Generally speaking, when we think of ‘kidney disease’, we think of dialysis or a kidney transplant. But it is less well known that kidney disease, which affects more than 10 per cent of the world’s population, can have significant consequences for the functioning of other organs.For example, the patients also suffer from high blood pressure, which is, incidentally, often a sign of chronic kidney disease. It is also known that kidney disease significantly increases cardiovascular risk.Even more surprisingly, research has revealed that kidney and brain function are closely linked: kidney dysfunction can be accompanied by cognitive impairment, the severity of which increases with the severity of the damage to the kidneys.Cognitive impairment: a common yet little-known complicationBy filtering waste products and maintaining the balance of water and numerous molecules in our bodies, the kidneys are vital organs for maintaining good health. However, they can sometimes malfunction and gradually lose their ability to filter and cleanse the blood: this is chronic kidney disease, which affects 6 million people in France, and 800 million people worldwide.This condition inevitably leads to the almost complete loss of kidney function. It can be caused by a variety of causes, such as diabetes (the most common cause in Western countries). It is partly linked to lifestyle, but can also result from genetic or autoimmune causes (in the latter case, the immune system attacks the body it is supposed to defend).Initially asymptomatic, kidney disease progresses at varying rates (often depending on the underlying cause), over a period of a few days or several years.Symptoms only appear in the most severe stages. These include neurological complications, which generally manifest as repeated forgetfulness (particularly regarding medication), difficulties managing everyday tasks (such as handling money and carrying out household chores), cognitive decline and difficulty concentrating.These cognitive impairments are sometimes subtle and can, therefore, be difficult to detect without specific screening. Their frequency and severity correlate with the severity of kidney disease: at the dialysis stage, they can affect up to 70 per cent of patients with kidney failure, and have a major impact on their independence and quality of life.The most severe form of this brain disorder is dementia.Patients with kidney disease are also three times more likely to suffer a stroke than the general population. Strokes occurring in patients with kidney failure are also more severe and associated with a lower chance of neurological recovery and a higher mortality rate.Why is kidney disease so harmful to the brain? How do the kidneys affect this organ? The answers to these questions lie in a very specific structure: the blood-brain barrier.The blood-brain barrier provides essential protection for the brainThe blood-brain barrier can be thought of as an extremely selective biological filter, whose purpose is to protect the brain not only from microorganisms that might attempt to invade it, but also from toxins and any other molecules that could have a harmful effect on it.This barrier is composed of several layers of cells that are particularly tightly packed and closely interconnected.Our research as well as that of other teams suggest, however, that this protection may be compromised by chronic kidney disease. This impairment would partly explain the cognitive disturbances. Several mechanisms contribute to the deterioration of the blood-brain barrier’s protective properties:Weakening of the blood vessels. The brain and kidneys are highly dependent on finely regulated blood microcirculation. However, it is known that kidney disease significantly weakens the cells of the blood vessels, particularly those in the brain. Damage to small blood vessels is very commonly observed on brain imaging (CT or MRI) in patients with kidney failure.In cases of kidney disease, the blood vessels thicken: more calcium is deposited in the muscular layer of their walls, which disrupts the exchange of substances between the blood and the brain. Furthermore, certain very common conditions, such as high blood pressure, diabetes or heart rhythm disorders, can also contribute to vascular complications, which affect both the kidneys and the brain. The calcification and stiffening of the blood vessels increase the pulsatility transmitted to the cerebral circulation (with each heartbeat, the resulting impacts are transmitted more forcefully). This situation promotes the development of cerebral small-vessel disease (which contributes to cognitive impairment) and has consequences for the blood-brain barrier.Inflammation. Chronic kidney disease leads to inflammation in the blood. Patients’ blood contains higher levels of inflammatory molecules and immune cells involved in the inflammatory response than those found in the blood of the general population. When these pro-inflammatory immune cells enter the brain and persist there, the inflammation they cause not only contributes to damage to the brain but also increases the permeability of the blood-brain barrier.The accumulation of toxins. As kidney disease progresses, the kidneys become less effective at eliminating waste products. These waste products, known as ‘uraemic toxins’, accumulate in the bloodstream, exerting harmful effects on the body. Over a hundred such toxins are currently known. Some of them have a harmful effect on the blood vessels in the brain, which can, in turn, contribute to weakening the blood-brain barrier.All these mechanisms therefore have negative impacts on the vital protective function of the blood-brain barrier. Several recent research studies suggest that impairment of the blood-brain barrier plays a significant role in the cerebral complications of kidney disease. In chronic kidney disease, the blood-brain barrier is impaired. Adapted from Bobot M., Nephrol Ther. (2023), CC BY. CC BY What this means for patientsThe weakening of the blood-brain barrier has numerous consequences for patients. It could exacerbate the severity of strokes by amplifying the inflammatory processes and oedema (swelling) that occur in the brain following such an event. This particularly serious complication itself increases the risk of cognitive impairment.Preventing the risk of stroke and identifying patients at particularly high risk is therefore crucial. In addition to common stroke risk factors, such as high blood pressure, diabetes or heart rhythm disorders – which are frequent in patients with kidney disease – there are risk factors specific to this condition. It is worth noting that, in some cases, preventive treatments can be put in place to reduce the likelihood of a stroke occurring.In addition to the increased stroke risk, the brains of patients with kidney failure are also more susceptible to damage or toxicity from certain medicines, again due to the impairment of the blood-brain barrier. This is the case, for example, with certain antibiotics, such as beta-lactams or carbapenems, which penetrate the brains of these patients to a greater extent.Finally, it should be noted that while brain damage resulting from kidney disease mainly manifests as cerebral small-vessel disease (or vascular dementia), some studies have revealed that patients are also at greater risk of developing Alzheimer’s disease.Taking cognitive impairment into accountIn cases of kidney disease, it is therefore important to always take patients’ cognitive condition into account. This requires better screening for cerebral complications, as the earlier these disorders are identified, the more effective their management will be. Consequently, it is equally important to screen for kidney disease at an early stage in patients with memory impairment or stroke history.This can be done very simply, using laboratory blood and urine tests combined with taking blood pressure. The earlier kidney disease is diagnosed, the more effective kidney-protective treatments will be in slowing its progression, and the lower the risk of complications, including those affecting the brain.It is also known that kidney transplantation can improve cognitive impairment in patients.Treatments currently under developmentEarly detection of kidney disease enables treatments to be introduced to slow the decline in kidney function and its effects on the brain.An early diagnosis is all the more important given that there is currently no specific therapy to protect patients’ brains in the event of kidney disease. However, research in this field has been expanding in recent years, and several avenues for new treatments are being explored.For a long time, kidneys were regarded primarily as an organ for filtering waste products. Recent research findings show that they are constantly communicating with the brain.Gaining a sounder understanding of this connection and improving screening would not only help to better preserve kidney function, it would also serve to protect the cognitive abilities of millions of people.Mickaël Bobot received funding from the French-speaking nephrology and dialysis groups, the Kidney Foundation, and from l'Assistance Publique - Hôpitaux de Marseille, for his research work. He is a member of the French-speaking nephrology and dialysis groups and the European Renal Association.