{"doi":"10.1111/jch.14186","title":"Chronic kidney disease: Definition, updated epidemiology, staging, and mechanisms of increased cardiovascular risk","abstract":"Chronic kidney disease (CKD) is a heterogeneous group of disorders that manifest in various ways depending upon the severity of disease and the underlying cause(s).1 Chronic kidney disease is defined by the presence of kidney damage or decreased kidney function for at least three months, irrespective of the cause.2 Kidney damage generally refers to pathologic anomalies in the native or transplanted kidney, established via imaging, biopsy, or deduced from clinical markers like increased albuminuria—that is, albumin-to-creatinine ratio (ACR) >30 mg/g (3.4 mg/mMol)—or urinary sediment alterations; decreased kidney function refers to a reduced glomerular filtration rate (GFR), which is usually estimated (eGFR) from the serum concentration of creatinine.3 According to the US Centers for Disease Control and Prevention (CDC), ~37 million people in the United States—~15% of adults—are estimated to have CKD. Of note, 90% of adults with CKD do not know they have it and 1 in 2 people with very low kidney function who are not on dialysis are not aware of the fact that they have CKD.4 Diabetes and hypertension are the major causes of CKD in adults: According to the CDC, 1 in 3 adults with diabetes and 1 in 5 adults with hypertension may have CKD. According to the current CDC statistics, CKD is more common in people aged 65 years or older (38%) than in people aged 45-64 years (13%) or 18-44 years (7%), and is slightly more common in women (15%) than men (12%); moreover, African Americans are about 3 times more likely than whites to develop ESKD.5 In the Western world, the main risk factor for CKD development is diabetes, which is present in 30%–50% of CKD patients.6 Hypertension and smoking are other strong factors increasing the risk of CKD as well as the speed of its progression.6 Instead, in India, Asia, and Sub-Saharan Africa, the leading cause of CKD is glomerulonephritis, followed by CKD of unknown genesis, probably prompted by soil pollution with heavy metals and pesticides and excessive use of herbal-based traditional medicines.7 HIV contributes significantly to CKD due to the direct glomerular interstitial damage caused by HIV per se and to the significant nephrotoxicity of antiretroviral therapies.6 Despite the diverse etiologies, the main mechanism of CKD is believed to heavily rely on microvasculature dysfunction. Indeed, hypertension, dyslipidemia, and smoking act on the endothelium in glomeruli and interstitium, eventually resulting in the infiltration of macrophages and other inflammatory cells.6 Macrophages activate mesangial cells in glomeruli, facilitating their expansion and extracellular matrix production, which results in substitution of capillaries with matrix, thus reducing the surface through which the blood filtration occurs resulting in a net filtration decrease and accumulation of uremic toxins.8 At the same time, glomerulosclerosis is accompanied by dysfunction of podocytes, cells playing a central role in the proper function of the glomerular filtration barrier. As a result, proteinuria develops and tubular epithelium becomes exposed to proteins such as albumin, compliment system components, and cytokines which further exacerbate the inflammatory response.8 Accumulation of damaged DNA in tubular epithelium through the chronic inflammation produces cell cycle arrest, accompanied by a switch to a specific type of secretory phenotype, which further facilitates pro-fibrotic modifications.8 Uncontrolled accumulation of extracellular matrix decreases the capillary density, thus obstructing oxygen and nutrient supply to tubular cells. Eventually, the kidney tissue ends up with tubular atrophy and ubiquitous fibrosis. The classification and staging of CKD are based on the cause(s), on the level of albuminuria, and on glomerular filtration rate (GFR).2 Kidney failure represents the end stage of CKD (ESKD: end-stage kidney disease) and is defined as severely reduced kidney function or treatment with dialysis. CKD has been","journal":"Journal of Clinical Hypertension","year":2021,"id":149329,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":108,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":497601,"name":"Pasquale Mone","orcid":"0000-0001-6267-5845","position":1,"is_corresponding":false},{"id":490256,"name":"Stanislovas S. Jankauskas","orcid":"0000-0002-0843-5098","position":2,"is_corresponding":false},{"id":225557,"name":"Jessica Gambardella","orcid":"0000-0001-5563-3153","position":3,"is_corresponding":false},{"id":225561,"name":"Gaetano Santulli","orcid":"0000-0001-7231-375X","position":4,"is_corresponding":false},{"id":635008,"name":"Scott Wilson","orcid":"0000-0001-5436-5863","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:42:51.282401Z","pmid":"33455061","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}