Carmelo Giordano (1930-2016): a giant in Nephrology

Giordano’s life

Carmelo Giordano (Carmine Louis, Joseph Giordano) (Figure 1) was born in the house of Rafael and Anna Tirone in Naples on August 23 1930 (Figure 2). His father held the title of Baron. He was baptized on the 28 September in the Catholic Parish of the Holy Cross and Saint Rita (Figures 3 and 4). Giordano attended primary, junior high and grammar schools in Naples. In the same city he studied medicine at the feet of Professor Flaviano Magrassi (Figure 5), at the University Federico II, and in 1954 he obtained the MD cum laude. During the fourth medical course he had joined the Institute of Medical Pathology directed by Professor Flaviano Magrassi, an expert in infectious diseases and leukaemia, originating in the famous Roman School of Cesari Frugoni. Magrassi, a forerunner of medical specialists in the university, had just arrived in Naples from Sassari in Sardinia. He attracted many talented young students who prepared their Ph.D theses with him and later achieved chairs in many specialties. After obtaining the MD Giordano started a laboratory for the assessment of renal function (mainly devoted to clearance studies) in various human models of renal and vascular disease.

In 1958 Giordano moved to Boston (MA, USA) and remained there for the next 3 years (Table 1). There he studied clinical nephrology, dialysis and transplantation at the feet of Prof. John Putnam Merrill (Figure 5) the “father of nephrology as a discipline” (Prof. Murray Epstein, Nobel prize in medicine in 1991), at the Peter Bent Brigham Hospital of the Harvard Medical School (“no Institution has done more for propagation of dialysis in the United States”- again Professor Epstein).

He had been able to contact Professor Merrill while the Harvard professor was travelling to conferences throughout Italy. Merrill was very impressed by the talents of the young Italian physician and even offered him hospitality at his home (1958). This resulted in a daily scientific exchange with the man who, in association with Professor Joseph E. Murray, had made the first successful renal transplant between identical twins: the brothers Herrick, namely Richard (the recipient) and Ronald (the donor). So Giordano was at the right time in the most prestigious place in the forefront of modern nephrology. There he learned and practiced at the same time dialysis and transplantation from top investigators.

Upon his return to Naples (1961) he developed a laboratory devoted to nutrition in renal disease, which was located in 3 large rooms on the 3rd floor of the Institute of Medical Pathology. Available equipment included a flame photometer, an osmometer, a spectrophotometer, laboratory centrifuges and one ultracentrifuge, a Warburg apparatus, equipment for acid base measurement in blood and urine, an amino acid analyser and Kjeldhal apparatus for measuring nitrogen in urine and faeces. However the most important piece of equipment was a Kolff-Brigham artificial kidney, which had been donated to Giordano by Mr. Edward Olson, its manufacturer. The artificial kidney was located in a special room (called room no. 6) on the fourth floor of the institute where dialysis for acute renal failure was performed. Dialysis for ESRD was started in 1966.

In 1959 Giordano applied a project for nutrition of patient with chronicc kidney disease to the National Institutes of Health of the United States of America. He was financed. He received grants and a contract for projects on nutrition, sorbents and peritoneal dialysis for the next 21 years (1959-1980).

At the University of Naples Federico II Giordano (Table 1) was ordinary assistant (1964-1971), and then Professor of Nephrology-after the national examination in 1975- until 1986. He was invited to take up the chair in Medicine and Nephrology at the Catholic University in Rome but he declined. Thus he was made full Professor of Medicine in Naples in the years 1986-2002. He was Dean for Curricula and founded the postgraduate school of nephrology. He was a member of the board of professors for the Ph. D. Program In Nephrological Science (1980-2002). He was one of the 10 founders of the Italian Society of Nephrology over which he subsequently presided. He was also a founder of the Italian Society of Artificial Organs, a founder of the International Paediatric Nephrology Association, International Society of Artificial Organs and the International Society of Peritoneal Dialysis. In addition he was instrumental in starting academic paediatric nephrology in Italy.

