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The Development of Percutaneous Renal Biopsy in Man
The Development of Percutaneous Renal Biopsy in Man Robert M. Kark, MD In the short time of 15 years, renal biopsy has made contributions to the diagnosis, treatment and management of patients ill with renal disorders. It has illuminated the anatomy, pathology and biochemistry of the kidney in health and disease. It has broadened our understanding of pathophysiology and pathogenesis. A. S. Roland and E. G. Dimond 1963 1
I
N 1939, Poul Iversen and Kaj Roholm, in Copenhagen, published their report on aspiration biopsy of the liver. Kaj Roholm had developed a special cutting needle with attached syringe to do this (Fig 1). Soon after the end of World War II, Iversen and Brun began to use Roholm's needle on kidneys (P. Iversen, personal communication). In 1946, I returned to Boston to work once again on the liver, blood, and food. After 6 years in military service, I had to reorient myself to civilian medicine at the Mayo Clinic. I worked for 3 months on Snell's liver service. I hurried back to Boston with Vim-Silverman needles, which Snell's team used on patients' livers. Like others, I aimed at a patient's liver and pulled out kidney tissue. No harm resulted. It was obvious one could deliberately biopsy the kidney to diagnose Bright's disease. This idea excited me. Elsewhere 2 there is described how the late Hans Popper arranged for me to visit Poul Iversen and Claus Brun in Copenhagen, who were doing aspiration biopsies of the kidneys; I had serious reservations with its use: the patients were upset and there was a low yield of tissue. In Chicago, I enlisted Robert C. Muehrcke, a medical student, and Murray Franklin to develop the FranklinVim-Silverman needle (Fig 2). Reference 2 described how we developed the technique of percutaneous renal biopsy (PRB) in the prone position. It was an exciting time. In those early years between 1950 and 1960, every renal biopsy taught us something new and remarkable. In 1936, Jean Hamburger, renowned physician and writer, received his PhD from the Sorbonne (Physiology de ['innervation renal, Paris, Mason et cie). In 1959, he was appointed Professor of Medicine at the University of Paris and organized a renal unit in the Hospital Neckar. This was to play an important role in the development of PRB.
Hamburger and his colleagues had produced an effective biopsy needle, which was the forerunner of early commercial ones. In addition, his unit became a major center for nephrology, and for the study of immunology in the diagnosis and treatment of renal disorders, especially transplantation. In Boston, a major center for nephrology, John Merrill, David Hume, George Thorn, Gustave Dammin, and their colleagues began to use renal biopsies to study homotransplantation in 1954. Later, biopsies were done on a wide variety of renal disorders. These were performed by the st!,lff, including Donald Oken and many others. In 1951, Conrad Pirani started to grade the various structures seen on biopsy sections from 0 to 4 +. Clinical pathologic correlations were attempted. From his histologic evaluations, one obtained the maximum useful information from renal tissues. This made an enormous difference to the total care of patients. In 1954, Muehrcke et al suggested the use of serial renal biopsies. 3 This illuminated studies on the natural history of diseases and disorders of the kidney, and we began to recognize the effects of treatment, with agents such as corticotropin. Between 1954 and 1957, we published observations on lupus nephritis and other collagen vascular disorders.4 It was apparent that one could make new approaches to pathologic analysis of the dynamic state of a disease and decide if there were florid, moderate, or minimal changes present. Pirani introduced the ideas of local, focal, and diffuse changes, with or without nephron dropout or baseFrom the Department of Medicine, Hines 11,4 Medical Center, Hines, IL; and the Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL. Supported in part by the Kidney Foundation of Illinois, the Department of Medicine and the Section of Nephrology, RushPresbyterian-St. Luke's Medical Center, The John Simon Guggenheim Jr Memorial Foundation, the Department of Medicine, Hines 11,4 Medical Center. The opinions expressed herein are those of the author and are not to be construed as official pronouncements of the U?terans Administration. Address reprint requests to Robert M. Kark, MD, Apartment 9-L, 860 N Lake Shore Dr, Chicago, IL 60611. © 1990 by the National Kidney Foundation, Inc. 02n-6386/90/1606-0013$3.00/0
American Journal of Kidney Diseases, Vol XVI, No 6 (December), 1990: pp 585-589
585
586
ROBERT M. KARK
Fig 1. Aspiration biopsy needle developed In 1939 by Iversen and Roholm, and used by Poullversen to take renal biopsies In 1947. Instrument presented to the author in 1950.
ment membrane obliteration. One could roughly correlate clinical and laboratory data with some histologic changes and even venture a prognosis . New and important terms were coined, such as "lupus nephritis." After 1954, Iversen and his colleagues used the biopsy technique developed in Chicag0 5 and made significant new observations, including studies of acute anuria. A skeptical editorial in Lancet6 implied that biopsy of the kidney was dangerous and never likely to be as valuable as hepatic biopsies. This opinion was widely held. In Scandinavia and North America, urologists and others had attacked those who were doing renal biopsies. With the approval of my colleagues in Chicago, I replied. 7 Unless one could study the early and treatable stages of renal disorders, for which biopsy was designed, physicians would have to continue to treat patients with end-stage kidneys. These were lumped together as chronic glomerulonephritis, the diagnosis of which was equivalent to a death sentence. Hopefully, treatments for renal disorders would be developed that would provide long-term benefits and a good quality of life.
