Italian Pioneers in Cardionephrology: how some fundamental Italian cardiorenal researches have passed into oblivion


A historical research was made on papers published by Italian scientists on cardiorenal diseases. The investigated period is between the beginning of the 20th century and the entry of Italy into the Second World War, 1940. 34 papers dealing with the relationship between the kidney and the cardiovascular system were retrieved. All but two articles were published in Italian medical periodicals. The topics covered are varied and range from cardiotoxicity of substances in uremia to the role of renal disease in vascular damage. Some articles are forerunners of later pathophysiological concepts and research technologies. These concern early atherosclerotic vascular damage and the presence of dialyzable cardiotoxic substances in renal insufficiency. Unfortunately, these highly innovative researches have had little diffusion and have fallen into oblivion in Italy and abroad. In conclusion, our research shows that in the first half of the 20th century in Italy there was a lively interest in cardio-renal diseases and that some researchers had produced precursor results of what was confirmed many years later.

Keywords: cardionephrology, cardiorenal studies, Italian scholars, history of nephrology

Ci spiace, ma questo articolo è disponibile soltanto in Inglese Americano. Per ragioni di convenienza del visitatore, il contenuto è mostrato sotto nella lingua alternativa. Puoi cliccare sul link per cambiare la lingua attiva.

  1. Introduction

    Thanks to the Mario Timio’s series of congresses in Assisi, dedicated to Cardionephrology, this branch of Nephrology has experienced growing success in Italy and in the world since 1987 [1]. Although the term Cardionephrology apparently was coined in 1991, studies on the relationship between kidney disease and the heart have a much longer history [24]. An attempt to define cardiorenal disease was made in 1914 in Philadelphia by the renowned clinician Alfred Stengel (1868-1939). According to this eminent clinician “the term comprises cases of combined cardiovascular and renal disease without such manifest predominance of either as to justify a prompt determination of the one element as primary and important and the other as secondary and unimportant” [5]. This term was also used in death certificates in USA [4]. Among the early studies on cardiorenal syndromes, the best known are those performed in UK, France and USA [3, 4]. 

    La visualizzazione dell’intero documento è riservata a Soci attivi, devi essere registrato e aver eseguito la Login con utente e password.

Pius X (1835-1914): the last gouty pope


Gout is a common, complex, systemic and well-studied form of chronic inflammatory arthritis in adults. It is due to the deposition of sodium monourate crystals in peripheral joints and periarticular tissues driven by hyperuricemia. Gout is the oldest recorded inflammatory arthritis to affect humankind, with roots stretching back to 2460 BC. It is known as “the rich man’s disease”, “the patrician malady”, “a disease of plenty”, “disease of kings”, “disease of Western Society”, and also “a life-style disease”. Few studies have addressed the problem of gout among popes, affluent people who usually live longer than their contemporaries and are among the most scrutinized persons. Pius X (1835-1914) was the last pope with gout.

Gout seems to have affected 26 out of 265 popes (9.81%) from Saint Peter to Benedict XVI (34-2013 AD). The first was Gregory I Magnus, who was pope in the years 590-604, the last was Pius X, who reigned from 1903 to 1914 at age 79. Their age at death was 71.7 ±9.2 years (Mean ± SD). All popes were elderly men, some had voracious appetites and/or were wine drinkers. Several were sedentary and obese, while others were sober eaters, who took long walks or went riding. Chiragra (arthritic pain in the hands), podagra (arthritic pain in the big toe) and renal stone disease were among the most frequent disturbances.

The causes of death, due to CKD, strokes and infections are discussed along with the fact that gout disappeared from the Vatican Palace on August 22, 1914. However, in accordance with the Theory of Epidemiological Transition, gout seems likely to become a problem for the general population, increasingly adopting unhealthy lifestyle choices, in the absence of a correct education.

Keywords: gout, popes, Pius X, renal death, death due to infection, death due to stroke


Gout is a chronic, painful, non-infectious, non-lethal disease associated with crystal deposition of uric acid, when uric acid concentration exceeds 6.8 mg/dl plasma. The kidneys may cause hyperuricemia – the prevalence of which increases in the old and very old, – but are also the target of hyperuricemia (renal stones, renal disease and its progression). Hyperuricemias are due to either renal overload, renal underexcretion or a combination of both; renal overload may be due to overproduction by dietary purines, endogenous purine synthesis, purine breakdown and purine salvage [16]. Gout, known also as the “patrician malady” and the “disease of distinction” [7,8] is the oldest recorded inflammatory arthritis to affect humankind, with roots stretching back to 2640 BC [9].

