Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects

Pafundi, Pia Clara; Garofalo, Carlo; Galiero, Raffaele; Borrelli, Silvio; Caturano, Alfredo; Rinaldi, Luca; Provenzano, Michele; Salvatore, Teresa; Nicola, Luca De; Minutolo, Roberto; Sasso, Ferdinando Carlo

doi:10.3390/diagnostics11020290

“…Albuminuria and tubular atrophy are also risk factors for the progression of CKD to ESRD, and kidney proximal tubule lipoapoptosis is caused by dysregulation of fatty acid transporter-2 (FATP2), which may be an appropriate molecular target for the treatment of CKD [ 43 ]. Proteinuria represents a significant prognostic factor for onset and progression of DKD and CVD, reducing proteinuria can improve the cardio-renal outcomes in diabetic patients [ 44 ]. On the other hand, CKD is one of the strongest risk factors for the development of CVD.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Progression of CKD with and without Diabetes

Zhang

¹

,

Fang

²

,

Zou

³

et al. 2022

Journal of Diabetes Research

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Objective. We aim to identify independent risk factors to predict CKD progression to end stage renal disease (ESRD) in patients with or without diabetes. Methods. In this retrospective study, we enrolled CKD stage 3-4 patients between January 2013 and December 2018 and followed them until December 2020 or the initiation of dialysis. We used Kaplan-Meier to plot the survival curve. Univariate and multivariable Cox proportional hazards model was used to explore risk factors affecting the progression of CKD. The final model was used to construct nomogram for predicting CKD progression. Calibration plots and concordance index (C-index) were used to evaluate the accuracy and discrimination of the risk model. Results. We enrolled 309 CKD patients, including 80 cases in G3a, 98 cases in G3b, and 131 cases in G4. Among them, 141 patients had diabetes and 168 did not. The mean age of patients at enrolled was 57.86 ± 15.10 years, and 67% were male. The median follow-up time was 25.6 months. There were 81 patients (26.2%) that started dialysis in the total CKD cohort, 52 cases (36.9%) in the CKD with diabetes group, and 29 cases (17.3%) in the CKD without diabetes group. Hypoalbuminemia (HR =2.655, P < 0.001 ), proteinuria (HR =2.592, P = 0.042 ), increased LDL (HR =2.494, P < 0.001 ), diabetes (HR =2.759, P < 0.001 ), hypertension (HR =3.471, P = 0.037 ), and CKD stage (HR =2.001, P = 0.046 ) were risk factors for CKD progression to ESRD in the overall population. For those without diabetes, only hypoalbuminemia (HR =2.938, P = 0.030 ) was a risk factor for CKD progression to ESRD. For those with diabetes, both hypoalbuminemia (HR =2.758, P = 0.002 ), the increased level of LDL (HR =3.982, P < 0.001 ), and CKD stage (HR =3.781, P = 0.001 ) were risk factors for CKD progression to ESRD. The C-index of the final nomograms was 0.760 ( P < 0.001 ). Conclusions. The results from our risk factor model suggest that CKD disease progression can be predicted and early strategic intervention is necessary for CKD patients to avoid renal function deterioration.

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“…In addition, the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study showed that reduction in albuminuria by 50% was associated with reduced risks of cardiovascular events by 18% and heart failure by 27%. 24 People with T2D and moderately to severely increased albuminuria have an approximately threefold, fourfold, and fivefold greater risk of myocardial infarction, cardiovascular death and hospitalization for heart failure, respectively, than those with T2D alone. 25 A recent study (n=512 700) showed that early CKD in people with diabetes may shorten life expectancy by 16 years, compared with 6 years for early CKD without diabetes (either type 1 or type 2), and 10 years for diabetes alone (either type 1 or type 2; figure 2 ).…”

Section: Albuminuria As a Marker Of Kidney Damage And Cardiorenal Riskmentioning

confidence: 98%

“…While elevated albuminuria can be indicative of CKD, incremental increases in albuminuria are associated with corresponding increases in cardiorenal risk. 24 Concomitant CKD and T2D is an independent risk factor for cardiovascular events, with this population being approximately three times more likely to die from cardiovascular-related causes than those with T2D alone, and almost six times more likely to die from cardiovascular-related causes than those with neither T2D nor CKD. 5 Based on a report from the Framingham Heart Study, the presence of albuminuria is associated with a higher risk of incident heart failure, specifically heart failure with reduced ejection fraction, in the general population.…”