EARLY STUDIES
In 1959, a review of 500 percutaneous biopsies in 368 patients was published. 8 A brief history of the development of PRB and open biopsies was described. Also new tools and techniques were noted. The indications and contraindications to biopsies were described, which were necessary in the selection of patients, and , with preoperative, postoperative, and perioperative monitoring, vital to the control of morbidity and mortality. The diagnostic adequacy and limitations were described, as was the clinical value of biopsies. Symptoms or signs of complications were observed in 9.8% of consecutive biopsies . Renal tissue was obtained in 93 %, adequate for pathologic diagnosis in 80 % . In an appendix, modifications of technique were presented for obese patients, infants, and children, in pregnancy, and in ascites. It was noted that some who wished to do biopsies were ham-handed and never learned to perform a biopsy without endangering the life of the patient. RENAL BIOPSIES IN PREGNANT PATIENTS
In 1960, I.B. Nettles and VE. Pollak published a review of clinical studies and renal biopsies in toxemia of pregnancy,9 and 5 years later L.E. Schewitz, LA. Friedman, and VE. Pollak discussed bleeding after renal biopsy in pregnancy and reviewed the literature. to THE ANATOMY OF THE BASEMENT MEMBRANES
Fig 2. The Franklin-Vim-Sllverman needle, short form. Note the cutting prong emerging from the hollow needle. The insert indicates Franklin's modification. The beveled tip of each cutting prong is filled with silver solder and sharpened. (Reprinted with permission·; © 1958 American Medical Association.)
In the decade 1951 to 1961, among those who helped to clarify the anatomy and response of the basement membrane to disease and noxious stimuli were Bergstrand, Farquhar, Movat, Palade, and particularly the late Vincent Hall. Hall made outstanding contributions to understanding the anatomy of glomerular tufts and the structures around it. This was done by electron microscopy
587
DEVELOPMENT OF PERCUTANEOUS RENAL BIOPSY
in animals and man. He could not find support for the existence of mesangial cells. l1 Pirani showed him light and electron microscopy from patients' biopsies, which he accepted with reluctance. THE CLINICAL PATHOLOGY AND SIGNIFICANCE OF RENAL BIOPSY
From 1949 to 1961 , approximately 5,000 percutaneous biopsies were performed in North America and Europe. A notable improvement in the art and science of nephrology resulted from the new knowledge gained by these biopsies. In 1960, Joekes of the Institute of Urology needled G.E.W Wolstenholme to organize an international symposium to assess the usefulness, risks, and potentialities of renal biopsies in London . 12 This gathering was a watershed. It firmly established renal biopsy as a unifying process in nephrology. There were 29 participants . A clinician and pathologist were invited from each major center doing biopsies. One notes the contributions to nephrology by the participants, particularly Milne, de Wardener, Hamburger, Habib, Heptinstall, Earle, Jennings, Bergstrand , Movat, Vernier, Pirani, and Brun. Unfortunately, Iversen was indisposed; Raaschau took his place. As one reads the text , particularly the discussions, it is apparent that it was difficult for some of the older pathologists and physicians to discard long held views and hypotheses about the pathology, pathogenesis, and nature of renal disorders. They could not bring themselves to accept that a small core of tissue could be representative of disease in the kidney. In fact , a number of arguments arose, some of which seemed to be rather acrimonious. These appear to have been settled in favor of the younger pathologists and clinicians. ATLASES OF RENAL BIOPSY
During and after the symposium, it was clear that there would continue to be different opinions about the value of biopsy. Nevertheless, Pirani's ideas, applied in major renal clinics everywhere, have taught us to avoid the indiscriminate use of PRB and also when to employ it. In 1963, George Schreiner described biopsy studies on the nephrotic syndrome made by him and his colleagues at Georgetown · University, which are landmarks of creative investigation. This was published as a chapter in the book by Strauss and Welt. 13 Schreiner, who has made
enormous contributions to nephrology, had reviewed 900 references. From these, he drew innovative suggestions, particularly in immunology, directed to the care of the patient. The chapter was filled with illustrations and tables and was the first atlas of renal biopsy published. In 1968, Pi rani and SalinaS-Madrigal published a classic report, also profusely illustrated. 14 Of the many atlases printed in the next 15 years, the one by Claus Brun and Steen Olsen 15 is for me the most illuminating and useful. It deals with every aspect of disorders of the kidney from infancy to old age, and includes common and very rare diseases. In 1987, Edmund J. Lewis, contributed a chapter in the book by Cameron and Glassock. lli Lewis describes the use of baths , bed rest , diets , diuretics , pharmaceutical agents, colloids, hormones, immunosuppressive agents, steroids, and other old and new modalities as they affect both children and adults with massive proteinuria. Figure 3, taken from his report, gives a distribution of glomerular lesions and response to treatment with steroids according to four age groups. The results indicate that remission diminishes with age. This means that nearly always infants and children will respond to steroids and most of the time do not need a biopsy. The contrary is true for adults . IMMUNOLOGY AND RENAL BIOPSY
