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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 1  |  Page : 53-54

Neurological manifestations of renal disease

1 Department of Renal Medicine, Flinders Medical Centre; Department of Renal Medicine, University of Adelaide, SA, Australia
2 Department of Renal Medicine, Flinders University, Bedford Park, SA, Australia

Date of Web Publication11-Jan-2018

Correspondence Address:
Dr. Rajiv Juneja
Department of Renal Medicine, Flinders Medical Centre, SA
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.222825

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How to cite this article:
Rao NN, Juneja R. Neurological manifestations of renal disease. Neurol India 2018;66:53-4

How to cite this URL:
Rao NN, Juneja R. Neurological manifestations of renal disease. Neurol India [serial online] 2018 [cited 2020 Jun 5];66:53-4. Available from:

Patients suffering from chronic kidney disease (CKD) are prone to a variety of neurological complications, affecting both central and peripheral nervous systems. The aetiology maybe due to a primary kidney related disorder or as a result of comorbidities like diabetes mellitus, which can cause involvement of multiple organs in the body. Detection and management of these conditions in the early stages is vital in reducing the severity of symptoms in patients with these neurological manifestations. Renjen et al., have described the various central nervous system (CNS), peripheral nervous system (PNS) and autonomic nervous system complications that can be seen in patients with CKD in their review.[1]

Central nervous system: In a broader sense, as described by Renjen et al., the CNS manifestations can be attributed to two main categories- those affecting the vascular system and the other being neurodegenerative causes. The vascular component is attributed to the traditional cardiovascular risk factors including diabetes mellitus, hypertension, hypercholesterolemia, smoking and increase in age. Non–traditional risk factors are higher in patients with CKD and include raised calcium and phosphate, hyperhomocysteinemia, inflammation and oxidative stress, leading to accelerated atherosclerosis and endothelial dysfunction.[2]

There is a high prevalence of cardiovascular disease from micro-bleeds and white matter disease in the brain in patients undergoing dialysis.[3]

Neurodegenerative causes have been attributed to uraemic toxins, especially indoxyl sulfate, p-cresyl sulfate, uric acid, interleukin (IL)-1beta. It has also been hypothesised that cystatin-C may lead to amyloid deposition. Anaemia and hyperparathyroidism have been attributed to neurocognitive impairment as a result of reduced delivery of oxygen, and parathyroid hormone (PTH) interfering with neurotransmission in the CNS as a result of elevated calcium levels in the brain, respectively. It is interesting to note that treatment with erythropoietin stimulating agents (ESA) have been shown to increase the risk of stroke.[4]

Intermittent haemodynamic shifts, as seen during dialysis, have been shown to result in perfusion related brain injury, although “dialysis dementia” that was seen in the earlier era due to exposure to aluminium is now rarely seen. The prevalence of cognitive decline in these patients is estimated to be up to 60%. Retention of uraemia related metabolites have been thought to be the main cause of 'uraemic encephalopathy'. Methyl- guanidine, guanidine, guadinosuccinic acid and even creatinine have been shown to cause convulsions in the animal experimentation settings. Elevated blood pressure may result in posterior reversible encephalopathy syndromes (PRES).

A special mention must be made of the 'dialysis disequilibrium syndrome' resulting from rapid changes in urea and other osmolytes when dialysis is initiated in the setting of severe uraemia. This can be minimised by initiating dialysis at a slower rate, by an increment in the duration of dialysis in a step-wise fashion, and by the use of 'concurrent dialysis' strategies in high-risk patients. Electroencephalography (EEG) in these patients may show changes like slowing of alpha-rhythm and increase in delta and theta waves. Triphasic sharp waves are considered as being specific indicators for metabolic complications.

Peripheral nervous system: Uraemic neuropathy may initially manifest distally with predominantly sensory system involvement resulting in loss of touch, pinprick, and vibration sensations, and later involving the motor system as well, subsequently leading to weakness in distal muscles. Uraemic myopathy affects proximal muscle groups especially around the hip. A study demonstrated the benefits of lowering serum potassium levels in reducing the progression of neuropathy.

