Lead nephropathy

The oldest interstitial renal disease?
Lead pipe in Roman Bath.  (Wikimedia Commons, see foot)
Severe abdominal colic and gout caused by lead poisoning was described by Nikander in Ancient Rome. Acute poisoning also causes nerve palsies, particularly wrist-drop, encephalopathy, fits and sometimes death.  Many patients became ill over weeks or months, with associated anaemia, malaise, weight loss, headaches, poor concentration and neuropsychiatric symptoms. There might be blue lines on the gums, and ‘basophilic stippling’ in red cells.  
Areas of high prevalence have been recognised repeatedly. Bellan in North Yorkshire, England occurred in a 16-17th century lead-mining region. At Leadhills, Scotland, the disease was called Mill Reek, and its cause recognised in 1754 (Seaton 2011). The West-India dry-gripes (1745) was attributed to lead in rum punch; soon after this Devonshire colic (first described in 1655) was attributed to lead in cider. Contamination of alcohol has been a recurring theme; in 18th century UK fortified wine from Portugal became popular and is thought to have often contained high levels of lead. Poisoning from water fed through lead plumbing is rare, but more likely in soft, acid water areas (Beattie). Poisoning from industrial causes dominates the modern world. 
Lead poisoning seems to be an inescapable feature of rapid industrialisation and economic development. Analysis of Roman skeletons confirms high lead content. The sources of exposure were cosmetics, paints, and wine prepared in leaden vessels – at least partly for the sweet flavour imparted.   
In 19th century Britain, sufferers included painters of the Forth Rail Bridge as well and those working to produce raw materials for paints, well described in Ouseburn, Tyneside. Similar problems could be encountered in lead mining regions as seen in Queensland.

By the end of the 1800s industrial legislation began to limit exposure. At Ouseburn, workers were now required to bathe at least once a week. In the modern era, improved precautions are accompanied by regular blood lead testing. However after acute exposure lead is stored in bone, so that blood levels are a poor guide to historic exposure.  

Lead nephropathy was first described in a painter who sucked his brushes, in 1863. At autopsy his kidneys were small and fibrosed. By 1900 the disorder was well recognised. Under the microscope it is an interstitial nephropathy (affecting tubules and their surroundings, not glomeruli) often associated with gout. The association of lead toxicity with gout, ‘Saturnine gout’, had become medically accepted a hundred years earlier. Gout (‘podagra’) also has a long history, everywhere described as associated with alcoholic and other excess. Ability to diagnose kidney disease then was very limited, but it seems likely that lead nephropathy was prevalent too.  

Interstitial renal diseases are difficult to diagnose as they generate symptoms only very late, and dipstick testing of urine shows little or no abnormality. Fluid retention is rarely marked and hypertension may not be prominent, though moderate hypertension is said to be common in lead nephropathy. There are no tell-tale signs on kidney biopsy, though this didn’t become available in living patients till the 1950s. Biopsy is equally unrevealing in many other interstitial diseases, which include uncommon genetic disorders (some also cause gout, interestingly), but also a long list of other toxins. A number of other heavy metals, and plant and fungal toxins cause interstitial damage. However in a large proportion of patients with chronic interstitial nephritis the cause remains unknown.
The delayed consequences of lead on the kidney have caused some to question the association with lead exposure. However early accounts convincingly described a high incidence of renal failure in populations with a history of acute lead toxicity (summarised very well by Henderson), and this has been subsequently backed up by findings of increased interstitial renal disease in those in high risk occupations with a history of moderately high blood lead levels.  
Lead additives have been removed from fuel, paints, and other potential sources, particularly because of concerns of effects on the developing brain.  However there is still much lead in the environment, and there may be a long delay between exposure and consequences. Could we be missing the diagnosis by failing to ask, or because patients are unaware of exposure? And many parts of the world are still at the phase of development with limited regulations or testing, so exposure may be high. The EDTA lead mobilisation test, to show increased excretion of lead into urine after infusion of the chelating agent EDTA, is inconvenient. Do we do it often enough?

Further info 
Batuman V 1993 Lead nephropathy, gout and hypertension.  Am J Med Sci 305:241-7
Porter R and GS Rousseau 1998  Gout, the patrician malady.  Yale University Press
Beattie AD et al 1972  Lead poisoning in rural Scotland. Br Med J 2 488-91 describes poisoning from lead water tanks in soft water areas.
Wikipedia on lead poisoning is comprehensive and good, covering treatment too.
The Ouseburn process and an account of Newcastle lead works explain how difficult it was to avoid being poisoned as a Victorian lead worker

Henderson DA 1958  The aetiology of chronic nephritis in Queensland. Med J Aust 45:377-86
Knight L 2014  The fatal attraction of Lead  BBC News magazine 
Seaton A 2014 Saturnism: an old story of poisoning.  Q J Med 107:501-2 
Seaton A 2011 The mill reek in 1754. Occupational Medicine 61:223. Described by Dr James Wilson in 1754.
Tishma M 2019 Rich man poor man: a history of lead poisoning. Hektoen International. Detail on suspicions of ancient lead poisoning from wine and port, back as far as Roman times perhaps. And the recent cautionary tale of lead (and other?) poisoning from the water supply in Flint, Michigan. 

The Zamfara outbreak, Northern Nigeria 2010. 400 children are estimated to have died in this catastrophic modern outbreak of lead poisoning associated with gold mining. MSF report.
Image of Roman water pipe in Bath by Ad Meskens (WIkimedia Commons

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