In Cameron and Glassock's book,17 immunologic staining of biopsies is illustrated from Al Coon's contributions to those who followed him, among whom were M.H. Kaplan , Henry Kunkel, Robert Good, and Frank Dixon. Advances in immunologic staining and serology by many investigators is recorded, particularly L.A. Van Es, WG. Couser, R.J. Glassock, J.S . Cameron, G.G. Glenner, A.N. Theofilopoulos , Jimmy Roberts , and L. Morel-Maroger. The studies ofD.K. Peters and P.J. Lachman on the alternate pathway of complement activation in nephritis 1s. 19 are particularly illuminating. D.K. Peters and his co-workers were the first to record that a genetic deficiency of complement disposes to an immune complex disease in a patient whose biopsy disclosed typical mesangiocapillary nephritis. The message from the contributors is that the nephrologist and the renal pathologist work as a team to provide care for the individual patient.
588
ROBERT M. KARK
~~~~~~~; :
0
. MeG
RESPONSE : . TO THERAPY COmplet.
~
FSGS
!Jill II1II II MGN
~
MPSN AMYLOIO OTHER
D No
R,mislk)n Rtmillion
CHILDREN ~ YR
<
CHILDREN
YOUNG ADULTS
ADULTS
100
75
50
25
o
Hiltol09ic Cole9Of'),
Fig 3. Distribution of glomerular lesions and response to therapy according to age group. The bar graphs indicate the relative frequency of various forms of glomerular histology and the expected response to therapy within that age group. As can be noted, the expected complete remission rate from a course of steroid therapy diminishes with age, as the prevalence of minimal change glomerulopathy diminishes in the nephrotic population. The corollary of this observation is that the population of nephrotic patients who could be exposed to the side effects of drug therapy without obtaining any positive benefit increases with age. (Reprinted with permission. 1S)
REAL-TIME RENAL BIOPSIES
The goal of the nephrologists doing PRBs was to develop a method that would not harm patients. No patient would die, there would be no complications, and adequate tissue would be taken for the pathologists to determine what disorders were present in the kidney. In 1964, Kark and Buenger20 developed television-monitored image-intensified fluoroscopy, using two television screens in a fully illuminated room. Intravenous Renografin or Hypaque solution opacified the kidneys and intensified their image on the screens. PRB was performed with meticulous technique. Of the first 44 biopsies, localization of the needle was successful in 42. Adequate tissue was obtained in 92 %. In 1985, Birnholz, Kasinath, and Corwin 21 published results of an improved technique for ultrasound-guided PRB, which is generally in use. It has particular advantages. Patients and staff are spared radiation exposure. The guidance device is
removed from the biopsy field, reducing the chances for infection. It also provides options for redirecting the needle after skin entry. Different sized needles can be used with great effect for infants, children, and pregnant, fat, or thin patients, with different disease processes. In 1968, Kark had described the early models of the Baxter-Travenol Tru-Cut needle, now modified and universally employed. 22 That year, Pasternack23 of the Department of Clinical Science, University of Tampere, Finland, did the first fineneedle aspiration biopsy (FNAB) on human renal allografts, to determine if rejection was occurring. FNAB is useful to follow pathologic changes occurring before, during, and after rejection. Because it is safe, the FNAB is used to get specimens several times during 24 hours. While everyone agrees that FNAB is ideal for frequent observations of renal allografts, there is no such agreement when FNAB is used to study patients with diffuse renal disorders. STATE OF THE ART: 1990
Stephen M. Korbet, MD (personal communication) has kindly made available to me unpublished data he collected on 189 percutaneous renal biopsies performed by members of the Section of Nephrology at Rush-Presbyterian-St. Luke's Medical Center (RPSLMC) in Chicago between 1983 and 1989, which were done using real-time ultrasound. 21 The patients were all adults and the indications for doing the biopsies were proteinuria and/or systemic disease. The position report on "Clinical Competence in Percutaneous Renal Biopsy"24 presents an overview of the procedure, selected indications, and contraindications (Table 1); gives a list of complications and frequency of occurrence; and details the minimal training required to do percutaneous biopsies competently, including both cognitive and Table 1.