With Wichtig Editore he set up the International Journal of Artificial Organs, the International Journal of Pediatric Nephrology (later changed by Karger AG into Child Nephrology and Urology), and Giornale Italiano di Nefrologia. There were problems in breaking the collaboration with the group of Minerva Nefrologica. However, as pointed out in the letter to the readers, this was just the act of independence of the Italian Society of Nephrology as confirmed by the nomination of Prof. Giuseppe Piccoli as Editor in Chief to express continuity with the work of the previous editorial staff.

Fellows and Collaborators

His first fellow was Dr Renato Esposito, a talented investigator with a great interest in clinical chemistry. Giordano also attracted two medical students working on their theses (Natale G. De Santo and Carlo de Pascale) who were the first to be tutored by Giordano for the MD. The initial group also included Mr. Antonio Ariano (laboratory technician), Ada Crescenzi (Ph.D in chemistry), Maria Pluvio and Lia Poderico (nutritionists). An incomplete list of collaborators is given in Table 2.

Table 3 lists some of Giordano’s achievements in science. Table 4 lists his active membership in various societies, and the congresses that he organized personally.

Investigators on sabbatical

Various creative clinical scientists worked during sabbaticals at the nephrology department directed by Carmelo Giordano (Table 5). The first was Prof. Kazimierz Backzyk, later Professor of Nephrology at the Medical University of Poznan (Poland). He arrived in Naples at a time when Eastern Europe began to separate from the West with the construction of the Berlin wall.

Dr. Malcolm Phillips came to Naples from London as a Welcome Trust Research Fellow for 2 years (1970-1972). His fellowship was arranged between Professors Hugh de Wardener and Carmelo Giordano. He studied amino acid losses on dialysis, the effects of essential amino acid supplements in hemodialysis patients and the utilisation of keto-acids in healthy and uremic subjects. Later, when back in London, Dr. Phillips was, for varying periods General Manager of the Charing Cross Hospital and Medical Director of the Charing Cross and Hammersmith Hospitals Trust.

Prof. Otto Busato came from the Department of Nephrology at the University of Porto Alegre, Brazil, to work on nutrition and peritoneal dialysis. Also Prof. Alejandro Trevino Becerra came with the same goal and subsequently was anchored long term to the topic. Francisco Gonzalez, Professor of Medicine and Chief of Nephrology at Louisiana State University in New Orleans, during his stay attracted many young investigators to study acid-base balance in HD and PD and focused his research on pharmacological means to augment peritoneal dialysis clearances.

The collaboration with Professors Ciro Balestrieri and Domenico Cittadini of the Department of Biological Chemistry at the University of Naples was long-lasting and produced outstanding results.

Drs. Gianfranco Romagnoli and Domenico Di Landro came from the Hospital of the University of Padua to learn about sorbent therapy.

The list of visiting scientists includes, among many others, Professors Jan Brod, Jan Roguski, Thadeus Orlowski, Geoffrey M. Berlyne, Karl Julius Ullrich, Shaul Massry, Klaus Hierholzer, Jules Traeger, Gerhard Malnic and Willem Kolff who was attracted by the use of sorbents for wearable kidneys from Professor Renato Esposito and wrote on this experience in Dialysis and Transplantation.

Giordano’s hobbies

Giordano had many interests. He enjoyed to play with words and look into their etymology, a reflection of his days at the grammar school (in Italian Liceo Classico). He was interested in soccer and had season tickets for the home matches of the Naples Soccer Club at the time of the great player Armando Maradona.

He also enjoyed driving Porsche cars, and sailing. He had a boat constructed in Finland (Black Swan), described in the Treccani Lexicon-where photos of Giordano and his crew appear- for its outstanding technical characteristics. He participated in many national and international races and developed an international reputation. Once, with a crew made of young investigators and professors including the famous Professor of Modern History, Giuseppe Galasso (a member of Accademia dei Lincei-Linx) who was responsible of the fiocco (jib), Giordano made third place in the Giraglia Cup. For those not experts the jib is a triangular sail placed in the ship’s bow and the Giraglia Cup is a race starting in St. Tropez, France, passes through the Îles d’Hyères off the French coast near Toulon, then around Giraglia, and finishes in Genoa, Italy, a total of 243 nautical miles.

Giordano also loved to cook simple Neapolitan dishes and from time to time he prepared, late in the evening, spicy spaghetti for his colleagues and guests.

