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May 25, 2011

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Kidney Health – Filter tips

The kidneys are the body’s filtration system, helping us absorb certain elements necessary for the healthy functioning of the body and get rid of others that we don’t need. But kidney function can be seriously compromised by various work processes and substances, warns Dr Chris Ide, who provides advice for practitioners on what to do.

We give our kidneys scant thought, at least until something goes dramatically wrong with them. They are paired, reddish brown, bean-shaped organs, each of which is 10-12 cms long and weighs about 125g. They lie at the back of our abdomen, snuggling just below the diaphragm – the muscular sheet that separates the chest and abdominal cavities – and are partially protected by the lowest two or three ribs.

The functional unit of the kidney is the nephron. Each kidney has about a million of them, each consisting of a little clump of capillaries, the glomerulus (Latin glomus = ball), which acts as a filter through which blood passes, allowing water and low molecular-weight compounds to escape into a collecting tubule, while retaining blood cells and proteins, etc. The capillary that leaves the glomus is then intertwined around a collecting tubule, and selectively re-absorbs water, glucose, some electrolytes, and other substances necessary for the proper functioning of the body.
The residual fluid (urine) is passed out of the kidneys via the ureters – muscular tubes that connect the kidneys to the bladder, where it is stored until it can be passed out of the body at a more convenient time.

The kidneys perform a number of important functions, some of which, if they become impaired, can have life-threatening effects. For example, under the influence of various hormones, the kidneys regulate the concentration of our blood plasma by getting rid of excess water, and maintain the pH (acid/base balance) of the blood within very narrow limits by selective elimination of certain electrolytes.

In addition, they dispose of the potentially toxic products of protein breakdown, and of many other substances that the body’s great chemical factory, the liver, has turned into water-soluble compounds to facilitate their excretion from the body in urine.

The kidneys also produce three hormones, or chemical messengers: renin, which is involved in the longer-term regulation of blood pressure; erythropoietin, which stimulates the production of red blood cells; and calcitriol, the active form of vitamin D, which regulates calcium balance, and thus has implications for bone health.

Renal function deteriorates a little as we get older but, like so much of the body, the kidneys have a huge surplus capacity. This is why it is possible for a person to donate one kidney for transplantation to another, and still remain alive, well, and enjoy a normal remaining lifespan.

In fact, fortunately for us, the kidneys can absorb colossal punishment, and biochemical markers of renal function, such as serum urea and creatinine levels, will only start to rise outwith normal levels when about 75 per cent of the nephrons have been wiped out. Symptoms of renal failure only begin to intrude when just 15 per cent of filtering capacity is left.1 However, once the proportion remaining falls towards 5 per cent, then some form of renal replacement therapy (dialysis or transplant) is necessary if the patient is to survive. 

Looking at this in population terms, about 10 per cent of us have a degree of impairment of kidney function, but only between 1 in 20 to 1 in 50 has severe reduction.2 Each year, 110 patients per million population begin renal replacement therapy (requiring dialysis or transplant); there are currently about 48,000 such patients in the UK.3

On this basis, it is reassuring that the majority of those with less-than-perfect renal function will not progress to the requirement for renal replacement therapy, since dialysis is costly both financially – more than £30,000 per patient per year – and in terms of time – four to five hours thrice weekly spent at the dialysis centre, to which needs to be added travel time to and from the centre, as well as variable time recuperating from the dialysis.

Workplace hazards

Nature’s bounty should be protected, rather than squandered. Safety advisors have an important role in ensuring that known renal toxins in the work environment, if not eliminated, are safely controlled by well-established and understood techniques, such as substitution, use of ventilation, and appropriate personal protective equipment. The decline in the manufacturing industry means that the numbers exposed to traditional nephrotoxins, such as lead, cadmium, arsenic and mercury, are now comparatively small. However, this does not reduce the duty of care to those individuals.

More recently, the roles of various hydrocarbon solvents have been appraised from the point of view of their association with various forms of kidney disease, such as glomerulonephritis. Environmental pressures have led to a reduction in use of some compounds, but others remain because of their valuable inherent properties, and as intermediates in a variety of other processes. They include aliphatic compounds, such as petrol, methylene chloride, carbon tetrachloride, and chloroform, and aromatic ones, like benzene, xylene, toluene, styrene; as well as ketones and glycol ethers, etc.

