Hypertensive nephropathy: revisiting the causal link between hypertension and kidney disease

In 1936, Kimmelstiel and Wilson wrote, “owing to the reciprocal relationship of hypertension and kidney disease, the later states of both conditions often present great difficulty in differentiation to both pathologist and clinician” [1]. They concluded that benign hypertension and benign nephrosclerosis may show a parallel development, but in the early stages are not causally related. Although there is nothing benign about hypertension or nephrosclerosis, in 2024 their statement still holds true. In 2010, a study from Mayo Clinic, Rochester, reported the association of histologic abnormalities in the kidney in 1203 adult living kidney donors [2]. These donors had core-needle biopsy of the renal cortex obtained during surgical implantation of the kidney. The investigators reported a strong association between the presence of nephrosclerosis and age. For each decade of life, the prevalence of nephrosclerosis increased by approximately 10%. For example, for patients aged 18–29 years, the prevalence was 16% and among patients aged 70–77 years it was 73%. There was also an inverse relationship between age and measured glomerular filtration rate (GFR). Yet, the presence or absence of nephrosclerosis had no association with measured GFR. In other words, compared with younger patients, measured GFR was lower in older patients whether they had nephrosclerosis or not. The study suggested that nephrosclerosis was related to age as was GFR and that the presence of nephrosclerosis might not cause the observed lower GFR [2]. If nephrosclerosis is not cause a lower GFR, it raises the question whether it can cause hypertension (Fig. 1).