Popes by definition belong to the most affluent class and their lifespan is longer than their contemporaries. In fact, a total of 51 pontiffs reigning in the years 1493 to 2005 lived to a mean age of 63.9 years and died an average of 10.0 years after being enthroned [10]. We have studied the narratives around popes, from Saint Peter to Benedict XVI [1115], and demonstrated a high prevalence of gout. In a recent review [16] we identified a total of 25 gouty popes: 14 out of 25 (58%) had risk factors; 5 out of 25 (25%) had comorbidities; 21 out of 25 (84%) were unable to perform their duties; 8 out of 25 (32%) died of stroke; 12 of them (68%) had renal disease; 12 out of 17 (70.6%) underwent a renal death. Renal disease did not affect age at death [16].

This paper focuses on the last gouty pope, Pope Pius X. His death has been traditionally but wrongly attributed, even by us, to acute pneumonia. The present study now points out that his death was most likely linked to uremia, due to lasting gout, the final straw being acute pulmonary infection.


Historical case report – Pius X (1835-1914), Pope (8/4, 1903-8/22,1914)

Pius X (Figure 1), born Giuseppe Melchiorre Sarto on June 2, 1835 at Reise (Province of Treviso), was ordained priest in 1858 and, in the same year, became parish priest. Later he was nominated bishop of Mantua (1884), cardinal and patriarch of Venice (June 1893) and elected Pope on August 4, 1903; he reigned until August 22, 1914. A renowned orator, he is remembered for his expertise in sacred music and for hiring Lorenzo Perosi for the Choir of the Sistine Chapel, for his antimodernism and the refusal of science, for the letters sent to European powers to avoid the First World War, and for the wide pastoral care and the love for the poor. In his last will and testament wrote “born poor, lived poor, want to die poor”. Roger Aubert, the Belgian historian Roger Aubert (1914-2009) has defined Pius X as the greatest reformer of the internal life of the Church after the Council of Trent [17].

His health has been described as good until the end of his days and his death ascribed to “acute tracheitis, bronchitis, infection-inflammation of the lower left lung lobe”, a disease of acute onset followed by rapid worsening. He was under the care of Andrea Amici (1870-1920), archiater and chief of medical services in the Vatican, and of Ettore Marchiafava (1847-1935), professor of pathology at the University La Sapienza in Rome. His disease lasted from Saturday August 15 (he celebrated the last mass) to the night of August 20, 1920. The course was characterized by a worsening fever that, in his last hours, peaked at 40°C and was associated with dyspnea [18-20].

Figure 1: Picture of Pope Pius X (1835-1914), October 1903, from Herder Verlag, Freiburg im Breisgau: Die katholischen Missionen (digitally colored). Image in the public domain,,_by_Francesco_De_Federicis,_1903_(retouched,_colorized).tif

However, we now know that Giuseppe Sarto, since his early years of priesthood, had suffered from gout, which flared painfully from time to time and was tolerated by him. As a pope, for obvious state reasons, he was forced to frequent health checks and restrictive dietary impositions [21]. The disease flared up in August 1920 and was associated with chest pain, fever, nephritis (uncurable at that time). The disease extended to the bronchial tree and caused the pneumonia that killed him [22]. So, the diagnosis was pneumonia, heart failure, pericarditis and uremia due to gout.

He was beatified in 1951 by Pius XII. As far as we know, he was the last gouty pope and after him the disease was never again associated with the papacy.



Recent studies have defined gout as a “papal disease” [16]. Pope Pius X is the last in the list of 26 gouty popes of the Catholic Church between the years 590-1914 (Table 1). Gout affected 9.77% of all popes and he was the 18th out of 26 (69.3%) gouty popes to die of a renal cause. The disease left him, like 22 out of 26 (84.6%) other popes, unable to perform his duties.