He aspired to perfection in work and used to say “we shall do without mistakes”. This imposed a strong work ethic and mental concentration in his collaborators.

The University Federico II: a university with two medical faculties

In Naples, for reasons difficult to explain in a few words, there were two medical faculties at the University Federico II. There was competition between the two schools (normal healthy university life) but there were also frictions, which surpassed the politically correct and affected the academic life of fellows. In 2014 there was finally peace, but it was too late. The wounds had healed with ugly scars.

Publishing or perish

Giordano had a great interest in teaching medical students and fellows. He was convinced that the best way to teach was through writing books. A complete list is given in Table 6. The frontispiece is depicted in Figures 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17. The first book (Figure 6) was the nicely printed Nefrologia. The outline was that of a U.K. manual, being fresh, modern and easy to read. It included dietary treatment for acute and chronic renal failure

The second book was a concise monograph on nutrition in renal disease (Figure 7), the first of its kind worldwide. It could be easily read by students and by practitioners. Giordano put great emphasis on electrolytes and acid base balance (Figures 8 and 12).

His most important book was Sorbents and their clinical applications (Figure 10), which opened the field to the use of sorbents in the clinical setting. It was the work of a renowned specialist in the field.

For many years Giordano laid great store in participating in congresses, including the Annual Contractors’ Conference in Bethesda, the Congress of the EDTA and of the International Society of Nephrology, the Italian Society of Nephrology, Giornate Nefrologiche of the Saint Carlo Hospital in Milan, as well as those relating to artificial organs work. Many outstanding data are contained in the proceedings of those congresses.

Nutrition in chronic kidney disease

Diets in CKD

In 1959 Giordano applied to the National Institutes of Health of the United States in Bethesda for funding for a project devoted to nutrition in kidney disease. He proposed the use of low protein diets in the form a) essential amino acids and b) as proteins of high biological value, both rich in energy. The project was financed and was the first of a series of grants (1959-1980). Giordano’s first study with L-essential amino acids was a classical example of self-experimentation. For 53 days Giordano ingested L-Essential amino acids in a quantity classically defined by Rose. The basic formulation was supplemented either with 3 g of nitrogen (N) derived from glycine (period A), or 0.5 g of N derived from glycine (period B), or 2 g of N in the form of ammonium citrate (period C) or 2 g of N in the form of urea (period D). Nitrogen balance was calculated by daily analysis of urine and fecal nitrogen. The study was published in the Bollettino della Società Italiana di Biologia Sperimentale (1).

The subsequent experiment (2) with amino acids (2 g of N/day) was carried out in two patients with very low GFR’s and this produced positivity of nitrogen balance.

The third crucial experiment was performed in one healthy person (C. Giordano himself) and in 8 patients with eGFRs of 9-26 ml/min (Table 7). These subjects received L- essential amino acids (2g N/ day – period A) followed by a diet (period B) containing 23 g of protein of high biological value. The energy intake was high in both periods. In that paper (3) there are data on the effects of a synthetic diet containing essential amino acids (17.7g/ 2g of N), 2300 calories in women, 3100 in man-followed by a low protein diet (3.8g/N, 68 % from milk, 23g of protein in total). The paper published in J Lab Clin Med  was cited 401 times. A typical experiment in 1 subject is depicted in Figure 18.

At the second congress of the International Society of Nephrology in Prague in 1963 Giordano presented unique work on low protein alimentation. This consisted of data in 23 patients with chronic kidney disease (plasma creatinine 2.6 to 9.0 mg/dl) treated for a total of 236 months. The patients underwent a dietary schedule for 5 weeks: in weeks 1 and 5 they ate a low protein diet (23g day in the form of protein of high biological value) and in weeks 2-4 a diet providing 2 g of N/day as L-essential amino acids (4). A typical experiment in 1 subject is depicted in Figure 19.

In 1964 Giovannetti and Maggiore published data on CKD patients with GFRs of 3-6 ml/min who received a protein poor diet (N 1.0-1.5 g/day) for 10-15 days followed for 2 weeks by a low nitrogen intake (1.74 g/day) as L- essential amino acids and then (indefinitely) by a restricted protein intake (2.2 g of N/day) in the form of egg protein, or egg albumen. Amino acids promoted a positive nitrogen balance, which was maintained under the low protein regime (5).

