Chronic kidney disease and incident cancer risk: an individual participant data meta-analysis

Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent. This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors. A total of 21978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94-1.60), compared with an eGFR of 60-89mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90mL/min/1.73 m2 was 1.10 (95% CI 1.00-1.22). In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer.

Disclosure: R.J. Marriott: None. K. Murray: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. L. Flicker: None. D.J. Handelsman: None. G.J. Hankey: None. R. Wilkening: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. H.W. Vesper: None. G.A. Wittert: None. F.C. Wu: None. B.B. Yeap: None. Aims: Whether differences in sex hormones relate to cancer, particularly prostate cancer, risk in men remains uncertain. We sought to clarify associations of testosterone, dihydrotestosterone and sex hormone-binding globulin (SHBG) with cancer risk via individual participant data (IPD) meta-analyses of major prospective cohort studies of community-dwelling men with testosterone measured using mass spectrometry. Methods: Eligible studies were identified via systematic literature review to July 2019, with bridge searches to March 2024. Ten studies provided IPD (24,510 men; 276,931 participant-years; 2847 cancer deaths), one provided aggregate data (1535 men; 184 cancer deaths). Five studies provided IPD for incident prostate cancer (12,280 men; 151,373 participant-years; 918 events). Two-stage random effects meta-analyses controlled for age, prior cancer, BMI, marital status, alcohol, smoking, physical activity, hypertension and diabetes. Results: Men with baseline testosterone at or below the lowest quintile median (Q1; 8.2 nmol/L), had higher risk of cancer death relative to Q5 (Q1:Q5 hazard ratio [HR]=1.15, 95% confidence interval [CI]=1.01-1.31). Baseline testosterone was not associated with risk of incident non-fatal and fatal cancer, nor incident prostate cancer. Men with lower baseline dihydrotestosterone had a higher risk of cancer death (Q1:Q5 HR=1.21, 95%CI=1.04-1.41), but not incident fatal and non-fatal cancer. SHBG was non-linearly associated with risk of cancer death (Q3:Q5 HR=0.79, 95%CI=0.66-0.95; Q4:Q5 HR=0.85, 95%CI=0.76-0.96). SHBG was not associated with incident non-fatal and fatal cancer. Men with lower baseline SHBG had higher risk of incident prostate cancer (Q1:Q5, HR=1.31, 95%CI=1.08-1.60; Q2:Q5 HR=1.26, 95%CI=1.04-1.52). Relative heterogeneity was negligible to moderate (estimates of I2 had 95%CI from 0.0-65.4%). Summary estimates from IPD were robust to the inclusion of aggregate data. Conclusions: Men with lower testosterone or dihydrotestosterone concentrations had higher risk, and men with mid-range SHBG lower risk, of cancer death. Testosterone was not associated with prostate cancer risk, while men with lower SHBG had a higher risk of incident prostate cancer. Testosterone, dihydrotestosterone and SHBG are biomarkers for cancer risk. The association between SHBG and prostate cancer risk merits further evaluation. Presentation: Saturday, July 12, 2025

Artículo especial por el Día Mundial del Riñón: Las sociedades científicas españolas ante la guía ESC 2021 de prevención de la enfermedad vascular: generalizar la medida de la albuminuria para identificar el riesgo vascular y prevenir la enfermedad vascular

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

ABSTRACTBackgroundInvestigation of circulating metabolites associated with kidney function and chronic kidney disease (CKD) risk could enhance our understanding of underlying pathways and identify new biomarkers for kidney function.MethodsWe selected participants from the population-based Rotterdam Study with data on circulating metabolites and estimated glomerular filtration rate based on serum creatinine (eGFRcreat) available at the same time point. Data on eGFR based on serum cystatin C (eGFRcys) and urine albumin-to-creatinine ratio (ACR) were also included. CKD was defined as eGFRcreat <60 ml/min per 1.73 m2. Data on circulating metabolites (ntotal = 1381) was obtained from the Nightingale and Metabolon platform. Linear regression, linear mixed, and Cox proportional-hazards regression analyses were conducted to study the associations between metabolites and kidney function. We performed bidirectional two-sample Mendelian randomization analyses to investigate causality of the identified associations.ResultsWe included 3337 and 1540 participants with data from Nightingale and Metabolon, respectively. A total of 1381 metabolites (243 from Nightingale and 1138 from Metabolon) were included in the analyses. A large number of metabolites were significantly associated with eGFRcreat, eGFRcys, ACR, and CKD, including 16 metabolites that were associated with all four outcomes. Among these, C-glycosyltryptophan (HR 1.50, 95%CI 1.31;1.71) and X-12026 (HR 1.46, 95%CI 1.26;1.68) were most strongly associated with CKD risk. We revealed sex differences in the associations of 11-ketoetiocholanolone glucuronide and 11-beta-glucuronide with the kidney function assessments. No causal associations between the identified metabolites and kidney function were observed.ConclusionOur study indicates that several circulating metabolites are associated with kidney function which are likely to have potential as biomarkers, rather than as molecules involved in the pathophysiology of kidney function decline.

