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EADERS OF THIS issue of Journal of RenalNutrition should note the Guest Lecture by

revı̃no-Becerra et al, entitled “A Personal Ex-erience on an Interface Between Clinical Nu-riopathy and Experimental Nephropathy: Fromwashiorkor to Nephrotic Edema.”Your gentle willingness to listen to a wind-

lown old Mexican pediatrician, known as aevotee of the study of nutritional disease inhildhood, within a range from protein–energyalnutrition to deficiency rickets, with an addi-

ional flair for a particular form of experimentalephropathy, is deeply appreciated. But as well,omeone who is more than pleased to point outo the dear colleagues from abroad that in Yu-atán, we are treading on sacred soil—not onlyegarding testimonies of ancient Mayan culture,ut also from a nutritional perspective.Whether this was or was not a conscious motif

or choosing the city of Mérida as the site for thisIII International Congress on Nutrition andetabolism in Renal Disease, you may also be

nterested in learning that the Yucatán peninsulaas, up to some 60 years ago, the only geo-raphic region in the Mexican Republic whereinellagra and vitamin A deficiency xerophthalmiaere rampant, to such a degree as to be endemic.lbeit rare nowadays, thanks to a general im-rovement in health in our country, it is a well-nown fact that these diseases may linger in aubclinical stadium for long periods, easily reap-earing when underprivileged individuals areubjected to a variety of medical or surgicaltresses. In addition, urinary lithiasis, particularlyladder stones, exhibit a high frequency, consid-rably surpassing national figures. For this, theainly calcareous composition of the soil has

een blamed. It is not surprising that calcium anditamin D deficiency rickets are exceptional inhese whereabouts. All of this, combined withther clinical pictures linked with local patterns

© 2007 by the National Kidney Foundation, Inc.1051-2276/07/1701-0001$32.00/0

kdoi:10.1053/j.jrn.2006.10.019

ournal of Renal Nutrition, Vol 17, No 1 ( January), 2007: pp 1-3

f infant feeding, explains why one of the earliestatin American references in the literature onhat nowadays is generally known as infantilerotein–energy malnutrition, is an article by doc-or José Patrón Correa, which back in the year908, appeared in the venerable, Revista Médica deucatán, on a disease locally known as “culebrilla”

meaning “little snake”), which is apparently aort of pellagrous skin lesion.

In terms of present-day nutritional problems,ucatán reports one of the highest rates for obe-

ity and type 2 diabetes mellitus in México, par-icularly among women from the poorest popu-ation strata. Actually, the first surveys on the statef nutrition in the Mexican population werearried out precisely in rural areas of this State, insmall towns (Sudzal and Sitilpech), during the

arly fifties, by a team led by Professor Salvadorubirán, the founder of our Instituto Nacional deiencias Médicas y Nutrición, which nowroudly bears his name. It is of great interest thatne of the surprising findings of these surveys,ow more than 50 years old, was an obesity–iabetes panorama very akin to the present situ-tion, as far as clinical appearance, sex rate, fre-uency, and other aspects are concerned.Is was precisely during those years when, hav-

ng been trained as an endocrinologist by Profes-or Karl E. Paschkis at Jefferson Medical Collegen the city of Philadelphia, I became the juniorember of the later internationally well-knownroup for the Study of Malnutrition in Childrenf the Hospital Infantil de México, headed byrofessor Federico Gómez-Santos. This giant ofniversal pediatrics is the author of the prevailingómez classification of childhood malnutrition.

n such an inspiring academic environment, Iould at once apply my recently acquired clinicalnd laboratory skills in a sunny hospital wardrammed with marasmic infants and preschool-ged toddlers, the latter showing the clinical va-iety of what our group called third-degreealnutrition of the hypoproteinemic, hence

dematous, type, which is internationally

nown by various names, such as Mehlnähr-

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chaden, distrofia farinácea, síndrome pluri-arencial infantil, sugar baby, shibi-gachaki, theearlong predominant type of kwashiorkor, orhe more recently adopted type of severe in-antile protein– energy malnutrition.

Typically, this clinical picture is seen mostften in children between 1 and 4 years of age.mong many others, one of the most impressivelinical features was that blatant overhydration,anifested as striking subcutaneous edema, could

oexist with signs of important clinical hypovo-emia, particularly in those children who alsoxhibited severe diarrheal disease. Moreover,any of these “dehydrated” children also exhib-

ted polyuria, with a hypo-osmolar diluted urine,ndeed an utterly unexplainable, pathologic pic-ure. Naming this ominous combination “dyshy-ration” did not help much to clarify the under-ying pathogenic mechanisms. Obviously, hererevailed a matter for intensive research into theeatures of body composition and kidney func-ion in severe childhood malnutrition—in otherords, a conundrum clearly waiting to be re-