In the same year Giordano published the aforementioned book on La Dieta nelle Malattie Renali/ Nutrition in Renal Disease, in which he suggested the use of L-essential amino acids for 2-3 weeks followed by a low protein diet with natural foods providing 23 g of protein/day (6). Additional data from the groups in Naples and Pisa were published in Minerva Nefrologica in 1965 (7, 8). This was the genesis of the Giordano-Giovannetti Diet, as said first by Geoffrey M. Berlyne (9, 10, 11, 12, 13). The pioneering nature of this work has been described elsewhere (14, 15, 16).

At the III Congress of Nephrology in Washington Giordano, De Pascale, Esposito and De Santo (14) presented data in 25 CKD patients kept on diets providing up to 25g proteins a day. It was shown that 85% of patients achieved a positive nitrogen balance when the diet provided 25g of protein/day (Table 8). Many other studies (17, 18, 19, 20, 21, 22, 23) confirming the feasibility and the usability of low protein diets were published in the years 1967 and 1968. Kopple at that time was ready to prescribe a 40g protein diet (20). Of course this diet was easy to take since 0.6g/kg is, according to nutritionists, a normal intake in adults.

At the Scottsdale Conference on Nutritional Aspects of Uremia (23) Giordano was applauded as is apparent from the proceedings, published in the American Journal of Clinical Nutrition, which contained favorable comments by very eminent scientists (Table 9).

Studies on ketoacids

Giordano had many doubts on the long-term usability of ketoacid analogs in CKD. However he worked hard on this topic. The first experiments dated back to 1968. At that time there was uncertainty about the possibility of utilizing D amino acids for protein synthesis in man (24). An experiment was devised on a young patient with chronic glomerulonephritis who underwent various amino acid regimens (Table 10). The diet provided 5 DL-essential amino acids and 3 L-essential amino acids (Period A), 8 L-Essential amino acids (Period B), 8 L-Essential amino acids with urea (Period C). In period D 8 L-essential amino acids + urea where given in association with paromomycin to sterilize the gut. Nitrogen balance was positive in periods A, C and D, negative in B (Figure 20). The experiment demonstrated that the α-amino nitrogen of D amino acids was fully utilized indicating that nitrogen balance was enhanced by the extra nitrogen of D-isomers.

In 1970 experiments were carried out at St Mary Hospital in London study in nitrogen balance and ¹⁵N incorporation in patients receiving the keto analogs of valine and phenylalanine in health and CKD. Nitrogen balance rapidly became negative when either or both phenylalanine and valine were withdrawn from the diet of healthy persons and patients with chronic renal failure. Replacement of these essential amino acids by their α-ketoacid analogs ameliorated or normalized nitrogen balance (25). Data on N incorporation went in the same direction as nitrogen balance pointing to the possibility of substituting amino acids with their keto analogues (26). However, with time, the enthusiasm for this was cooled by data, which showed absence of catch-up growth in infants switched from an amino acid to a ketoacid diet (27). In that study 6 children with GFRs of 0.9 -3 ml/min and two babies (GFRs of 22 and 15 ml/min) were fed either with a formula diet (28) according to the data of Holt and Snyderman (diet D) or according to the uremia reference pattern (29) of Giordano, De Santo and Pluvio (diet C). Both formulae (27) were made either with amino acids or amino acid + 4 ketoacid analogs and a hydroxyacid: alfa-keto-isocraproic acid, L-ketoβmethylvaleric acid, alfa-ketoisovaleric acid, phenylpyruvic acid, αhydroxy-γmethylbutiric acid as keto analogues of L-leucine, L-isoleucine, L-valine, L-phenylalanine, and as the hydroxyacid of L-methionine, respectively.

In children taking formula C diets (amino acids) nitrogen balance was +0.54+018g whereas with the formula C (keto analogues) it averaged +0.14+0.16g (Table 10). In infants formula C (amino) and fomula D (amino) provided growth superior to formula C (keto) and formula D (keto) diets, as indicated in Table 11.

