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Elevation of circulating TNF receptors 1 and 2 increases the risk of end-stage renal disease in American Indians with type 2 diabetes.

Pavkov ME, Nelson RG, Knowler WC, Cheng Y, Krolewski AS, Niewczas MA - Kidney Int. (2014)

Bottom Line: Here we examined this relationship in a longitudinal cohort study of American Indians with type 2 diabetes with measured glomerular filtration rate (mGFR, iothalamate) and urinary albumin-to-creatinine ratio (ACR).ESRD was defined as dialysis, kidney transplant, or death attributed to diabetic kidney disease.Thus, elevated serum concentrations of TNFR1 or TNFR2 are associated with increased risk of ESRD in American Indians with type 2 diabetes after accounting for traditional risk factors including ACR and mGFR.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

ABSTRACT
In Caucasians with type 2 diabetes, circulating TNF receptors 1 (TNFR1) and 2 (TNFR2) predict end-stage renal disease (ESRD). Here we examined this relationship in a longitudinal cohort study of American Indians with type 2 diabetes with measured glomerular filtration rate (mGFR, iothalamate) and urinary albumin-to-creatinine ratio (ACR). ESRD was defined as dialysis, kidney transplant, or death attributed to diabetic kidney disease. Age-gender-adjusted incidence rates and incidence rate ratios of ESRD were computed by Mantel-Haenszel stratification. The hazard ratio of ESRD was assessed per interquartile range increase in the distribution of each TNFR after adjusting for baseline age, gender, mean blood pressure, HbA1c, ACR, and mGFR. Among the 193 participants, 62 developed ESRD and 25 died without ESRD during a median follow-up of 9.5 years. The age-gender-adjusted incidence rate ratio of ESRD was higher among participants in the highest versus lowest quartile for TNFR1 (6.6, 95% confidence interval (CI) 3.3-13.3) or TNFR2 (8.8, 95% CI 4.3-18.0). In the fully adjusted model, the risk of ESRD per interquartile range increase was 1.6 times (95% CI 1.1-2.2) as high for TNFR1 and 1.7 times (95% CI 1.2-2.3) as high for TNFR2. Thus, elevated serum concentrations of TNFR1 or TNFR2 are associated with increased risk of ESRD in American Indians with type 2 diabetes after accounting for traditional risk factors including ACR and mGFR.

No MeSH data available.


Related in: MedlinePlus

Cumulative incidence of diabetic end-stage renal disease during 10 years of follow-up,when 48 of the 62 events occurred, according to quartiles of TNFR1 and TNFR2 at baselineand albuminuria status. Cut-points for the 25th, 50th, and75th percentiles of TNFRs distributions are presented in Table 3. Numbers of participants at risk at the end of each2-year interval are indicated along the x-axes. ACR=albumin/creatinine ratio,Qt=quartile, TNFR=tumor necrosis factor receptor.
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Figure 3: Cumulative incidence of diabetic end-stage renal disease during 10 years of follow-up,when 48 of the 62 events occurred, according to quartiles of TNFR1 and TNFR2 at baselineand albuminuria status. Cut-points for the 25th, 50th, and75th percentiles of TNFRs distributions are presented in Table 3. Numbers of participants at risk at the end of each2-year interval are indicated along the x-axes. ACR=albumin/creatinine ratio,Qt=quartile, TNFR=tumor necrosis factor receptor.

Mentions: Figure 3 shows the cumulative incidence ofESRD at 10 years of follow-up, when 48 of the 62 cases of ESRD had occurred, according tothe level of albuminuria and TNFRs. The highest quartile of each TNFR is compared with thelowest three quartiles combined. Among participants with severe albuminuria, the cumulativeincidence of ESRD at 10 years of follow-up was 96.2% in those in the highest TNFR1quartile at baseline and 44.6% in those in lower TNFR1 quartiles (p<0.001).Similarly, for TNFR2 the cumulative incidence of ESRD was 88.7% and 47.3%,respectively (p<0.001). Among participants without severe albuminuria, the 10-yearcumulative incidence of ESRD was 14.4% and 6.1% in the highest and lowerTNFR1 quartiles, respectively (p=0.51), and 26.9% and 4.7% in thehighest and lower TNFR2 quartiles, respectively (p=0.049).