Selected Contraindications to PRB
Absolute
Relative
Uncooperative patient Severe azotemia Solitary native kidney Renal anatomic anomalies Uncontrolled moderate that would increase risk of or severe hypertension the procedure (eg, arterial Uncontrolled bleeding aneurysm) Drugs that impair hemostasis diathesis Pregnancy Urinary tract infection Reprinted with permission. 24
DEVELOPMENT OF PERCUTANEOUS RENAL BIOPSY
589
technical skills, which the resident or fellow must have after training to care for patients without supervision. Continuing education is necessary to ensure appropriate up-to-date knowledge and judgment, to know when to do the procedure. Obviously, the more experienced the nephrologist, the better the decision. Quality review demands that there be some means of periodic review of the nephrologist's activity. This report from the American College of Physicians 24 is generally recognized as presenting the state of the art.
This history of percutaneous biopsy would not be complete without a final tribute to Poul Iversen, who started it all, in 1939. It is sad to note that his great contributions to both nephrology and hepatology, which merited a Nobel prize, were passed over. ACKNOWLEDGMENT I wish to thank Edmund J. Lewis, MD, Stephen M. Korbet, MD, Melvin M. Schwartz, MD, Robert C. Muehrcke, MD, Conrad L. Pirani, MD, Victor E. Pollak, MD, Gary E. Kaatz, Helen Follmer, and Janet Iapichino for their assistance.
REFERENCES 1. Roland AS, Dimond EG: The value of percutaneous biopsy in the hypertensive patient. Am Heart J 66:140-142, 1963 2. Kark RM: Renal biopsy and the modern era, in Cameron JS, Glassock RJ (eds): The Nephrotic Syndrome. New York, NY, Marcel Dekker, 1988, pp 57-86 3. Pirani CL, Muehrcke RC, Kark RM: Percutaneous renal biopsies in systemic lupus erythematosus. Proceedings of the Institute of Medicine of Chicago 20: 170-173, 1954 4. Muehrcke RC, Kark RM, Pirani CL, et al: Lupus nephritis: Clinical and pathologic studies based on renal biopsies. Medicine 36:1-145, 1957 5. Iversen P, Brun C: Aspiration biopsy of the kidney. Am J Med 11:324-330, 1951 6. Needle biopsy of the kidney. Lancet 2:1231-1231,1955 (editorial) 7. Kark RM: Needle biopsy of the kidney. Lancet 1:51-52, 1956 (letter) 8. Kark RM, Muehrcke RC, Pollak VE, et al: An analysis of five hundred renal biopsies. Arch Intern Med 101:439-451, 1958 9. Pollak VE, Nettles JB: The kidney in toxemia of pregnancy. A clinical and pathological study based on renal biopsies. Medicine 39:469-526, 1960 10. Schewitz U, Friedman lA, Pollak VE: Bleeding after renal biopsy in pregnancy. Obstet Gynecol 26:295-304, 1965 11. Hall BV: The protoplasmic basis of glomerular ultrafiltration. Am Heart J 54:1-9, 1957 (editorial) 12. Wolstenhome GEW, Cameron MP (eds): Ciba Foundation Symposium on Renal Biopsy: Clinical and Pathological Significance. London, England, Churchill, 1962
13. Strauss MB, Welt L (eds): Diseases of the Kidne.y (ed 1). Boston, MA, Little Brown, 1963 14. Pirani CL, Salinas-Madrigal L: Evaluation of percutaneous renal biopsy, in Pathology Annual 3. Norwalk, CT, Appleton, 1968, pp 249-296 15. Brun C, Olsen S: Atlas of Renal Biopsy (ed 1). Philadelphia, PA, Saunders, 1981 16. Lewis EJ: Management of the nephrotic syndrome in adults, in Cameron JS, Glassock RJ (eds): The Nephrotic Syndrome. New York, NY, Marcel Dekker, 1988, pp 461-521 17. Cameron JS, Glassock RJ (eds): The Nephrotic Syndrome. New York, NY, Marcel Dekker, 1988 18. Booth C: A clinician in search of the soluble. The Harvean Oration. London, England, Royal College of Physicians, 1989, p 28 19. Peters DK, Gwyn Williams D, Charles Worth JA, et al: Mesangiocapillary nephritis, partial lipodystrophy and hypocomplementemia. Lancet 2:535-539, 1973 20. Kark RM, Buenger RE: Television-monitored fluoroscopy in percutaneous renal biopsy. Lancet 1:904-905, 1966 21. Birnholz JC, Kasinath BS, Corwin HL: An improved technique for ultrasound guided percutaneous renal biopsy. Kidney Int 27:80-82, 1985 22. Kark RM: Renal biopsy. JAMA 205:80-86, 1968 23. Pasternack A: Fine needle aspiration biopsy of human renal allografts. Lancet 2:82-85, 1968 24. Health and Public Policy Committee, American College of Physicians, Philadelphia, Pennsylvania: Clinical competence in percutaneous renal biopsy: A position paper. Ann Intern Med 108:301-303, 1988
I