However the results of the studies data of Professor Mackensie Walser on ketoacids were more and more convincing and were confirmed in other laboratories. Thus on the occasion of the plenary lecture at the Athens Congress of the International Society of Nephrology Giordano, while acknowledging the impossibility for nutrition to compete with dialysis and transplantation, made the point that appropriate alimentation should be used very early in the course of chronic kidney disease. He was finally able to bring opinions together from available studies on the use of ketoacids and supported their use as one modality of nutrition in chronic kidney disease (30).

Further studies on nitrogen metabolism in health and uremia

Plasma aminograms from uremic patients showed, for the first time, an impaired tyrosine to phenylalanine ratio, an increase in 3- methylhistidine and a depression of the histidine to methylhistidine ratio. Loss of free amino acids and small peptides was 15-20 g per each hemodialysis session (31).

Labeled molecular nitrogen was administered subcutaneously in a CKD patient (creatinine clearance 7.5 ml/min). Labeled nitrogen was subsequently found in amino acids of plasma albumin, indicating that molecular nitrogen is not an inert gas in humans (32).

In another study the energy load from dialysate (800 cal/day) in CAPD patients was described (Figure 21). The patients were undergoing 2 liters exchanges five times a day (33). Nitrogen balance studies were performed for the first time in CAPD patients and it was demonstrated that a protein intake of 1 g/kg/day was sufficient (Figure 22) to keep a neutral or positive nitrogen balance (34).

Giordano was also first to describe (i) amino acid losses in CAPD in children, (ii) the protein requirements of children on CAPD, (iii) the energy load of children on CAPD. In addition he showed that nitrogen balance of diabetic patients on CAPD was maintained by prescribing a diet containing 1.3 g/kg of protein per day (35).

Although dialysis and transplantation (a procedure available to a minority of patients) are vital treatments they are expensive. Giordano continuously searched for improvements in renal nutrition. Even one year of dietary treatment would spare relevant resources. This interest was not lessened by the negative results of the very publicized MDRD study (14, 15).

Giordano’s last thoughts of low protein alimentation

The last time Carmelo Giordano participated in a scientific meeting (Survival is not Enough no.10, Naples March 10, 2016 at the Italian Institute for Philosophical Studies) he declared his interest in promoting transplantation because of the quality of life it offered (36). However he declared himself very pleased by the paper of Denis Fouque and William E Mitch which stated: “In the history of medical sciences fewer topics have been the focus of so many clinical trials, reviews, speculation, and discussions than the question of what constitutes an optimal protein intake for patients with kidney disease… But probably we are reaching a consensus” (37).

He felt that this tenet was strongly supported by: (i) the studies of Massimo Cirillo et al. in middle aged subjects of the Gubbio Population Study (the whole population of that city in central Italy) showing that higher protein intake is associated cross-sectionally with higher GFR but longitudinally with greater GFR decline over time (38); (ii) data of Bruno Cianciaruso et al (39); (iii) data of Vincenzo Bellizzi et al. (40), (iv) a report on the costs of CKD therapy in the Campania Region co-authored by many authorities and coordinated by Giorgio Liguori (41), and (v) by data of Vincenzo Bellizzi and Biagio Di Iorio et al. (42) as well as (vi) by the data of Di Iorio’s team on the effects of very low protein diets on Fibroblast Growth Factor 23 (43) and on indoxyl sulphate (44).

Studies on sorbents in uremia

Giordano was interested in the use of sorbents in uremia, having developed the idea that the intestine could be used as a third kidney, and having been fascinated by Professor Yatzidis and his studies on carbon. He imprinted this enthusiasm in Professor Renato Esposito, nephrologist and expert in clinical chemistry, Professor of Nutrition and Immunologist (Table 2). He was chief of the laboratory for the development of sorbents (Table 2) which included doctors in chemistry (Pietro Bello, Giovanni Demma, C. Rufolo), a mathematician, bioengineer and associate professor (Ernesto Quarto), a full university Professor of Biochemistry (Giacomino Randazzo), a Ph. D and nephrologist (Norina Lanzetti), a doctor in biological science, Ph.D and nephrologist (Maria Pluvio), a technician (Antonio Ariano) and Carmelo Giordano. We provide here a synopsis of their major achievements (45-75).