Time spent sitting is distinctly different from accumulating too little physical activity and may have independent deleterious effects. Few studies have examined the association between sitting time and site-specific cancer incidence. Among 69,260 men and 77,462 women who were cancer-free and enrolled in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, 18,555 men and 12,236 women were diagnosed with cancer between 1992 and 2009. Extended Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) of leisure-time spent sitting with total and site-specific cancer incidence. Longer leisure-time spent sitting, after adjustment for physical activity, BMI, and other factors, was associated with risk of total cancer in women (RR = 1.10; 95% CI, 1.04-1.17 for ≥6 hours vs. <3 hours per day), but not men (RR = 1.00; 95% CI, 0.96-1.05). In women, sitting time was associated with risk of multiple myeloma (RR = 1.65; 95% CI, 1.07-2.54), invasive breast cancer (RR = 1.10; 95% CI, 1.00-1.21), and ovarian cancer (RR = 1.43; 95% CI, 1.10-1.87). There were no associations between sitting time and site-specific cancers in men. Longer leisure-time spent sitting was associated with a higher risk of total cancer risk in women, and specifically with multiple myeloma, breast, and ovarian cancers, but sitting time was not associated with cancer risk in men. Further research is warranted to better understand the differences in associations between men and women. For women, these findings support American Cancer Society guidelines for cancer prevention to reduce sitting time when possible.

Background: Previously, it has been demonstrated that obesity is one of the strongest risk factors for incident chronic kidney diseases (CKDs). Currently, we examine the association between Body mass index (BMI) and CKD in first degree relatives (FDRs) of renal failure patients on hemodialysis. Materials and methods: In a cross-sectional study, 135 FDRs of end-stage renal disease (ESRD) patients on hemodialysis were included. Serum creatinine, uric acid, calcium, phosphate, and alkaline phosphatase were measured. Glomerular filtration rate (e-GFR) and albumin to creatinine ratio (ACR) were estimated. The height in Cm, weight in Kg was measured, and the BMI was calculated. Results: Females 64% were found to have a higher frequency than males 36%. The frequency of BMI categories was found to be 26.7% obese, 26.7% overweight, and 46.6. % normal weight. The mean BMI was (26.0 ± 6.62). The prevalence of CKDs is 19.3% among relatives. CKDs were more frequent 42.3 % in obese, followed by 30.8 % in overweight and 26.9% in normal-weight relatives. Obese and overweight relatives have significantly higher ACR than normal weight (P= 0.012). GFR found to be significantly higher in obese and overweight relatives than normal weight (P = 0.000). GFR was negatively correlated with BMI (R = - 0.430, P = 0.000). Conclusion: Obese and overweight RF relatives had higher ACR and lower eGFR. Therefore, obese and overweight members are at higher risk of developing CKD. Keywords: CKDs, Family members, BMI, Obesity, ACR, eGFR. Corresponding author: Abozaid Mohammed Hamid, email: elemam69@hotmail.com

A Nested Case–Control Study on Plasma Vitamin E and Risk of Cancer: Evidence of Effect Modification by Selenium

Development of a Genetic Risk Score for Albuminuria in Pediatric Patients with Sickle Cell Anemia

