Renal “hyperfiltrators” are at elevated risk of death and chronic diseases

Abstract

BackgroundThe definition of glomerular hyperfiltration has not been agreed upon and the pathophysiological mechanisms have not been well explored. Low serum creatinine concentrations may be associated with increased risk of coronary heart disease (CHD) or cardiopulmonary events the impact of which needs further study.MethodsConsecutive applicants to a cardiovascular hospital free of moderate/severe chronic kidney disease (age 55.6 ± 8.2 years) were grouped into those without (“healthy”, n = 469) and with CHD (320 stable and acute coronary syndrome cases) at baseline and into sex-specific quartiles of CKD-EPI equation-estimated glomerular filtration rate (eGFR). New or recurrent cardiovascular (myocardial infarction, stroke, heart failure [HF]) events, obstructive pulmonary disease (COPD) and death were determined during 3-years’ follow-up.ResultsAmong 25 deaths and 75 cardiopulmonary events, HF was the leading nonfatal event. Age, serum uric acid and left ventricular ejection fraction proved the best independent inverse covariates of eGFR in the “healthy” sample. The highest eGFR quartile (“hyperfiltrators”), exhibiting significantly lower serum LDL-cholesterol levels, significantly predicted the combined outcome (at a RR of 6) in “healthy” subjects, after adjustment for sex, age, body mass index, smoking status and presence of hypertension. This finding was paralleled by the highest eGFR quartile calculated also by the MDRD equation, replicating this also in the CHD group.ConclusionRenal “hyperfiltrators” represent individuals with autoimmune activation (involving serum creatinine, partly escaping assay), are misclassified into optimal renal function and actually are at significantly higher risk of death, HF or cardiopulmonary events. Low serum creatinine levels may represent a clue to the existence of autoimmune activation.

Increased Microalbuminuria Risk in Male Cigarette Smokers: Results from the “Olivetti Heart Study” after 8 Years Follow-Up

“…This relation was so far evaluated only in selected groups of population, such as patients affected by diabetes mellitus, primary kidney disease [3] or hypertension [4]. Our data indicated, for the first time, that in subjects without evidence of initial renal damage, i.e.…”

“…Moreover, epidemiologic studies proved that cigarette smoking is associated with an increased risk of chronic kidney disease progression and kidney failure in patients affected by diabetes and hypertension [4-5]. …”

Underlying Autoimmune Activation Rendering Paradoxical Non-Linear Relationship between Biomarkers and Cardiometabolic Risk

“…Renal "hyperfiltrators" represent individuals with autoimmune activation (involving serum creatinine partly escaping assay) and are misclassified into a category of "optimal" renal function. By contrast, they are at significantly higher risk of cardiopulmonary events and death due to the underlying autoimmune process [20].…”

“…Low serum creatinine levels (<0.7/<0.8 mg/dl) may represent a clue to the existence of autoimmune activation [19,20]. This may again manifest itself in one sex in the general population.…”

Cigarette smoking and cardio-renal events in patients with atherosclerotic renal artery stenosis

“…The deleterious effects of smoking on kidney function have been reported in patients with diabetes mellitus and primary kidney diseases including polycystic kidney disease, glomerulonephritis and lupus nephritis [3][4][5][6][7][8][9]. Recently, epidemiologic studies demonstrated that smoking increases the risk of chronic kidney disease progression and kidney failure in patients with diabetes and hypertension [10,11]. However, the importance of active smoking in patients with renal artery stenosis has not been described.…”