Joseph H. Magee

Renal Homotransplantation in Man in Modified Recipients

Studies are presented in six patients receiving renal homotransplants from non-twin donors. A cadaver donor was used in one instance, a brother or sister in three instances, and a mother or father in two. No attempt was made to match the subgroups of the blood between donor and recipient. All six kidney transplants functioned well enough to maintain the patient. The function of the transplant persisted up to death in two patients who died of complications of radiation aplasia. None of the patients, however, have yet passed the one-year milestone required for assessment of long-term results. Several factors relating to the early management of patients with renal homotransplants are discussed. (P.C.H.)

STUDIES OF RENAL HOMOTRANSPLANTATION IN MAN.

During the past 16 months, we have carried out 3 1 nontwin renal homotransplants in man at the Medical College of Virginia. The present report constitutes a brief summary of some of the observations made in this group of patients and certain data accumulated in the experimental laboratory which were subsequently applied to clinical cases. The first four cases were treated with “sublethal” total-body irradiation and prednisone, followed subsequently in two cases by Imuran. All subsequent cases have been treated by Imuran, prednisone, and local irradiation to the transplanted kidney.l.2 All patients were in the terminal stages of chronic renal failure. The earlier cases were prepared and maintained by peritoneal dialysis, while the later cases were prepared by hemodialysis on the Kiil k i d n e ~ , ~ using the chronic A-V shunt technique described by Scribner and his colleague^.^ The results to be discussed will be considered under several headings.

General and Regional Circulatory Effects of Synthetic Bradykinin in Man

The general and regional circulatory effects of synthetic bradykinin were investigated in 19 healthy volunteers. During intravenous infusion of bradykinin (25 μg/min) mean arterial pressure decreased initially, but returned to control levels within a few minutes. Heart rate increased during the hypotensive period, but subsequently returned toward preinfusion levels. Cardiac output increased, mainly as a result of increased stroke volume, and systemic vascular resistance decreased. Blood flow to hand increased during such infusions of bradykinin, but blood flow to forearm was not altered significantly. Intravenous infusions of 40 μg/min produced an increase in blood flow to the forearm, resulting solely from cutaneous vasodilatation in most subjects. The distensibility of hand veins increased both during intravenous infusions of 25 μg/min and during infusions of 0.2 μg/min into the brachial artery. Renal clearance of inulin was slightly decreased during infusion of 25 μg/ min bradykinin; there was no detectable change of PAH clearance.

Changes in renal function associated with drug or placebo therapy of human hypertension

Abstract Results in 103 participants in a double-blind study of antihypertensive agents, in whom inulin and para-aminohippurate clearances were determined prior to therapy, are reported. Twenty-six of the patients were lost to a follow-up longer than two years; forty-two have died since inception of the study (mean survival time 15.8 months); thirty-five of the patients have returned for three or more annual reevaluations of renal function. A third of the deaths were from uremia, a third from congestive heart failure or myocardial infarction, 21.3 per cent from cerebral vascular accidents and 12 per cent from miscellaneous causes. (Table II.) The deceased group included a half of those originally seen with diastolic pressure of 130 mm. Hg or more (mean survival time 13.2 months) and three-fourths of those with eyegrounds of grade 3 or 4 (mean survival time 9.2 months). The thirty-five patients who returned for longer follow-up include fifteen whose diastolic pressure fell 15 mm. Hg or more following initiation of a drug or placebo regimen and twenty whose diastolic pressure decreased to a lesser degree, or rose. In the former group mean inulin clearance had decreased 15 ml. per minute per 1.73 M 2 . at the time of latest reevaluation and in the latter group 17 ml. per minute per 1.73 M 2 . In the former group the mean para-aminohippurate clearance had increased 24 ml. per minute per 1.73 M 2 ., while in the latter it had decreased 33 ml. per minute per 1.73 M 2 . However, when subjected to statistical analysis, these differences are insignificant (0.1 The results obtained do not confirm the supposition that decreased target organ damage accompanies decreased diastolic pressure, over a study period of three years, assuming the appropriateness of selecting the kidney as a representative target organ.

Exertional idiopathic paroxysmal myoglobinuria: Evidence for a defect in skeletal muscle metabolism

Abstract A fifty-four year old Negro man who at age forty-four began to experience episodes of myoglobinuria precipitated by exertion is described. Nine years following his first episode of myoglobinuria atrophy of the proximal muscle groups of his limbs developed. Forearm muscle metabolism was normal at rest. The capacity for performing muscular work was markedly diminished due to the early development of fatigue and pain in the exercising muscles. Exercise tolerance increased following administration of glucose, glucagon, or glucose and insulin. The patients energy expenditure for performing muscular work was increased in comparison to that of a control subject. A large portion of this energy was derived from anaerobic metabolism. These abnormalities suggest the presence of uncoupling of oxidative phosphorylation in skeletal muscle during activity.

MASSIVE DIURESIS FOLLOWING RENAL HOMOTRANSPLANTATION.

Summary Characterization of the diuresis experienced by a 19-year-old recipient of a renal homotransplant revealed certain features in common with the diuresis seen in experimental osmotic diuresis in normal subjects, and with the diuresis seen following relief of urinary tract obstruction and in other salt-wasting syndromes. The preponderant unreabsorbed solutes were sodium and chloride rather than urea. Since the salt wasting state did not persist, it may have been due to volume expansion and to an enhanced filtration rate, rather than to a tubular reabsorptive defect.

Renal extraction of monosubstituted guanidines.

Summary Renal extractions of arterial glycocyamine and arginine were determined by sampling urine and right renal venous blood in 25 males studied during diuresis because of hypertensive or urologic disease. Both positive and negative extractions of both compounds were observed. The finding of negative extractions is compatible with the capacity for renal synthesis of these compounds shown in vitro in other species. The finding of positive extractions is discussed in terms of utilization of these compounds in local renal metabolism, in addition to previously postulated roles as substrates for extra-renal syntheses.