No. Popes Family name Start of pontificate End of pontificate Inhability to perform Renal/non renal death** Age of death
1 St Gregory I Anici 9/3, 590 3/12, 604 yes Non-renal 64
2 Sisinnius NK 1/15, 708 2/4, 708 yes Non-renal 58
3 Sergius II Sergio 1/2 844 1/17 847 yes Non-renal 57*
4 Boniface VI NK 4/5, 896 4/20 896 Non-renal NK
5 Honorius IV Giacomo Savelli 4/2, 1285 4/3, 1297 yes Non-renal 77*
6 Boniface VIII Benedetto Caetani 12/24, 1294 10/11, 1303 yes Non-renal 73
7 Clement VI Pierre Roger 5/7, 1342 12/6, 1352 Non-renal 62
8 Nicholas V Tommaso Parentucelli 3/6, 1447 3/24, 1455 yes Renal 58
9 Callistus III Alonso de Borja 4/8, 1455 8/6, 1458 yes Renal 80
10 Pius II Enea Silvio Piccolomini 8/19, 1458 8/15, 1464 yes Renal 66
11 Sixtus IV Francesco della Rovere 8/9, 1471 8/12, 1484 yes Renal 70*
12 Pius III Francesco Todeschini Piccolomini 9/22, 1503 10/18, 1503 yes Renal 64
13 Julius II Giuliano della Rovere 11/1, 1503 2/21, 1513 Non-renal 70
14 Julius III Giovanni Maria del Monte 2/7, 1550 3/23, 1555 yes Non-renal 68
15 Marcellus II Marcello Cervini degli Spannoni 4/1, 1555 4/30, 1555 yes Renal 54*
16 Pius IV Giovanni Angelo Medici di Marignano 12/25, 1559 12/9, 1565 yes Renal 66
17 Clement VIII Ippolito Aldobrandini 1/30, 1592 3/3, 1605 Renal 70*
18 Gregory XV Alessandro Ludovisi 2/9, 1621 7/8, 1623 yes Renal 69
19 Innocent X Camillo Pamphilj 10/4, 1644 1/7, 1655 yes Non-renal 80
20 Clement X Lorenzo Altieri 4/29, 1670 7/22, 1676 yes Non-renal 86
21 Innocent XI Benedetto Odescalchi 9/21, 1676 8/12, 1689 yes Renal 78
22 Innocent XII Antonio Pignatelli 7/12, 1691 9/28, 1700 yes Non-renal 85*
23 Clement XII Lorenzo Corsini 7/12, 1730 2/6, 1740 yes Renal 88*
24 Benedict XIV Prospero Lorenzo Lambertini 8/17, 1740 5/3, 1758 yes Renal 83*
25 Pius VIII Francesco Saverio Castiglioni 3/31, 1829 11/30, 1830 yes Non-renal 69
26 Pius X Giuseppe Melchiorre Sarto 8/4, 1903 8/20, 1914 yes Renal 79
All popes 84.6% 50% Renal 71.9 ±9.2#
Table I: Gouty popes (no. 26). Data for popes nos. 1-25 in reference no.16. (* affected by stroke; ** presumed Renal/Non Renal death; # Mean ±SD; NK = not known).

The mean age at death of the 26 popes listed in Table I was 71.7 ±9.7 years and no difference was found between the age at death of popes who died of a renal cause and those who died of a non-renal cause. Pius X died from an acute infectious disease, which is always a risk for a gouty person. In fact, compared to the general population, gout patients have an increased association with all-cause disease mortality, especially attributed to cardiovascular diseases, cancer, and infectious diseases [23].

In a study by Vargas-Santos et al. [24] enrolling 19,497 people with a new diagnosis of gout and 194,947 controls, a strong association was found between gout and risk of death due to renal disease. Furthermore, a study by Spaetgen et at. [25] investigated the risk of various types of infections (pneumonia and urinary tract infection), and infection-related mortality in patients with gout using data from the UK Clinical Practice Research Datalink. Their study was the first evaluating the risk of community-acquired infections in patients with gout versus matched controls. Gout was associated with a 34% increased risk of pneumonia. Also, in a national study across the United States [26], the most common infection was pneumonia (52%) in 1998-2000 and sepsis (52%) in 2015-2016. Older age was associated with a greater risk.

There is a strong suspicion, still to prove, of an association between lung infection and the lung dysfunction described in uremia for the first time in 1932 by Ehrich and McIntosh in 3 patients with Bright’s disease [27]. They believed that some toxic or metabolic factor resulted in edema and congestion with “formation of an exudate which failed to resorb and then went on to organization” [27], a dysfunction that has been extensively studied in recent years. A restrictive dysfunction, associated with gravity of CKD, was disclosed by Mukai et al. [28], whereas Zoccali et al. [29] have shown, by systematically applying chest ultrasound in ESRD patients, that hidden or clinically manifest lung congestion is exceedingly frequent in this population an may be detected at a preclinical stage.

Gout, probably the first known non-communicable disease, might not represent in principle the best candidate to be discussed in terms of “Theory of Epidemiologic Transition”. This theory was advanced in a landmark paper by Abdel R. Omran [30] after infectious diseases were conquered [31] after World War II and degenerative and “man-made diseases” started emerging. Using demographical tools, Omran analyzed the changing patterns of population age distribution in relation to changes in mortality, fertility, life expectancy, causes of death. He identified 3 ages in humankind: the age of famine and pestilence (life expectancy <30 years), the age of “receding pandemics” (life expectancy 30-50 years), and the “age of degenerative diseases and man-made disease” (life expectancy >50 year). The theory has been updated frequently, and finally poverty (initially neglected) has been taken into consideration along with incomes and education [3036].

This is relevant and makes the theory suitable to explain the high prevalence of gout in popes and the low, but slightly increasing, prevalence in the general population. The data shall be discussed in terms of lifestyles, income and education. It has been shown that affluent and educated people also adopt immoderate lifestyles causing non-communicable diseases associated with morbidity and mortality [3036]. However, these people, when made aware of the risks, often agree to modify their lifestyles choices, whereas poorer, uneducated people do not. Thus, the latter group tends to experience the morbidity and mortality of the disease (third transition phase) at the time when rich well-educated individuals achieve protection [36].

