The term “hypertension-mediated organ damage” (HMOD) (previously defined as “target organ disease”) defines hypertension-induced, subclinical structural, and/or functional changes in major organs (ie the heart, brain, retina, kidney, and vasculature). HMOD assessment is important in patients with hypertension since it helps identify high-risk or very high-risk hypertensive patients who may otherwise be misclassified.1 On the other hand, the term “established cardiovascular disease” refers to hypertensive target organ disease that induces clinical, radiographic, or analytical manifestations that could be symptomatic or easily detected by the usual clinical tests. The main organs affected by high blood pressure are the brain, heart, kidney, and vessels. Table 1 shows the categories of HMOD established by the 2018 European Clinical Guidelines for the Management of Hypertension. Kidney HMOD is considered where there is an estimated glomerular filtration rate below 60 mL/min (or KDIGO stages III-V) or an increased urinary albumin excretion (above 30 mg/g). The guidelines describe several forms of established cardiovascular (see Table 2) or renal disease, but the latter is not defined.1 On the other hand, the 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension considered established renal disease equivalent to chronic kidney disease (CKD), with eGFR <30 mL/min/1.73m2 or proteinuria (urinary albumin excretion >300 mg/24 h).2 The reasons for this change are not explained in the new guidelines. In 1914, Franz Volhard and Theodor Fahr3 introduced a novel classification of renal diseases. They differentiated between degenerative (nephroses), inflammatory (nephritides), and arterial (scleroses) diseases. Nephrosclerosis was divided into benign and malignant forms, of which the latter stood the test of time as a new disease entity. Fahr4 further divided benign nephrosclerosis into compensated and decompensated forms, depending on the presence or absence of glomerular injury. Volhard5 made the distinction between “pale” hypertension, characterized by generalized intense vasospasm and concomitant renal involvement, and “red” hypertension, in which patients looked robust and healthy and showed no renal or clinical signs. The former had a rapidly progressive course (malignant hypertension), whereas the latter was deceptively benign until stroke or heart attack ensued (“benign” essential hypertension). In 1925, Fahr4 further classified sclerotic diseases of the kidney into benign nephrosclerosis, characterized by pure arteriosclerotic changes, and malignant nephrosclerosis, in which productive endarteritis, periarteritis, and angionecrosis were most predominant among the pathologic features in his handbook description of Bright's disease. Schurmann and MacMahon6 gave a detailed characterization of the pathologic anatomy of malignant nephrosclerosis, which described structural changes in the layers of the vascular walls along the course of arterial trees in the whole body, as well as alterations of various organ tissues. The histological changes consisted of hyperplasia, histolysis with or without ensuing organization and concentric sclerosis, and fibrinoid necrosis, which usually developed, in order of vascular calibers, from the proximal segments of larger and small arteries to the distal arterioles and capillaries. Currently, “nephrosclerosis” is the easy way out for classifying a case of chronic renal insufficiency in a hypertensive and/or aging patient in the absence of a kidney biopsy. In the same way, real, histologically identified nephrosclerosis in white Europeans rarely leads to end-stage renal disease in the absence of malignant hypertension, but vascular lesions play a major role in inducing glomerular ischemic shrinking and sclerosis along with glomerulomegaly and focal segmental glomerulosclerosis. These lesions are accompanied by tubulointerstitial inflammation and fibrosis that predict the decline of renal function. Nevertheless, a specific linkage between mild-to-moderate essential hypertension and nephrosclerosis has been debatable, because these histologic abnormalities have also been described in the aging process, in diabetic nephropathy, and in advanced stages of various nephropathies.7, 8 It is likely that benign nephrosclerosis is usually over-diagnosed. Zucchelli and Zuccala9 investigated 136 patients who were diagnosed, after renal biopsy, as having “benign nephroangiosclerosis.” The final diagnoses were renovascular atherosclerotic disease (26.5%), renal cholesterol crystal emboli (29.4%), and true nephroangiosclerosis in only 44.1%. However, no other studies support these results. Zarif et al10 claimed that hypertensive nephropathy is less frequent in an end-stage renal disease (ESRD) population than is commonly assumed if strict “clinical” criteria are used, but only 4 patients in a sample of 2728 had a kidney biopsy; therefore, no histological confirmation supported this opinion. However, in a survey of the renal biopsy findings of 39 subjects enrolled in the African American Study of Kidney Disease pilot