Section: Albuminuria As a Marker Of Kidney Damage And Cardiorenal Riskmentioning

confidence: 98%

Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria

McGill

¹

,

Haller

²

,

Roy‐Chaudhury

³

et al. 2022

BMJ Open Diab Res Care

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Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review discusses albuminuria as a marker of kidney damage and cardiorenal risk, highlights the importance of early screening and routine testing for albuminuria in people with T2D, and provides new insights on the optimum management of CKD in T2D using albuminuria as a target in a proposed algorithm. Elevated urine albumin can be used to detect CKD in people with T2D and monitor its progression; however, obstacles preventing early detection exist, including lack of awareness of CKD in the general population, poor adherence to clinical guidelines, and country-level variations in screening and treatment incentives. With albuminuria being used as an entry criterion and a surrogate endpoint for kidney failure in clinical trials, and with novel treatment interventions available to prevent CKD progression, there is an urgent need for early screening and diagnosis of kidney function decline in people with T2D or pre-diabetes.

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“…One of the risk factors for kidney damage is oxidative stress. 24 One of the markers of oxidative stress found to be increased in patients with CKD is a product of nucleic acid oxidation, which is 8-OHdG. 25 8-OHdG or 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) are free radicals commonly found due to oxidative injury and often become markers of oxidative stress or carcinogenesis.…”

Section: -Ohdg and Chronic Kidney Diseasementioning

confidence: 99%

The role of oxidative stress markers in Indonesian chronic kidney disease patients: a cross sectional study

Alsagaff

¹

,

Pikir

²

,

Susilo

³

et al. 2022

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Background: Several aspects of chronic kidney disease (CKD) such as the incidence rate and mortality rate are concerning. Oxidative stress contributes to progression and mortality in patients with CKD; however, a specific correlation between several markers of oxidative stress and the estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in the Indonesian population has not been sufficiently described yet. Methods: This study was an analytic observational study with a sample of 56 patients with CKD in Universitas Airlangga Hospital, Surabaya, Indonesia, from December 2019 – March 2020. The markers for oxidative stress investigated were urinary 8-hydroxy-2 deoxyguanosine (8-OHdG), serum symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). The correlations between each variable of oxidative stress and CKD were analyzed using Pearson analysis. Results: There was a positive correlation between 8-OHdG and eGFR (p=0.00, r=0.51); however, there was a negative correlation between 8-OHdG and ACR (p=0.025, r=-0.30). SDMA and eGFR showed a negative correlation (p=0.00, r=-0.648), while SDMA and ACR showed a positive correlation (p=0.03, r=0.349). ADMA showed a negative correlation with eGFR (p=0.00, r=-0.476). There were significantly decreased 8-OHdG but increased ADMA and SDMA as the CKD stage progressed (p=0.001, p=0.00, and p = 0.00, respectively). Higher urine 8-OHdG was detected in patients without history of hemodialysis, whereas ADMA and SDMA showed higher value in patients with hemodialysis (p=0.00, p=0.00, and p=0.004, respectively), patients with history of diabetes mellitus (DM) had higher mean 8-OHdG (p 0.000) yet lower serum ADMA and SDMA (p=0.004 and p=0.003, respectively). Conclusions: In patients with CKD in Indonesia, the markers for oxidative stress 8-OHdG, SDMA, and ADMA are correlated with eGFR and ACR levels. There were also significant difference in 8-OHdG, SDMA, and ADMA levels among CKD stages, between dialysis vs non dialysis, and DM vs non DM patients.

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Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects

Cited by 21 publications

References 121 publications

Risk Factors for Progression of CKD with and without Diabetes

Risk Factors for Progression of CKD with and without Diabetes

Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria

The role of oxidative stress markers in Indonesian chronic kidney disease patients: a cross sectional study

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