BACKGROUND: Chronic kidney disease (CKD) is one of the most common diseases in adult age and it is typical of older adults. Recent data suggest that almost half of the elders have CKD. It is now clear that CKD is accompanied, in the early stages, by cognitive impairment, together with depression and subtle abnormalities in motor control (such as gait and balance alterations). SUMMARY: Several data suggest a link between brain dopamine and kidney diseases. Metabolic syndrome and diabetes can affect dopamine neuron survival (leading to Parkinson’s Disease). Several uremic toxins in CKD (uric acid, indoxyl sulphate) and trace elements accumulating in CKD (aluminium, manganese) can also modify the dopaminergic system. Hormones produced by the kidney such as vitamin D are neuroprotective for dopamine neurons. Dopaminergic drugs are useful for the treatment of a common sleep disorder in CKD, the restless legs syndrome. However, experiments on animal models of CKD show conflicting results regarding a modification of dopamine neurons. KEY MESSAGES: Several observations suggest a limited relevance of the dopaminergic system in CKD-related cognitive impairment. However, a common sleep disturbance in CKD, the restless leg syndrome, improves with dopaminergic drugs. Therefore, it remains to be established the role of the dopamine system in subtle motor dysfunction observed in CKD, such as tremors, gait alterations, and central sleep apnea.
Background and Aims Mild Cognitive Impairment (MCI) has been found to be highly prevalent amongst patients with Chronic Kidney Disease (CKD). In this cohort, the prevalence of MCI was estimated to be between 30% and 63%. Mild cognitive impairment is an intermediate state between normal aging and dementia. An individual suffering from MCI has difficulty in remembering, sustaining attention, or decision making which can negatively affect their daily lives. The aim of this study was to verify the role of different glomerular diseases diagnosed by kidney biopsy on the MCI through a retrospective study. Method We recruited 45 patients with bioptic diagnosis of the following glomerular diseases: Focal Segmental Glomerulo Sclerosis (FSGS), minimal change disease (MCD), membranous glomerular disease (MG), IgA nephropathy. The renal function was analyzed using clinical variables, while Cognitive functions using the MoCA test. Patients were divided into two groups based on 24h proteinuria. Results The MoCA score was directly correlated to the uric acid levels (R=0.13; p=0.03). The MoCa score in the group with higher proteinuria levels was significantly lower than those of the group with lower proteinuria levels (p = 0.03). Finally, the MoCA score in subjects with FSGS or MCD is significantly higher compared the other groups (p<0.05). Conclusion Our data suggest that serum uric acid and proteinuria in glomerular diseases influence cognitive functions. Interestingly, uric acid plays a neuroprotective role, as low levels of uric acid reduce the MoCA score. This result agrees with previous observations of a protective role of uric acid on dopamine neurons. Conversely, the extent proteinuria seems to negatively affect cognitive functions, suggesting a role of the endothelial dysfunction. Finally, glomerulopathies with a lower degree of inflammation (FSGS, MCD) have minor impact on cognitive functions.
Background and Aims The classification of renal diseases is dependent on the evaluation of kidney biopsies using light microscopy techniques. Ultrastructural details (e.g. podocyte foot processes, amyloid fibrils, Fabri's intracellular inclusions) need transmission electron microscopy (TEM) which has high costs, requires specialized personnel and is time consuming. Therefore, alternative techniques are highly desirable. Here we report our experience with scanning electron microscopy (SEM) and atomic force microscopy (AFM). Method Paraffin-embedded kidney sections (3μm thick) were examined after dewaxing and Jones-methenamine methane staining for type IV collagen fibers. Dried urine sediments were prepared using standard methods for urine cytological analysis. Analysis was then performed using atomic force microscopy (nGauge system) on dried specimens and with Scanning Electron Microscopy (Zeiss) after gold-spattering of the surface. Reference images were obtained by standard microscopy. Results The combination of SEM and thin paraffin sections allows the observation of ultrastructural details in kidney biopsies with a very simple and fast preparation. AFM is even faster than SEM, as it does not require any preparation of the surface of the sample. An important advantage of SEM is the possibility to view the sample at low magnification, which makes it easier to identify the location of the glomeruli. It is thus possible to switch from small magnifications (100x) to very extreme magnifications (10000x). Notably, the interpretation of the images requires knowledge of the artifacts induced by paraffin inclusion. Specifically, structures and cells containing lipids (for example foamy cells) appear empty. Chromatin is also condensed in the nuclei around the periphery of the nucleus and in spike structures whit large empty areas. The recognition of nuclei in SEM and AFM is important for the subsequent interpretation of the images. Podocyte pedicles fusion can be identified relatively easily in SEM and in AFM. Both techniques add relevant ultrastructural details of urine sediment cells, from epithelial cells to isolated tubular cells. Also, casts show many ultrastructural features which are not evident in classical optical microscopy. It is also possible to measure the thickness of the basement membrane with great precision both in SEM and with AFM. The major limitation of this approach is the limited experience of pathologists with these methods and the absence of an atlas of normal and pathological kidney. Conclusion Considering the affordable costs of SEM and AFM instruments and the simple preparation of samples for their analysis, these should be considered a valid alternative to TEM. SEM and AFM are alternative methods, simple and relatively cheap and very fast to obtain ultrastructural details of renal biopsies. We thank ANED and AST for the great support given to research.
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