UK Kidney History

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Renal Pathology in the UK

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Renal Pathology in the UK

Introduction

Renal pathology began to emerge in the 1950s as a distinct entity, a significant sub-specialty within clinical histopathology. A main stimulus to its development was the advent of renal biopsy as a routine clinical diagnostic technique.

Until then the pathology of kidney disease had  not been well studied. The most active area had been in the diagnosis and staging of renal tract cancer.  That aside the study of parenchymal renal disease had advanced little and was mainly restricted to the morbid anatomy of surgical resection and autopsy specimens.

Surprisingly little progress had been made since the work of the Guy’s physician  Richard Bright in the  19th century;  his beautifully illustrated ‘Reports of Medical Cases’ (1827)R Bright Medical Cases illustrations showing the morbid anatomy in cases of kidney disease with proteinuria. Although Bright is rightly famed for  this seminal work, he  was also as far as we know responsible for the illustrations. In the preface to  ‘Reports of Medical Cases’ says of the colour  illustrations “…. for the accuracy with which they present the objects they are intended to illustrate, I cheerfully make myself responsible”.  F.R. Say W.Say,  who are only acknowledged in the smallest of small print at the bottom the colour plates were the engravers.  Nor does Bright give any credit to those who performed the autopsies and removed the kidneys.

In follow-up studies with improved microscopy, the role of glomeruli began to be appreciated. Eknoyan (2020) describes that in an 1842 letter Bright wrote “one of the most interesting features of the morbid anatomy of this disease is to be found in the condition of the corpora Malpighiana. ” This information came from work performed by his assistant Joseph Toynbee (1815–1866) published in 1846. Eknoyan identified Jones Quain (1796–1865), professor of anatomy at University College London, as first using the term glomeruli to describe Malpighian corpuscles. This was only 4 years after English surgeon/ anatomist William Bowman beautifully illustrated the structure of the glomerulus familiar to us. He didn’t get its function right though.

The change in clinical terminology to Ellis Type I and Type II nephritis in the 1940s had not been accompanied by any fresh insights into the description or classification of pathological appearances in the kidney.

There was however a growing  body of UK research from  the 1950s in experimental kidney disease. For example, work on the renal changes in hypertension by Robert Heptinstall  (St. Mary’s Hospital) working with the physician George Pickering , and work on  the nephrotic syndrome and the mechanisms of proteinuria, led by John Squire  (Birmingham).

Renal biopsy

It was the advent of percutaneous renal biopsy which changed things. Prior to that renal  biopsy material was obtained at open surgery (as reported for example in children as early as 1930) but there was little systematic reporting of the morphology.

Percutaneous renal biopsy was first described by Brun and Iversen in Copenhagen in 1951 using aspiration, and then by Muehrcke and Kark in Chicago using a needle technique.

 Bob Muehrcke brought their technique to the UK in 1956, when he was visiting the then president of the Renal Association Malcolm Milne at the Royal Postgraduate Medical School (RPMS) Hammersmith Hospital. He demonstrated the technique to Mark ‘Jo’ Joekes at St Mary’s. Joekes had recenlty worked at RPMS. (See Joekes ISN interview and transcript, and Heptinstall interview at Johns Hopkins). Other centres were soon to pick up the technique. The first percutaneous renal biopsy in a child in the UK was performed by Richard White at Great Ormond Street in 1959. Although open renal biopsy had been reported  in children as early as 1930.

Biopsies were at first used to add diagnostic and prognostic information mainly in cases with nephrotic syndrome and other clinical features of glomerulonephritis. When kidney transplantation emerged as a viable treatment from the 1960s, insights into the pathology of transplant rejection were soon being sought from graft biopsies (a technically more straightforward procedure compared to biopsy of native kidneys given the placement of the transplant kidney superficially in the iliac fossa).

Renal pathology in the biopsy era

It was inevitable  that a cadre of pathologists would soon emerge who had developed the experience and expertise to study biopsies and provide diagnostic and prognostic information, and guidance for therapy.  Among the   important pioneers of renal pathology in the UK were

Robert Heptinstall and

Kendrick Porter,   both at St. Mary’s Hospital London, who rapidly earned worldwide recognition for their expertise;

and in Edinburgh, Mary Macdonald.

Porter was soon recognised as a world leader in renal transplant pathology.  He was appointed to a chair in renal pathology  at St. Mary’s and remaining there for the rest of his career.

Heptinstall’s paper  with Joekes describing the findings on 136 renal biopsies among the first performed in the UK (Heptinstall RH, Joekes AM. Proc Roy Soc Med 1959; 52:211) was highly influential in defining the field of modern clinical renal pathology. But doubting the opportunities afforded him in the UK, Heptinstall moved in 1960 to Johns Hopkins, Baltimore, USA, where he worked until retirement building a formidable reputation as a teacher, mentor and leader. His textbook Renal Pathology (the first edition written entirely by Heptinstall himself)  was published in 1966.  Though now a multiauthor book with many subsequent editions it continues simply to be known as ‘Heptinstall’, and has maintained its position as the definitive book in the field, found on the shelves of pathology departments all over the world.

