Association of metabolic syndrome traits with urinary biomarkers in Japanese adults

Background Although metabolic syndrome traits are risk factors for chronic kidney disease, few studies have examined their association with urinary biomarkers. Methods Urinary biomarkers, including A-megalin, C-megalin, podocalyxin, albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase, were cross-sectionally assessed in 347 individuals (52.7% men) with a urine albumin-to-creatinine ratio (ACR) < 300 mg/g in a health checkup. Metabolic syndrome traits were adopted from the National Cholesterol Education Program (third revision) of the Adult Treatment Panel criteria modified for Asians. Results Participants had a mean body mass index, estimated glomerular filtration rate (eGFR), and median ACR of 23.0 kg/m2, 74.8 mL/min/1.73 m2, and 7.5 mg/g, respectively. In age- and sex-adjusted logistic regression analysis, A-megalin and albumin were significantly associated with the clustering number of metabolic syndrome traits (3 or more). After further adjustment with eGFR, higher quartiles of A-megalin and albumin were each independently associated with the clustering number of metabolic syndrome traits (adjusted odds ratio for A-megalin: 1.30 per quartile, 95% CI 1.03–1.64; albumin: 1.42 per quartile, 95% CI 1.12–1.79). Conclusions Both urinary A-megalin and albumin are associated with the clustering number of metabolic syndrome traits. Further research on urinary A-megalin is warranted to examine its role as a potential marker of kidney damage from metabolic risk factors.

Mineralocorticoid Receptor Antagonist Use and Hard Renal Outcomes in Real-World Patients With Chronic Kidney Disease

Background: Real-world evidence about mineralocorticoid receptor antagonist (MRA) use has been limited in chronic kidney disease, particularly regarding its association with hard renal outcomes. Methods: In this retrospective cohort study, adult chronic kidney disease outpatients referred to the department of nephrology at an academic hospital between January 2005 and December 2018 were analyzed. The main inclusion criteria were estimated glomerular filtration rate ≥10 and <60 mL/min per 1.73 m 2 and follow-up ≥90 days. The exposure of interest was MRA use, defined as the administration of spironolactone, eplerenone, or potassium canrenoate. The primary outcome was renal replacement therapy initiation, defined as the initiation of chronic hemodialysis, peritoneal dialysis, or kidney transplantation. A marginal structural model using inverse probability of weighting was applied to account for potential time-varying confounders. Results: Among a total of 3195 patients, the median age and estimated glomerular filtration rate at baseline were 66 years and 38.4 mL/min per 1.73 m 2 , respectively. During follow-up (median, 5.9 years), 770 patients received MRAs, 211 died, and 478 started renal replacement therapy. In an inverse probability of weighting-weighted pooled logistic regression model, MRA use was significantly associated with a 28%-lower rate of renal replacement therapy initiation (hazard ratio, 0.72 [95% CI, 0.53–0.98]). The association between MRA use and renal replacement therapy initiation was dose-dependent ( P for trend <0.01) and consistent across patient subgroups. The incidence of hyperkalemia (>5.5 mEq/L) was somewhat higher in MRA users but not significant (hazard ratio, 1.14 [95% CI, 0.88–1.48]). Conclusions: MRA users showed a better renal prognosis across various chronic kidney disease subgroups in a real-world chronic kidney disease population.

Usefulness of estimated pulse wave velocity for identifying prevalent coronary heart disease: findings from a general Chinese population