The Kidney Failure Risk Equation (KFRE) predicts the need for dialysis or transplantation using age, sex, estimated glomerular filtration rate (eGFR), and urine albumin to creatinine ratio (ACR). The eGFR and ACR have known biological and analytical variability. We examined the effect of biological and analytical variability of eGFR and ACR on the 2-year KFRE predicted kidney failure probabilities using single measure and the average of repeat measures of simulated eGFR and ACR. Previously reported values for coefficient of variation (CV) for ACR and eGFR were used to calculate day to day variability. Variation was also examined with outpatient laboratory data from patients with an eGFR between 15 and 50 mL/min/1.72 m2. A web application was developed to calculate and model day to day variation in risk. The biological and analytical variability related to ACR and eGFR lead to variation in the predicted probability of kidney failure. A male patient age 50, ACR 30 mg/mmol and eGFR 25, had a day to day variation in risk of 7% (KFRE point estimate: 17%, variability range 14% to 21%). The addition of inter laboratory variation due to different instrumentation increased the variability to 9% (KFRE point estimate 17%, variability range 13% to 22%). Averaging of repeated measures of eGFR and ACR significantly decreased the variability (KFRE point estimate 17%, variability range 15% to 19%). These findings were consistent when using outpatient laboratory data which showed that most patients had a KFRE 2-year risk variability of ≤ 5% (79% of patients). Approximately 13% of patients had variability from 5–10% and 8% had variability > 10%. The mean age (SD) of this cohort was 64 (15) years, 36% were females, the mean (SD) eGFR was 32 (10) ml/min/1.73m2 and median (IQR) ACR was 22.7 (110). Biological and analytical variation intrinsic to the eGFR and ACR may lead to a substantial degree of variability that decreases with repeat measures. Use of a web application may help physicians and patients understand individual patient’s risk variability and communicate risk (https://mccudden.shinyapps.io/kfre_app/). The web application allows the user to alter age, gender, eGFR, ACR, CV (for both eGFR and ACR) as well as units of measurements for ACR (g/mol versus mg/g).

Background: Higher aortic valve calcium (AVC) burden is associated with an increased risk of cardiovascular disease (CVD) and non-CVD. Despite shared risk factors between AVC and chronic kidney disease (CKD), the association of AVC with incident albuminuria is unknown. Methods: We examined 5,464 MESA participants who had AVC quantified by cardiac CT at Visit 1 (2000-02), an eGFR of ≥60 mL/min/1.73 m2, a normal spot urine albumin to creatinine ratio (ACR) (&lt;30 mg/g at baseline), and at least 1 follow up ACR measurement. AVC was analyzed as a log transformed variable, due to its right skewed distribution, and categorized as 0, 1-99, and ≥100. Incident albuminuria was defined as ACR ≥30 mg/g. We performed multivariable Cox proportional hazard regression along with mixed-effect linear regression models to examine the association of AVC with incidence, and progression of albuminuria per 5 years follow up, respectively. Models adjusted for baseline eGFR, sociodemographic and CVD risk factors, with further adjustment for coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype. Results: At MESA Visit 1, participants had a mean age 61.6±9.9 years, 2894 (53%) were women, and 616 (11%) had AVC &gt; 0. During a median follow up of 14.2 years, 921 (17%) developed albuminuria. There was a significantly increased rate of incident albuminuria with higher AVC values (p &lt; 0.001) (Figure). In multivariable adjusted models, a higher risk of incident albuminuria was observed when AVC was examined as a continuous variable (per log-unit [AVC+1]) HR 1.05; p = 0.03 and for participants with AVC ≥100 HR 1.43; (p = 0.02) compared to AVC=0, but not for participants with AVC 1-99 (HR 1.13; p = 0.29). A significant progression in log transformed ACR was observed for AVC as a continuous variable (β 0.03; p &lt; 0.001) along with participants who had AVC 1-99 (β 0.13; p &lt; 0.001), and AVC ≥100 (β 0.16; p = 0.001), compared to AVC=0. The associations between continuous AVC and incident albuminuria remained after further adjusting for CAC score (p = 0.04), Lp(a) (p = 0.03), and the APOE-ε4 genotype (p = 0.04). The signal was consistent for ACR progression after further adjusting for CAC score (p &lt; 0.01), Lp (a) (p &lt; 0.01), and the APOE-ε4 genotype (p &lt; 0.01). Conclusions: In a multi-ethnic cohort of participants free of CVD and CKD at baseline, AVC was independently associated with a higher risk of incident albuminuria and progression of ACR.

