Ralph Goldman

Anatomic and physiologic age changes in the kidney

Cross-sectional studies of renal function in man indicate there is a progressive decline with age after the age of 40 years. The blood vessels, glomeruli, tubules and interstitium are all potential sites of primary involvement in the aging process as well as for renal disease. Regardless of the anatomic structure initially affected, most chronic renal conditions evolve with destruction of the entire nephron. Whether the observed decrease in renal function associated with aging is the result of intervening pathologic processes, e.g. ischemia (vascular obliteration) or infection, or is the result of a more insidious involutional process, it has generated much discussion but few answers. The purpose of this report is to review the descriptive studies documenting the changes in renal morphology and physiology with age and to focus on what is known about the mechanisms involved in these losses of renal substances and function.

Creatinine excretion in renal failure.

Summary and Conclusions 1. The urinary excretion of creatinine decreases as the filtration rate falls and the serum creatinine rises in chronic renal failure. This is especially apparent when the serum creatinine exceeds 6 mg/100 ml. 2. This decrease is due to either a reduced rate of creatinine production or an alternate excretory pathway. The muscle mass is not significantly decreased, and therefore should not account entirely for decreased production. Alternative excretion in the urine as creatine, or in the feces as creatinine is excluded by the data presented. Other possible mechanisms are suggested, but have not been studied.

Kidney transplantation: A comparison of results using cadaver and related living donors☆

Abstract One hundred renal homotransplantations were performed between April 15, 1964 and December 15, 1967. Fifty live donor kidneys and fifty cadaver donor kidneys were transplanted to ninety-five patients during this period. The data are summarized as of June 15, 1968, at which time 80 per cent of the living donor recipients were still alive and 70 per cent had functioning kidneys, whereas 60 per cent of the cadaver donor recipients were still alive and 48 per cent had functioning kidneys. An actuarial projection indicated kidney function in 66 per cent living donor and 40 per cent cadaver donor recipients at three years. The largest number of failures in both groups occurred within the first three months, a smaller number during the second three months, with relatively small subsequent attrition. The difference between the two groups was characterized by a greater rate of failure during the first period in the cadaver donor recipients, but similar survival subsequently. Donor and recipient age appeared to be important factors in cadaver donor success but were less important with the living donors. The types of complications were comparable in both groups. The drug regimens were similar. Hypertension was significantly more frequent and the level of serum creatinine higher in the cadaver donor recipients than in the living donor recipients. However, response to antihypertensive therapy was usually satisfactory and, although higher, the serum creatinine level in the cadaver donor recipients appeared to be stable in most instances.

Rest: Its Use and Abuse in the Aged†

Rest is essential, even though its exact physiologic functions and quantitative requirements are far from clear. Sleep appears to be the primary and most imperative form of rest. The nature, the role, and the necessity for rest as simple relaxation and leisure are elusive and poorly defined. The rejuvenating effects of leisure and diversion are apparent, over and above the pleasure and enjoyment they bring to life. Absolute rest has in the past been an important component of therapy for disease and injury. Relatively recent evidence that bed rest may prolong invalidism and contribute to complications, combined with the development of more specific therapies, has reduced both the necessity and prescription for bed rest. However, it should be emphasized that the data are incomplete, and in some situations such as myocardial disease or hepatitis, there is no final proof that early activity does not have late effects. This article presents a perspective and a classification that can serve as a more precise and restrictive context in which the concept of rest can be used and prescribed. Further study is necessary to establish whether rest which is not sleep, not diversion, nor a discredited prescription of immobility, is physiologically or psychologically valid, and to determine a more precise measure of required “dosage.”

Diagnostic Problems in Retroperitoneal Disease

Excerpt Dr. Willard E. Goodwin: The urologist finds the retroperitoneal space a veritable jungle of strange things; I shall try to give a birds eye view of some of the conditions which may be conf...