Background Aortic stiffness and coronary heart disease (CHD) share a similar spectrum of risk factors; previous studies have identified the association between aortic stiffness and CHD. Recent studies have demonstrated estimated pulse wave velocity (ePWV) as a simple and easy-acquired indicator of aortic stiffness. Our work aims to evaluate the association between ePWV and the prevalence of CHD and assess the value of ePWV for the identification of prevalent CHD. Methods The current cross-sectional work included 7012 subjects from rural areas of southeastern China between September 2020 and February 2021. ePWV was calculated from age and mean blood pressure by specific algorithm. Results The prevalence of CHD in our population was 3.58% (251 patients among 7012 subjects). After adjusting for age, sex, education, income and exercise level, current smoking and drinking status, body mass index, waist circumference, fasting plasma glucose, total cholesterol, high density lipoprotein, estimated glomerular filtration rate and cerebrovascular diseases, each standard deviation increment of ePWV would produce an additional 37.8% risk of prevalent CHD. Moreover, after dividing ePWV into quartiles, the 4th quartile of ePWV showed a significant risk of prevalent CHD (OR (95% CI): 3.567 (1.963–6.479)) when compared with the 1st quartile. Additionally, the subgroup analysis showed the association between ePWV and prevalent CHD was robust to several common risk factors of CHD, including age, sex, body mass index, hypertension, diabetes and reduced estimated glomerular filtration rate. Finally, the area under curve (AUC) displayed an improvement when adding ePWV into common CHD risk factors (0.705 vs. 0.718. P = 0.044). Consistently, net reclassification index (0.436, 95% CI: 0.301–0.571, P < 0.001) and integrated discrimination index (0.004, 95% CI: 0.001–0.006, P = 0.002) demonstrated the value of ePWV to optimize the identification of prevalent CHD in the general population. Conclusion The present analysis implicates the robust association between ePWV, a simple, rapid, and practical marker of aortic stiffness, and prevalent CHD in the general Chinese population. More importantly, the results suggest the value of ePWV as a potential marker to improve the identification of prevalent CHD.

Identification of biomarkers of chronic kidney disease among kidney-derived proteins

Background Chronic kidney disease (CKD) has few objective symptoms, and it is difficult to make an early diagnosis by using existing methods. Therefore, new biomarkers enabling diagnosis of renal dysfunction at an early stage need to be developed. Here, we searched for new biomarkers of CKD by focusing on kidney-derived proteins that could sensitively reflect that organ’s disease state. Methods To identify candidate marker proteins, we performed a proteomics analysis on renal influx and efflux blood collected from the same individual. Results Proteomics analysis revealed 662 proteins in influx blood and 809 in efflux. From these identified proteins, we selected complement C1q as a candidate; the plasma C1q level was significantly elevated in the renal efflux of donors. Moreover, the plasma concentration of C1q in a mouse model of diabetic nephropathy was significantly increased, in association with increases in blood glucose concentration and urinary protein content. Importantly, we demonstrated that the tendency of C1q to increase in the plasma of CKD patients was correlated with a decrease in their estimated glomerular filtration rate. Conclusion Overall, our results indicate that our approach of focusing on kidney-derived proteins is useful for identifying new CKD biomarkers and that C1q has potential as a biomarker of renal function.

Effects of estimated glomerular filtration rate on clinical outcomes in patients with intracerebral hemorrhage

Background The influence of chronic kidney disease (CKD) on the severity and prognosis of spontaneous intracerebral hemorrhage (ICH) has been scarcely investigated. We aimed to explore the association of admission estimated glomerular filtration rate (eGFR) levels with hemorrhagic stroke severity and outcomes in ICH patients. Materials and methods The patients enrolled in this study were from the China Stroke Center Alliance study (CSCA). Patients were divided into four groups according to differences in eGFR at admission (≥90; 60–89; 45–59; < 45). Multivariable logistic regression analysis was used to determine the association of the eGFR at admission with hemorrhagic stroke severity, in-hospital complications, discharge disposition, and in-hospital mortality after ICH. Results A total of 85,167 patients with acute ICH were included in the analysis. Among them, 9493 (11.1%) had a baseline eGFR<60 ml/min/1.73 m2. A low eGFR was associated with an increased risk of in-hospital mortality [eGFR 60–89 ml/min/1.73 m2, odds ratio (OR) 1.36 (95% confidence interval (CI) 1.21–1.53); eGFR 45–59, 2.35 (1.97–2.82); eGFR<45, 4.18 (3.7–4.72); P for trend < 0.0001], non-routine discharge [eGFR 60–89, 1.11 (1.03–1.2); eGFR 45–59, 1.16 (1–1.35); eGFR<45, 1.37 (1.23–1.53); P for trend < 0.0001], hemorrhagic stroke severity [eGFR 60–89, 1 (0.95–1.05); eGFR 45–59, 1.39 (1.26–1.53); eGFR<45, 1.81 (1.67–1.96); P for trend < 0.0001], in-hospital complications of pneumonia [eGFR 60–89, 1.1 (1.05–1.14); eGFR 45–59, 1.3 (1.2–1.4); eGFR<45, 1.66 (1.57–1.76); P for trend < 0.0001] and hydrocephalus [eGFR 60–89, 0.99 (0.87–1.12); eGFR 45–59, 1.37 (1.1–1.7); eGFR<45, 1.54 (1.32–1.8); P for trend = 0.0139] after adjusting for confounding factors. With the decline in eGFR, the risk of hematoma evacuation increased in patients with an eGFR 45 to 59 ml/min/1.73 m2 (OR 1.48; 95% CI 1.37–1.61). No significant association between differences in eGFR at baseline and in-hospital complication of recurrent intracerebral hemorrhage was observed. Conclusions Low eGFR at baseline was associated with an increased risk of in-hospital mortality, non-routine discharge, hemorrhagic stroke severity and in-hospital complications such as pneumonia, hydrocephalus and hematoma evacuation in acute ICH patients.

