EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Many Roman pontiffs are known to have had kidney stone disease. However, no specific report has explored the prevalence of the various stones in popes, which is the purpose of this study.
Materials and Methods: We extensively studied the histories of all popes (n = 264) from Saint Peter to John Paul II (34-2005).
Results: Among 206 popes reigning from 537 to 2005, 26 popes (12.6%) had uric acid stones. In the same period, 11 of 206 popes (5.3%) had nongouty stones (mainly calcium stones). In total, 37 of 208 (17.8%) popes complained of kidney stone disease. The ratio of calcium stone formers to other stone formers (including uric acid) was 0.42.
Conclusions: The data suggest a higher prevalence of uric acid stones, which is linked to higher consumption of meat and sodium chloride. However, the last pope with kidney stone disease died in 1914. Although renal stone disease disappeared from papal palaces, population studies now indicate an increase in uric acid levels in the general population. The data can be explained based on the “Theory of Epidemiological Transition,” pointing to the importance of education in eradicating poor lifestyles.

Key words : Gouty stone disease, Nongouty stone disease

Kidney stone disease (KSD) is a complex clinical condition with a prevalence of 8% to 10% in population-based studies and with recurrence rate of 30% to 50% at 5 years.¹ About 70% to 85% of renal stones are made of calcium (approximately 60%-70% as calcium oxalate, 10%-15% as calcium phosphate) and 5% to 10% as uric acid.^2,3 We also know that, since 1986, calcium nephrolithiasis is a systemic disease.⁴

It is widely known that many pontiffs formed renal stones and that the disease negatively affected their ability to perform duties. We also know that the first pope who died of KSD was Vigilius (the 59th pontiff), who reigned from March 23, 537, to June 7, 555.^5-11 However, no specific report has explored the prevalence of the various stones in popes, which is the aim of this study.

Materials and Methods

Assuming a 10% prevalence of people who form stones (70% calcium oxalate, 15% calcium phosphate, 5%-10% uric acid, 5% others) among the 206 popes from Vigilius to John Paul II (537 to 2005), we hypothesize a total of 21 popes with KSD, 18 with calcium stone disease (15 with calcium and oxalate stones and 2 or 3 with calcium phosphate stones), 1 or 2 popes with uric acid stones, and 1 pope with other stones (the latter impossible to define historically). We assume that all popes with KSD who had gout were uric acid stone formers, with the remaining popes not having gout and being calcium stone formers.

Gout was diagnosed through narratives pointing to an acutely painful condition of the big toe (podagra), its onset at night, and its recurrence over the years. Importance was given to the association with fever, flank pain, sands, stones, tophi, autopsy findings, difficulties in standing and walking, the need for special chairs, the inability to carry out papal duties, and absence at special celebrations during the liturgical year. Chiragra was identified by acute and recurrent painful attacks of inflammation in the joints of the hands, presenting with swelling, tenderness, redness, and lack of function. Notes were taken on the chronic deformity of the hands and the difficulties in raising drinks and food to the mouth, riding to and celebrating mass, and need for surgeries for stones.

For this study, we gathered data on the quality of foods and drinks, physical exercise, obesity, visits to spas for baths and special waters, and the written suggestions of archiaters and special consultations with great physicians.

The methods to study documents have been described elsewhere.^5-7 We studied the histories of papacy of Bartolomeo Sacchi (1421-1481), Luigi Gaetano Marini (1782-1815), Giuseppe de Novaes (1736-1821), Mathieu-Richard A. Henrion (1805-1862), and Ludwig Von Pastor (1850-1928) and the papal medical histories of Gualino,⁸ Paravicini Bagliani,⁹ Ceccarelli,¹⁰ and Cosmacini.¹¹

Uric acid stone formers

Among 206 popes who reigned from 537 to 2005, 26 popes (12.6%) were uric acid stone formers (Table 1). Twenty-four popes were born in Italy, 1 came from Syria (Sisinnius), and 1 from France (Clement VI). The first gouty pope was Gregory I, who reigned from September 3, 590, to March 13; the last was Pius X, who died in 1914.

Some pontiffs were frugal, such as Gregory I (who ate cabbages and died malnourished), Pius II, Pius III, Gregory XV, Innocent XI, Benedict XIV, and Benedict XV. Benedict XIV was a sober eater and dined with cinnamon-flavored water. On the other hand, some pontiffs gave considerable importance to food. Julius III invested no less than 8,000 ducats per month in food and wine. Boniface VIII, Julius II, and Julius III were voracious eaters. Pius IV ate 5 times per day. Gregory I, Pius II, Honorius IV, and Pius III, despite their attitudes toward foods, used to fast as a sign of repentance. Julius II loved to exercise.

Pius IV and Julius II enjoyed drinking wine. Pius II mixed it with water. Nicholas V, a sober drinker, had “two wide bodied jugs with a narrow necks on his table, one for red wine and the other for white wine.” He used wine to impress important visitors from France, Germany, and Hungary who might appreciate the value of the wine. Pope Benedict XIV drank a small amount of wine from Montepulciano at lunch and preferred to drink water for the rest of the day.

Boniface VIII, Clement VI, Callixtus III, Nicholas V, Pius II, Sixtus IV, Pius III, Julius II, Marcellus II, Clement VIII, Gregory XV, Pius IV, Clement X, Innocent X, Innocent XI, Clement XII, and Pius X had narratives of podagra, chiragra, sands, renal stone disease, flank pain, dysuria, with or without fever, bouts of hematuria, and small kidneys and/or stones at autopsy.