Chronic kidney disease is the most common complication of diabetes. Without interventions, diabetic kidney disease (DKD) progresses to end stage renal disease (ESRD). In the United States, minority ethnic groups (e.g. African Americans) are disproportionately burdened by DKD. While genetic factors contribute to the disparities in DKD, little is known about the underlying cellular and molecular mechanisms. Several studies have shown that inflammation plays a role in the pathophysiology of DKD and the fibrosis observed in diabetic nephropathy. The goal of the current study was to determine the association between specific inflammation markers and diabetic kidney injury in diabetic African American men, an underrepresented sub‐population with high risk for diabetes and DKD. To this end, diabetic patients with (n=21) and without (n=88) diagnosed kidney disease were recruited at the Cone Health Community Health and Wellness Center in Greensboro, NC. Age‐matched, non‐diabetic subjects (n=81) served as controls. Assays for albumin and creatinine were used for biochemical assessment of kidney function. The diabetic patients were then stratified into three groups based on their albumin to creatinine ratios (ACR); normoalbuminuria (ACR&lt;30 mg/g), microalbuminuria (30 mg/g&lt;ACR&lt;300 mg/g), and macroalbuminuria (ACR&gt;300 mg/g). Enzyme‐linked immunosorbent assays were used to measure the plasma and urinary levels of five inflammatory markers; two markers of system‐wide markers (adiponectin and C‐reactive protein (CRP)); and three markers involved in renal inflammation (tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), intercellular cell adhesion molecule‐1 (ICAM‐1)). Plasma levels of the pro‐inflammatory cytokines TNF‐α and IL‐6 were significantly higher in diabetic patients with micro‐ and macroalbuminuria when compared to non‐diabetic controls and diabetic patients with normoalbuminuria. Urinary levels for ICAM‐1 and the anti‐inflammatory cytokine, adiponectin, were higher in diabetic patients with macroalbuminuria than the other three groups. Plasma CRP was elevated in diabetic subjects compared to non‐diabetic controls, but did not correlate with the extent of diabetic kidney injury. In contrast, urinary ICAM‐1, plasma TNF‐α, and plasma adiponectin had moderate positive correlations with ACR. The plasma levels for ICAM‐1, IL‐6, and CRP were not significantly correlated with the ACR. The data suggest that certain inflammation pathways play a role in the pathogenesis of DKD in African American men.Support or Funding InformationThis study was supported by the Minority Men's Health Initiative (MMHI) through NIH/NIMHD Center Award # U54MD008621 (CFDA 93.307), Sub‐Awards # HU140400 (to RHN and EMO) and HU150006 (to EMO and SHH); and the NIH/NIGMS Award Number SC3GM102049 to EMO.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Aspirin in the prevention of cancer

The association of chronic kidney disease and dialysis treatment with foot ulceration and major amputation

ABSTRACTCancer is the second leading cause of death in people with chronic kidney disease (CKD) after cardiovascular disease. The incidence of CKD in patients with cancer is higher than in the non-cancer population. Across various populations, CKD is associated with an elevated risk of cancer incidence and cancer death compared with people without CKD, although the risks are cancer site-specific. Higher risk of cancer is detectable in mild CKD [estimated glomerular filtration rate (eGFR) 60–89 mL/min/1.73 m2], although this risk is more obvious if sensitive markers of kidney disease are used, such as cystatin C. Independent of eGFR, albuminuria is associated with increased risk of site-specific cancer incidence and death. Here, we explore the potential mechanisms for the increased risk of cancer observed in CKD, including patient factors (shared risks such as cardiometabolic disease, obesity, smoking, diet, lifestyle and environment), disease (genetic, inflammatory and infective) and treatment factors. In particular, we discuss the ways in which renal adverse events associated with conventional chemotherapies and newer systemic anti-cancer therapies (including targeted and immunotherapies) may contribute to worse cancer outcomes in people with CKD. Finally, we review the potential benefits of acknowledging increased risk of cancer in risk prediction tools used for the management of CKD.