As a rule, most workplace exposure to solvent vapours can be well controlled by enclosure, local extraction processes, or personal protective equipment (PPE), but it is important to remember that several solvents are capable of being absorbed through the skin. Gross contamination of the skin by solvent liquid seems rare, but vapours can still contribute to a significant body burden of solvent at levels near to the Workplace Exposure Limit by percutaneous (through the skin) uptake, and PPE may not necessarily effectively protect against entry through the skin.

For example, Jones and others write that up to 14 per cent of the body burden of 1-methoxy 2-propanol, a solvent used in inks and paints, can be derived from skin absorption. When studying another solvent (2-butoxyethanol), the authors report that 11 per cent of the body burden of this substance was absorbed through the skin. This was only slightly reduced by the use of coverall overalls. It was also reported that, in a reasonably foreseeable workplace environment simulation, the proportion taken up rose to 39 per cent.4

If there is a risk of significant solvent uptake, then some form of health surveillance is necessary. The simplest way of doing this would be by regularly asking employees whether they experience drowsiness or skin problems, but this would probably only be useful in conditions of very poor exposure control to easily vaporised solvents, or if there was scope for extensive gross skin contamination.

Specimens of urine can be tested for blood and protein – potential indicators of kidney damage – with various proprietary ‘stix’. Significant cadmium uptake is specifically associated with the presence of the protein b 2 microglobulin, but this substance can be broken down if the urine is very acidic. Retinol-binding protein is much more stable.

Some solvents, such as toluene, can be detected in blood samples, and residues of solvent metabolism, e.g. methyl hippuric acid, a breakdown product of xylene, and mandelic acid, derived from toluene, can be measured in urine. Exhaled breath analysis can be used to test for some solvents. However, any form of biological monitoring is fraught with difficulty, and would involve the use of appropriately trained occupational-health staff to take the appropriate samples and assess the many factors that can interact with the substances being sampled.

It’s not all about the chemicals

Those who work with natural materials are often thought to live a risk-free life, since they are not exposed to any harmful ‘artificial’ chemicals. However, a paper demonstrated that those involved in the manufacture or sale of Chinese herbal medicines were between three and four times more likely to suffer renal failure than a control population. The most likely culprit is a group of substances known as aristolochic acids.5

A rapid way to acute kidney failure is to suffer a significant crush injury. Should this occur, then proteins in the muscles and soft tissues flood into the general circulation and are swept into the kidneys where, for lack of a better way of putting it, they clog up the system. This may also be associated with a surge in the concentration of potassium ions in the bloodstream. This can lead to life-threatening irregularities of the heartbeat, with the patient at risk for longer than necessary because their kidneys are no longer functioning. Thus there is plenty of scope for the exercise of the traditional knowledge and skills of the safety advisor.

Inadequate fluid intake can result in the gradual development of renal calculi (stones), which can produce excruciating pain, and repeated attacks of colic caused by freshly forming, or increasing numbers or size of stone, can eventually lead to kidney failure. While few people now work in the blistering heat of forges and furnaces, many more will travel abroad on business, and even larger numbers will seek the sun on holiday in foreign lands. For these people, adequate fluid replacement is an essential part of the safety drills, as it will avoid the gradual dehydration that can contribute to stone formation.

It is not sufficient to take in enough fluid merely to slake thirst; the drinker should aim to consume just beyond this point, to the extent that the urine produced is pale in colour (OK, it’s a bit easier for us gents to judge this!)
However, all the substances mentioned above, many chemically-related ones and probably many others as yet unknown, only contribute a relatively small proportion of cases of end-stage renal failure. At least 70 per cent of cases in Caucasians are due to diabetes, poorly controlled high blood pressure, and atherosclerosis. In sub-Saharan Africa, malaria is prominent, while in the Middle East, schistosomiasis – an infection caused by a parasitic worm that passes part of its life in water snails – is important.

