Renal physiology in the oldest old: The Sphinx remakes her question

MUSSO, CARLOS G.; MACÍAS NÚÑEZ, JUAN F.

INTERNATIONAL UROLOGY AND NEFROLOGY

Springer

Año: 2005 vol. 37 p. 653 - 654

0301-1623

If the Thebanian Sphinx were to ask Edipus today, she would have to ask which is the living creature that goes through four stages, instead of three, during its life; that it is not only childhood, youth and old age but also the oldest age. The reason for this is that the increase in human life expectancy has led to the appearance in the community of such a large number of ??oldest olds,?? who have become a new social group. We call ??oldest old?? any person beyond 79 years of age [1]. Medically, the ??oldest olds?? have their particular characteristics both in their physiology and in the features of their diseases and their therapeutic management that distinguish them from the other age groups [2] Following are some characteristic findings of their renal physiology that have been described in various recent studies: (1) Glomerular function tests have demonstrated that glomerular filtration rate is normally reduced in the elderly, being at around 30?50 ml/ min/l.73 m2 in the healthy ??oldest old??. Despite this reduction in the creatinine clearance their plasma creatinine level is in the normal range which is attributed to concomitant and proportional decrease in their lean body mass in this people [3?5]. (2) With regards to their tubular function, there is no disturbance in sodium reabsorbtion in proximal tubules between young, and ??oldest old?? volunteers [2]. However, this study has also shown that sodium reabsorption is reduced in the ascending loop of Henle of the ??oldest old??. As a result ??oldest old?? people are prone to salt wasting [2]. Consequentely, in sodium deprivation states the ??oldest old?? people are unable to reduce their fractional excretion of sodium below 0.5% and in such situations of sodium deprivation they usually reach higher fractional excretion of sodium: of around 1.4±1% [6] and they tend to become sodium depleted. (3) Two potassium handling parameters have been studied in the ?? oldest old??: fractional excretion of potassium (FEK: 13±6%) and transtubular potassium gradient (TTKG: 4) [2]. Even though the previous values are within the normal range for people with a glomerular filtration rate of 120?90 ml/min/1.73 m2 , in fact they are low values if we consider that the studied population had a glomerular filtration rate around 30?50 ml/min/1.73 m2 [7, 8]. This relatively reduced potassium excretion was attributed to a reduced potassium secretion and an increased potassium reabsorbtion in the distal tubules. Both are reasons for the high incidence of hyperkalemia in this group, especially when they are on angiotensin converting enzyme inhibitors, angiotensin receptor blockers and/or spironolactone [9?11]. (4) The same disturbance that reduces salt reabsorption in the ascending loop of Henle, is the one that generates a hypotonic medulla and consequently a reduced water reabsorption capability in the senile collecting tubules [2]. A possible explanation for this fact could be a reduced function in the ?? sodium?potassium?two cloride cotransporter?? (NKCC2) of the loop of Henle. The reduced capability of water reabsorbtion together with a thirst reduction (primary hypodipsia) makes ??oldest old?? people prone to dehydration and hypernatremia, especially in wasting water situations such as fever syndromes and treatments based on loop diuretics [10]. (5) In ??oldest old?? people, it has been shown that renal urea excretion is increased (fractional excretion of urea: 65%), even in situations in which it should be decreased such as on renal hypoperfusion states [2]. Since urea accounts for 50% of the renal medulla tonicity, perhaps the International Urology and Nephrology (2005) 37:653?654 Springer 2005 DOI 10.1007/s11255-005-0401-3 increased urea excretion contributes to the hypotonicity of the medulla [12]. This high fractional excretion of urea could explain the low plasma urea levels that this population usually have. It was postulated that this increased urea excretion could be secondary to a reduced urea reabsorption in the distal tubules [2]. (6) A recent study has shown that in healthy ??oldest old?? people, plasma erythropoietin levels are within normal range, which means that they do not differ from the ones shown by young people. Since erythropoietin is secreted by the peritubular interstitial cells near the convoluted proximal tubular ones, the finding of normal plasma erythropoietin levels reinforces the hypothesis that the proximal tubule is preserved during ageing [5]. Conclusion Healthy ??oldest-olds?? are successful individuals. They bear important information about clues of the healthy senescence and they may be the key to understand the real border between pure ageing process and, not yet detected, chronic entities. After centuries, the Sphinx question might be: ??what is the ageing process and how it happens??? Perhaps our centenarians have the answer this time.