By applying the above concepts to gout (Figure 2), we can say that popes before 1915 had a high prevalence of gout due to lifestyles choices causing it. These were later corrected through education and gout disappeared. Thus, in 2021, gout has no room in the apostolic palaces. At the same time, poor people, because of undernutrition, working conditions, and frequent movements back and forth from the workplace, were “protected” from gout, and therefore, before 1915, the prevalence of gout was zero. After World War II the general population has become sedentary, while the availability of proteins and the abuse of spirits, wines and other alcoholic beverages, as well as beverages rich in glucose, has sharply increased. Therefore, in the USA, Italy and France, the blood concentration of uric acid has been slightly but steadily increasing; the prevalence of gout is still minimal, but increasing, and will continue to do as long as education fails to encourage healthier lifestyles.

Lifestyles causing and preventing gout
Figure 2: Lifestyles causing and preventing gout, and trends in the prevalence of gout in popes and general population before 1915 and in 2021


We thank for the English revision Joseph Sepe MD, Professor of Biological Sciences, University of Maryland Global Campus, USA and Adjunct Professor – Department of Mathematics and Physics University of Campania, Luigi Vanvitelli, Naples, Italy.



  1. Dalbeth N, Merriman TR, Stamp LK. Lancet 2016; 388(10055): 2039-52
  2. Ragab G, Elshahaly M, Bardin T. Gout: An old disease in new perspective – A review. J Adv Res 2017; 8:495-511.
  3. Igel TF, Krasnokutsky S, Pillinger MH. Recent advances in understanding and managing gout. F1000Res 2017; 6:247.
  4. Dalbeth N, Choi HK, Joosten LAB, Khanna PP, Matsuo H, Perez- Ruiz F, Stamp LK. Gout. Nature Reviews Disease Primers 2019; 5:69.
  5. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystaks activate the NALP3 inflammasome. Nature 2006; 440:237-41.
  6. McCarty DJ, Hollander JL. Identification of urate crystals in gouty synovial fluid. Ann Intern Med 1961; 54:45-64.
  7. Porter R, Rousseau GS. Gout: The Patrician Malady. New Haven, Yale University Press: 1988.
  8. Savica V, Santoro D, Ricciardi B, Ricciardi CA, Calo LA, Bellinghieri G. Morbus dominorum: gout as the disease of lords. J Nephrol 2013; 26(S22):113-16. https://doi: 10.5301/jn.5000349
  9. McKeown T. The origins of human disease. Oxford, Blackwell: 1988.
  10. Retief FP, Cilliers L. Disease and causes of death among popes. Acta Theologica 2006; 26(2):S7.
  11. De Santo NG, Bisaccia C, De Santo Causes of death due to disease of the genito-urinary system and of the heart among 264 popes in the years 65-2005 AD: First approach. Nephrol Dial Transplant 2019; 34(S1): gfz103.SP804.
  12. De Santo NG, Bisaccia C, De Santo LS. Deaths caused by cardiorenal disease among 264 popes from St. Peter to St. John Paul II. Hellenic Nephrology 2019; 31:158.
  13. De Santo NG, Bisaccia C, De Santo LS. Papal deaths caused by cardiorenal disease. First Approach. Arch Hell Med 2020; 37(S2):177-81.
  14. Bisacccia C, De Santo LS, De Santo NG. Gout a papal disease: a study in 20 pontiffs (540-1830. Nephrol Dial Transplant 2020; 35(S3):gfaa144.P1836.
  15. De Santo N, Bisaccia C, De Santo (2021). Renal stone disease in 193 pontiffs from Vigilius to Pius VIII (537-1830). Nephrol Dial Transplant 2021; 36(S1):gfab105.001.
  16. De Santo NG, Bisaccia C, De Santo LS. Gout: a papal disease-a historical review of 25 gouty popes (34-2005 AD). J Nephrol 2021; 34(5):1565-67.
  17. Aubert R. Documents relatifs au movement catholique italien sous le pontificat de S. P. X. ibid., XII (1958), pp. 202-43, 304-70. In: Pius X, Enciclopedia Treccani online. Accessed on December 9, 2021.
  18. Merry del Val R. San Pio X. Verona, Fede e Cultura: 2012.
  19. Occelli P. Il beato Pio X. Roma, ed. Paoline: 1951, p. 237.
  20. Siccardi C. San Pio X. Roma, San Paolo ed.: 2014, p. 369.
  21. dal Gal G. Pio X il papa santo. Firenze, Libreria Editrice: 1940, p. 283.
  22. Sanguinetti O. Pio X: Un pontefice santo alle soglie del secolo breve. Milano, Sugarco Edizioni: 2014, p. 283
  23. Disveld IJM, Zoakman S, Jansen TLTA, Rongen GA, Kienhorst LBE, Janssens HJEM, Fransen J, Janssen M. Crystal-proven gout patients have an increased mortality due to cardiovascular diseases, cancer, and infectious diseases especially when having tophi and/or high serum uric acid levels: a prospective cohort study. Clin Rheumatol 2019; 38(5):1385-91.
  24. Vargas-Santos AB, Neogi T, da Rocha Castelar-Pinheiro G, Kapetanovic MC, Turkiewicz A. Cause-Specific Mortality in Gout: Novel Findings of Elevated Risk of Non-Cardiovascular-Related Deaths. Arthritis Rheumatol 2019; 71(11):1935-42.
  25. Spaetgens B, de Vries F, Driessen JHM, Leufkens HG, Souverein PC, Boonen A, van der Meer JWM, Joosten LAB. Risk of infections in patients with gout: a population-based cohort study. Scientific Reports 2017; 7:1429.
  26. Singh JA, Cleveland JD. Serious Infections in Patients With Gout in the US: A National Study of Incidence, Time Trends, and Outcomes. Arthritis Care Res 2020; 73(6):898-908.
  27. Ehrich W, McIntosh JF. The pathogenesis of bronchiolitis obliterans. Arch Path 1932; 13:69-76.
  28. Mukai H, Ming P, Lindholm B, Heimbürger O, Barany P, Anderstam B, Stenvinkel P, Qureshi AR. Restrictive lung disorder is common in patients with kidney failure and associates with protein-energy wasting, inflammation and cardiovascular disease. PLoS One 2018; 13(4):e0195585.
  29. Zoccali C, Tripepi R, Torino C, Bellantoni M, Tripepi G, Mallamaci F. Lung congestion as a risk factor in end-stage renal disease. Blood Purif. 2013; 36(3-4):184-91.
  30. Mc Keown R. The epidemiologic Transition: Changing Patterns of Mortality and Population Dynamics. Am J Lyfestyle Med 2009; 3(S1): 19S-26S.
  31. Omran AR. The epidemiologic transition. A theory of the Epidemiology of Population Change. Milbank Memorial Fund Quarterly 1971; 49(4):509-38.
  32. Caldwell JC. Population health in transition. Bull World Health Org 2001; 71(1):159-60.
  33. Pearson TA. Education and income: double edged swords in the epidemiologic transition of cardiovascular disease. Ethnicity & Disease 2003; 13(S2):158-63.
  34. Pearson TA. Socioeconomic status and cardiovascular disease in rural population. In Stamler J, Hazuda H (eds). Report on the conference on Socioeconomic Status and cardiovascular disease. Washingtoon DC, National Heart, Lung, and Blood Institute: 1995, pp. 101-08.
  35. Marmot MG, Smith GA, Stansfeld S, Patel C, et al. Health inequalities among British civil servants. Lancet 1991; 337:1387-93.
  36. Kaplan G, Keil J. Socioeconomic factors and cardiovascular disease: a review of the literature. Circulation 1993; 88:1973-88.

