The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy

Cvetković, Tatjana; Vlahović, Predrag; Đorđević, Vesna; Zvezdanovic, Lilika; Pavlović, Dušica; Kocic, Gordana; Sokolović, Dušan

doi:10.2478/v10011-008-0019-y

Cited by 6 publications

(5 citation statements)

References 36 publications

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“…The urinary TBARS and RCD levels may refer to an oxidative damage occurring in the kidney ( 10 ). Previous studies as well indicated that renal transplant recipients had higher TBARS levels than healthy individuals ( 8 , 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

“…The protein oxidation level was monitored by a spec-trophotometric determination of carbonyl content by the method of Levine et al ( 13 ) using 2,4-dinitro-phenylhydrazine (DNPH) as a classic carbonyl reagent. Spectrophotometric measurement of reactive carbonyl derivates (RCD) values was performed and calculated using the extinction coefficient of DNPH-reactive carbonyl derivates at 370 nm and expressed as μmol/mmol creatinine ( 10 ). Urinary N-acetyl-β-d-glucosaminidase (NAG) activity was determined according to the method of Horak et al ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

“…Oxidative damage leads to the lipid peroxidation process, forming the end products, primarily malondialdehyde (MDA), which can react with thiobarbituric acid (TBA) and form thiobarbituric acid reactive substances (TBARS). Urinary levels of TBARS and reactive carbonyl derivates (RCD) were used as parameters of the renal oxidative injury, as well as tubular damage markers in different renal diseases, such as diabetic nephropathy ( 10 ). Also, increased urinary activities of tubular ectoenzymes, N-acetyl-β-D-glucosaminidase (NAG), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV) may be useful markers of proximal tubular injury ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacogenetics May Influence Tacrolimus Daily Dose, But Not Urinary Tubular Damage Markers In The Long-Term Period After Renal Transplantation

Stefanović¹,

Cvetković²,

Veličković‐Radovanović³

et al. 2015

Journal of Medical Biochemistry

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SummaryBackgroundThe primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients.MethodsThe study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-β-D-glucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage.ResultsThe carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with TT genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients’ genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes’ activities.ConclusionsOur findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug’s tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacogenetics May Influence Tacrolimus Daily Dose, But Not Urinary Tubular Damage Markers In The Long-Term Period After Renal Transplantation

Stefanović¹,

Cvetković²,

Veličković‐Radovanović³

et al. 2015

Journal of Medical Biochemistry

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“…Previous studies also showed that the monitoring of NAG urine activity is useful in the evaluation of early proximal tubule damage (31) and in predicting the long-term function of the transplanted kidneys recipients ( 32 , 33 ).…”

Section: Biomarkers After Organ Transplantation and Risk Managementmentioning

confidence: 99%

Current Biochemical Monitoring and Risk Management of Immunosuppressive Therapy after Transplantation

Catić‐Đorđević

Cvetković

Stefanović

et al. 2017

Journal of Medical Biochemistry

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SummaryImmunosuppressive drugs play a crucial role in the inhibition of immune reaction and prevention of graft rejection aswell as in the pharmacotherapy of autoimmune disorders. Effective immunosuppression should provide an adequate safety profile and improve treatment outcomes and the patients' quality of life. High-risk transplant recipients may be identified, but a definitive prediction model has still not been recognized. Therapeutic drug monitoring (TDM) for immunosuppressive drugs is an essential, but at the same time insufficient tool due to low predictability of drug exposition and marked pharmacokinetic variability. Parallel therapeutic, biochemical and clinical monitoring may successfully optimize and individualize therapy for transplanted recipients, providing optimal medical outcomes. Modern pharmacotherapy management should include new biomarkers with better sensitivity and specificity that can identify early cell damage. The aim of this study was to point out the importance of finding new biomarkers that would enable early detection of adverse drug events and cell damage in organ transplant recipients. We wanted to confirm the importance of routine biochemical monitoring in improving the safety of immunosuppressive treatment.

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“…It has been shown that early renal tubular damage is characterized by increased proximal tubular enzymuria. [17][18][19][20][21][22] However, contradictory findings were noted. 15,23 Hence it needs to be further studied.…”

Section: Introductionmentioning

confidence: 99%

Urinary brush border enzymes for early diagnosis of tubular dysfunction in patients with type 2 diabetes mellitus

2019

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Background: Diabetic nephropathy is a major cause of premature morbidity and mortality in type 1 and type 2 diabetes mellitus (T2DM) and hence new markers with better sensitivities are being investigated. The study was taken up to investigate whether urinary activities of N-acetyl-β-D-glycosaminidase (NAG), alkaline phosphatase (ALP), lactate dehydrogenase LDH) and Gamma glutamyl transferase (γ-GT) can be used as screening markers of renal dysfunction in patients suffering from T2DM.Methods: One hundred and four patients with T2DM along with 30 age- and gender-matched healthy individuals were included in the study. Patients were divided into three groups based on their u-MA levels i.e. normoalbuminuric (group1), micro albuminuric (group 2) and macroalbuminuric (group 3).Results: Urinary enzymes activity was significantly higher in patients with T2DM compared to controls (p<0.05). NAG, ALP, LDH, and GGT were significantly higher in group 3 compared to group1 and group 2 (p<0.0001). NAG, ALP, LDH and GGT showed significant positive correlation with MA (p=0.0001, r=0.308; p=0.0001, r=0.369; p=0.002, r=0.304, p=0.044, r=0.202 respectively). GGT and LDH showed highest sensitivity (86.21%, 84.00% respectively) and specificity (78.57%,53.49% respectively) for diagnosing renal dysfunction in patients with normoalbuminuria.Conclusions: The study suggests that u-GGT and LDH can be useful markers for assessing renal dysfunction in T2DM patients even before microalbuminuria manifests.

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The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy

Cited by 6 publications

References 36 publications

Pharmacogenetics May Influence Tacrolimus Daily Dose, But Not Urinary Tubular Damage Markers In The Long-Term Period After Renal Transplantation

Pharmacogenetics May Influence Tacrolimus Daily Dose, But Not Urinary Tubular Damage Markers In The Long-Term Period After Renal Transplantation

Current Biochemical Monitoring and Risk Management of Immunosuppressive Therapy after Transplantation

Urinary brush border enzymes for early diagnosis of tubular dysfunction in patients with type 2 diabetes mellitus

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