Elevation of circulating TNF receptors 1 and 2 increases the risk of end-stage renal disease in American Indians with type 2 diabetes.

Pavkov ME, Nelson RG, Knowler WC, Cheng Y, Krolewski AS, Niewczas MA - Kidney Int. (2014)

Cumulative incidence of diabetic end-stage renal disease during 10 years of follow-up,when 48 of the 62 events occurred, according to quartiles of TNFR1 and TNFR2 at baselineand albuminuria status. Cut-points for the 25th, 50th, and75th percentiles of TNFRs distributions are presented in Table 3. Numbers of participants at risk at the end of each2-year interval are indicated along the x-axes. ACR=albumin/creatinine ratio,Qt=quartile, TNFR=tumor necrosis factor receptor.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4382420&req=5

Figure 3: Cumulative incidence of diabetic end-stage renal disease during 10 years of follow-up,when 48 of the 62 events occurred, according to quartiles of TNFR1 and TNFR2 at baselineand albuminuria status. Cut-points for the 25th, 50th, and75th percentiles of TNFRs distributions are presented in Table 3. Numbers of participants at risk at the end of each2-year interval are indicated along the x-axes. ACR=albumin/creatinine ratio,Qt=quartile, TNFR=tumor necrosis factor receptor.
Mentions: Figure 3 shows the cumulative incidence ofESRD at 10 years of follow-up, when 48 of the 62 cases of ESRD had occurred, according tothe level of albuminuria and TNFRs. The highest quartile of each TNFR is compared with thelowest three quartiles combined. Among participants with severe albuminuria, the cumulativeincidence of ESRD at 10 years of follow-up was 96.2% in those in the highest TNFR1quartile at baseline and 44.6% in those in lower TNFR1 quartiles (p<0.001).Similarly, for TNFR2 the cumulative incidence of ESRD was 88.7% and 47.3%,respectively (p<0.001). Among participants without severe albuminuria, the 10-yearcumulative incidence of ESRD was 14.4% and 6.1% in the highest and lowerTNFR1 quartiles, respectively (p=0.51), and 26.9% and 4.7% in thehighest and lower TNFR2 quartiles, respectively (p=0.049).

Bottom Line: Here we examined this relationship in a longitudinal cohort study of American Indians with type 2 diabetes with measured glomerular filtration rate (mGFR, iothalamate) and urinary albumin-to-creatinine ratio (ACR).ESRD was defined as dialysis, kidney transplant, or death attributed to diabetic kidney disease.Thus, elevated serum concentrations of TNFR1 or TNFR2 are associated with increased risk of ESRD in American Indians with type 2 diabetes after accounting for traditional risk factors including ACR and mGFR.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

ABSTRACT
In Caucasians with type 2 diabetes, circulating TNF receptors 1 (TNFR1) and 2 (TNFR2) predict end-stage renal disease (ESRD). Here we examined this relationship in a longitudinal cohort study of American Indians with type 2 diabetes with measured glomerular filtration rate (mGFR, iothalamate) and urinary albumin-to-creatinine ratio (ACR). ESRD was defined as dialysis, kidney transplant, or death attributed to diabetic kidney disease. Age-gender-adjusted incidence rates and incidence rate ratios of ESRD were computed by Mantel-Haenszel stratification. The hazard ratio of ESRD was assessed per interquartile range increase in the distribution of each TNFR after adjusting for baseline age, gender, mean blood pressure, HbA1c, ACR, and mGFR. Among the 193 participants, 62 developed ESRD and 25 died without ESRD during a median follow-up of 9.5 years. The age-gender-adjusted incidence rate ratio of ESRD was higher among participants in the highest versus lowest quartile for TNFR1 (6.6, 95% confidence interval (CI) 3.3-13.3) or TNFR2 (8.8, 95% CI 4.3-18.0). In the fully adjusted model, the risk of ESRD per interquartile range increase was 1.6 times (95% CI 1.1-2.2) as high for TNFR1 and 1.7 times (95% CI 1.2-2.3) as high for TNFR2. Thus, elevated serum concentrations of TNFR1 or TNFR2 are associated with increased risk of ESRD in American Indians with type 2 diabetes after accounting for traditional risk factors including ACR and mGFR.

No MeSH data available.


Related in: MedlinePlus