La nefrologia italiana ed i suoi cultori tra le due Guerre Mondiali


La prima guerra mondiale segnò una svolta per la medicina nel mondo che fu alla base  delle molte importanti innovazioni cui si assistette nei successivi 20 anni. Gli studi nefrologici in Italia facevano parte di questa tendenza generale. In questo lavoro vengono recuperati ed esaminati tutti i lavori relativi alla fisiologia, patologia e terapia renale, prodotti da scienziati italiani negli anni tra le due guerre mondiali. Vengono inoltre individuati gli autori che hanno prodotto più articoli nefrologici e descritta la loro attività. Questa ricerca ha recuperato 638 articoli riguardanti il rene pubblicati da scienziati italiani nel periodo. I temi trattati risultano essere attuali e al livello dei contemporanei stranieri. Tra gli autori emerge un gruppo di giovani scienziati particolarmente dediti allo studio del rene. La maggior parte di questi sarà in futuro tra i fondatori del SIN e leader della nefrologia italiana.

Parole chiave: storia, nefrologia, Italia, scienziati, guerre mondiali

Ci spiace, ma questo articolo è disponibile soltanto in Inglese Americano. Per ragioni di convenienza del visitatore, il contenuto è mostrato sotto nella lingua alternativa. Puoi cliccare sul link per cambiare la lingua attiva.


World War I was a turning point for medicine. Giorgio Cosmacini, doctor and historian of medicine, in his book “War and Medicine” defines war as a “paradoxical” source of progress from a medical point of view [1]. The need to treat a huge number of soldiers wounded and/or suffering from serious and new pathologies forced doctors to seek new, previously unknown, answers to deal with new emergency situations. The results of this research had a tremendous impact on world medicine in the years following the conflict.

The Italian doctors, especially the younger ones, who found themselves serving in war zones also benefited from those experiences and from contacts with colleagues in the allied armies. The clinical and research approach changed, both in terms of timing and methods. Kidney diseases occupied a prominent position among war-related morbidities. For example, since the first months of the conflict, there had been reports of an apparently new type of “nephritis”: the “trench nephritis” or war nephritis.
This new form of nephropathy attracted the attention of the greatest clinicians of the time including William Osler (1849-1919) [2]. Italian doctors promptly turned their attention to this new form and such was the interest that the first post-war congress of the Italian Society of Internal Medicine dedicated a session to it. Significantly, this meeting was held in Trieste that, at the time, had just become Italian (Fig. 1) [3]. Due to the techniques used and the progress achieved, we may consider this as the start of a new cycle of nephrology studies compared to the previous two decades [4].

