Hypertension in Man with a Kidney Transplant: Role of Familial versus Other Factors

Abstract

Genetic factors are clearly involved in the pathogenesis of essential hypertension in man. In at least three rat models of genetic hypertension it is possible to transplant the hypertension with the kidney. To see whether or not the same is true for humans, we carried out a 2-year retrospective study of 50 selected recipients of a cadaver kidney. We correlated the following factors by multivariate statistical analyses: presence or absence of hypertension in the family of donor and recipients; donor’s and recipient’s age; mean blood pressure (MBP) and antihypertensive therapy (AHT) score during dialysis; months of dialysis and body surface before transplantation; body weight, plasma creatinine, prednisone dosage and cumulative rejections with MBP and AHT score at various time intervals after transplantation. The results obtained showed that, considering the recipients coming from normotensive families, the AHT score after transplantation was significantly greater (p < 0.05 1st and p < 0.0l 2nd year) in the patients receiving a kidney removed from donors with hypertensive families than in the patients receiving a kidney removed from donors with normotensive families. This difference was not present when the recipients coming from hypertensive parents were considered. AHT score after transplantation is also correlated with AHT score on dialysis (p < 0.01 1st and 2nd year), body weight (p < 0.02 1st and p < 0.01 2nd year), cumulative rejections (p < 0.025 1st and 2nd year) and inverse MBP after dialysis (p < 0.025 2nd year).

Two point mutations within the adducin genes are involved in blood pressure variation.

“…Thus, a generalized and genetically determined cellular defect involving faster Na transport across the renal cell membranes (19) was considered a probable cause of hypertension in MHS. Some of the erythrocyte and kidney dysfunctions seen in these rats have also been found in a subset (=25%) of human patients with primary hypertension (10,(20)(21)(22). In the rat model, the difference in membrane ion transport disappeared after elimination of the membrane skeleton, which indicated the involvement of some ofits components (23,24).…”

“…This work demonstrates an interaction between two independently segregating genes determining the expression of a single protein that is involved in inheritance ofprimary hypertension. Considering the many similarities in kidney and cellular dysfunctions between MHS and subsets of patients with primary hypertension (10,(20)(21)(22) and the very high degree of sequence homology between rat and human adducin (data not shown), it is possible that these molecular mechanisms are also relevant to humans.…”

The Kidney as a Determinant of Genetic Hypertension

“…Two other studies took the opposite approach by showing that grafts from donors with presumed hypertension 4 or from donors with known family background of essential hypertension 2 caused more severe hypertension and the need for more rigorous antihypertensive treatment in the recipients. The results of one of these studies 2 were later confirmed by a long-term historic prospective follow-up. 3 …”

Type 4 Cardiorenal Syndrome: Myocardial Dysfunction, Fibrosis, and Heart Failure in Patients with Chronic Kidney Disease

“…Many studies on essential HTN have implicated the kidney's ability to excrete sodium and maintain extracellular fluid volume as key elements in the pathogenesis of systemic HTN. In both rat [20] and human [21,22] models cross transplant of a kidney from a hypertensive donor to a normotensive host results in the development of HTN in the recipient thus implicating the kidney as the culprit [18]. Hypertension in CKD is associated with increased peripheral vascular resistance, major mechanisms responsible for this include activation of neurohormonal systems and increased arterial wall stiffness.…”