Mary Macdonald was drawn into the analysis of the first renal biopsies in Edinburgh (perhaps unsurprisingly since she was married to James Robson, nephrologist and professor of medicine who  performed those first biopsies!) and became a leader in the field, especially in the application of electron microscopy to biopsy material.

There was needless to say no learning course or qualification of competence at that time. Pathologists learnt rapidly from experience based on well-defined principles of histopathology, and from education offered  by the few ‘experts’.   A small number of nephrologists also developed and maintained expertise  in reviewing and reporting renal biopsies.

Notably the paediatric nephrologist Richard White at Guy’s and later in Birmingham, and  Stewart Cameron at Guy’s.

 

At first biopsy specimens were only examined by light microscopy, usually with haematoxylin and eosin (H&E) staining. But a widening range of techniques were soon to be applied to biopsy evaluation. By 1957 there were already reports of techniques for the detection of immune reactants (mainly immunoglobulin and complement components) at first by indirect immunofluorescence and later by immunoperoxidase staining. The benefits of reviewing unusually thin sections were also becoming apparent in defining glomerular anatomy. And in 1958  electron microscopy to define ultrastructure was first reported. These additional modalities quickly refined the understanding and classification of  parenchymal renal disease, particularly glomerular disease. Although they were much less used for diagnosis in transplant biopsies, which at that time  still relied mainly on light microscopy.  Thus centres using renal biopsy soon needed to provide access to all these techniques and the technical expertise to cut very thin sections and prepare high quality specimens for both light and electron microscopy.

Patterns of working

From the early days, well integrated working between nephrologists and renal pathologists became the norm.  Weekly renal biopsy meetings were typical in major centres where clinical information would be presented alongside the pathological findings to agree diagnoses and develop case-specific treatment plans (predating by decades the MDT (multidisciplinary team) meetings of modern cancer care and other disciplines). The importance of urgent biopsy with rapid reporting was also  quickly appreciated  – for example in cases of rapidly progressive renal failure, and in acute transplant care. Sections for viewing by light microscopy could be available with 4-6 hours of biopsy, clinical nephrology staff would often move immediately to view the biopsy with the pathologist via a double-headed microscope to make diagnostic and urgent therapeutic decisions. This further cemented the integration of nephrology and renal pathology in day-to-day clinical work.

Renal pathology as a specialty choice

By the 1980s  the growth in nephrology required at least one dedicated renal pathologist in every major renal and transplant centre (Table 1).

Although it would be facile to imply that there was  a typical renal pathologist,  the specialty undoubtedly attracted those who enjoyed the intellectual challenge of unusually complex diagnostic and prognostic clusters, who relished the team working with nephrologists and transplant surgeons (not in general ‘shrinking violets’!)  and enjoyed the acute on-call service provision in which urgent pathological evaluation had clear impact on patients treatment and outcome.

 The description of ‘new’ diseases

The impact of renal biopsy on our understanding of parenchymal renal disease was transformative, but at the same time the sustained use of renal replacement therapy was leading to the emergence of new pathologies, which were the consequence of keeping people alive with end-stage kidney  disease who nevertheless had very incomplete replacement renal function by dialysis.

Acquired cystic disease

Acquired cystic disease was first described by Michael Dunnill in Oxford.  Dunnill was a lung pathologist who did the pathology for the Nuffield Department of Surgery at the  time   Philip Allison, a thoracic surgeon, held the chair. When Peter Morris replaced Allison in 1974 and began a kidney transplant programme, Dunnill offered to do the transplant work although he recalls he had no experience of it at all. He taught himself and then wrote a book on it a year later!

Dunnill  also took on the interpretation of native renal biopsies but there were not that many performed in Oxford at that time. But he was not exclusively a renal pathologist, like most in that era also doing general pathology work.

Morris had a low threshold for bilateral nephrectomy in dialysis  patients awaiting transplant because he feared infection so if there was any reflux or scarring, out they came. Many of the kidneys removed had been in situ but non-functional for a long time, since there had previously been no transplants in the nine years since haemodialysis started in Oxford. Dunnill’s first report in 1977 was of autopsies findings in longstanding haemodialysis patients whose original causes of kidney failure had been well-defined by imaging and biopsies and were non-cystic. Acquired cystic disease was found in 30 of 51 autopsies. Haemorrhage and malignant changes were important  complications  Dunnill et al Acquired cystic disease 1977. A nephrology registrar,  Peter Ratcliffe noted the raised haematocrit in some and attributed this to epo production from the cystic kidney Ratcliffe et al Acquired cystic disease & Hb BMJ 1983.

