Dataset Information

Serum lipopolysaccharide activity is associated with the progression of kidney disease in finnish patients with type 1 diabetes.

ABSTRACT:

Objective

The aim of the study was to investigate whether serum lipopolysaccharide (LPS) activities are associated with the progression of kidney disease in patients with type 1 diabetes.

Research design and methods

For this prospective study, we chose 477 Finnish patients with type 1 diabetes, who were followed for 6 years. At the baseline visit, 239 patients had a normal albumin excretion rate (normoalbuminuria) and 238 patients had macroalbuminuria. Patients were further divided into nonprogressors and progressors based on their albumin excretion rate at follow-up. Eighty normoalbuminuric patients had developed microalbuminuria, and 79 macroalbuminuric patients had progressed to end-stage renal disease. Serum LPS activity was determined with the Limulus amoebocyte lysate chromogenic end point assay.

Results

Serum LPS activity was significantly higher in the macroalbuminuric group than in the normoalbuminuric group (P < 0.001). Notably, normoalbuminuric progressor patients had a significantly higher LPS activity at baseline than normoalbuminuric nonprogressor patients (median 49 [interquartile range 34-87] vs. 39 [29-54] EU/ml; P = 0.001). The normoalbuminuric progressor patients exhibited features of the metabolic syndrome with higher triglyceride concentrations and lower estimated glucose disposal rate. A high LPS-to-HDL ratio was associated with the progression of kidney disease in both groups. Insulin resistance (P < 0.001) and serum LPS activity (P = 0.026) were independent risk factors of disease development, when A1C was removed from the regression analysis.

Conclusions

High serum LPS activity is associated with the development of diabetic nephropathy in Finnish patients with type 1 diabetes.

SUBMITTER: Nymark M

PROVIDER: S-EPMC2732155 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Publications

Serum lipopolysaccharide activity is associated with the progression of kidney disease in finnish patients with type 1 diabetes.

Nymark Mariann M Pussinen Pirkko J PJ Tuomainen Anita M AM Forsblom Carol C Groop Per-Henrik PH Lehto Markku M

Diabetes care 20090605 9

<h4>Objective</h4>The aim of the study was to investigate whether serum lipopolysaccharide (LPS) activities are associated with the progression of kidney disease in patients with type 1 diabetes.<h4>Research design and methods</h4>For this prospective study, we chose 477 Finnish patients with type 1 diabetes, who were followed for 6 years. At the baseline visit, 239 patients had a normal albumin excretion rate (normoalbuminuria) and 238 patients had macroalbuminuria. Patients were further divide ...[more]

PMID: 19502539

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Project description:ObjectivesGrowing evidence demonstrated that vitamin D levels had been linked to type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in light of various extraskeletal effects. Therefore, the present study aimed to evaluate the association of 25-hydroxyvitamin D [25(OH)D] level with the clinicopathological features and CKD progression in T2DM.MethodsA total of 182 patients with T2DM with CKD stages 1 through 4 (G1-G4) were retrospectively included. Identification of the serum 25(OH)D level associated with CKD progression was executed by Kaplan-Meier survival analysis and Cox proportional hazards models. We further performed sensitivity analyses with a time-weighted average (TWA) of the serum 25(OH)D level in 75 participants to reinforce the findings.ResultsThe median serum 25(OH)D level was 26 (IQR, 14; 39) nmol/L in the study participants. Median follow-up time was 42 months, during which 70 (38%) patients confronted CKD progression. Cumulative kidney outcomes were significantly higher in the lowest tertile of the serum 25(OH)D level in Kaplan-Meier analyses (P < 0.001). Consistently, the analyses of Cox proportional hazards regression models indicated a significantly greater risk for CKD progression in the lowest tertile of the serum 25(OH)D level compared with the highest tertile of the serum 25(OH)D level (P = 0.03). These relationships remained robust with further sensitivity analysis of data with TWA of the serum 25(OH)D level, showing an independent association between lower TWA of the serum 25(OH)D level and an unfavorable renal outcome in patients with T2DM with CKD.ConclusionsOur findings demonstrated that patients with T2DM with a decreased 25(OH)D level had deteriorated renal function. Both lower levels of baseline and TWA of serum 25(OH)D were associated with an increased risk of CKD progression in patients with T2DM, which suggested that the long-term maintenance of optimal vitamin D levels from early in life might be associated with reduced future risk of CKD development in T2DM.