Seven popes (26.6%) died of stroke or after 1 or more bout of transient ischemic attacks (Marcellus II at age 54, Sergius II at age 57, Sixtus IV and Clement VIII at age 70, Honorius IV at age 77, Innocent XII at age 85, and Clement XII at age 88 years) and underwent various transient ischemic attacks before death.

Of 26 popes with gout, 21 (80.8%) had inability to perform, and 14 (53.9%) had risk factors. Five popes (19.3%) were obese.

Calcium stone formers

In the years from 537 through 2005, 11 of 206 popes (5.3%) were nongouty stone formers (calcium stone formers). Gregory XI was born in France and Hadrian VI in Utrecht; all the others were Italian (Table 2).

Hadrian VI was robust, ascetic, dined on small quantities of meat, sometimes had bowls of soup, and ate some fish on lean days. Pius IV was a frugal eater, sober wine drinker, and a great walker. Leo XI was a great drinker of wine (Greek wine, Malvasia, and/or robust French wines). Clement IX drank just plain water. Innocent XIII was sedentary and affected by progressive obesity.

Mean age at death for 9 of 11 pontiffs of whom we know the exact date of birth was 62.8 ± 2.39 years; 3 of 11 (27.2%) died from renal disease and 8 of 11 (71.3%) died from sepsis of the urinary tract, with 8 of 11 (72.3%) unable to perform duties. The first pope with KSD of nongouty origin was Gregory I who died in 604; the last was Innocent XIII who died in 1724.

Comparison of uric acid stone formers and nongouty stone formers

Table 3 indicates that the percentage of popes affected by uric acid stones was higher than the percentage of popes affected by calcium stones. The percentage of popes unable to perform was high in both groups. Popes with calcium stones were significantly younger at death, and the percentage who died of urosepsis was higher.

In the years from 537 through 2005, 37 of 208 (17.8%) popes had possible KSD: 12.5% had uric acid stones and 5.3% had nongouty stones (calcium stones). Based on current epidemiology of stone formers, we estimate 21 popes had KSD: 18 popes (85%) with calcium stones and 1 or 2 with uric acid stones, and 1 of other nature. Thus, this study disclosed a high prevalence of KSD associated with high prevalence of stones made of uric acid (12.6%). The prevalence of gout in popes was high (12.5%); today, gout is no longer a papal disease, with the last reported incidence in 1914 with the death of Pius X.⁷ This is in contrast with the literature.^1-3

For many centuries, gout has been a disease of wealthy people with intemperant lifestyles and practically absent in populations that were not wealthy. Being gouty was also seen as a disease associated with longevity and as a protection from more serious diseases. Thus, gout became a topic for writers and artists.

The main reasons for gout were the eating habits of the times, which were rich in meat and seasoned with high quantity of sodium.

In 1850, life expectancy was below 40 years, increased to 45 years by 1900, and to 75 years by 1980.¹² This occurred as a result of socioeconomical changes, with safer water, better nutrition, better working conditions, improved personal hygiene, and reduced infant mortality. Gout is ever present in the adult population today, but its prevalence is still below that of popes. Gout slightly but progressively increases with age and is associated with declining kidney function, availability of proteins, the use of beer, spirits, and wine, glucose added to fruit juices, the use of diuretics, and the prevalence of comorbidities like obesity, hypertension, diabetes mellitus, and chronic kidney disease.

Gout is probably the first known noncom-municable disease in principle and can be discussed in terms of the “Theory of Epidemiologic Transition.”^12,13 Omran analyzed the changing patterns of population age distribution in relation to changes in mortality, fertility, life expectancy, and causes of death. The theory has been adjourned frequently, and finally poverty has been taken into consideration along with incomes and education. This makes the theory suitable to explain the differences between high prevalence of gout in popes and low but slightly increasing prevalence in the general population. Gout should be discussed in terms of lifestyles, income, and education. In general, rich and educated people are aware of the risk and agree to modify their lifestyles, whereas people who are poor and uneducated may not. Those who do not understand the risk factors will experience greater morbidity and mortality of the disease while people who have access to education will achieve protection.¹⁴

By applying the above concepts to gout, we can say that popes before 1914 had high prevalence of gout due to lifestyles causing gout. Those lifestyles were later corrected by education, with gout disappearing in popes by 1914. Those with poor nutrition, mostly people with low incomes, were not prone to gout. Their diets, working conditions, and daily commute to and from work provided them protection from gout.

Since World War II, the general population has lived in a gouty environment because of the easy availability of proteins, alcohol, wines, and beverages rich in glucose.

In the United States, Italy, and France, blood levels of uric acid are steadily rising, with prevalence of gout, although minimal, slowly increasing. Gout’s prevalence is expected to continue to increase, as education efforts have not convinced people to adopt healthy lifestyles.

Seven of 26 popes had uric acid stones and died either of stroke (26.9%) or after one or more bouts of transient ischemic attacks. The possibility that hyperuricemia is a risk factor for stroke has long been debated. However, hyperuricemia was shown to be a significant risk factor for stroke.^15,16 Although the relationship of hyperuricemia with stroke is unquestionable, a direct causality has not been ascertained.¹⁷

Volume: 21 Issue: 6 June 2023 - Supplement - 2

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