Figure 1: Session of the 1919 Internal Medicine Congress held in Trieste, dedicated to war nephritis
Figure 1: Session of the 1919 Internal Medicine Congress held in Trieste, dedicated to war nephritis

We, too, chose to start from this date for an excursus on Italian nephrology between the two wars.


Materials and methods

We have searched all the scientific articles concerning kidney studies (anatomy, physiology, clinic) published by Italian authors between the two World Wars. The specific nephrological items searched in the literature between 1918 and 1939 are listed in Table I.

Subject N. of Papers %
Nephropaty (general) 118 18.4
Glomerulonephritis 82 12.8
Renal function 73 11.4
Hematuria 63 9.8
Kidney stones 45 7.0
Polycystic kidney 38 5.9
Diuretics 38 5.9
Albuminuria 36 5.6
Azotemia 37 5.7
Renal diabetes 26 4.0
Hypertension & Kidney 21 3.2
Creatinine 17 2.6
Nephrosis 15 2.3
Nephrosclerosis 12 1.8
Uremia 10 1.5
Pielonephritis 7 1.0
Total 638 100
Table I: Kidney studies published by Italian authors between World War One and World War Two

Within these subject areas, we have also singled out specific issues, emerged during the observed period, that were not dealt with in previous years and that that are still of scientific interest today. We also examined the respective chapters of two major Italian medical treatises, published in 1931 and 1939.

Of each author we have encountered, we have reported the age and the subsequent professional development, searching for those who, in the second post-war period, would have a role in modern Italian nephrology and in the foundation of the Italian Society of Nephrology (SIN) in 1957 [5].



We retrieved 638 published papers dealing with kidney studies published by 343 Italian authors (Table I). The mean number of papers per author was 1.6.

Subject of the papers

The largest group has been labeled “general nephropathies” and includes different types of conditions, investigations, and therapies.

The second group concerns glomerulonephritis. This includes 10 papers on “trench nephritis”. These are of particular interest since they show that their authors were up to date on research carried out in other countries and that their pathogenetic hypotheses were sufficiently well founded [6]. It was believed that the conditions of the soldiers in the war environment had created a general and/or renal vulnerability and that this favored infectious processes, causing glomerulonephritis. Histologically it was identified as a diffuse proliferative form. The long-term prognosis was considered poor. Most concepts, especially those concerning the infective etiology, were in good keeping with the conclusions drawn on the matter by the top medical figures of the time [7].

The investigation of renal function is the subject of 11.8% of the papers. The analysis shows that in Italy in the mid ’30 this was a much-debated topic. In a 1931 medical treatise, the concentration-dilution test was deemed the most reliable assessment of renal function [8]. No clearance tests were taken into account. In the following years new concepts and new tests came into play. The urea clearance as a measure of the efficiency with which the kidneys remove urea from the blood stream was introduced after the WW1 and spread rapidly [9]. Its precision in assessing glomerular filtration was however invalidated by the rate of urea reabsorption by the tubules.

Rehberg had tried to overcome this drawback by devising a clearance method aimed at measuring the glomerular filtration based on an administration of a substance only filtered by the glomeruli [10]. Unfortunately, the load of creatinine administered was so large that the high blood concentration attained caused a tubular excretion of the substance together with glomerular filtration, altering the results [11]. Therefore, in Italy, the assessment of glomerular filtration through the recently proposed formula caused enthusiasm and controversy at the same time. Some studies did not fully support the results obtained by applying Rehberg’s method to the measurement of glomerular filtration in renal diseases [12]. On the other hand, other scientists found that this method could be improved to provide reliable results. In this way, by introducing the concentration of naturally occurring plasma creatinine in the formula of Rehberg, the Italian doctor Ferro-Luzzi was the first in the world to describe the clearance of endogenous creatinine and to obtain reliable results (Fig. 2) [13,14,15]. These studies were among the few to be published on foreign journals. The same applies to a basic science study on glomerular filtration published on an American journal and that deserves particular attention as it was written by a young Italian scientist destined for a very brilliant academic career Fig. 3 [16].

Figure 2: One of the papers on the use of the creatinine clearance by Ferro-Luzzi published in a German journal
Figure 2: One of the papers on the use of the creatinine clearance by Ferro-Luzzi published in a German journal
Figure 3: The first nephrological paper published by an Italian scientist in an American Journal
Figure 3: The first nephrological paper published by an Italian scientist in an American Journal

Azotemia (BUN) and creatinine are the subject of 8.3% of published research and are closely related to the studies of semeiology and renal physiology.

