Abstract
MicroRNAs (miRNA) are endogenously produced short non-coding regulatory RNAs that can repress gene expression by posttranscriptional mechanisms. They can therefore influence both normal and pathological conditions in diverse biological systems. Several miRNAs have been detected in kidneys where they have been found to be crucial for renal development and normal physiological functions as well as significant contributors to the pathogenesis of renal disorders such as diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and others due to their effects on key genes involved in these disease processes. miRNAs have also emerged as novel biomarkers in these renal disorders. Due to increasing evidence of their actions in various kidney segments, in this mini-review, we discuss the functional significance of altered miRNA expression during the development of renal pathologies and highlight emerging miRNA-based therapeutics and diagnostic strategies for early detection and treatment of kidney diseases.
Introduction microRNAs (miRNAs/miRs) are a unique class of short (∼22 nucleotides) single stranded endogenous noncoding RNAs (7, 8). miRNAs contain nucleotide sequences complementary to binding sites on the 3′ untranslated regions (3′ UTRs) of protein-coding messenger RNA (mRNA) transcripts. Through direct binding to the mRNA 3′-UTRs, miRNAs can induce repression of target gene expression (57). Individual miRNAs can often engage
Chronic kidney disease (CKD) is a worldwide problem that is currently three times higher for African Americans, Hispanics, Pacific Islanders, American Indians and seniors (The National Kidney Foundation, 2013). CKD occurs when the kidneys are damaged by a pathogen or injury and they can no longer adequately maintain proper levels of regulated chemicals in the bloodstream. There are many risk associated with CKD. According to the National Kidney Foundation, two of the major risks are Chronic Renal Failure (CRF) and Cardiovascular Disease. Currently twenty million American adults have CKD and millions of others are at increased risk. Age has no barrier on getting CKD. People with pre-existing health issues, and a part of certain population
Ms. S.M. was a patient admitted for the management of renal failure. During morning rounds, we noticed her potassium levels to be elevated. She was asymptomatic and her EKG did not show any abnormal changes. As a team, we coordinated with each other and successfully managed her potassium levels. The hours spent to manage this patient helped me to understand the importance of clear communication and the dynamics of team work in a hospital setting. Though we managed her hyperkalemia, the patient was still facing an uncertain prognosis with her kidney disease. Her family members were worried about providing financial support for her care, which is a major problem in India. It made me wonder if there was anything more we could do for her. However, along with providing clinical care, establishing a relationship with her and her son gave me a sense of satisfaction. It made me realize the potential of developing long term relations with my patients in this field.
MiR-21 has been found to be over expressed in 20 pancreatic carcinoma tissues and cell lines compared to normal tissue or cell lines. (15)
Acute renal failure is the most common kidney disease that exists today. It occurs when blood flow to the kidneys is in some way compromised which causes a sudden stop in kidney function. Acute renal failure is a very serious complication for a already hospitalized patient since they are already in a vulnerable state from staying in the hospital, in fact, it is the most common cause of death amongst hospitalized patients, and most commonly they occur because of a hospital workers error. Acute renal failure causes many serious problems for patients, including abnormal electrolyte and acid-base balance, excess in fluid volume, and an excess in nitrogenous wastes.
The kidneys are essential towards the human body; They maintain fluid, electrolyte and acid-base balance. Also, they excrete waste products, like urine, help control blood pressure, and blood cell production. The nephrons inside the kidneys, responsible for removing waste products, can become damaged. Thus, will be the start of kidney disease. Chronic Kidney Disease is constant nephron damage for several years. In Addition to the damage of the nephrons there’s a decrease in glomerular filtration rate (GFR). GFR is a test that measures how well your kidneys are working. One of the major causes of CKD is diabetes and hypertension. (Silberberg, 2015) If CKD progress without the proper medical help, it will result to kidney failure and a transplant or dialysis may be necessary. Along with all other diseases, kidney diseases have a negative effect on metabolism, nutritional status and nutritional requirements. Patients with chronic kidney disease should limit their intake on protein, sodium, potassium, calcium and phosphorus (Dudek., 2014) The purpose of this paper is to discuss the macro and micronutrients important to prevent chronic kidney disease.
Dialysis is a life-saving treatment for adults and children with acute and chronic kidney failure. While it is a life-saving treatment, it can also be life threatening. There are steps and precautions that a healthcare professional must take when assisting a patient with the initiation of dialysis treatment. Patients must also take personal precautions. Training is provided to patient care technicians, nurses and other direct patient care staff. This is to ensure the safety of the patients by having knowledgeable and educated staff. Patients are also trained on certain aspects of the treatment to ensure they receive proper care.