Oxystarch

Oxystarch -binding urea and nitrogenous substances- was obtained by oxidizing potato or maize starch (Figure 23). Oxystarch reacts with urea in a manner proportional to the concentration. The isotherm of oxystarch is given in Figure 24. At urea concentrations typical of uremia the reaction yields interesting results at low and neutral pH values. Oxystarch was developed in 1968 and data was published in Bollettino Società Italiana di Biologia Sperimentale (45). Oxystarch administered to uremic patients caused increased fecal nitrogen excretion (Figure 25) along with decreased blood urea nitrogen. In a patients treated by peritoneal dialysis (Figure 26) increased fecal nitrogen and reduced blood urea nitrogen were observed and dialysis was postponed by 3 weeks. In a patient on HD oxystarch allowed a prolongation of the interdialytic interval (Figure 27). The data were confirmed by different groups and were shown to be dependent on the fecal mass and the quality of foods. Sorbents bind urea in the stomach and ammonia in the colon. It was shown that the amount of oxystarch could be increased in order to obtain up to 4 g. of nitrogen in feces, which is equivalent to the quantity of urea generated by a protein intake of 24g/day (46, 47, 48, 61, 53, 54).

Oxycellulose

Oxycellulose-binding urea and nitrogenous toxins-was obtained by treating wood cellulose with hot acids, cellubiase and cellulase (Figure 28). It reacted with urea at blood concentrations typical of uremia (Figure 29). The reactivity was pH dependent and higher at pH 1 than at pH 7.4 (Figure 30) and is maximal at pH 1 (Figure 31). Oxycellulose could be administered orally (49, 50, 53, 54).

Carbon reactivity with urea between 1 and 90 ˚C

The group on sorbents studied carbon reactivity towards urea (Figure 32) and introduced the use of carbon at 0˚C to bind urea and nitrogenous waste products (Figure 33). They also introduced the concept that working between 1˚C (maximal adsorption) and 90˚C (complete desorption they could indefinitely regenerate carbon (Figure 34), as described in references nos. 54,56, 60.

Studies on a carbon based portable artificial kidney

The study allowed the construction of a cold carbon apparatus (35). Carbon is very active at 0˚C so it can be used to regenerate dialysis fluid in a closed circuit. With this approach catabolic products are adsorbed onto cold carbon without interfering with electrolytes which are not adsorbed on carbon. Carbon can also be treated to avoid adsorption of useful metabolites. Adsorption and desorption of solutes is an independent operation for each solute, thus the strategy resembles a natural process. Therefore a portable artificial kidney was envisaged using only a few liters of tap water with low expenditure of energy (around 100 watts) by recovery of energy via a thermal exchanger (52, 54, 59, 60, 61, 62, 63).

A combination of sorbents for portable and wearable artificial kidneys

A portable as well as a wearable kidney were also built by combining, resins, carbon, oxycellulose, oxystarch and 2 liters of dialysis fluid (Figure 36) continually regenerated (55, 56, 61, 62, 63).

A peritoneal dialysis belt

The group on sorbents finally proposed a peritoneal dialysis belt by using a cartridge containing oxycellulose, active carbon and ion exchange resins. It could work without sorbents for urea as oxystarch and oxycellulose could be given orally. Thus the peritoneal dialysis belt was devised to remove urea and non-urea toxins and to restore fluid and electrolyte balance (Figure 37). The belt was assembled using a strong cation exchange resin in H⁺ form, oxycellulose and a weak cationic resin in Na⁺ form. The first resin acidified the fluid to pH so that oxycellulose was able to react maximally, the second resin would reconstitute the pH and the electrolytes (62, 63).

Sorbents and their clinical applications

The group gained international reputation. Their place in academic medicine is indicated by an incomplete list of papers (ref. from 45 up to 75), published in the years 1968-1984 and the details of congresses to which they were invited. Pim Kolff came to visit Renato Esposito and Carmelo Giordano and their group and worked with them. He wrote in Dialysis and Transplantation of his cultural experience in Naples. Finally in 1980 a provocative book-mentioned before-was edited by Carmelo Giordano (64) on Sorbents and their clinical application (Figure 10 and Table 6) and this included a broad view of future applications. The book, dedicated to Arthur Gordon, was published even in Russian. It hosted papers from thirty illustrious specialists including Renato Esposito (66, 68), Carmelo Giordano(66, 68), Pietro Bello (67), Ernesto Quarto (65), Thomas Ming Swi Chang, Eli A. Friedman, R.E. Sparks, William J Asher, Kenji Maedaand Roger Williams.

