PERSPECTIVE www.jasn.

org

On the Etymology of Nephritis: A Historical Appraisal of

its Origins
Garabed Eknoyan
Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine,
Houston, Texas

JASN 31: ccc–ccc, 2020. doi: https://doi.org/10.1681/ASN.2019050510

the excretion of albuminous dropsical The manner Bright reported his obser-
fluid and elevated blood urea levels of vations also reflects his changing times. It
But these are deeds which should not
some cases, but failed to link dropsy to is in the 19th century that the publication
pass away.
kidney disease.5 of books and pamphlets began to be re-
placed by medical journals; there were
barely ten medical journals in England at
And names that must not wither.1
the beginning of the century, and about
For most of medical history the kidney NEPHRITIS: A DISEASE WHOSE
479 new ones had been started by its end.7
was considered a glandular secretory or- TIME HAD COME
Bright’s original 1827 report was pub-
gan subservient to nutrition for the elim-
lished as a book; his subsequent major
ination of excess “fluidities.” When the It is in this state of the art and due ac-
publication of two articles was in the in-
kidney failed or as then considered “not knowledgment of Blackall that Richard
augural volume of Guy’s Hospital Reports
strong enough,” the accumulated excess Bright (1789–1858) developed an interest
in 1836. The second of his articles, titled
fluidities (hydremia, hydremic plethora) in the kidney in dropsy in 1815, which
“Tabular View of the Morbid Appearances
were considered to collect in serous spaces would lead to his 1827 Reports of Medical
Occurring in One Hundred Cases in Con-
as “hydrops, hydropsy, or dropsy,” ancient Cases, wherein he described a causal rela-
nection with Albuminous Urine,” reflects
terms popularized in the early 1700s. The tion of dropsy and heat coagulable urine
the emerging approach to medical re-
principal renal ailments then considered with kidney disease, a momentous con-
search using the new “numerical method”
were obstruction (dropsy of the kidney) clusion whose time had come.6 Bright’s
launched by the Paris physician Pierre
and calculous disease (calculous nephri- transformative deduction is a classic ex-
Louis (1787–1872) in the 1820s, an early
tis), but it was studies on dropsy that led to ample of the discovery process that Isaac
venture into quantification in medicine
the identification of the actual wider range Newton (1643–1727) had described in
from which medical statistics would
of nephritic diseases. Interest in dropsy 1679 as, “If I have seen further, it is by
emerge by the close of the century.8,9
increased following the after of its treat- standing on ye sholders of giants.”
ment with foxglove by William Withering Subsequent recognition of the kidney
(1741–1799) in 1785. Subsequent reports as a site of disease was a product of the
documented the association of dropsy and intellectual and technological changes of NEPHRITIS: AN INFLAMMATORY
heat coagulable urine with contacted kid- the times that followed. The 19th cen- DISEASE
neys, gout, diabetes, and scarlet fever.2,3 tury was a transformative period in the
Meanwhile, studies of calculous nephritis evolution of medicine from its conjec- That was also the time that worldwide
beginning in the 1760s led to the detection tural past into the scientific discipline it interest in “statistical nosology” was on
of urinary solutes (urea, uric acid, etc.) would become by the end of the century. the rise, a concept spearheaded in
excreted by the kidney in addition to wa- The change begun with studies in mor-
ter.4 In his well known book Observations bid anatomy within which the systematic
Published online ahead of print. Publication date
on the Nature and Cure of Dropsies, pub- naming, description, and classification available at www.jasn.org.
lished in 1813, John Blackall (1771–1860) of diseases were done; a movement that
Correspondence: Dr. Garabed Eknoyan, Renal
of Exeter documented the association of started in the opening decades of the
Section, Department of Medicine, Baylor College
dropsy with albuminous urine and attrib- century in Paris before moving to Eng- of Medicine, One Baylor Plaza, Houston, TX 77030.
uted to the kidney a “selective power of land, and then on to Germany by midcen- Email: geknoyan@bcm.edu
separating from the blood whatever was tury, where it was enriched by studies in Copyright © 2020 by the American Society of
hurtful to the body” as an explanation for physiology, chemistry, and microscopy.4,7 Nephrology

