All Blacks rugby player Jonah Lomu has died, aged 40. Lomu died of a heart attack, thought to have been a complication of the rare kidney disorder he’d been suffering from for most of his adult life.
The disorder, nephrotic syndrome, is a fairly rare disease with just two or three new cases per 100,000 of the population each year. But what exactly is it?
A nephron is a functioning unit within the kidney. Each nephron has a filter (called a glomerulus) and a drainpipe (a tubule), and there are about a million nephrons in a kidney, each acting in concert to clean the blood and regulate the body’s salt and water content.
The kidney cleans the blood over and over, at an incredible rate of 180 litres a day. Most of us have two kidneys which normally allows a lifetime’s worth of blood filtering to be performed.
There are several diseases of the kidney where the filters of the nephron become damaged. This leads to a loss of large amounts of protein in the urine (when there should normally be very little), which leads to low blood protein levels and body swelling, known as oedema. It is this combination of symptoms and signs that is called nephrotic syndrome. It was first described in 1821, yet we are still learning new features of this condition.
There may be many different underlying causes, which include rare inherited forms, specific diseases of the glomerulus and secondary causes due to other medical conditions, such as diabetes, and drugs, such as Gold, which is used to treat rheumatoid arthritis.
The consequences of nephrotic syndrome are severe. Complications that commonly occur include blood clotting problems (due to urinary loss of key proteins that prevent blood clotting), risk of serious infections (due to low blood protein levels) and kidney failure.
There are treatments for nephrotic syndrome, but no cure. Treatment often includes high dose steroid therapy and anticoagulants to prevent blood clots as well as diuretic tablets to control body swelling.
Certain underlying causes of nephrotic syndrome will eventually lead to complete kidney failure. This has devastating consequences and often means the patient has to rely on renal dialysis - where a machine does the job of the kidneys - until a kidney transplant can be performed. People can survive for many years on dialysis, but survival is often a long way from full health.
Dialysis may be performed by cleaning the blood three times a week using an artificial kidney (haemodialysis) or by using the abdominal cavity on a daily basis (peritoneal dialysis). Both treatments can be performed at home with the support of a healthcare professional.
However, life expectancy of a dialysis patient is severely limited, with the average being just five to ten years. It is possible to live for 20 or more years on dialysis but this is the exception rather than the rule.
A kidney transplant is the best treatment for kidney failure. A transplant returns life expectancy to near normal values. But transplanted kidneys tend to wear out faster than the kidneys you were born with and sometimes the original cause of nephrotic syndrome can recur after the kidney transplant. Often a second kidney transplant is needed when this happens.
It seems that, over several years, Lomu’s own kidneys failed and he received a transplant at the age of 29, which went on to function for the next seven years before failing.
Understanding the genetic causes
Research at Newcastle University aims to understand the genetic causes of nephrotic syndrome. This is where an inherited change in a gene predisposes patients to kidney disease resulting in a protein leak. Although we are born with our set of genes, often it isn’t until adult life that these conditions appear. Knowing the underlying genetic condition can allow early detection of the disease in other family members and allow treatments to be developed. It also gives information about whether the condition will recur in a kidney transplant.
The Genomics England 100,000 genomes project, which has been piloted at our university over the past few years, is a platform to study inherited kidney conditions such as nephrotic syndrome. Here, the genome is sequenced and analysed to identify disease causing variants. It was through this project that whole genome sequencing successfully identified the underlying genetic cause in a Newcastle family with an inherited form of nephrotic syndrome and kidney failure.
Knowing the underlying genetic predisposition for rare kidney disorders such as nephrotic syndrome is the starting point for developing a better understanding of the disease and developing treatments that can prevent the ongoing kidney damage that leads to kidney failure and all its devastating consequences.