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Introduction: Tubular biomarkers may shed insight into progression of kidney tubulointerstitial pathology complementary to traditional measures of glomerular function and damage., Methods: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years. Measurements included the following: kidney injury molecule 1 (KIM-1), soluble tumor necrosis factor 1 (sTNFR1) in serum or plasma, epidermal growth factor (EGF), monocyte chemoattractant protein-1 (MCP1) in timed urine, and a composite tubular secretion score. We described biomarker trajectories and examined how these were affected by intensive glucose-lowering therapy and glycemia., Results: At baseline, participants had a mean age of 28 years, 45% were women, and 50% were assigned to intensive glucose-lowering therapy. The mean estimated glomerular filtration rate (eGFR) was 125 ml/min per 1.73 m 2 and 90% of participants had a urinary albumin excretion rate (AER) <30 mg/24h. Mean changes in biomarkers over time (percent/decade) were: KIM-1: 27.3% (95% confidence interval [CI]: 21.4-33.5), sTNFR1: 16.9% (14.5-19.3), MCP1: 18.4% (8.9-28.8), EGF: -13.5% (-16.7 to -10.1), EGF-MCP1 ratio: -26.9% (-32.2 to -21.3), and tubular secretion score -0.9% (-1.8 to 0.0), versus -12.0% (CI: -12.9 to -11.1) for eGFR and 10.9% (2.5-20.1) for AER. Intensive versus conventional glucose-lowering therapy was associated with slower increase in sTNFR1 (relative difference in change: 0.94 [0.90-0.98]). Higher HbA1c was associated with faster increases in sTNFR1 (relative difference in change: 1.06 per 1% higher HbA1c [1.05-1.08]) and KIM-1 (1.09 [1.05-1.14])., Conclusion: Among participants with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in serum or plasma sTNFR1 and KIM-1, when followed-up longitudinally., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

The cholesteryl ester transfer protein (CETP) plays a key role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP activity and concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration; however, controversies remain about whether these genetic variants are associated with atherosclerosis. We genotyped the CETP R451Q, A373P, -629C/A, Taq1B, and -2505C/A polymorphisms in a cohort of Caucasian, Chinese, African-American, and Hispanic individuals within the Multi-Ethnic Study of Atherosclerosis. Genotypes were examined in relationship to HDL-C, CETP activity, CETP concentration, and three measures of subclinical cardiovascular disease (CVD): coronary artery calcium (CAC) measured by fast CT scanning, carotid intimal-medial thickness (IMT), and carotid artery plaque measured by ultrasonography. Carriers of the 451Q and 373P alleles have a significantly higher CETP concentration (22.4% and 19.5%, respectively; p<0.001) and activity (13.1% and 9.4%, respectively; p<0.01) and lower HDL-C (5.6% and 6.0%, respectively; p<0.05). The minor alleles of the R451Q and A373P polymorphisms are associated with the presence of CAC, even after adjusting for CVD risk factors and HDL-C (p=0.006 and p=0.01, respectively). The R451Q polymorphism is also associated with presence of carotid artery plaque (p=0.036). Polymorphism is associated with neither common nor internal carotid IMT. We confirmed that the -629A, Taq1B B2, and -2505A alleles are significantly associated with lower CETP concentration (20.8%, 25.0%, and 23.7%, respectively; p<0.001) and activity (14.8%, 19.8%, and 18.4%, respectively; p<0.001) and higher HDL-C concentration (9.7%, 11.5%, and 10.4%, respectively; p<0.01). However, we did not find any associations between these non-coding polymorphisms and subclinical CVD.

Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P < .01 absolute values, P < .001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). No significant changes were seen in mean concentrations of IL-2 soluble receptor alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. Of the lipids, significant decreases in mean concentrations of normalized triglyceride values were seen on days 1 (P < .05), 3 (P < .001), and 7 (P < .05) after vaccination. Our findings show that the influenza vaccination causes transient changes in select markers of inflammation and lipids. Consequently, clinical and epidemiologic interpretation of the biomarkers affected should take into account the possible effects of influenza vaccination.

An increased prevalence of hyperhomocysteinemia has been observed among patients with end-stage renal disease, and numerous studies have demonstrated that kidney function is one of the most important determinants of plasma total homocysteine (tHcy) concentration. In an effort to understand the mechanism of hyperhomocysteinemia in renal disease, we chose, as our model, living kidney donors who had undergone uninephrectomy. We studied 10 living kidney donors and measured fasting plasma tHcy, plasma creatinine, folate, vitamins B(12) and B(6), and high-sensitivity C-reactive protein (hsCRP) 24 hours before nephrectomy and 2 days, 6 weeks, and 6 months after nephrectomy compared to the values 24 hours before nephrectomy. Mean fasting tHcy and creatinine concentrations were significantly higher in donors 2 days, 6 weeks and 6 months after nephrectomy they were 24 hours before nephrectomy. Both the increases in tHcy levels 2 days after nephrectomy and subsequent decreases 6 weeks and 6 months after are paralleled by the changes in plasma creatinine values, although neither returned to its presurgery value. Decreases in tHcy are significantly correlated with decreases in creatinine values. The B vitamins were unchanged, and the hsCRP level was increased 2 days after surgery but had returned to the baseline level after 6 weeks. We conclude that tHcy and creatinine levels parallel each other after uninephrectomy and that the gradual decrease in tHcy is accounted for by hypertrophy of the remaining kidney. Our results, the first to be obtained from living kidney donors, support the hypothesis that renal metabolism of tHcy is the mechanism responsible for the correlation between renal function and plasma tHcy level.