N 1939, Poul Iversen and Kaj Roholm, in Copenhagen, published their report on aspiration biopsy of the liver. Kaj Roholm had developed a special cutting needle with attached syringe to do this (Fig 1). Soon after the end of World War II, Iversen and Brun began to use Roholm's needle on kidneys (P. Iversen, personal communication). In 1946, I returned to Boston to work once again on the liver, blood, and food. After 6 years in military service, I had to reorient myself to civilian medicine at the Mayo Clinic. I worked for 3 months on Snell's liver service. I hurried back to Boston with Vim-Silverman needles, which Snell's team used on patients' livers. Like others, I aimed at a patient's liver and pulled out kidney tissue. No harm resulted. It was obvious one could deliberately biopsy the kidney to diagnose Bright's disease. This idea excited me. Elsewhere 2 there is described how the late Hans Popper arranged for me to visit Poul Iversen and Claus Brun in Copenhagen, who were doing aspiration biopsies of the kidneys; I had serious reservations with its use: the patients were upset and there was a low yield of tissue. In Chicago, I enlisted Robert C. Muehrcke, a medical student, and Murray Franklin to develop the FranklinVim-Silverman needle (Fig 2). Reference 2 described how we developed the technique of percutaneous renal biopsy (PRB) in the prone position. It was an exciting time. In those early years between 1950 and 1960, every renal biopsy taught us something new and remarkable. In 1936, Jean Hamburger, renowned physician and writer, received his PhD from the Sorbonne (Physiology de ['innervation renal, Paris, Mason et cie). In 1959, he was appointed Professor of Medicine at the University of Paris and organized a renal unit in the Hospital Neckar. This was to play an important role in the development of PRB.
Hamburger and his colleagues had produced an effective biopsy needle, which was the forerunner of early commercial ones. In addition, his unit became a major center for nephrology, and for the study of immunology in the diagnosis and treatment of renal disorders, especially transplantation. In Boston, a major center for nephrology, John Merrill, David Hume, George Thorn, Gustave Dammin, and their colleagues began to use renal biopsies to study homotransplantation in 1954. Later, biopsies were done on a wide variety of renal disorders. These were performed by the st!,lff, including Donald Oken and many others. In 1951, Conrad Pirani started to grade the various structures seen on biopsy sections from 0 to 4 +. Clinical pathologic correlations were attempted. From his histologic evaluations, one obtained the maximum useful information from renal tissues. This made an enormous difference to the total care of patients. In 1954, Muehrcke et al suggested the use of serial renal biopsies. 3 This illuminated studies on the natural history of diseases and disorders of the kidney, and we began to recognize the effects of treatment, with agents such as corticotropin. Between 1954 and 1957, we published observations on lupus nephritis and other collagen vascular disorders.4 It was apparent that one could make new approaches to pathologic analysis of the dynamic state of a disease and decide if there were florid, moderate, or minimal changes present. Pirani introduced the ideas of local, focal, and diffuse changes, with or without nephron dropout or baseFrom the Department of Medicine, Hines 11,4 Medical Center, Hines, IL; and the Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL. Supported in part by the Kidney Foundation of Illinois, the Department of Medicine and the Section of Nephrology, RushPresbyterian-St. Luke's Medical Center, The John Simon Guggenheim Jr Memorial Foundation, the Department of Medicine, Hines 11,4 Medical Center. The opinions expressed herein are those of the author and are not to be construed as official pronouncements of the U?terans Administration. Address reprint requests to Robert M. Kark, MD, Apartment 9-L, 860 N Lake Shore Dr, Chicago, IL 60611. © 1990 by the National Kidney Foundation, Inc. 02n-6386/90/1606-0013$3.00/0
American Journal of Kidney Diseases, Vol XVI, No 6 (December), 1990: pp 585-589
585
586
ROBERT M. KARK
Fig 1. Aspiration biopsy needle developed In 1939 by Iversen and Roholm, and used by Poullversen to take renal biopsies In 1947. Instrument presented to the author in 1950.
ment membrane obliteration. One could roughly correlate clinical and laboratory data with some histologic changes and even venture a prognosis . New and important terms were coined, such as "lupus nephritis." After 1954, Iversen and his colleagues used the biopsy technique developed in Chicag0 5 and made significant new observations, including studies of acute anuria. A skeptical editorial in Lancet6 implied that biopsy of the kidney was dangerous and never likely to be as valuable as hepatic biopsies. This opinion was widely held. In Scandinavia and North America, urologists and others had attacked those who were doing renal biopsies. With the approval of my colleagues in Chicago, I replied. 7 Unless one could study the early and treatable stages of renal disorders, for which biopsy was designed, physicians would have to continue to treat patients with end-stage kidneys. These were lumped together as chronic glomerulonephritis, the diagnosis of which was equivalent to a death sentence. Hopefully, treatments for renal disorders would be developed that would provide long-term benefits and a good quality of life.