Project description:ImportanceThe appropriate target of glycemic control in diabetic kidney disease is unclear.ObjectiveTo investigate optimal on-treatment glycemic levels associated with slowing of diabetic kidney disease progression.Design, setting, and participantsThis retrospective cohort study was conducted using nationwide Korean cohorts from the National Health Information Database from 2005 to 2019. Included individuals were adults with diabetes using antihyperglycemic agents with and without chronic kidney disease (CKD) identified from participants aged 40 to 74 years in a nationwide health screening survey conducted from 2009 to 2010. Data were analyzed from October 2020 through March 2021.ExposureOn-treatment fasting blood glucose (FBG) level.Main outcomes and measuresThe primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death from CKD.ResultsAmong 183 049 adults with diabetes using antihyperglycemic agents (mean [SD] age, 61.7 [8.4] years; 99 110 [54.1%] men), there were 131 401 individuals with dipstick albuminuria or an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 (mean [SD] age, 62.4 [8.3] years; 71 280 [54.2%] men) and 51 648 individuals with no CKD (mean [SD] age, 59.6 [8.4] years; 27 830 [53.9%] men). During 9 years of follow-up, the primary outcome occurred among 13 802 individuals with CKD (10.5%) and 1421 individuals with no CKD (2.8%). On-treatment FBG level had a J-shaped hazard ratio (HR) curve for the primary outcome. Among patients with albuminuria, FBG levels of 126 mg/dL to less than 140 mg/dL (HR, 0.87; 95% CI, 0.81-0.94) and 140 mg/dL to less than 160 mg/dL (HR, 0.90; 95% CI, 0.84-0.96) were associated with decreased risk and levels of 160 mg/dL to less than 180 mg/dL were associated with increased risk (HR, 1.10; 95% CI, 1.03-1.18) compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with decreased eGFR, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.30; 95% CI, 1.20-1.42) and levels of 160 mg/dL to less than 180 mg/dL (HR, 1.13; 95% CI, 1.04-1.23) were associated with increased risk of the primary outcome compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no CKD, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.29; 95% CI, 1.01-1.65) and levels of 126 mg/dL to less than 140 mg/dL (HR, 1.23; 95% CI, 1.03-1.47) were associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no albuminuria at baseline, FBG levels of 140 mg/dL to less than 160 mg/dL (HR, 1.14; 95% CI, 1.09-1.20) were associated with increased risk of new-onset albuminuria, while levels of 100 mg/dL to less than 110 mg/dL were not associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. For all-cause mortality, while FBG levels of 160 mg/dL to less than 180 mg/dL (HR, 1.20; 95% CI, 1.12-1.28) were associated with increased risk among patients with albuminuria, FBG levels of 140 mg/dL to less than 160 mg/dL were associated with increased risk among patients with decreased eGFR (HR, 1.10; 95% CI, 1.04-1.16) and those with no CKD (HR, 1.10; 95% CI, 1.00-1.21) compared with levels of 110 mg/dL to less than 126 mg/dL.Conclusions and relevanceThese findings suggest that intensive vs standard glucose control may not be associated with increased protection for the progression of established diabetic kidney disease and that timely control is important for prevention. However, careful glycemic control would still be associated with improved overall outcomes among patients with CKD, particularly those with no albuminuria.

Project description:Diabetic kidney disease (DKD) is a topic of increasing concern among clinicians involved in the management of type 2 diabetes mellitus (T2DM). It is a progressive and costly complication associated with increased risk of adverse cardiovascular (CV) and renal outcomes and mortality. Ongoing monitoring of the estimated glomerular filtration (eGFR) rate alongside the urine albumin:creatinine ratio (ACR) is recommended during regular T2DM reviews to enable a prompt DKD diagnosis or to assess disease progression, providing an understanding of adverse risk for each individual. Many people with DKD will progress to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT), typically haemodialysis or kidney transplantation. A range of lifestyle and pharmacological interventions is recommended to help lower CV risk, slow the advancement of DKD and prevent or delay the need for RRT. Emerging evidence concerning sodium-glucose co-transporter-2 inhibitor (SGLT2i) agents suggests a role for these medicines in slowing eGFR decline, enabling regression of albuminuria and reducing progression to ESKD. Improvements in renal end points observed in SGLT2i CV outcome trials (CVOTs) highlighted the possible impact of these agents in the management of DKD. Data from the canagliflozin CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) have since demonstrated the effectiveness of this medicine in reducing the risk of kidney failure and CV events in a population comprising individuals with T2DM and renal disease. CREDENCE was the first SGLT2i study to examine renal outcomes as the primary end point. Real-world studies have reaffirmed these outcomes in routine clinical practice. This article summarises the evidence regarding the use of SGLT2i medicines in slowing the progression of DKD and examines the possible mechanisms underpinning the renoprotective effects of these agents. The relevant national and international guidance for monitoring and treatment of DKD is also highlighted to help clinicians working to support this vulnerable group.

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Dataset Information

Serum lipopolysaccharide activity is associated with the progression of kidney disease in finnish patients with type 1 diabetes.

Objective

Research design and methods

Results

Conclusions

Publications

Serum lipopolysaccharide activity is associated with the progression of kidney disease in finnish patients with type 1 diabetes.

Similar Datasets

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