UK investigators also made significant contributions to other ‘new’ conditions in those with longstanding renal failure maintained by dialysis. These include renal bone disease, aluminium toxicity, and beta2-microglobulin-related amyloid (Athanasou N et al. Q J Med. 1991 78:205 & NDT 1995;10:1672)

Renal pathologists and research

Since nephrology in those early days was almost exclusively a teaching hospital specialty and many of the first nephrologists were clinical academics, it was inevitable   that many of the early renal pathologists would also be academics whose instincts were to develop research alongside the provision of a clinical renal pathology service. As well as investigation into disease mechanisms developed and led by renal pathologists, there were many opportunities for collaborative research with nephrologists, immunologists and others. Renal pathologists were co-authors in a large proportion of the early UK papers defining the natural history, morphology, and thence the classification of glomerular disease. For example David Turner and later Barry Hartley, pathologists at Guy’s working with Stewart Cameron.  Some renal pathologists also became expert in the pathology of the many rodent models of experimental GN  which dominated much glomerular disease research in the second half of the 20th century,  notably David Evans at RPMS.

A CIBA symposium held on London in 1961 on Glomerulonephritis proved to be  a seminal meeting at which UK pathologists and nephrologists presented  their growing achievements in the field  for international comparison.

And, while there was an explosion of interest in glomerular pathology, a less heralded but important observation was made by the pathologists RA Risdon and  JC Sloper working with Hugh de Wardener at Charing Cross Hospital that the extent of chronic tubulo-interstitial injury correlated well with prognosis (Risdon RA, Sloper JC, De Wardener HE. Lancet. 1968 Aug 17;2(7564):363-6).

Renal pathologists also played a critical role in the early treatment trials in renal disease, funded among others by the MRC. Pathological inclusion and exclusion criteria for trials were equally as important as clinical criteria, and definitions of morphological features needed to be agreed. Mary Macdonald played a notable  role in coordinating pathology opinions for the early MRC trials.

Renal pathology since 2000

External Quality Assurance

In the early stages of the development of renal pathology, it was inevitable that expert opinion held sway. But as the number of pathologists grew, issues of consistent practice and quality assurance became more prominent. Renal pathology was one of the early subspecialities in the UK to introduce an external  quality assurance scheme to improve practice. From 2000 onwards slides were regularly circulated and the diagnostic decisions of each pathologist compared. The UK National Renal Pathology EQA Scheme  was first developed and managed by Peter Furness (professor of renal pathology, Leicester), and later by Ian Roberts (professor of renal pathology, Oxford). Participation has always been on a voluntary basis.

Clinical service

Since the turn of the century, there has been some retrenchment in the provision of renal pathology in the UK.  The number of those with specialist expertise has shrunk, and it would appear that despite its obvious attractions,  it is proving a less welcome career choice for pathology trainees.

A reduction in the number of  renal  pathologists has fortunately coincided with improvement in digital microscope technology making  satisfactory the  remote reporting and virtual biopsy meetings now required for many clinical renal teams. But inevitably there is some loss of the close working between renal pathologists and the clinical team.

International impact

Terry Cook (Imperial), Peter Furness (Leicester) and Ian Roberts (Oxford) were the most prominent UK renal pathologists in the first two decades of the 21st century. All  had international reputations for the quality of their teaching. One notable achievement was the development of  Oxford Classification of IgA nephropathy, in which Cook & Roberts played a critical role in corralling the opinions of an international group of renal pathologists.  They ensured that an evidence-based rather than opinion-based classification was developed, and that honest debate ensured pathological features were not used in the classification if their reporting was not consistently reproducible.

Other research fields have been strongly influenced by UK renal pathologists mostly in close collaboration with nephrologists or other physicians, for example complement-associated GN.

Table: Renal pathologists in the UK 1955-2000

We welcome additions and corrections to this table..

Birmingham John Squire, Alec Howie

Richard White (paediatrics)
Barts
Bristol Colin Tribe, Angus Mceever
Cambridge Satia Thiru
Exeter
Guy’s David Turner, Barry Hartley
Hammersmith David Evans, Terry Cook
Leicester Peter Furness
Liverpool
Manchester George Williams, Bill Lawler, Ian Roberts
Oxford Michael Dunnill, David Davies, Ian Roberts
Newcastle
Nottingham David Turner
Royal Free
Royal London
St Mary’s Robert Heptinstall, Kendrick Porter, Vicky Cattell
Southampton Paul Bass
Stoke
Cardiff
Belfast
Aberdeen
Glasgow
Edinburgh Mary Macdonald

 

Further info

Authorship

First published April 2025

Last Updated on April 30, 2025 by neilturn

Authors: Chris Winearls, John Feehally - see Contributors