EARLY STUDIES
In 1959, a review of 500 percutaneous biopsies in 368 patients was published. 8 A brief history of the development of PRB and open biopsies was described. Also new tools and techniques were noted. The indications and contraindications to biopsies were described, which were necessary in the selection of patients, and , with preoperative, postoperative, and perioperative monitoring, vital to the control of morbidity and mortality. The diagnostic adequacy and limitations were described, as was the clinical value of biopsies. Symptoms or signs of complications were observed in 9.8% of consecutive biopsies . Renal tissue was obtained in 93 %, adequate for pathologic diagnosis in 80 % . In an appendix, modifications of technique were presented for obese patients, infants, and children, in pregnancy, and in ascites. It was noted that some who wished to do biopsies were ham-handed and never learned to perform a biopsy without endangering the life of the patient. RENAL BIOPSIES IN PREGNANT PATIENTS
In 1960, I.B. Nettles and VE. Pollak published a review of clinical studies and renal biopsies in toxemia of pregnancy,9 and 5 years later L.E. Schewitz, LA. Friedman, and VE. Pollak discussed bleeding after renal biopsy in pregnancy and reviewed the literature. to THE ANATOMY OF THE BASEMENT MEMBRANES
Fig 2. The Franklin-Vim-Sllverman needle, short form. Note the cutting prong emerging from the hollow needle. The insert indicates Franklin's modification. The beveled tip of each cutting prong is filled with silver solder and sharpened. (Reprinted with permission·; © 1958 American Medical Association.)
In the decade 1951 to 1961, among those who helped to clarify the anatomy and response of the basement membrane to disease and noxious stimuli were Bergstrand, Farquhar, Movat, Palade, and particularly the late Vincent Hall. Hall made outstanding contributions to understanding the anatomy of glomerular tufts and the structures around it. This was done by electron microscopy
587
DEVELOPMENT OF PERCUTANEOUS RENAL BIOPSY
in animals and man. He could not find support for the existence of mesangial cells. l1 Pirani showed him light and electron microscopy from patients' biopsies, which he accepted with reluctance. THE CLINICAL PATHOLOGY AND SIGNIFICANCE OF RENAL BIOPSY
From 1949 to 1961 , approximately 5,000 percutaneous biopsies were performed in North America and Europe. A notable improvement in the art and science of nephrology resulted from the new knowledge gained by these biopsies. In 1960, Joekes of the Institute of Urology needled G.E.W Wolstenholme to organize an international symposium to assess the usefulness, risks, and potentialities of renal biopsies in London . 12 This gathering was a watershed. It firmly established renal biopsy as a unifying process in nephrology. There were 29 participants . A clinician and pathologist were invited from each major center doing biopsies. One notes the contributions to nephrology by the participants, particularly Milne, de Wardener, Hamburger, Habib, Heptinstall, Earle, Jennings, Bergstrand , Movat, Vernier, Pirani, and Brun. Unfortunately, Iversen was indisposed; Raaschau took his place. As one reads the text , particularly the discussions, it is apparent that it was difficult for some of the older pathologists and physicians to discard long held views and hypotheses about the pathology, pathogenesis, and nature of renal disorders. They could not bring themselves to accept that a small core of tissue could be representative of disease in the kidney. In fact , a number of arguments arose, some of which seemed to be rather acrimonious. These appear to have been settled in favor of the younger pathologists and clinicians. ATLASES OF RENAL BIOPSY
During and after the symposium, it was clear that there would continue to be different opinions about the value of biopsy. Nevertheless, Pirani's ideas, applied in major renal clinics everywhere, have taught us to avoid the indiscriminate use of PRB and also when to employ it. In 1963, George Schreiner described biopsy studies on the nephrotic syndrome made by him and his colleagues at Georgetown · University, which are landmarks of creative investigation. This was published as a chapter in the book by Strauss and Welt. 13 Schreiner, who has made
enormous contributions to nephrology, had reviewed 900 references. From these, he drew innovative suggestions, particularly in immunology, directed to the care of the patient. The chapter was filled with illustrations and tables and was the first atlas of renal biopsy published. In 1968, Pi rani and SalinaS-Madrigal published a classic report, also profusely illustrated. 14 Of the many atlases printed in the next 15 years, the one by Claus Brun and Steen Olsen 15 is for me the most illuminating and useful. It deals with every aspect of disorders of the kidney from infancy to old age, and includes common and very rare diseases. In 1987, Edmund J. Lewis, contributed a chapter in the book by Cameron and Glassock. lli Lewis describes the use of baths , bed rest , diets , diuretics , pharmaceutical agents, colloids, hormones, immunosuppressive agents, steroids, and other old and new modalities as they affect both children and adults with massive proteinuria. Figure 3, taken from his report, gives a distribution of glomerular lesions and response to treatment with steroids according to four age groups. The results indicate that remission diminishes with age. This means that nearly always infants and children will respond to steroids and most of the time do not need a biopsy. The contrary is true for adults . IMMUNOLOGY AND RENAL BIOPSY