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England by Willian Farr (1807–1883), “one of the most interesting features of cells that had been described recently
widely considered a founder of medical the morbid anatomy of this disease is to by his Swedish colleague and Virchow
statistics. In 1853, the First International be found in the condition of the corpora trainee Axel Key (1832–1901) in 1865.
Statistical Congress asked Farr to pre- Malpighiana,” in connection to an ongo- Klebs classified his glomerulonephritis
pare a uniform nomenclature of the cau- ing study he had sponsored of the mi- as different from Bright’s nephritis and
ses of death, a task he completed and croscopic renal changes by his assistant described it as, “One can designate
published in 1857, 10 a forerunner of Joseph Toynbee (1815–1866) published glomerulo-nephritis as a form of inter-
what would become the International in 1846.2,9 Malpighian bodies is also the stitial nephritis in which the interstitial
Classification of Diseases. Two of the term used by William Bowman tissue of the glomerulus is involved ex-
30 notables Farr asked to review his (1816– 1892) in the 1842 milestone clusively”.4,15 Introduction of the term
list were Richard Bright and Robert report of his eponymous capsule. Refer- “glomerulitis” in 1885 as “inflammation
Christison (1797–1892), the Edinburgh ence to the glomerulus as the Malpigh- of the glomeruli of Malpighi and their
medicine professor and one of the first to ian corpuscle, tuft, or body continued capsule” failed to replace Klebs’ glomer-
confirm Bright’s observations on kidney until 1848, when Jones Quain ulonephritis, which went on to gradually
disease. Farr’s list of renal diseases re- (1796–1865), professor of anatomy at assume a broader meaning as any glo-
flects the prevailing notion of Bright’s University College London, first referred merular disease that ultimately was listed
disease as an inflammatory lesion of to them as “These small red bodies, or in the International Classification of
the kidney that is different from other glomeruli, discovered by Malpighi” Diseases as GN, alongside Klebs disease.
nephritides (Table 1).10 In Volume 2 of (Figure 1).4,14 Preliminary reports of glomerular le-
his landmark Traité des Maladies des sions notwithstanding, it was the tubular
Reins, published in 1840, the noted Paris changes of parenchymatous nephritis
physician Pierre Rayer (1793–1876) ar- NEPHRITIS: A that continued to attract attention, par-
gued for naming the disease albuminous MULTIDIMENSIONAL DISEASE ticularly those of tubular desquamation,
nephritis rather than Morbus Brightii, epithelial cell proliferation, and fatty
but Bright’s disease prevailed and would Although improved microscopy and tis- degeneration considered “lipoid” in na-
remain in use into the 1950s.11 sue processing were instrumental in the ture. To distinguish them from the in-
Bright had considered the lesions he progress that followed, it was the intel- flammatory lesions of nephritis, these
observed to be “a decidedly inflamma- lectual stimulus of the cell theory, es- were termed “nephrosis” by the Munich
tory state of the kidney” and reported poused and promulgated by Rudolph internist Friedrich Müller (1858–1941)
them as “nephritis,” an ancient term Virchow (1821–1902) in his 1858 Cellu- in 1905, and the tubular lesions dubbed
meaning “pertaining to the kidney” lar Pathology, that defined the progress “lipoid nephrosis” in 1913 by the Berlin
that was reintroduced in the 1560s to de- that followed. Virchow classified kidney pathologist Fritz Munk (1879–1950),
note “inflammation of the kidnies” ob- diseases into those of the renal paren- who also described the urinary aniso-
served in horses.12,13 He classified the chyma or tubules as “parenchymatous tropic lipoid droplets of these cases. To
diseased kidney on the basis of gross ap- nephritis,” those of the interstitium as represent their clinical and laboratory
pearance, color, and texture into three “interstitial nephritis” that progressed features rather than just their pathology,
forms—a large, pale, yellowish-white to the atrophic end-stage kidney, and the New York internist Louis Leiter
kidney; a congested, red granular kid- those of the vasculature or “amyloid kid- (1898–1986) introduced the term “ne-
ney; and a contracted, granular, hard- ney” (Figure 1, Table 2).4 Importantly, it phrotic syndrome” in 1930 (Figure 1).16,17
ened kidney—a classification that would was students of Virchow who would For the noninflammatory lesions of
prevail through the 1950s, albeit with a characterize the details of the glomeru- interstitial nephritis, Lewellys Barker
changing nosology (Table 2).9 lus, notably Edwin Klebs (1834–1913), (1867–1943), successor to William Osler
Further progress in understanding who introduced the term “glomerulo- at Johns Hopkins, popularized the term
Bright’s disease was as much the result nephritis” in 1869 (Figure 1). The lesion “nephropathy,” after the French term
of scientific interest as that of ongoing Klebs described has been attributed to “néphropathie” that had been introduced
technological developments, notably inflammatory exudation and leukocyte in 1895 by the Paris internist Émile
the microscope and the sphygmoma- infiltration. However, Klebs’ report is Achard (1860–1944) (Figure 1). This
nometer in the 19th century, and the more consistent with what would be de- led to the use of “membranous nephrop-
electron microscope, immunofluores- scribed in 1968 as IgA nephropathy or athy” for noninflammatory glomerular
cence, and kidney biopsy in the 20th some other form of mesangial prolifera- lesions, such as thickening of the glomer-
century. tive lesion. Klebs makes it clear that glo- ular basement membrane, in 1946 by the
Early microscopic observations had merulonephritis is a proliferation of the Minnesota pathologist Elexious T. Bell
called attention to glomerular changes “connective tissue that binds the capil- (1880–1963).18 Identification of “acute in-
in Bright’s disease. Bright himself had laries of the Malpighian tufts into com- terstitial nephritis” as a distinct entity in
alluded to them in an 1842 letter as plete balls,” in essence, the mesangial 1898 by the Harvard pathologist William