Association Between Baseline Buccal Telomere Length and Progression of Kidney Function: The Health and Retirement Study

We aimed to evaluate associations of baseline telomere length with overall and annual change in estimated glomerular filtration rate (eGFR) and trajectory of kidney function during an 8-year follow-up. A total of 3,964 participants of the Health and Retirement Study (HRS) were included. We identified three trajectory groups of kidney function: consistently normal (n=1,163 or 29.3%), normal to impaired (n=2,306 or 58.2%), and consistently impaired groups (n=495 or 12.5%). After controlling for age, sex, race, education, smoking, drinking, diabetes, heart disease, blood pressure, body mass index, total cholesterol, and hemoglobin A1c, participants with longer telomere length were 20% less likely (odds ratio [OR]=0.80, 95% confidence interval [CI]: 0.69-0.93, P=0.003) to have a normal to impaired kidney function trajectory than a consistently normal function trajectory. Telomere length was not associated with changing rate of eGFR over 8 years (P=0.45). Participants with longer telomere length were more likely to have consistently normal kidney function.

Early Trajectory of Estimated Glomerular Filtration Rate and Long-term Advanced Kidney and Cardiovascular Complications in Type 1 Diabetes

OBJECTIVE Rapid loss of estimated glomerular filtration rate (eGFR) within its normal range has been proposed as a strong predictor of future kidney disease. We investigated this association of eGFR slope early in the course of type 1 diabetes with long-term incidence of kidney and cardiovascular complications. RESEARCH DESIGN AND METHODS The annual percentage change in eGFR (slope) was calculated during the Diabetes Control and Complications Trial (DCCT) for each of 1,441 participants over a mean of 6.5 years and dichotomized by the presence or absence of early rapid eGFR loss (slope ≤−3% per year) as the exposure of interest. Outcomes were incident reduced eGFR (eGFR &lt;60 mL/min/1.73 m2), composite cardiovascular events, or major adverse cardiovascular events (MACE) during the subsequent 24 years post-DCCT closeout follow-up. RESULTS At DCCT closeout (the baseline for this analysis), diabetes duration was 12 ± 4.8 years, most participants (85.9%) had normoalbuminuria, mean eGFR was 117.0 ± 13.4 mL/min/1.73 m2, and 149 (10.4%) had experienced early rapid eGFR loss over the preceding trial phase. Over the 24-year subsequent follow-up, there were 187 reduced eGFR (6.3 per 1,000 person-years) and 113 MACE (3.6 per 1,000 person-years) events. Early rapid eGFR loss was associated with risk of reduced eGFR (hazard ratio [HR] 1.81, 95% CI 1.18–2.79, P = 0.0064), but not after adjustment for baseline eGFR level (HR 0.94, 95% CI 0.53–1.66, P = 0.84). There was no association with composite cardiovascular events or MACE. CONCLUSIONS In people with type 1 diabetes primarily with normal eGFR and normoalbuminuria, the preceding slope of eGFR confers no additional association with kidney or cardiovascular outcomes beyond knowledge of an individual’s current level.

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study

Background Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. Methods Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9–15 months after PTX (PTX group) or 9–15 months after diagnosis (non-PTX group). Results At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median − 4% vs. − 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80–89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. Conclusion Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.