References

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32. Giordano C, De Pascale C, De Santo NG, Fürst P, Stangherlin P, and Esposito R. Use of different sources of nitrogen in uremia. Arch Intern Med 1970; 126: 787-789
33. De Santo NG, Capodicasa G. Cicchetti T et al. Glucose utilization from dialyate in patients on Continuous Ambulatory Peritoneal Dialysis. Int J Artif Organs 1979; 2: 119-124.
34. Giordano C, De Santo NG, Pluvio M. et al. Protein requirements in patient on CAPD. Int J Artif Organs 1980; 3: 11-4.
35. Giordano C, De Santo NG, Capodicasa G, Di Leo VA. Studies in end stage diabetic nephropathy. Data on nitrogen balance during CAPD therapy. In Friedman EA and L’Esperance FA Jr, Eds. Diabetic Renal Retinal Syndrome vol 2. Grune and Stratton Inc, New York, 1982; pp.345-351.
36. De Santo NG. In Memoriam. Prof Carmelo Giordano (1930-2016). ERA-EDTA Obituaries. http://era-edta.org/Carmelo_Giordano_obituary.html
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43. Di Iorio B, Di Micco L, Torraca S, et al. Acute effects of very-low-protein diet on FGF23 levels: a randomized study. Clin J Am Soc Nephrol. 2012; 7(4):581-7.
44. Marzocco S, Dal Piaz F, Di Micco. Very low protein diet reduces indoxyl sulfate levels in chronic kidney disease. Blood Purif. 2013; 35(1-3):196-201.
45. Giordano C, Esposito R, Demma G. Possibilities of reducing azotemia in humans by administration of a polyaldehyde. Boll Soc Ital Biol Sper. 1968 Dec 31;44(24):2232-4
46. Giordano C, Esposito R, Randazzo G, Pluvio M. Trapping of urea and ammonia in the gut of uremic patients.Adv Nephrol Necker Hosp. 1972;2:251-62
47. Giordano C, Esposito R, Randazzo G, Pluvio M. Oxystarchas a Gastrointestinal Sorbemt in Uremia. In Kluthe R, Berlyne G, and Burton B, Eds, Uremia. George Thieme Verlag, Stuttgart 1972, pp.231-238.
48. Giordano C, Esposito R, Pluvio M. The effects of oxidised starch on blood and faecal nitrogen in uraemia.Proc Eur Dial Transplant Assoc. 1973;10(0):136-42
49. Giordano C, Esposito R, Pluvio M. Oxycellulose and ammonia-treated oxystarch as insoluble polyaldehydes in uremia. Kidney Int Suppl. 1975 Feb;(3):380-2
50. Giordano C, Esposito R, Bello P, Pluvio M. Oxycellulose for adsorption of urea from dialytic fluid. Proc. VI Congr. Nephrol, Karger, Basel 1976; pp. 618-624.
51. Giordano C, Esposito R, Pluvio M. Further studies with oxystarch. Kidney Int 1976 Dec;(7):S266-8
52. Giordano C, Esposito R, Bello P. A cold charcoal depurator for the adsorption of high quantities of urea. Kidney Int 1976 Dec ;(7):S284-8.
53. Giordano C, Esposito R, Pluvio M, Gonzalez F. Oxycelluloses: a group of sorbents to remove extracorporeal urea. Kidney Int 1976 Dec;(7):S348-50
54. Giordano C, Esposito R, Bello P, Quarto E, Gonzalez FM. Cold carbon apparatus for hemodialysis. J Dial. 1976-1977;1(2):165-79.
55. Giordano C, Esposito R, Bello P, Quarto E. A resin-sorbent system for dialysate regeneration. Kidney Int Suppl. 1978 Jun;(8):S138-44
56. Giordano C, Esposito R, Bello P, Quarto E. A resin-sorbent system for regeneration of peritoneal fluid for dialysis. Dialysis and Transplantation 1979; 8: 351-353.
57. Giordano C, Esposito R, Di Leo VA, Pluvio M. Oxycellulose as oral sorbent in uremia. ClinNephrol. 1979 Mar;11(3):142-4.
