Of Nephrology and Nephrologists Spotlighting new and provocative developments in world nephrology and featuring nephrologists who occupy leadership roles Manuel Mart�nez-Maldonado, MD Editor-at-Large Renal Osteodystrophy in Iberoamerica Jorge B. Cannata-And�a, MD RENAL OSTEODYSTROPHY is a frequent complication of end-stage renal disease (ESRD). Its main histological forms are mild to severe hyperparathyroid bone disease characterized by a high-bone turnover, adynamic bone disease, and osteomalacia with low bone turnover and mixed osteodystrophy. The prevalence of the forms of renal osteodystrophy varies around the world, including in the countries of Spanish and Portuguese descent in the Western hemisphere that, together with Spain and Portugal, are collectively called "Iberoamerica." FACTORS INFLUENCING RENAL OSTEODYSTROPHY IN IBEROAMERICA The prevalence of high-bone turnover lesions in the world has decreased over the last 20 year!
s and the most common form of low-bone turnover, aluminum-induced osteomalacia, is being replaced by adynamic bone disease not induced by aluminum. 1 In Central and South America, aluminum toxicity remains a great problem for renal patients. 2 Other factors in the changing nature of renal osteodystrophy 3 include the frequent use of calcium carbonate, calcium acetate, and vitamin D metabolites in ESRD patients. The type of patients treated by dialysis, which includes diabetics, older patients, and patients who previously underwent transplant, is also a factor. In Spain and Portugal, as in the rest of Europe, water purification has significantly reduced the prevalence of the aluminun-induced forms of renal osteodystrophy. Bone biopsy specimens from patients with symptomatic osteodystrophy 4 indicate that forms of aluminum-related renal osteodystrophy are diminishing from less than 5% in prevalence studies 1 to a maximum of 25% to 30% in clinical studies. 4 The percentage of hem!
odialysis centers in Spain and Portugal 5,6 having an adequate and safe aluminum concentration in the dialysate (<4 mcg/L) has increased from 70.7% in 1988 to 86% in 1994, 5 and to 93% in 1999. Presently, 70% of centers have undetectable concentrations of aluminum in the dialysate (<1 mcg/L). Oral consumption of aluminum-containing phosphate binders has also been reduced, but our last survey conducted in 1995 showed that 24% of patients in Spain were still receiving aluminum salts. The reduction of aluminum exposure in Spain, however, has decreased the mean serum aluminum levels from 61.8 mcg/L in 1988 to 22.7 mcg/L in 1998. 6 Aluminium toxicity in Central and South America is comparable with what it was in Europe and North America in the 1980s. Great differences exist among the countries of South and Central America in relation to aluminum toxicity control, but they fall into three groups. One group is unable to study the problem, the second group can study the problem, but d!
oes not have adequate means to eradicate it, and the third group has studied the problem and has implemented adequate strategies. Aluminum exposure in Central and South America has been reported to the dialysis and transplant registry of the Latin American Society of Nephrology and Hypertension (SLANH). 7 A questionnaire answered by 41% of centers found erratic prevention of aluminum exposure, and no data specifically related to bone disease. Water treatment systems were not used in South and Central America in 11.4% (the range of use was from 0 to 100% of the dialysis units surveyed in different countries). Reverse osmosis was used for water treatment in 45.3%; 41.7% used a deioniser, but this also varied from center to center and country to country. The aluminum concentration in the dialysate was never checked in 37% of centers; only 27% of centers checked it regularly. The concentration of aluminum in dialysis fluids from different countries in South America reveals importa!
nt geographical differences with ranges from 1.9 to 205 �g/L. Free or low-aluminum dialysate in South America is further complicated by contamination of the salts used for dialysis concentrates. Secondary hyperparathyroidism management with the use of calcium salts as phosphate binders and vitamin D metabolites, and the type of patients (two-thirds of the dialysis population is older than 65 years, nearly one-fourth are diabetics, and there is an increase in post transplant patients) are similar in Portugal, Spain, and the rest of Europe. By contrast, the SLANH registry 7 and other data 5,6 indicate that in Central and South America dialysis patients are younger, fewer have diabetes, and few have had a renal transplantation. In Brazil, low phosphorus intake may have also played a role in the pathogenesis of low-bone turnover. BONE BIOPSY RESULTS FROM IBEROAMERICA In the Canary Islands, Spain, there is a similar prevalence of high- and low-bone turnover bone disease in predialy!
sis and dialysis patients, and a low prevalence of aluminum-induced bone lesions (<5%). Prevalence studies are not available from other areas of Spain, Portugal, or Central and South America. Nevertheless, patients biopsied because they were symptomatic or have presented either radiological or biochemical abnormalities, such as hypercalcaemia or hyperaluminemia, have shown marked bone involvement. A study of 1,209 biopsy specimens from Brazil, Uruguay, Argentina, Portugal, and Spain 4 found hyperparathyroid bone disease in 66% of dialysis patients from Spain and in 71% of those from Portugal. In Spain and Portugal, respectively, mixed lesions were 10% and 4%, osteomalacia 14% and 7%, and adynamic bone disease 21% and 22%. In South America, hyperparathyroid bone disease was seen less often, although mixed lesions and osteomalacia were more frequent and adynamic bone disease was comparable with that seen in the Iberian Peninsula. Bone biopsies from Uruguay and Brazil performed a!