study,11 none of them showed any clinical evidence of diabetic or immune complex disease. All but one of the 39 biopsies showed arteriosclerosis and/or arteriolosclerosis. There were extensive global glomerulosclerosis and moderate interstitial fibrosis. Looking at the effects of antihypertensive treatment, a meta-analysis of 10 randomized controlled trials of antihypertensive drug therapy suggested that patients randomized to antihypertensive therapy (or more intensive therapy) did not show a significant reduction in their risk of developing renal dysfunction.12 None of the studies that were included in this meta-analysis had been designed to test the effect of blood pressure reduction on CKD progression; rather, they were all “post hoc” analyses using renal outcome criteria not defined in the original protocol. Moreover, a threshold blood pressure level for vessel lesions has not been identified. It is likely that vascular injury could appear with various degrees of hypertension in different patients. Hence, the renal vessels in some patients with high blood pressure may be exquisitely sensitive, and hypertensive nephropathy may result from minimally elevated pressures.13, 14 It should therefore be kept in mind that atherosclerosis and arteriosclerosis are multifactorial processes where hypertension is the most common but not the only cardiovascular risk factor.15 In the last decades, nephrosclerosis has been recognized as a progressively increasing cause of ESRD. Registries from the United States and Europe indicate that nephrosclerosis is one of the leading causes of ESRD. The United States Renal Data System (USRDS) Annual Data Report provides information on temporal trends in the major causes of ESRD. The adjusted rate of diabetes as a cause of ESRD declined between 2001 and 2014, from 175.2 to 156 per million population (PMP), whereas the rate of hypertension was relatively stable (102.3 PMP, 2001; 100.9 PMP) in 2014. The rate declined substantially for glomerulonephritis (from 38 to 27.2 PMP) and only slightly for cystic disease. As the overall adjusted rate of ESRD in 2014 was approximately 354 PMP, diabetes is attributed to 44% and hypertension to 29% of individuals who develop ESRD; these two leading causes therefore contribute to nearly three-quarters of the total.16 The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry 2016 Annual Report also showed that nephrosclerosis was a main cause of starting renal replacement therapy after diabetic nephropathy and glomerulonephritis/sclerosis.17 Although the survival rate of patients with malignant hypertension has considerably improved with the introduction of antihypertensive therapy, malignant hypertension is frequently complicated by kidney disease, and ESRD still remains a significant cause of morbidity and mortality in this patient group. In patients hospitalized with acute severe hypertension, the presence of acute kidney injury was associated with a greater risk of serious outcomes, including mortality and additional HMOD.18 If left untreated, the 1-year survival rate has been reported to be only 10%-20%, with most patients dying within 6 months. Effective treatment has led to a substantial improvement in the survival rate, with the rate at 5 years reaching 60%-75% in developed countries.19, 20 Moreover, even after starting renal replacement therapy, mortality rates are higher in nephrosclerosis patients than in other groups (ie interstitial nephropathies).21 Thus, we have a clinical entity described in 1914 with a distinctively histopathological description, well-known signs and symptoms, and increased cardiovascular risk. The question is, then, why do current clinical guidelines not include hypertensive nephropathy as a kind of established cardiovascular disease? Our proposal is that this disorder should be added to the list when malignant hypertension is diagnosed or severe renal vascular lesions are described in a kidney biopsy sample. This would also improve the previous definition (from the 2013 European Guidelines) of established cardiovascular renal disease based only on proteinuria and reduced estimated GFR, since it includes a clear relationship with the cardiovascular background of this disease. For comparison, a patient with reduced GFR and proteinuria due to other causes who starts renal replacement therapy has a better cardiovascular prognosis than those who have nephrosclerosis.21, 22 We think that this new definition would help to improve diagnosis and staging of cardiovascular patients. Otherwise, the current list of established cardiovascular diseases will remain incomplete, and the patients with these results will continue to be inadequately classified in terms of cardiovascular risk. The authors declare no conflict of interest. Nicolas R. Robles and Guido Grassi conceived of the presented idea. Francesco Fici and Elif Ari Bakir developed the theory and performed the bibliographic research. Nicolas R. Robles wrote the manuscript supervised by Guido Grassi and Francesco Fici. All authors discussed the issue and contributed to the final manuscript.