Autonomic dysfunction: This disorder is highly prevalent in dialysis patients and may result in impotence and gastrointestinal symptoms. Sympathetic outflow has been shown to be significantly higher in these patients.

Restless leg syndrome affects up to 25% patients on dialysis. This is a neurological disorder with a circadian rhythmicity, characterised by an overwhelming urge to move the legs during rest, which is temporarily relieved by movement. This has been associated with a poor sleep, a higher cardiovascular morbidity and a poor quality of life in patients undergoing dialysis. The aetiology is thought to be an imbalance in iron metabolism and dopamine neurotransmission in the brain. Interventions, including exercise, gabapentin, ropinirole, levodopa, iron dextran and vitamin C and E, either administered individually or in combination, have all been shown to improve symptoms in these patients.[5]

Majority of renal transplant recipients have a calcineurin inhibitor (CnI) as one of the long-term immunosuppressive agents in their drug regimen. Up to 30% of the patients receiving CnI experience some form of neurotoxic and psychiatric adverse events. Mild symptoms may include tremor, neuralgia, and peripheral neuropathy. Severe symptoms affect nearly 55% of the patients and these may include psychosis, hallucinations, blindness, seizures, cerebellar ataxia, motor weakness or posterior reversible encephalopathy syndrome. The etiology of these manifestations appear to be due to injury to major vessels as well as micro- vasculature and due to alterations in the sympathetic outflow. Symptoms can be reversed in most patients by reducing the dose or by discontinuation of these drugs.

Thrombotic microangiopathy (TMA) may be caused by a number of conditions including Shiga toxin producing E-coli (STEC), pregnancy, drugs, as well as systemic autoimmune and infective illnesses. Neurological manifestations may be seen in association with renal impairment in causes secondary to STEC E Coli. An atypical haemolytic uraemic syndrome and the clinical spectrum of thrombotic thrombocytopenic purpura (TTP) as well as their pathological manifestations are mostly limited to the kidney in calcineurin inhibitor (CnI) induced TMA in kidney transplant recipients (which is a rare but well-recognised complication seen only in upto 1% of the transplant population on CnI).

A mention should also be made of a rare, but potentially fatal disease called progressive multifocal leukoencephalopathy (PML) in renal transplant recipients on mycophenolate mofetil (MMF). The incidence density of PML in MMF users was 14.4 cases/100,000 persons-years at risk versus 0 for non-MMF users by log rank test in a study by Neff et al.[6],[7]

In conclusion, neurological complications are common in patients with chronic kidney disease. A different set of manifestations may occur when these patients with CKD move from dialysis onto kidney transplantation. Early identification of these manifestations may be vital to avoid long-term neurological sequelae.

  References Top

Renjen PN, Chaudhari D, Sagar G, Jasuja S. Neurology of renal disorders. Neurol India 2018:66:163-7.  Back to cited text no. 1
McQuillan R, Jassal SV. Neuropsychiatric complications of chronic kidney disease. Nat Rev Nephrol 2010;6:471-9.  Back to cited text no. 2
Bugnicourt JM, Godefroy O, Chillon JM, Choukroun G, Massy ZA. Cognitive disorders and dementia in CKD: The neglected kidney-brain axis. J Am Soc Nephrol 2013;24:353-63.  Back to cited text no. 3
Chillon JM, Massy ZA, Stengel B. Neurological complications in chronic kidney disease patients. Nephrol Dial Transplant 2016;31:1606-14.  Back to cited text no. 4
Arnold R, Issar T, Krishnan AV, Pussell BA. Neurological complications in chronic kidney disease. JRSM Cardiovascular Disease 2016;5:2048004016677687.  Back to cited text no. 5
Neff R, Hurst F, Falta E, Bohen E, Lentine K, Dharnidharka V, et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 2008;86:1474-8.  Back to cited text no. 6
Rao N, Schepetiuk S, Choudhry M, Juneja R, Passaris G, Higgins G, Barbara J, et al. JC viraemia in kidney transplant recipients: To act or not to act? Clinical Kidney Journal 2012;5:471-3.  Back to cited text no. 7


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