In Cameron and Glassock's book,17 immunologic staining of biopsies is illustrated from Al Coon's contributions to those who followed him, among whom were M.H. Kaplan , Henry Kunkel, Robert Good, and Frank Dixon. Advances in immunologic staining and serology by many investigators is recorded, particularly L.A. Van Es, WG. Couser, R.J. Glassock, J.S . Cameron, G.G. Glenner, A.N. Theofilopoulos , Jimmy Roberts , and L. Morel-Maroger. The studies ofD.K. Peters and P.J. Lachman on the alternate pathway of complement activation in nephritis 1s. 19 are particularly illuminating. D.K. Peters and his co-workers were the first to record that a genetic deficiency of complement disposes to an immune complex disease in a patient whose biopsy disclosed typical mesangiocapillary nephritis. The message from the contributors is that the nephrologist and the renal pathologist work as a team to provide care for the individual patient.
588
ROBERT M. KARK
~~~~~~~; :
0
. MeG
RESPONSE : . TO THERAPY COmplet.
~
FSGS
!Jill II1II II MGN
~
MPSN AMYLOIO OTHER
D No
R,mislk)n Rtmillion
CHILDREN ~ YR
<
CHILDREN
YOUNG ADULTS
ADULTS
100
75
50
25
o
Hiltol09ic Cole9Of'),
Fig 3. Distribution of glomerular lesions and response to therapy according to age group. The bar graphs indicate the relative frequency of various forms of glomerular histology and the expected response to therapy within that age group. As can be noted, the expected complete remission rate from a course of steroid therapy diminishes with age, as the prevalence of minimal change glomerulopathy diminishes in the nephrotic population. The corollary of this observation is that the population of nephrotic patients who could be exposed to the side effects of drug therapy without obtaining any positive benefit increases with age. (Reprinted with permission. 1S)
REAL-TIME RENAL BIOPSIES
The goal of the nephrologists doing PRBs was to develop a method that would not harm patients. No patient would die, there would be no complications, and adequate tissue would be taken for the pathologists to determine what disorders were present in the kidney. In 1964, Kark and Buenger20 developed television-monitored image-intensified fluoroscopy, using two television screens in a fully illuminated room. Intravenous Renografin or Hypaque solution opacified the kidneys and intensified their image on the screens. PRB was performed with meticulous technique. Of the first 44 biopsies, localization of the needle was successful in 42. Adequate tissue was obtained in 92 %. In 1985, Birnholz, Kasinath, and Corwin 21 published results of an improved technique for ultrasound-guided PRB, which is generally in use. It has particular advantages. Patients and staff are spared radiation exposure. The guidance device is
removed from the biopsy field, reducing the chances for infection. It also provides options for redirecting the needle after skin entry. Different sized needles can be used with great effect for infants, children, and pregnant, fat, or thin patients, with different disease processes. In 1968, Kark had described the early models of the Baxter-Travenol Tru-Cut needle, now modified and universally employed. 22 That year, Pasternack23 of the Department of Clinical Science, University of Tampere, Finland, did the first fineneedle aspiration biopsy (FNAB) on human renal allografts, to determine if rejection was occurring. FNAB is useful to follow pathologic changes occurring before, during, and after rejection. Because it is safe, the FNAB is used to get specimens several times during 24 hours. While everyone agrees that FNAB is ideal for frequent observations of renal allografts, there is no such agreement when FNAB is used to study patients with diffuse renal disorders. STATE OF THE ART: 1990
Stephen M. Korbet, MD (personal communication) has kindly made available to me unpublished data he collected on 189 percutaneous renal biopsies performed by members of the Section of Nephrology at Rush-Presbyterian-St. Luke's Medical Center (RPSLMC) in Chicago between 1983 and 1989, which were done using real-time ultrasound. 21 The patients were all adults and the indications for doing the biopsies were proteinuria and/or systemic disease. The position report on "Clinical Competence in Percutaneous Renal Biopsy"24 presents an overview of the procedure, selected indications, and contraindications (Table 1); gives a list of complications and frequency of occurrence; and details the minimal training required to do percutaneous biopsies competently, including both cognitive and Table 1.