58. Giordano C, Esposito R, Bello P, Quarto E. Use of oral polyaldehydes and attachable peritoneal artificial kidney in the treatment of chronic uremia. Artif Organs. 1980 Feb;4(1):44-7.
59. Giordano C, Esposito R, Di Leo VA, Bello P, Quarto E. Further studies on the realization of a cold carbon portable artificial kidney. Artif Organs. 1980 Feb;4(1):44-7.
60. Giordano C, Esposito R, Bello P, Quarto E, Pluvio M. Cold carbon haemofiltration apparatus. Proc Eur Dial Transplant Assoc. 1980;17:186-91.
61. Esposito R, Capodicasa G, Bello P, Quarto E, Savoia S, Manzo M, Giordano C. Regeneration of diafiltrate by cool carbon in a close-circuit system. Minerva Nefrol. 1980 Apr-Jun;27(2):393-6.
62. Giordano C, Esposito R, Bello P, Quarto E, Pluvio M. Peritoneal dialysis belt. Int J Artif Organs. 1980 May;3(3):139-41
63. Esposito R, Pluvio M, Bello P, Quarto E, Savoia S, Giordano C. Use of oral polyaldehydes and attachable peritoneal artificial kidney in the treatment of chronic uremia Minerva Nefrol. 1980 Jul-Sep;27(3):425-8.
64. Giordano C Sorbents and their clinical applications. Academic Press Inc, New York, 1980
65. Quarto E Engineering Problems in Cyclic Adsorption of Artificial Organs. In Giordano C, Ed. Sorbents and their clinical applications. Academic Press Inc, New York, 1980, pp. 64-111.
66. Esposito R and Giordano C Polyaldehydes. In Giordano C, Ed. Sorbents and their clinical applications. Academic Press Inc, New York, 1980, pp. 131-154
67. Bello P and Giordano C Conditions for the Regeneration of Exhausted Sorbents. In Giordano C, Ed. Sorbents and their clinical applications. Academic Press Inc, New York, 1980, pp. 155-195.
68. Giordano C, Esposito R. Urea Removal in Closed Circuit Systems. In Giordano C, Ed. Sorbents and their clinical applications. Academic Press Inc, New York, 1980, pp. 333-353.
69. Giordano C, Friedman EA. Uremia. Pathobiology of patients treated for 10 years or more. Wichtig Editore, Milan, 1981.
70. Esposito R, Bello P, Quarto E, Pluvio M, Cirillo D, Lanzetti N, Giordano C. The feasibility of electrolyte management in closed circuit system. In Giordano C and Friedman EA, Eds, pp.259-266.
71. Giordano C, Esposito R, Mazzola G, Vecchio G, Pluvio M, Cirillo D, Capasso GB, Buonanno G. L-Glutaminase and L-asparaginase by extracorporeal route in acute lymphoblastic leukemia therapy.Int J Artif Organs. 1981; 4 (5): 244-248
72. Giordano C, Esposito R, Bello P, Quarto E, Cirillo D, Pluvio M, Lanzetti N, Calabria L. Hemoperfusion in diabetic coma. Contrib Nephrol 1982;29:82-9.
73. Capodicasa G, De Santo NG, Vaccaro F, Manzo M, Maione S, Capasso G, Giordano C.. CAPD + hemoperfusion once a week in the management of children with end-stage renal disease. Int J Artif Organs. 1983 Sep; 6(5):241-5.
74. Capodicasa G, Daví G, Picone F, Mattina A, Giannetto V, Vinti V, Vaccaro F, Strano A, De Santo NG, Giordano C. Platelet thromboxane formation and BTG levels after intensive charcoal HP in uremics on regular hemodialytic treatment (RHT). Int J Artif Organs. 1983 Jul;6(4):183-6.
75. Giordano C, Esposito R, Cirillo D, Betuel H, Fredel A, Pluvio M, Mazzola G, Longhi R, Manzo M. Active carbon and its controversial ability to adsorb uremic toxins. Int J Artif Organs. 1984 Jul;7(4):177-8

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