According to the Centers for Disease Control and Prevention (CDC), diabetes and hypertension are the leading causes of kidney failure in the United States. In 2011, approximately 44% of new cases of kidney failure, as a primary diagnosis, were attributed to diabetes with an additional 28% attributed to hypertension. Adults with diabetes, hypertension, or both have a higher risk of developing CKD than those without these diseases. (CDC, 2014)
We have also noticed, the absence of miR-4792, miR-4485-3p, miR-4532 and miR-486-5p in our Ago2-complex, compared to total cellular miRNA profile. No proper signal was detected, using NB. These miRNAs might be part of transfer RNA, or associated with other type of Ago protein, or could be a degraded tRNA product. The function of aforementioned potential miRNAs should be investigated in more details. Mir-221-3p and miR-155-5p were induced in U2932-EBV cells, compared to U2932 cell line. These results were consistent with Lawrie et al. data [137]. Mir-221-3p was not detected in neither of SUDHL5-EBV or SUDHL5 cell line.
Renal Failure is a common condition that could also be described as Acute renal failure (ARF) or Chronic renal failure(CRF), both conditions occur when there is a loss of kidney function. Kidney disease or renal failure is the ninth leading cause of death in the United States (Pradeep ,2014). Specifically, acute renal failure is characterized by the kidney’s sudden inability to filter blood, excrete wastes, concentrate urine, preserve electrolytes, and sustain fluid balance which leads to many problems in the human body. Acute renal failure alone is a frequent clinical problem, especially in the intensive care unit, where according to Clin (2004), “is associated with mortality of between 50% and 80%” (p5). As for the pathophysiology
Diabetic nephropathy, an irreversible kidney failure, continues to be the most common cause of end stage renal disease requiring either a kidney transplant or renal replacement therapies, such as dialysis (Bilous, 2013). Worldwide, approximately fifty percent of cases of end-stage chronic kidney disease are caused by diabetes mellitus, with type II comprising the majority (Vladu, 2014). The prevalence of diabetes has been estimated to increase worldwide with the total number of diabetics rising from 285 million in 2010 to 439 million in 2030 (Mantelo, Oliveira, Ferraz, Lima, & Silva, 2015). This rise in diabetes is a concern to public health, as the effects of diabetes can have life altering consequences.
Diabetic nephropathy (DN) is one of the leading causes of chronic kidney diseases worldwide and most of the affected patients have T2DM. A considerable number of patients newly diagnosed with T2DM may already have developed nephropathy due to a preceding period of undiagnosed diabetes and impaired glucose tolerance [11]. According to the classification of American Diabetes Association, DN is divided into three stages, incipient nephropathy (micro-albuminuria), clinical diabetic nephropathy (macro-albuminuria) and ESRD. To diagnose those DN patients in its early stage can effectively prevent or delay the progression to ESRD [12]. Renal biopsy is a useful way to diagnose DN but is an invasive method so we are in need to simple, accurate and non-invasive test for early diagnosis and/or monitoring DN progression [13]. Several mechanisms, including hyperglycemia, advanced glycation end products (AGEs), oxidative stress, and inflammation are the main contributors to DN pathogenesis through activation of nuclear factor κB (NF-κB) signaling which is the key regulator of inflammation and apoptosis [14].
One of the diseases is diabetes mellitus which is a major cause of renal failure. This disease can be defined as an increase of fasting blood glucose that is affected by a deficiency in insulin hormone. The normal range for glucose (fasting) in the blood is 2.8-6.0 mmol/L. It is classified into two groups, type 1 (insulin-dependent diabetes mellitus) and type 2 (non insulin-dependent diabetes mellitus). Stein (2008, p.6) points out that kidney failure happens most often when patients have suffered from diabetes mellitus for more than 10 years. According to United States Renal Data System (USRDS) report in 2007, approximately 44% of primary causes of renal failure is diabetes mellitus in the United States in 2005. Also, Stein (2008) indicates that 15% of dialysis patients are influenced by diabetes mellitus in the United Kingdom. Diabetes mellitus has negative affects throughout the kidneys where the increase of the range of blood sugar causes the damages to the cells in the kidneys. This leads to the presence of the glucose in the urine which is known as glycosuric.
miRs constitute a large class of phylogenetically conserved single-stranded RNA molecules of 19 to 25 nucleotides that are implicated in post-transcriptional gene silencing. They arise from exonic and intronic genomic regions that are transcribed by RNA polymerase II as long primary RNA transcripts. These primary transcripts undergo processing steps that produce a short “mature” molecule. Approximately 70-bp precursor miR product is processed by the enzymes Drosha and Dicer in conjuction with DGCR8/Pasha to
To understand what renal failure is, it is important to know how the kidneys work and what the main functions are. The body has two kidneys on either side of the spine and the kidneys work to remove toxic waste and excess water by producing urine. The kidneys also help with controlling blood pressure and produce erythropoietin as well as aiding in keeping bones strong by producing calcetrol hormones. When the kidneys are unable to perform these functions it causes the kidneys to fail.
About 1 % of the genome encodes for miRNA, and it is estimated that about one third of all human genes might be targeted by miRNAs. MiRNAs are transcribed from either intronic (coding and non-coding), or exonic regions of the genome. The primary transcription is typically several kilobases long with (a) hairpin structure(s) that contain(s) either one miRNA or a cluster of miRNA hairpin structures, as shown in Figure 1[31, 36, 37].