Dr. Arthur C. Guyton (1919-2003) was one of the greatest physiologists of our time. One of Dr. Guyton’s many seminal contributions to medicine was to establish the role of kidneys in long-term blood pressure regulation via a mechanism known as pressure natriuresis.
Even though essential hypertension is considered a systemic multifactorial disorder associated with complex genetic traits, there is a significant amount of evidence supporting Guyton’s view, i.e. the kidneys play an important role in the genesis of hypertension via extracellular fluid volume (ECF) expansion caused by an intrinsic renal defect in sodium chloride excretion. Multiple observations support this hypothesis:
(1) Essential hypertension is cured when rats and patients receive a kidney transplant. If essential hypertension was a systemic disease that secondarily involved the kidney, then a well-tolerated allograft would not cure that disease. In contrast, hypertension went into remission after kidney transplantation.
(2) Multiple epidemiological observations have clearly shown that essential hypertension is rarer in societies consuming a low salt diet. For instance, the Yanomami Indians, a tribe of the Amazon rainforest that has had very little contact with the Western civilization, have a very low sodium intake as demonstrated by their 24-h urine Na+ excretion of 0.9 mEq. The mean systolic and diastolic blood pressure levels in Yanomami Indians are 95.4 and 61.4 mmHg respectively.
(3) Many mendelian forms of hypertension such as Liddle syndrome , Gordon syndrome , and Activating Mutation of Mineralocorticoid Receptor are associated with mutations in genes that encode renal sodium transporter proteins or related molecules.
(4) Many population studies have identified single nucleotide polymorphisms and haplotypes in genes encoding renal sodium transporter proteins or related molecules such as ENaC or WNK1 that are associated with blood pressure variation, hypertension severity, and response to certain diuretics.
Nephrologists could proudly say now, thanks to Dr. Guyton, that blood pressure “goes with the kidney”.