olved within the realms of renal physiology.My good fortune put me in the path of Pro-

essor Jack Metcoff. With the help of a generousrant-in-aid, I got the opportunity to join hiseam at Children’s Hospital in the city of Boston,here, at that time, a group of young foreignephrologists, among them Dr. Gustavo Gor-illo, were being trained. May I utter a few wordsn the memory of Doctor Metcoff, who was toecome my mentor in matters of scientific inves-igation, as well as a close friend. He undoubtedlyas one of the mainstays of pediatric nephrologyuring the second half of the past century. Ifnyone who may have known him is present athis audience, she or he may agree that he was anxtremely wise, brilliant, cultivated person, anvid learner, and a stupendous teacher. Hisnowledge in scientific matters was astounding,nd his manual dexterity in the laboratory im-ressive. Any new procedure that he deemedseful for his research projects was quickly assim-lated and mastered by him.

Beyond biomedicine, he loved and understoodrt, particularly the graphic arts, and was himself aifted draftsman and painter, as well as a skillfularpenter and an outstanding sportsman. His andis wife Elinor’s deep interest and fascination

ith archeology explain why Yucatán was one of D

heir preferred visit sites, and Mayan culture onef their many areas of expertise.Significantly, one of Jack’s early academic in-

erests had been pediatric nutrition. Among manyther of his achievements in this field is his articlen vitamin D–deficient rickets in Italy, writtenuring his stay there as a medical officer with themerican occupation army.Under his guidance, I could set up an experi-ental approach to the question of the distribution

nd shifts of water and electrolytes in nutritionaldema. However, to start with, my experimentalats refused to eat the casein-free diet by which Iad tried to induce hypoproteinemia. Enters Deusx machine in the person of the world-famousediatric pathologist–oncologist Sidney Farber,ho had been testing one of the earliest known

ancer antibiotics but forthwith had to withdrawreatment because of the occurrence of unex-ected subcutaneous edema. We immediatelyoresaw the potential of this compound for ourxperimental purposes. By then, discouraged byhe failure of the dietary approach to the produc-ion of hypoproteinemic edema, I was not caringnymore about the best way of getting edematousnimals. So, provided with plenty of the stuff,hich later turned out to a side product in the

ynthesis of puromycin, I continued with theroject.The results were dramatic. In a matter of 6 todays, the rats developed generalized edema,hich, after the animals had been loaded with a

alt solution, progressed to full-blown anasarca.assive proteinuria and hypercholesterolemiaere part of the picture. However, if one let the

nimals alone after the experiment had finished, aeemingly complete recovery occurred. Theseesults were published in the year 1955, andventually, this paper became a citation classic.ince then, puromycin aminonucleoside or, pres-ntly, adriamycin aminonucleoside has remainedtool for inducing experimental nephrotic syn-rome—that is, the procedure itself, because theesults of the study, namely, the distribution ofater compartments in edema, did not seem toave awakened any further academic interest.Nevertheless, the methods used in this work

erved as a starting point for the ascertainment ofuscle and skin composition and corresponding

odium and potassium shifts in edematous pro-ein–energy malnutrition in Mexican children.

uring the following 25 years, Metcoff gener-

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GUEST LECTURE 3

usly collaborated with this project in his almostearly inspiring “expeditions” to our laboratory.n this way, the biochemical basis of those find-ngs was unravelled. Simultaneously, the charac-eristics of renal dysfunction in childhood malnu-rition were clarified, with the help of his otherisciples, the aforementioned Gustavo Gordillo,nd David Santos. Thus, Metcoff returned to hisriginal devotion to nutritional disease, later fo-using his interest on the newborn child and onerinatal disease. Collaterally, an excellent train-ng program for our technicians was started in hisaboratories, to the benefit of many of our ownoung collaborators.Here I must stop. I do hope to have been able

o briefly tell you the story of a specific instancef an interface between nutriology and nephrol-gy, or, if you wish, between kidney disease anduman edematous malnutrition.By this fruitful academic interaction, the fea-

ures of body composition and kidney dysfunc-

ion in protein–energy malnutrition could benown in detail and are now a seemingly closedhapter in human pathology. But, still more im-ortant from the humane standpoint, a lifelongnternational friendship between investigators andheir institutions had evolved. Surely, this Con-ress is one more manifestation of those ideals. Itsertain success will pave the way for tackling thessue of the very recently defined 15th grandhallenge for global public health: “To ensurehat everyone in the world can have access tolean, clear, knowledge” relevant to the healthroblems of any given country.

Silvestre FrenkSenior Investigator, Unit of Genetics in Nutrition,

Institute of Biomedical Investigations, NationalAutonomous University of Mexico—National

Institute of Pediatrics, Secretary of Health, Mexico