Inflammatory and Prothrombotic Markers and the Progression of Renal Disease in Elderly Individuals

Fried, Linda F.; Solomon, Cam; Shlipak, Michael G.; Seliger, Stephen L.; Stehman‐Breen, Catherine; Bleyer, Anthony J.; Chaves, Paolo; Furberg, Curt D.; Kuller, Lewis H.; Newman, Anne B.

doi:10.1097/01.asn.0000146422.45434.35

Cited by 199 publications

(158 citation statements)

References 26 publications

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“…Alternatively, it is possible that rs3093058 is not a key pathogenic mediator for CKD in this population. Although epidemiologic data support the role of inflammation, including CRP in the pathogenic process (11,(13)(14)(15), CRP is a surrogate marker of the inflammatory process (33). CKD patients have a high burden of comorbidities, and reverse causation may explain the associations with CRP.…”

Section: Discussionmentioning

confidence: 99%

CRP Polymorphisms and Progression of Chronic Kidney Disease in African Americans

Hung

Crawford

Griffin

et al. 2010

Clinical Journal of the American Society of Nephrology

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Results: The MAF was higher for the rs2808630_G allele (P ‫؍‬ 0.03) and lower for the rs1205_A allele (P ‫؍‬ 0.03) in the AASK compared with NHANES III. Among AASK participants, the rs3093058_T allele predicted higher CRP concentrations (P < 0.0001) but not CKD progression. The rs2808630_GG genotype was associated with higher risk of the composite endpoint compared with the AA genotype (P ‫؍‬ 0.002). Participants with the rs2808630_GG genotype on angiotensin converting enzyme inhibitors (ACEIs) versus ␤ blockers had increased risk of progression (P ‫؍‬ 0.03).Conclusion: CRP SNPs that were associated with higher levels of CRP did not predict CKD progression. The rs2808630_GG genotype was associated with higher risk of CKD progression, and in patients with this genotype, ACEIs did not slow progression.

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Section: Discussionmentioning

confidence: 99%

CRP Polymorphisms and Progression of Chronic Kidney Disease in African Americans

Hung

Crawford

Griffin

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…Both periodontitis and kidney disease are associated with inflammatory markers such as C-reactive protein (29,30), and chronic low-level inflammation associated with periodontitis may lead to endothelial dysfunction, which plays a role in the pathogenesis of kidney disease (31,32). Periodontitis is treatable, and treatment by tooth extraction (33) or other mechanical procedures and locally administered antibiotics (34) lowers levels of C-reactive protein and other inflammatory markers.…”

Section: Conclusion -P E R I O D O N T I T I Smentioning

confidence: 99%

Effect of Periodontitis on Overt Nephropathy and End-Stage Renal Disease in Type 2 Diabetes

et al. 2007

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OBJECTIVE -The purpose of this study was to investigate the effect of periodontitis on development of overt nephropathy, defined as macroalbuminuria, and end-stage renal disease (ESRD) in type 2 diabetes. RESEARCH DESIGN AND METHODS -Individuals residing in the Gila River IndianCommunity aged Ն25 years with type 2 diabetes, one or more periodontal examination, estimated glomerular filtration rate Ն60 ml/min per 1.73 m 2 , and no macroalbuminuria (urinary albumin-to-creatinine ratio Ն300 mg/g) were identified. Periodontitis was classified as none/ mild, moderate, severe, or edentulous using number of teeth and alveolar bone score. Subjects were followed to development of macroalbuminuria or ESRD, defined as onset of renal replacement therapy or death attributed to diabetic nephropathy.RESULTS -Of the 529 individuals, 107 (20%) had none/mild periodontitis, 200 (38%) had moderate periodontitis, 117 (22%) had severe periodontitis, and 105 (20%) were edentulous at baseline. During follow-up of up to 22 years, 193 individuals developed macroalbuminuria and 68 developed ESRD. Age-and sex-adjusted incidence of macroalbuminuria and ESRD increased with severity of periodontitis. After adjustment for age, sex, diabetes duration, BMI, and smoking in a proportional hazards model, the incidences of macroalbuminuria were 2.0, 2.1, and 2.6 times as high in individuals with moderate or severe periodontitis or those who were edentulous, respectively, compared with those with none/mild periodontitis (P ϭ 0.01). Incidences of ESRD in individuals with moderate or severe periodontitis or in those who were edentulous were 2.3, 3.5, and 4.9 times as high, respectively, compared with those with none/mild periodontitis (P ϭ 0.02).CONCLUSIONS -Periodontitis predicts development of overt nephropathy and ESRD in individuals with type 2 diabetes. Whether treatment of periodontitis will reduce the risk of diabetic kidney disease remains to be determined. Diabetes Care 30:306 -311, 2007P eriodontitis is a common infection of the periodontal tissues (1) and a major cause of tooth loss in adults (2,3). The most prevalent form is chronic periodontitis (1). Individuals with diabetes are at increased risk of developing periodontitis, and, once established, periodontitis is more severe in people with diabetes (3-6). Poor glycemic control hastens the progression of periodontitis and, in turn, periodontitis appears to further impair glycemic control (6 -8).Periodontitis predicts cardiovascular disease risk (9) and deaths from diabetic kidney disease and cardiovascular disease in individuals with type 2 diabetes (10). However, the relationship between periodontitis and diabetic kidney disease has not been fully explored. Among nonobese individuals with type 2 diabetes in Japan, IgG titers for Porphyromonas gingivalis (a periodontal pathogen) were correlated with the urinary albumin-to-creatinine ratio (ACR), although analyses were not adjusted for confounding factors (11). In the Atherosclerosis Risk in Communities (ARIC) Study, a largely nondiabetic p...