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Table 1. Classification of kidney diseases in 1856

English Latin French German
NEPHRITIS Nephritis Néphrite Nierenentzündung
ISCHURIA Ischuria Ischurie Harnverhaltung
Diuresis Diuresis Diurèse Unvermogen den Harn zu halten
NEPHRIA (Bright’s disease, albuminuria) Nephria Néphrine Brightsche Krankheit
DIABETES Diabetes Diabète Harnruhr
STONE (uric acid and c.) Calculus Calcul Stenkrankheit
GRAVEL Calculus Gravelle Harngries
Hematuria Haematuria Hématurie Blutharnen
CYSTITIS Cystitis Cystite Blasenentzündung
Disease of prostate gland Morbus prostaticus Prostatite Vorsteherdrüsen-krankheit
CONTRACTURA URETHRAE Contractura urethrae Uréthrosténie Verengerung der Harnröhre
Table of the nephritides from the 1856 “Report of the Nomenclature and Statistical Classification of Diseases for Statistical Returns” by William Farr (1807–1883).
c, calculus.10

Councilman (1854–1933) led to the recog- Professor of Physic T. Clifford Allbutt time, nephrosclerosis replaced the in-
nition of interstitial nephritis as an entity (1836–1925) in 1895. He termed the creasingly rare occurrence of amyloid-
different from GN and its gradual disap- condition “hyperpiesia,” today’s essen- osis as the principal vascular lesion of
pearance from the nosology of Bright’s dis- tial hypertension.19,20 This was a new kidney disease (Table 2). The suffix for
ease (Table 2).4 entity classified as separate from hardening (sclerosis) was applied to the
Introduction of the sphygmomanom- Bright’s disease, and was labeled “arte- glomerular capillaries as “glomerulo-
eter was fundamental in distinguishing riosclerosis,” a term introduced in 1833 sclerosis” by the Harvard pathologist
the renal lesions of hypertension from by the Frenchman Jean Lobstein Paul Kimmelstiel (1900–1970) in 1935.
those of Bright’s disease. In his 1836 (1777–1835) for the thickened wall of Parallel functional studies elucidated
article, Bright had referred to the arteries, implying their hardening (Fig- the clinical features of nephritis. Notable
“hardness of the pulse” in patients ure 1). Ensuing reports of malignant among them are those by the German
with ventricular hypertrophy. Their hypertension further clarified the renal Herman Strauss (1866–1944) and par-
associated microscopic lesions were de- vascular lesions of hypertension, which ticularly of the Frenchman Fernand Wi-
scribed in 1872 as “arterio-capillary fi- in 1919 was termed “nephrosklerose,” dal (1859–1929). Between 1903 and
brosis” by the Guy’s Hospital clinician from the English “nephrosclerosis” 1906, Widal demonstrated that changes
William Gull (1816–1890) and London that had been introduced in 1890 by in blood urea are induced by protein in-
Hospital pathologist Henry Sutton John S. Billing (1838–1913), a London take, that edema is caused by salt (mea-
(1837–1891). That the vascular lesions surgeon and a founder of the Index sured as chloride) retention, and that
of high BP are independent of nephritis Medicus, for the nonspecific indura- prognosis depends on blood urea level.
was elucidated by the Cambridge tion of the kidney (Figure 1). Over He classified kidney diseases as either