DIURNAL VARIATION IN THE URINARY EXCRETION OF NEUTRAL LIPID-SOLUBLE REDUCING STEROIDS IN CONGESTIVE CARDIAC FAILURE AND CIRRHOSIS OF THE LIVER WITH ASCITES

Pincus and his collaborators (1-4) have demonstrated that there is a normal cycle of excretion of neutral, lipid-soluble reducing steroids which has a maximum between 7 a.m. and 11 a.m., decreases during the afternoon, and is at a minimum during the night. This corresponds to the normal excretory cycle of other urinary constituents (5-13). It has also been shown that in congestive cardiac failure (14, 15) and in cirrhosis of the liver with ascites (16) there is a reversed diurnal cycle of water and sodium excretion, with maximum values during the night in a high proportion of the individuals studied. This investi

Salt-losing syndromes following renal transplantation.

Abstract Persistent renal salt-wasting beyond the immediate postoperative period is an unusual complication in patients with kidney transplantation. We describe two patients with renal homografts who presented with renal salt-wasting of different etiologies accompanied by marked extracellular volume contraction. In Case 1, isolated hypoaldosteronism, rarely seen in patients with chronic uremia, was present before and after transplantation. The metabolic disorder responded to treatment with 9-α-fluorohydrocortisone with complete recovery. In Case 2, renal salt-wasting occurred immediately after transplantation and persisted for more than three weeks. In the absence of common causes of impaired renal salt conservation, e.g., osmotic urea diuresis, enhanced glomerular filtration rate, ischemic or mechanical damage to the graft, it was speculated that persistent release of “third factor” due to chronic pretransplantation extracellular volume expansion was of pathogenetic significance. This could be viewed in analogy with the persistent hormone secretion in the absence of normal stimuli observed in post-transplant secondary hyperparathyroidism.

Effects of Hypophysectomy and Growth Hormone on Renal Compensatory Hypertrophy in Rats.

Summary The effect of hypophysectomy on renal compensatory hypertrophy (RCH) was observed in unilaterally nephrectomized rats receiving no therapy and those receiving replacement therapy and was compared to the RCH attained by non-hypophysectomized unilaterally nephrectomized rats at 2, 5, and 10 days. In the latter group there was an initial rapid RCH seen at day 2 which continued, but at a slower rate, through day 10. In the hypophysectomized group without replacement therapy there was also an initial RCH in the first 48 hours. However, instead of the RCH continuing there was a regression in kidney size at 5 days and with no subsequent change at 10 days. In the hypophysectomized group receiving hormone replacement there was an initial RCH comparable to the other two groups, but the further renal enlargement at 10 days was much less than that of the non-hypophysectomized animals. The results of this experiment and of other reported studies imply the existence of a renotropic factor which is not produced in the pituitary, but which requires an intact pituitary for full effectiveness.

Creatine synthesis after creatinine loading and after nephrectomy.

Summary Previously, it was demonstrated that nephrectomy causes a 90% reduction in creatine synthesis in rats. In the present study, nephrectomy was found to cause a 37.5% decrease in methylation of guanidinoacetic acid (GAA)-2-C14. Rats loaded with creatinine by intraperitoneal injection demonstrated a 30% reduction in GAA methylation and a 45% reduction in total synthesis of creatine from glycine. It is concluded that chronic renal disease causes reduced creatine (and creatinine) synthesis both by loss of the renal mechanism and by interference with methylation. It is suggested that extra-renal (pancreatic?) synthesis may be relatively increased to partially compensate for these 2 inhibitory factors.

Ethical Confrontations in the Incapacitated Aged

ABSTRACT: Effective factors that have made it possible for an increasing proportion of the population to reach old age have nevertheless presented society with new problems and ethical dilemmas. Several questions that arise include: 1) What are the responsibilities of the medical profession in providing medical care or supervision for patients who manifest irreversible decremental processes associated with old age?; 2) Under what circumstances is there a moral imperative to preserve life, especially in patients who manifest an irreversible loss of awareness or are sustained by purely mechanical means?; 3) What are the limits of the resources which can be allocated to health care in general, and to the aged in particular, in a society in which resources are no longer infinite and allocations may become necessary?; 4) What is the professions responsibility for identifying decremental aging changes and characterizing them, even if this information is personally threatening and socially disturbing to those who would prefer to consider them diseases, and thus reversible by traditional means?; and 5) Is there a moral mandate to identify mechanisms of aging and techniques for slowing the process, in order to prolong life beyond what appears to be the normal biologic limit of three generations?