Patients with chronic kidney disease (CKD) are frequently afflicted with neurological complications. These complications can potentially affect both the central and peripheral nervous systems. Common neurological complications in CKD include stroke, cognitive dysfunction, encephalopathy, peripheral and autonomic neuropathies. These conditions have significant impact not only on patient morbidity but also on mortality risk through a variety of mechanisms. Understanding the pathophysiological mechanisms of these conditions can provide insights into effective management strategies for neurological complications. This review describes clinical management of neurological complications in CKD with reference to the contributing physiological and pathological derangements. Stroke, cognitive dysfunction and dementia share several pathological mechanisms that may contribute to vascular impairment and neurodegeneration. Cognitive dysfunction and dementia may be differentiated from encephalopathy which has similar contributing factors but presents in an acute and rapidly progressive manner and may be accompanied by tremor and asterixis. Recent evidence suggests that dietary potassium restriction may be a useful preventative measure for peripheral neuropathy. Management of painful neuropathic symptoms can be achieved by pharmacological means with careful dosing and side effect considerations for reduced renal function. Patients with autonomic neuropathy may respond to sildenafil for impotence. Neurological complications often become clinically apparent at end-stage disease, however early detection and management of these conditions in mild CKD may reduce their impact at later stages.

Aims To investigate changes in corneal nerve morphology in Type 2 diabetes and to establish relationships between in vivo corneal confocal microscopy and markers of peripheral nerve structure and function.Participants and methods We recruited 57 participants with Type 2 diabetes and 26 healthy controls of similar age and sex distribution. We also recruited a disease control group of 54 participants with Type 1 diabetes. All participants were assessed for distal symmetrical polyneuropathy using the Total Neuropathy Score. In vivo corneal confocal microscopy was used to assess corneal nerve fibre length, corneal nerve fibre density, corneal nerve branch density and inferior whorl length. Peripheral nerve structure was assessed using median nerve ultrasonography. Large fibre function was assessed according to median nerve axonal excitability. Small fibre function was assessed using Sudoscan TM and the Survey of Autonomic Symptoms.Results Corneal nerve fibre length, fibre density and branch density and inferior whorl length were significantly lower in individuals with Type 2 diabetes compared to controls (P<0.001 for all). In the Type 2 diabetes cohort, correlations were observed between neuropathy severity and corneal nerve fibre density (P=0.004), corneal nerve branch density (P=0.003), corneal nerve fibre length (P=0.002) and inferior whorl length (P=0.01). Significant correlations were observed between corneal confocal outcomes and axonal excitability measurements. No association was found between corneal confocal microscopy and median nerve cross-sectional area, Sudoscan measurements or the Survey of Autonomic Symptoms.Conclusions This study demonstrated significant changes in corneal nerves in individuals with Type 2 diabetes. Reductions in corneal nerve measures correlated with increasing neuropathy severity. Associations were found between corneal confocal microscopy and markers of voltage-gated potassium channel function.

This study has identified correlation between markers of axonal membrane function and structural abnormalities in peripheral nerves of type 1 diabetes patients. The differential relationship in nerve function and structure between type 1 and type 2 diabetes provides clinical evidence that different pathophysiological mechanisms underlie the development of neuropathy in these patient groups.

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Background Impaired physical function drives adverse outcomes in chronic kidney disease (CKD). Peripheral neuropathy is highly prevalent in CKD, though its contribution to physical function in CKD patients is unknown. This study examined the relationships between neuropathy, walking speed and quality of life (QoL) in CKD. Methods This was a prospective observational study investigating neuropathy in CKD patients with an eGFR 15-60ml/kg/min-1. A total of 109 patients were consecutively recruited. The presence and severity of neuropathy was determined using the Total Neuropathy Score (TNS). Walking speed was assessed at both usual and maximal speed, and QoL was assessed using the SF-36 questionnaire. Results Peripheral neuropathy was highly prevalent: 40% demonstrated mild neuropathy and 37% had moderate-severe neuropathy. Increasing neuropathy severity was the primary predictor of reduced walking speed (R2=-0.41, p&lt;0.001) and remained so after multivariable analysis adjustment for diabetes. This association was evident for both usual and maximal walking speeds. Neuropathy correlated significantly with low scores on multiple domains of SF-36 including physical function (r=-0.570, p&lt;0.001). Subanalysis according diabetic status revealed a high prevalence of neuropathy both with-and-without diabetes; relationships to walking speed remained evident in subgroup analysis. However, those with diabetes demonstrated greater severity of neuropathy, slower walking speed and lower scores in QoL. Conclusions Moderate to severe peripheral neuropathy was common in stage 3-4 CKD, associated with reduced walking speed independent of diabetes status and was correlated with patient reported QoL. This suggests that neuropathy is an important contributor to declining physical function in CKD irrespective of diabetes status. Targeted diagnosis and management of peripheral neuropathy during CKD progression may improve functional outcomes and QoL.