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“…The rate of annual decline in eGFR (⌬ eGFR) over the course of the study was determined from the slope of the plot of all measurements of eGFR for each individual (median 8 times [range 4 -13]) calculated with linear regression analysis and was expressed as ml/min per 1.73 m 2 /year. Also, we dichotomized the annual decline in eGFR as accelerated decline (⌬ eGFR Ն3 ml/min per 1.73 m 2 /year) on the basis of previous studies (12,13).…”

Section: Definition Of Outcomesmentioning

confidence: 99%

Polymorphisms of the Protein Kinase C-β Gene (PRKCB1) Accelerate Kidney Disease in Type 2 Diabetes Without Overt Proteinuria

et al. 2006

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OBJECTIVE -We investigated the contribution of PKC-␤ gene (PRKCB1) polymorphisms to diabetic kidney disease in a prospective observational follow-up study.RESEARCH DESIGN AND METHODS -A total of 364 Japanese subjects with type 2 diabetes without overt proteinuria were enrolled during 1996 -1998 and followed until 2004. Five single nucleotide polymorphisms (Ϫ1504C/T, Ϫ546C/G, Ϫ348A/G, Ϫ278C/T, and Ϫ238C/G) in the promoter region of PRKCB1 were genotyped. The end points were transition from stage to stage of diabetic nephropathy as a time-to-event outcome and the annual decline rate of estimated glomerular filtration rate (eGFR) as a slope-based outcome.RESULTS -During the study (median 6 years), 34 of 364 subjects (9.3%) progressed. Kaplan-Meier estimation revealed that subjects with both T allele at Ϫ1054 C/T and G allele at Ϫ546 C/G polymorphisms frequently showed transition to advanced stages of diabetic nephropathy (P ϭ 0.015). The annual change rate in eGFR in the subjects with both alleles was also significantly higher than in others (Ϫ2.96 Ϯ 0.62 vs. Ϫ1.63 Ϯ 0.15 ml/min per 1.73 m 2 /year, P ϭ 0.02). The estimated frequency of this risk T-G haplotype was significantly higher in the progressors who showed transition to advanced nephropathy stages (12%) than in the nonprogressors (5%) (odds ratio 2.3 [95% CI 1.0 -5.2]), and it was also higher in those with accelerated decline of the ⌬ eGFR (Ն3 ml/min per 1.73 m 2 /year) than in those without (2.1 [1.1-3.9]).CONCLUSIONS -Our study indicates that PRKCB1 is a predictor for worsening of kidney disease in Japanese subjects with type 2 diabetes. Diabetes Care 29:864 -868, 2006D iabetic nephropathy associated with type 2 diabetes is a leading cause of end-stage renal disease. While clinical studies clearly show that prolonged hyperglycemia is an important risk factor for this microvascular complication (1,2), epidemiological and familial studies (3-6) suggest that genetic susceptibility also plays a pivotal role.An abnormal activation of protein kinase C (PKC)-␤ under diabetic condition is proposed as a putative mechanism in the pathogenesis of diabetic nephropathy (7). Thus, the gene (PRKCB1) encoding this protein is considered to be a candidate gene for susceptibility to diabetic nephropathy. Recently, we first reported the association between the PRKCB1 polymorphisms and diabetic nephropathy in type 1 diabetic patients by using two independent methods, a case-control study and a familybased study (8). In our previous study (8), a T-G haplotype consisting of two single nucleotide polymorphisms (Ϫ1504C/T and Ϫ546C/G) in the promoter region was associated with twofold increased risk of diabetic nephropathy. Although our report provided the first evidence that the PRKCB1 polymorphisms may contribute to genetic susceptibility to diabetic nephropathy (8), several questions remain unclear: whether this relevance extrapolates to type 2 diabetic subjects, whether the risk haplotype is associated with early diabetic nephropathy, and whether this risk haplotype of PRKCB1 i...

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Inflammatory and Prothrombotic Markers and the Progression of Renal Disease in Elderly Individuals

Cited by 199 publications

References 26 publications

CRP Polymorphisms and Progression of Chronic Kidney Disease in African Americans

CRP Polymorphisms and Progression of Chronic Kidney Disease in African Americans

Effect of Periodontitis on Overt Nephropathy and End-Stage Renal Disease in Type 2 Diabetes

Polymorphisms of the Protein Kinase C-β Gene (PRKCB1) Accelerate Kidney Disease in Type 2 Diabetes Without Overt Proteinuria

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