fter 1990 revealed a significant reduction in the percentage of low-bone turnover osteomalacia induced by aluminum compared with the biopsies performed before 1990. In Uruguay, the pattern of renal osteodystropy found after 1990 was similar to that observed in Portugal and Spain during the same period, except the higher percentage of patients with mixed lesions. These differences could not be explained by sex, age, time on dialysis, or percentage of chronic ambulatory peritoneal dialysis and diabetic patients; the most likely factor was correction of aluminum overload. In the study (before and after 1990) there was a 59% rate of positive aluminum staining in bone biopsy specimens from South America, which correlates with the degree of aluminum exposure reported in that area. This high percentage of aluminum-related toxicity contrasted sharply with the 19% observed in Spain using the same histological criteria and staining techniques. However, aluminum staining still covered gr!
eat percentages of the bone surface in adynamic bone disease studied in Spain and Portugal, 4 suggesting that aluminum still plays a role in the pathogenesis of the adynamic forms of low-bone turnover. The differences in the type of bone disease found in Iberoamerica appear to be predominantly the result of aluminum exposure. ACKNOWLEDGMENT To the staff of the author's unit and to all their supporters for bone research (FIS, FICYT, CICYT, and JRSIN). REFERENCES 1. Torres A, Lorenzo V, Hern�ndez D, Rodriguez JC, Concepci�n MT, Rodr�guez AP, Hern�ndez A, De Bonis E, Darias E, Gonz�lez-Posada JM, Losada M, Rufino M, Felsenfeld AJ, Rodriguez M: Bone disease in predialysis, hemodialysis and CAPD patients: Evidence of a better response to PTH. Kidney Int 47:1434-1442, 1995 2. Massari P: Disorders of bone and mineral metabolism after renal transplantation. Kidney Int 52:1412-1421, 1997 3. Cannata JB: Hypokinetic azotemic osteodystrophy. Kidney Int 54:1000-1016, 1998 4. Diaz L�pez JB,!
Jorgetti V, Caorsi H, Ferreira A, Palma A, Men�ndez P, Olaizola I, Ribeiro S, Jarava C, Moreira E, Cannata JB: Epidemiology of renal osteodystrophy en Iberoamerica. Nephrol Dial Transplant 13:41-45, 1998 (suppl 3) 5. Douthat W, Acu�a G, Fernandez JL, Serrano M, Canteros A, Menendez P, Cannata JB: Exposici�n al aluminio y calidad de los l�quidos de di�lisis. Repercusi�n sobre los Niveles de aluminio s�rico. Nefrologia 14:695-700, 1994 6. Fern�ndez-Mart�n JL, Canteros A, Serrano M, Gonz�lez-Carcedo A, D�az-Corte C, Cannata JB: Prevention of aluminum exposure through dialysis fluids. Evolutive analysis of the last eight years. Nephrol Dial Transplant 13:78-81, 1998 (suppl 3) 7. Mazucchi N (on behalf of the Latin American Society of Nephrology and Hypertension [SLANH] registry). Informe de di�lisis 1998. Nefrolog�a Latinoamericana 5:123-125, 1998 Jorge B. Cannata-And�a, MD Head, Bone and Mineral Research Unit Instituto Reina Sof�a de Investigaci�n Hospital Central de Asturias Uni!
versidad de Oviedo, Spain THE Argentinean city of Mendoza begins where the Andes start their climb to the sky. It is wine country and the site where Jorge Cannata was born. Cannata went to medical school in Mendoza and then to the Complutenese University in Madrid where he fell in love with Spain. An exceptional college student, Cannata also excelled in medical school and graduated cum laude. He began his nephrology training at the famed Jim�nez D�az Foundation in Madrid and completed it at the Hospital General de Asturias in Oviedo, Spain. Cannata also spent time in the Western Infirmary in Glasgow, Scotland, where he solidified his interest in bones and bone disease in uremia. In a remarkable twist of destiny, Cannata stayed in Oviedo where he began his investigative career. He and his group have conducted extensive studies on the epidemiology and pathophysiology of renal osteodystrophy, particularly as it relates to aluminum toxicity. As the subject of his American Journal !
of Kidney Diseases feature article, Cannata has chosen the incidence of renal osteodystrophy in Iberoamerica, a term that is more cultural than geographical and refers to the combination of Spain and Portugal (Iberia) and all Spanish- and Portuguese-speaking countries in the Western Hemisphere. In the United States we take for granted that anyone, including immigrants, can achieve whatever they set their minds to, but this is not true around the world. It is recognition of Cannata's talent that in a relatively short time he became chief of the bone and mineral metabolism unit in the Hospital Central de Asturias and later chief of the research service of that hospital and the medical school in Asturias. Cannata's investigative work has brought attention to the role of iron in aluminum toxicity and to the relationship between aluminum and parathyroid gland function. He has contributed over 100 articles to the nephrology literature, edited 8 books, and presented his group work at!
innumerable meetings around the world. A gregarious man, Cannata belongs to various nephrology societies and has been treasurer of the Spanish Society of Nephrology and a member of the council of the European Dialysis and Transplant Association. Cannata serves on several editorial boards, including Kidney International. In addition, he has been recognized by his national nephrology society, which has bestowed on him numerous scientific awards. An epicurean and oenophile, Cannata contributes his good humor and charm to many a social gathering. Those who work for him admire his hard work and penetrating intellect, but most important, as they are quick to point out, his kindness. Cristina, his wife for over 25 years, is an artist who claims (with a twinkle in her eyes) to have met Cannata "accidentally"; she lived two doors down from him on a street in Mendoza. They have two children who intensely admire their parents: Jimena, a physician, and Pablo, who is soon to be a physicia!
n. --Manuel Mart�nez-Maldonado, MD � 1999 by the National Kidney Foundation, Inc. |