glomerular filtration rate (eGFR) (≥90 mL/min/1.73 m2) to investigate whether tubular injury markers could accurately predict the risk of DKD in patients with normal renal function. We defined the rate of GFR decline as a prognostic indicator of renal function in patients and collected the information of the re-hospitalized DKD patients to determine whether the relevant indicators had an impact on the renal prognosis.Results: The patients with DKD had higher levels of tubular injury markers than patients with DM. URBP, α1-MG, eGFR were statistically different in both univariate and multivariate logistic regression analyses and displayed great predictive power after modeling with an area under curve of 0.987. The calibration curve showed medium agreement. Decision curve showed it would add more net benefits for clinical decision. After adjusting eGFR and serum creatinine (Scr), URBP was demonstrated to be associated with early renal function impairment.Conclusion: Tubular injury markers play an important role in early diabetic renal function impairment.

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Bad players in AL amyloidosis in the current era of treatment

Kreiniz

Gertz

2023

Expert Review of Hematology

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Urinary retinol binding protein predicts renal outcome in systemic immunoglobulin light‐chain (AL) amyloidosis

Cited by 3 publications

References 17 publications

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

Diagnostic value of α1-MG and URBP in early diabetic renal impairment

Bad players in AL amyloidosis in the current era of treatment

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