Table 2. The evolving nosology of nephritis

1827 1914 Volhard 1931 Addis
1856 Virchow 1878 Charcot 1895 Allbutt 1942 Ellis 1951 Smith
Bright and Fahr and Oliver
Large white Parenchymatous Parenchymatous Parenchymatous Nephroses Degenerative Type 2 nephritis Nephrotic
kidney nephritis nephritis nephritis degenerative Bright’s insidious, syndrome
chronic . disease edema,
acute recover/
chronic
Congested Interstitial Interstitial Glomerular Nephritis Hemorrhagic Type 1 nephritis Glomerulonephritis
granular nephritis nephritis nephritis inflammatory Bright’s acute, high acute, chronic,
red acute . hemorrhagic disease BP hematuria, subacute
kidney chronic recover/
chronic
Contracted Contracted Contracted Contracted Contracted Contracted Contracted Contracted kidney
kidney kidney kidney kidney kidney kidney kidney
? Vascular Amyloid kidney Amyloid kidney Hyperpiesia Sclerosis Arteriosclerosis Nephrosclerosis Nephrosclerosis
hypertension
The first row gives the last name of the author and the year of their contribution.

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F. VOLHARD
T. FAHR T. ADDIS
E. KLEBS Nephroses, J. OLIVER A. ELLIS
Glomerulo-nephritis Nephritides,
R. BRIGHT R. CHRISTISON W. FARR T.C. ALBUTT F. MÜLLER Glomerular Nephritis Nephritis Type I,II H. SMITH
Renal Disease Diseased Kidney Bright’s Disease Hyperpiesia Nephrosis Scleroses in Bright’s Disease Nephrosclerosis The Kidney
W. GULL
H. SUTTON
M. SOLON Arterio-capillary T. FAHR
Albuminuria fibrosis Nephrosklerose

1827 1837 1839 1857 1869 1872 1896 1905 1914 1919 1931 1942 1951

1833 1840 1842 1848 1858 1865 1890 1895 1904 1913 1916 1925 1930 1935 1946 1951

W. BOWMAN R. VIRCHOW J.S. BILLINGS L. BARKER

J. LOBSTEIN P. KIMELSTIEL
Capsule Cellular Nephrosclerosis Nephropathy
Arteriosclerosis Glomerulosclerosis
Pathology F. WIDAL
Azotemic&/or F. MUNK H. CHRISTIAN P. IVERSEN
P. RAYER E. ACHARD Subacute E. T. BELL C. BRUN
J. QUAIN C. BERNARD Chlorerumic Lipoid
Albuminous Néphropathie Membranous Kidney Biopsy
Glomerulus Experimental Nephritis Nephrosis L. LEITER
Nephritis Medicine Nephropathy
Nephrotic
Syndrome

Figure 1. Timeline of the evolving terminology of nephritis. The name of authors are shown in capital, bold letters, and their contri-
bution to nosology in italics.