Among the other studies, those dealing with the relationship between kidney and hypertension should be highlighted. These 21 papers represent 12.5% of all hypertension articles and provide interesting insights into the research trends of the time. Renal denervation was attempted as a treatment for arterial hypertension [17]. The possibility of irradiating the carotid sinus to reduce blood pressure was also explored [18]. Finally, attempts at surgical therapy for arterial hypertension proposed by important clinicians of the time also deserve to be reported [19].

Other subject listed in table I are of lesser relevance or are tainted by concepts that have completely disappeared in the evolution of nephrology. An example is represented by the “nephrosis” group: this word, at the time, indicated conditions completely different from what we mean today.

The progress made in Italy, with the aforementioned studies, and abroad during the decade 1930-40 is well evidenced and discussed in the ponderous section (397 pages) on the kidney of the “Ceconi and Micheli” internal medicine treatise of 1940 [20]. From those pages, and the relative bibliographic references, we could also identify the Italian authors considered as “opinion leaders” in kidney studies at the time.


In order to single out the authors with a greater nephrological interest, we have arbitrarily selected those with a number of publications on the topic equal to or greater than five. In Table II these authors are listed along with their age and research location. All of them came from the most prestigious Italian universities, where studies on the kidney had already developed in previous years [4].

Author N°papers Birth and death City of work
Ferro-Luzzi Giovanni 28 1903-2000 Roma-Messina
Marcolongo Fernando 23 1905-1969 Torino
Condorelli Luigi 17 1899-1985 Napoli-Catania
Cesa-Bianchi Domenico 6 1879-1956 Milano
Gavazzeni Mauro 6 1904-1935 Pavia
Bufano Michele 5 1901-1993 Parma
Fieschi Aminta 5 1904-1991 Pavia
Table II: Authors with 5 or more nephrological papers

Interestingly, all but one were quite young at the time of the nephrological research we have retrieved. Three of them stand out for the number of published articles and their quality: Ferro-Luzzi, Marcolongo and Condorelli.

Ferro-Luzzi produced a series of studies on the kidney published in important international German-language journals between 1931 and 1939. The most interesting were those on plasma creatinine and its pioneering use in the calculation of clearance [13, 22]. Ferro-Luzzi is also the most cited Italian author in the chapter on renal function of the aforementioned treatise by Ceconi and Micheli [20]. For historical purposes, it should be noted that Filippo Romeo (1908-1981), who was a little younger than Ferro-Luzzi, conducted some nephrological research in association with him and, many years later, was one of the founders of the SIN [22]. This collaboration was interrupted when Ferro-Luzzi went to direct the Italian hospital in Asmara in 1939, where he founded the local medical school and remained until 1955.

Marcolongo belonged to the Turin academic school of Ferdinando Micheli (1872-1937). Since his degree in medicine in 1927, he devoted much of his research activity to the study of the kidney under all its physio-pathological, clinical and therapeutic aspects. In recognition of his experience in the nephrology field, he was entrusted with writing the chapter on kidney diseases of various medical treatises, first of all the Ceconi-Micheli of 1939 [20]. He obtained the academic position of professor of medicine in Siena and, years later, he appears among the members of the first board of the newly formed SIN.

Condorelli appears in this list not only for the number of kidney studies published, but also because he is the first Italian to publish a nephrological article in an American journal (Fig. 3, above) [16]. After this early interest in nephrology, Condorelli extended his research to other organs, especially the heart, where he obtained even more brilliant results. At the height of his career, he became a renowned professor of medicine at the University of Rome.

The presence of Bufano and Fieschi in our list of authors is of particular interest, since both of these researchers played an important role in post-war nephrology. Bufano created one of the most important Italian nephrological schools in Parma and was one of the founders of SIN. From an academic point of view, he achieved the position of professor of medicine in Rome. Fieschi, later a member of the first board of the SIN, was a pioneer of renal dialysis. In fact, in 1947, before becoming professor of medicine in Genoa, he conceived and built his original model of artificial kidney [23].

A sad fate awaited the last of these authors. Gavazzeni, who had carried out some brilliant research in the department of Adolfo Ferrata (1880-1946) in Pavia, died as a hero in the war of 1935 [24]. The city of Bergamo named a street after him.

Finally, after having considered some of the most prolific authors in the nephrological field, we cannot forget those who were taking their first steps back then. Among them, especially noteworthy are Domenico Campanacci (1898-1986) and Cataldo Cassano (1902-1998) who, in the early ’30s, had proposed their theories on the nature of lipoid nephrosis [25]. Years later, both authors founded important nephrological schools.



