The Application of Nanoparticles in Diagnosis and Treatment of Kidney Diseases

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Introduction

Nanomedicine is currently demonstrating considerable potential for new diagnostic and treatment methods for a variety of ailments, including kidney disease and transplantation. The diversity of size effects employed to develop tailored nanoparticles for certain cells or tissues, taking renal clearance and tubular secretion systems into account, gives nanoparticles their unique features. Surface particle design on nanoparticles opens up a wide range of possibilities, with antibodies playing a key role. Nanoparticles are used in encapsulated drug delivery systems containing immunosuppressants and other medications, as well as imaging, gene therapy, and a variety of other medical fields. They have the potential to revolutionise kidney transplantation by reducing and preventing ischemia–reper-fusion injury, delivering drugs to the graft site more efficiently. They avoid systemic effects, accurately localising and visualising the diseased site, and enabling continuous graft function monitoring. There are nanoparticles that have been found to have no hazardous effects on human tissue, but more research is needed to ensure their safety.

Materials and Methods

The literature search was performed by two authors. We found about 9000 records that were screened by the authors. We included 162 papers, which were mainly the newest ones but which specifically concerned kidneys and kidney transplantation. Abstracts in a language other than English were excluded. Publication review included deceased and live donor types, cellular, animal and human studies. Prospective and retrospective clinical studies including center studies, meta-analyses and review articles were included. Formal institutional review board (IRB) approval for this study was not required. The search strategy is presented in Figure 1.

Medical Applications of Nanomaterials

With technological advancement and new clinical trials, the indications for using NPs in this field are constantly expanding. Small size, shape, unique mechanical, electrical and optical properties, as well as a large variety of NP formulations allowed for their extensive use in many fields of medical science (Figure 2).

Nanoparticles in Diagnosis and Treatment of Kidney Diseases

Monitoring of Kidney Function and Structure

NPs can be used in CT imaging as contrast to assess renal fibrosis. Fibrosis is central to ischaemic renal damage caused by renal artery stenosis. No significant changes in haematology, electrolyte, liver and kidney function were observed aßer injection of gold NPs. Nanocarriers are light chains on the surface that interact with membrane protein megalin. Megalin expression was demonstrated not only in the primary tumour but also in lymph node metastases. NPs showed no renal toxicity in the mice tested and excreted by the kidney without signs of toxicity.

Potential Therapeutic Application

Midgley et al. investigated the utility of NPs in delivering anti-fibrotic therapies to damaged cells and tissues. They conducted the study on mice with a narrowed ureter. The mice were administered plasmid DNA expressing bone morphogenetic protein 7 or hepatocyte growth factor by encapsulation within chitosan NPs coated with hyaluronan. The eRect of the NPs included improved renal function and halted progression of chronic kidney disease by eliminating the accumulation of collagen fibres, revers- ing fibrosis and regenerating renal tubules. Iron oxide NPs bind rapidly to the endothelium and can deliver drugs and imaging agents. Vascular cell adhesion molecule-1 (VCAM-1) expression increases in the kidney ischemia–reperfusion injury. Drug delivery systems can overcome the previous prob- lems of tailoring the pharmacological profile of the drug load. A rapidly growing branch of nanotechnology is cancer diagnosis and treatment. Nanomaterials can release drugs in a controlled manner and target renal cells. Fluorophores on the surface of NPs can emit separate and intense fluorescence to kidney cancer cells. Such NPs are anchored to the cancer tumour using an antibody that binds to antigens on its surface.

Nanoparticles in Kidney Transplants

After organ transplantation, the main clinical problem is rejection, which requires lifelong immunosuppression, accompanied by susceptibility to infections and cancer. One of our works describes the potential use of cell-free DNA in monitoring patients aßer transplantation.There is also a necessity for proper qualification of donors and prediction of graß function aßer kidney transplantation (KTx).

Prevention of Transplant Rejection

Currently, the gold standard for assessing kidney func- tion is an invasive biopsy. Non-invasive markers are needed to allow continuous monitoring of transplanted organ function. NPs hold promise for replacing cell-based therapies due to their reproducibility, ease of storage and lower cost. Thrombin-targeted perfluorocarbon NPs (PFC-NP) protect against ischaemic kidney damage aßer transient arterial occlusion. Another method using NPs for tolerance includes hybrid models using synthetic molecules coated with cell-derived components. Control of immune-activating factors to improve trans- plant outcomes is essential. Targeted delivery of immu- nosuppressive drugs to the lymph nodes can alleviate graß rejection. NPs can improve drug solubility in water, increase circu- lation time, decrease systemic toxicity and increase accumulation in the diseased site. NMP increases the number of available organs for transplantation by resus- citating organs that could be rejected. The delivery by machine perfusion of drugs that act directly on vascular ECs is a major goal for treating and reducing perioperative damage to ECs. Studies also demonstrated the therapeutic potential for targeted NP delivery during NMP.

Monitoring Patients after KTx

The Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group recommends main- taining immunosuppressive therapy for 8–16 weeks aßer KTx on the condition of no rejection. The KDIGO 2009 recommendations state that tacroli- mus should be the first-choice drug to prevent rejection. It reduces the incidence of AR in the first year aßer KTx.

Conclusions and Future Directions

Our work summarises the findings to date of nanomedi- cine in nephrology, but also in kidney transplantation. NPs are a very promising form of kidney disease therapy and diagnostics. Non-invasive markers are expected in nephrological and kidney transplant societies to avoid invasive biopsy of one’s own or transplanted kidney. NPs should allow for earlier diagnosis of kidney injuries, which should help to avoid dialysis or prolong trans- plant survival. Calcineurin inhibitors (CI) should be started before or during KTx. If acute cellular rejection occurs corticoste- roids are recommended as initial treatment . KTx recipi- ents should be monitored aßer surger (Figure 3). NPs provide valuable information by targeting specific diseased sites, which is superior to other diagnostic and therapeutic methods. Studies to date report that NPs show no toxicity, display durability and are relatively easy to produce. The broad potential of NP designs represents the future of kidney transplantation, for which selective action on the immune system, assessment of transplanted organ function and damage detection are critical. However, data on the toxicity and efficacy of NPs are insufficient and further studies are required. References
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