Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases

Background: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). Methods: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, > 25 to ≤30 kg/m2 and > 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. Results: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1–66.2) years and BMI 28.2 (IQR 24.9–32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI > 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m2, 7.9% in BMI 25–30 kg/m2 and 10.7% in BMI > 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97–1.01, p = 0.31) nor blood pressure or GN diagnosis. Conclusion: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression

Kidney disease patient representation in trials of combination therapy with VEGF-signaling pathway inhibitors and immune checkpoint inhibitors: a systematic review

No abstract available

The ‘other’ big complication: how chronic kidney disease impacts on cancer risks and outcomes

Cancer 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 to people without CKD, though 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 management of CKD

Sex differences in the diagnosis of advanced cancer and subsequent outcome in people with chronic kidney disease: an analysis of a national population cohort

Background: In the general population, advanced cancer stage at presentation is associated with poorer health outcomes. People with chronic kidney disease (CKD) have increased incidence and mortality from most cancer types. We sought to determine whether people with CKD were more likely to present with advanced stage cancer, whether this was associated with survival, and whether these associations varied by sex. Methods: Data were from Secure Anonymised Information Linkage Databank (SAIL), a Welsh primary care database with linkage to cancer and death registries. We included patients with a de- novo cancer diagnosis (2011-2017), and at least two kidney function tests in the two years prior to diagnosis. Estimated glomerular filtration rate based on serum creatinine (eGFRcr) was calculated using the CKD-EPI 2009 equation (mL/min/1.73m2). Logistic regression models determined odds of presenting with advanced cancer (stage 3 or 4 at diagnosis) by different values of eGFRcr at baseline. Cox proportional hazards models tested associations between eGFRcr at baseline and all-cause mortality risk (reference eGFR 75 to <90). Findings: There were 66,128 patients: 30,857 (46.7%) were female, mean age was 69.1 (standard deviation [SD] 13.8) years in females and 70.6 (SD 11.1) years in males; median eGFRcr at baseline was 78 (interquartile range [IQR] 63 – 90) mL/min/1.73m2 in both females and males. Over a median follow-up time of 3.1 (IQR 0.5 – 5.7) years in females and 2.9 (IQR 0.5-5.5) years in males, there were 17,303 deaths in females and 20,855 in males. An eGFRcr <30 was associated with higher odds of presenting with advanced cancer in males (OR 1.33 95% CI 1.09-1.62), but not in females (OR 1.17 95% CI 0.92-1.50); positive associations were primarily driven by prostate and breast cancers. With lower eGFRcr, hazards of cancer death increased in both sexes, but lower eGFRcr was associated with greater hazards of cancer death in females (eGFRcr <30: HR 1.71, 95% CI 1.56-1.88, p<0.001; male versus female comparison HR 0.88, 95% CI 0.78-0.90; p=0.037). Interpretation: CKD was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites (except prostate and breast), but was associated with reduced survival. Despite an initial survival advantage compared to males, females with CKD had disproportionately higher hazards of death. Though potential explanations for reduced survival after a cancer diagnosis are manifold, scrutiny of access to, efficacy, and safety of cancer treatments in people with CKD – particularly females with CKD – are warranted

A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes

No abstract available