Selected Contraindications to PRB
Absolute
Relative
Uncooperative patient Severe azotemia Solitary native kidney Renal anatomic anomalies Uncontrolled moderate that would increase risk of or severe hypertension the procedure (eg, arterial Uncontrolled bleeding aneurysm) Drugs that impair hemostasis diathesis Pregnancy Urinary tract infection Reprinted with permission. 24
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technical skills, which the resident or fellow must have after training to care for patients without supervision. Continuing education is necessary to ensure appropriate up-to-date knowledge and judgment, to know when to do the procedure. Obviously, the more experienced the nephrologist, the better the decision. Quality review demands that there be some means of periodic review of the nephrologist's activity. This report from the American College of Physicians 24 is generally recognized as presenting the state of the art.
This history of percutaneous biopsy would not be complete without a final tribute to Poul Iversen, who started it all, in 1939. It is sad to note that his great contributions to both nephrology and hepatology, which merited a Nobel prize, were passed over. ACKNOWLEDGMENT I wish to thank Edmund J. Lewis, MD, Stephen M. Korbet, MD, Melvin M. Schwartz, MD, Robert C. Muehrcke, MD, Conrad L. Pirani, MD, Victor E. Pollak, MD, Gary E. Kaatz, Helen Follmer, and Janet Iapichino for their assistance.
REFERENCES 1. Roland AS, Dimond EG: The value of percutaneous biopsy in the hypertensive patient. Am Heart J 66:140-142, 1963 2. Kark RM: Renal biopsy and the modern era, in Cameron JS, Glassock RJ (eds): The Nephrotic Syndrome. New York, NY, Marcel Dekker, 1988, pp 57-86 3. Pirani CL, Muehrcke RC, Kark RM: Percutaneous renal biopsies in systemic lupus erythematosus. Proceedings of the Institute of Medicine of Chicago 20: 170-173, 1954 4. Muehrcke RC, Kark RM, Pirani CL, et al: Lupus nephritis: Clinical and pathologic studies based on renal biopsies. Medicine 36:1-145, 1957 5. Iversen P, Brun C: Aspiration biopsy of the kidney. Am J Med 11:324-330, 1951 6. Needle biopsy of the kidney. Lancet 2:1231-1231,1955 (editorial) 7. Kark RM: Needle biopsy of the kidney. Lancet 1:51-52, 1956 (letter) 8. Kark RM, Muehrcke RC, Pollak VE, et al: An analysis of five hundred renal biopsies. Arch Intern Med 101:439-451, 1958 9. Pollak VE, Nettles JB: The kidney in toxemia of pregnancy. A clinical and pathological study based on renal biopsies. Medicine 39:469-526, 1960 10. Schewitz U, Friedman lA, Pollak VE: Bleeding after renal biopsy in pregnancy. Obstet Gynecol 26:295-304, 1965 11. Hall BV: The protoplasmic basis of glomerular ultrafiltration. Am Heart J 54:1-9, 1957 (editorial) 12. Wolstenhome GEW, Cameron MP (eds): Ciba Foundation Symposium on Renal Biopsy: Clinical and Pathological Significance. London, England, Churchill, 1962
13. Strauss MB, Welt L (eds): Diseases of the Kidne.y (ed 1). Boston, MA, Little Brown, 1963 14. Pirani CL, Salinas-Madrigal L: Evaluation of percutaneous renal biopsy, in Pathology Annual 3. Norwalk, CT, Appleton, 1968, pp 249-296 15. Brun C, Olsen S: Atlas of Renal Biopsy (ed 1). Philadelphia, PA, Saunders, 1981 16. Lewis EJ: Management of the nephrotic syndrome in adults, in Cameron JS, Glassock RJ (eds): The Nephrotic Syndrome. New York, NY, Marcel Dekker, 1988, pp 461-521 17. Cameron JS, Glassock RJ (eds): The Nephrotic Syndrome. New York, NY, Marcel Dekker, 1988 18. Booth C: A clinician in search of the soluble. The Harvean Oration. London, England, Royal College of Physicians, 1989, p 28 19. Peters DK, Gwyn Williams D, Charles Worth JA, et al: Mesangiocapillary nephritis, partial lipodystrophy and hypocomplementemia. Lancet 2:535-539, 1973 20. Kark RM, Buenger RE: Television-monitored fluoroscopy in percutaneous renal biopsy. Lancet 1:904-905, 1966 21. Birnholz JC, Kasinath BS, Corwin HL: An improved technique for ultrasound guided percutaneous renal biopsy. Kidney Int 27:80-82, 1985 22. Kark RM: Renal biopsy. JAMA 205:80-86, 1968 23. Pasternack A: Fine needle aspiration biopsy of human renal allografts. Lancet 2:82-85, 1968 24. Health and Public Policy Committee, American College of Physicians, Philadelphia, Pennsylvania: Clinical competence in percutaneous renal biopsy: A position paper. Ann Intern Med 108:301-303, 1988