From the results of this investigation on kidney studies in Italy between the two World Wars we can draw a few conclusions. Italian scholars were very active in this area of medicine and their knowledge was up to date and on the same level of their colleagues abroad. The most productive researchers were young, which may indicate that the complex issues inherent to kidney function required a fresh and prepared mind. Therefore, only few selected researchers chose to approach this field. All of them carried out their research in the context of the most advanced medical schools in Italy. Here, a fruitful synthesis took place between these researchers’ new ideas and the structures most suitable for supporting their work. The quality of these young researchers is also confirmed by their success in their subsequent academic career. It is astonishing that all of them obtained positions of great importance in Italian medicine and inspired internal clinical schools or, more specifically, nephrological institutions. Finally, the names of many of these scholars appear in the formal act of foundation of the SIN, which ratified the existence of a substantial number of clinicians and researchers dedicated to the study of the kidney in Italy. This confirms the very close connection existing between “modern” Italian nephrology and what was achieved in this field between the two World Wars.



  1. Cosmacini G. Guerra e medicina. Dall’antichità a oggi. Laterza (Bari): 2011.
  2. Smogorzewski MJ. William Osler and investigation on trench nephritis. G Ital Nefrol 2016; 33(S66).
  3. Cesa-Bianchi D. Esame critico delle più importanti acquisizioni fatte durante la guerra nel campo delle nefropatie. Policlinico 1919; 26:1208-1210.
  4. Losito A. The origin of the modern Italian nephrology at the dawn of the 20th century. G Ital Nefrol 2020; 37:6.
  5. Fogazzi GB. 28 Aprile 1957: la fondazione della Società Italiana di Nefrologia. In: Fogazzi GB, Schena FP. Persone e fatti della Nefrologia Italiana (1957-2007). Wichtig Editore: 2007, p. 135.
  6. Giugni, F.Sulle nefriti acute delle truppe operanti. Policlinico 1917; 24: 977-986.
  7. Medical Section and Therapeutical and Pharmacological Section: Discussion on Trench Nephritis. Proc R Soc Med 1916; 9(Joint Discuss):i-xl.
  8. Ascoli M, Serio F. Le malattie dell’apparato uropoietico. In: Trattato Italiano di Medicina Interna. Società Editrice Libraria (Milano): 1931.
  9. Moller E, McIntosh JF, Van Slyke DD. Studies of urea excretion. ii. relationship between urine volume and the rate of urea excretion by normal adults. J Clin Invest 1928; 6:427-465.
  10. Rehberg P. The rate of filtration and reabsorption in the human kidney. Biochem J 1926; 20:447-461.
  11. Van Slyke DD, Dole VP. The significance of the urea clearance. J Clin Path 1949; 2:273-274.
  12. Gavazzeni M. La funzionalità renale studiata col metodo di Rehberg; considerazioni generali e suo comportamento di fronte a sostanze vasomotorie. Policlinico 1933; 40:294-306.
  13. Ferro-Luzzi G, Saladino A, Santamaura S. Bestimmung des harnstoffes und kreatinins durch fällung nach Somogyi, anwedung bei der rehbergschen probe. Zschr ges exp Med 1935; 96:250-265.
  14. Ferro-Luzzi G. Die Nierenfunktion im Lichte moderner Anschauungen; Studien über die Tubuliresorption. Zschr ges exp Med 1934; 94:708-721.
  15. Losito A, Fogazzi GB. A forgotten trailblazing Italian nephrologist: Giovanni Ferro-Luzzi (1903-2000) and the first measurement of endogenous creatinine clearance. J Nephrol 2021.
  16. Edwards JG, Condorelli L. Studies of aglomerular and glomerular kidneys. Am J Physiol 1928; 86:383-398.
  17. Gerbi C, Martinetti R. Denervazione renale ed ipertensione arteriosa. Arch Sc Med 1936; 61:397-409.
  18. Gavazzeni A. Risultati dell’irradiazione del seno carotideo nella ipertensione arteriosa. Radiol Med 1936; 23:694-708.
  19. Donati M, Greppi E. Primi rilievi sull’ operazione di Pende (resezione del N. splancnico di sin.) nell’ ipertensione arteriosa. Monit Endocr 1934; 2:734-739.
  20. Micheli F, Marcolongo F. Malattie degli organi orinari. In: Ceconi A, Micheli F. Medicina Interna 2a ed. Vol 3. Edizioni Minerva Medica(Torino): 1940, pp. 519-916.
  21. Ferro-Luzzi G. Ueber das sogenannte wahre Kreatinin des Blutes. Biochem Zschr 1935; 275:422-429.
  22. Ferro-Luzzi G, Romeo F. Nefrosi lipoidea. Minerva Med 1936; 27(pt 1): 43-59.
  23. Fogazzi GB. Historical Archives of Italian Nephrology: the artificial kidney commissioned in 1947 by Aminta Fieschi (1904-1991). G Ital Nefrol 2003; 20:43-48.
  24. Gavazzeni M. Raffronto fra urea clearance e valori del filtrato glomerulare (metodo Rehberg) nelle nefropatie. Boll Soc Med Chir Pavia 1934; 48:85-95.
  25. Ascoli M, Serio F. La nefrosi lipoidea. Le malattie dell’apparato uropoietico. In: Trattato Italiano di Medicina Interna. Società Editrice Libraria (Milano): 1931, p.