Fat is a definite issue

Regular readers will know that I am not wildly enthusiastic about lifestyle screening activities forming a substantial part of the role of an occupational health service. Nevertheless, I am gravely concerned about the increasing tide of obesity that seems to be engulfing us, particularly given its association with maturity onset (type 2, or non-insulin dependent) diabetes, raised blood pressure, and the so-called ‘metabolic syndrome’, with its disorders of lipid metabolism leading to furred up arteries, which may, in turn, lead to end-stage renal failure.

Safety advisors should consider supporting workplace-based educational campaigns encouraging healthy eating, etc. and using techniques with demonstrable long-term success. For reasons stated below, it is also important to encourage employees to join the organ donation register, allowing harvesting of kidneys, hearts, lungs, corneas, etc. for transplant, in the event of that person’s untimely death.

While the individual risk is small, if large numbers are exposed to that risk, then considerable numbers of cases of renal failure may still arise and, at £30,000 annually, place considerable costs – about £1.44 billion a year – on the National Health Service. This does not include the costs borne by the individual, who may lose their job, or have major restrictions placed on their employment.

For example, a survey involving the Manchester and Oxford renal units showed that, while at the outset 73 per cent of participants were still in work, within a year of starting dialysis this proportion had fallen to just over 40 per cent.6 Similar proportionate falls have been found in Holland, Croatia and the US. However, this may be due to people – including employers, medical staff and the patients themselves and their relatives – taking too gloomy a view and concentrating solely on contra-indications.

If one were to contemplate instead what the person could actually do, and try to find ways of maximising this, perhaps seeking assistance from the Access to Work scheme administered by the Disability Employment Advisors from the local Jobcentres, then more employees might be able to be retained. The most successful form of renal replacement therapy is a transplant, with 70 per cent of recipients able to resume work.7

Bladder beware

Moving south, the urine produced by the kidneys is stored in the bladder. The main work-related disease affecting the bladder is cancer. This was first described by the German urologist, Rehn, in 1895, who wrote about three affected employees from a workforce of 45 dyers. The precise agents eluded discovery until half a century later, when Case pinpointed

1 and 2-napthylamine, and similar chemicals used as antioxidants in the rubber industry. The removal of these materials solved the problem in that industry, but evidence of risk continued to be demonstrated in more than 40 different occupations, even though it was often inconsistent.

However, a large study based on a population in New England reported sustained higher risks in men employed as precision metalworkers, textile-machine operatives, and car mechanics, among other occupations that reported the use of metalworking fluids. This would suggest the presence of cancer-causing substances in this material.8
In summary, safety advisors need to deploy their knowledge, skills and experience to protect workers in a wide variety of jobs against a number of risks to the health of the kidneys and bladder, which, although they may both be insidious in onset and rare, can still be potentially life-threatening.


1    Yaqoob, MM (2009): ‘Chronic kidney disease’, in Clinical Medicine 7th Edition Saunders 2009 625-644
2    Tomson, CRV (2009): ‘Summary of findings in the 2009 UK Renal Registry Report’, in UK Renal Registry Report, 12th Edition (Eds: Ancell D, Castledine C, Feeharty J et al), Chapter 1, Bristol
3 newsroom/fact_sheets/cost_effectiveness_of_transplantation.jsp (accessed 19 March 2011)
4    Jones K, Crocker J, Dodd LJ, Fraser I (2003): ‘Factors affecting the extent of dermal absorption of solvent vapours: A human volunteer study’, in Ann Occup Hyg 2003, 47;2:145-150
5    Yang H-Y, Wang J-D, Lo T-C, Chen P-C (2011): ‘Occupational kidney disease among Chinese herbalists exposed to herbs containing aristolochic acids’, in Occup Environ Med 2011,68;4:286-290 
6    Auer J, Gokal R, Stout JP et al (1990): ‘The Oxford-Manchester study of dialysis patients’, in Scand J Urol Nephrol 1990;131 (supplement);31-37
7    Hobson J, Brown EA (2007): ‘Renal and urological disease’, in Fitness for Work, 4th Edition (Eds: Palmer KT, Cox RAF, Brown I), Oxford University Press, 2007, 429-444
8    Colt JS, Karagas MR, Schwenn M et al (2100): ‘Occupation and bladder cancer in a population-based case-control study in Northern New England’, in Occup Environ Med 2011,68;4:239-249

Chris Ide is an occupational physician and regular contributor to SHP.

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