associated with edema (chlorérumique) FUNDING 11. Rayer PFO: Traité des Maladies des Reins.
Tome Second, Paris, J. B. Baillière, 1840
or azotemia (azotémique) or a combina-
12. Christian HA: What is nephrosis. N Engl
tion of both (Figure 1).21 None.
J Med 208: 129–131, 1933
13. Blundeville T: The Fower Chiefyst Offices
Belongying to Horsemanshippe, London,
CONCLUSION REFERENCES William Seres, 1565
14. Quain J: Elements of Anatomy. Vol. II, 5th
Continued attempts at classification of 1. Rosetti WM: The Political Works of Lord Ed., edited by Quain R, Sharpey W, London,
Byron. London, Ward, Lock & Co, 1847, Taylor, Walton and Maberly, 1848
Bright’s disease culminated in that of
pp 42 15. McGregor L: The cytological changes oc-
the German clinician Franz Volhard 2. Peitzman SJ: Dropsy, Dialysis, Transplant. A curring in the glomerulus of clinical glomer-
(1878–1950) and pathologist Theodor Short History of Failing Kidneys, Baltimore, ulonephritis. Am J Pathol 5: 559–586, 3,
Fahr (1877–1945) in 1914 (Figure 1, Ta- MD, Johns Hopkins University Press, 2007 1929
ble 2).22 Discontent with prevailing ter- 3. Cameron JS: Milk or albumin? The history of 16. Bell ET: The relation of lipoid nephrosis to
proteinuria before Richard Bright. Nephrol nephritis. Ann Intern Med 6: 167–182, 1932
minologies, in 1931 Stanford clinician
Dial Transplant 18: 1281–1285, 2003 17. Cameron JS, Hicks J: The origins and devel-
Thomas Addis (1881–1949) and the 4. Eknoyan G: The early modern kidney--ne- opment of the concept of a “nephrotic syn-
New York University pathologist Jean phrology in and about the nineteenth cen- drome”. Am J Nephrol 22: 240–247, 2002
Oliver (1889–1976) resurrected the label tury. Part 1. Semin Dial 26: 73–84, 2013 18. Glassock RJ: The pathogenesis of idiopathic
Bright’s disease as a preferred inclusive 5. Blackall J: Observations on the Nature and membranous nephropathy: A 50-year odys-
Cure of Dropsies. London, Longman, Hurst, sey. Am J Kidney Dis 56: 157–167, 2010
term that covered the varied lesions be-
Rees, Orme, Brown and Green, 1814 19. Thomson WW: The renal aspects of essential
ing described.23 Displeasure over the use 6. Bright R: Reports of Medical Cases, London, hypertension. (Hyperpiesia of Clifford All-
of nephrosis, the terminology was fur- Longman, Rees, Orme, Brown and Green, butt). BMJ 2: 910–914, 1933
ther altered to type 1 and 2 nephritis by 1827 20. Fishberg AB: Hypertension and Nephritis,
the Canadian-born University of Lon- 7. Ackerknecht EH: Medicine at the Paris Hos- Philadelphia, Lea & Febiger, 1954
pital 1794-1848, Baltimore, MD, Johns 21. Eknoyan G: On the contributions of Fernand
don professor of medicine Arthur Ellis
Hopkins University Press, 1967 Widal to the classification of chronic kidney
(1883–1966) in 1942 (Table 2).24 What 8. Bynum WF, Loch S, Porter R: Medical Jour- disease. G Ital Nefrol 35[Suppl 70]: 18–22,
lay ahead with the advent of investigative nals and Medical Knowledge. Historical Es- 2018
nephrology is foretold in the 1951 mile- says, Abington, UK, Routledge, 1992 22. Heidland A, Gerabek W, Sebekova K: Franz
stone book of Homer Smith 9. Berry D, Mackenzie C: Richard Bright (1789- Volhard and Theodor Fahr: Achievements
1858). Physician in an Age of Revolution and and controversies in their research in renal
(1895–1962) The Kidney in Health and
Reform, London, Royal Society of Medicine disease and hypertension. J Hum Hypertens
Disease.25 Bright’s disease is not men- Services Limited, 1992 15: 5–16, 2001
tioned in its 898 pages of text, nor is Ri- 10. Farr W: Report on the Nomenclature and 23. Addis T, Oliver J: The Renal Lesion in Bright’s
chard Bright listed in its 2300 references. Statistical Classification of Diseases for Sta- Disease, New York, Hoeber, 1931
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printsec5frontcover&dq5William1Farr&hl5 servations. Lancet 239: 1–7, 1942
DISCLOSURES en&sa5X&ved50ahUKEwjB8ZeKkKfiAhUMD 25. Smith HW: The Kidney. Structure and Func-
60KHTEfAiUQ6AEIMzAC. Accessed May 19, tion in Health and Disease, New York, Ox-
None. 2019 ford University Press, 1951

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