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Why Does Diabetes Damage Blood Vessels?

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How Diabetes Impacts The Liver And Kidneys

Diabetes can cause a great deal of damage to many parts of the body. The eyes, the nerve endings and the blood vessels are all among the body systems at risk when diabetes is present and not well controlled. So are the liver and the kidneys. Liver Damage Liver disease is the 4th leading cause of death for those with type 2 diabetes. Cirrhosis, which is scarring of the liver, often results from the many diseases that are caused by diabetes. Cirrhosis can cause the liver to fail. The liver is a part of the process that manages blood glucose levels. When carbohydrates are consumed they are stored within the liver as glycogen. Later, when the body calls for energy, the liver converts this glycogen to glucose. If there isn’t enough glycogen stored, then the liver has the capacity to turn fats, waste products and amino acids into glucose. The liver is also full of millions of blood vessels, which transport waste products into the liver and nutrients out. These vessels are subject to the same sort of damage from diabetes that happens in other parts of the body: damaged epithelial cells which cause inflammation, hardening of blood vessels and blockage of blood vessels. Among the liver di Continue reading >>

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  1. Daniel Schwartz

    Drugs can negatively impact kidneys in multiple ways
    Interstitial nephritis
    Also called tubulo-interstitial nephritis, this is is when a drug reaction leads to an inflammatory infiltrate in the kidney interstitium (the supporting & connective tissue in the kidney).
    While the most common cause of this abnormality is drugs, it can also be caused by autoimmune disease, infections and other systemic diseases.
    Some of the more commonly implicated agents include:
    NSAIDs (Nonsteroidal anti-inflammatory agents ) eg ibuprofen
    Proton pump inhibitors eg omeprazole
    Penicillins and cephalosporins
    Rifampin
    Diuretics

    Allopurinol
    Damage is minimized by recognizing the drug toxicity, discontinuing the medication and avoiding re-exposure. Specific treatment may be required depending on the clinical scenario.
    Reference:
    Drug-induced Acute Interstital Nephritis: Pathology, Pathogenesis, and Treatment
    Krishnan N, Perazella MA.
    Iran J Kidney Dis. 2015 Jan;9(1):3-13.
    http://qxmd.com/r/25599729
    Tubular injury
    The tubules of the kidney are where molecules are transported and the urine is created. Some drugs can injure these tubules, either quickly or over prolonged exposure. This can result in reduced kidney function.
    Some of the more common offending agents include:
    Aminoglycosides eg gentamicin
    Lithium
    Cisplatin
    Radiocontrast media

    Pentamidine
    Occasionally, drugs such as statins can cause muscular injury (rhabdomyolysis) which results in myoglobin (a muscle protein) being released into the bloodstream and causes kidney tubular injury.
    Damage is minimized by recognizing the drug toxicity and discontinuing the medication.
    Glomerular disease
    Occasionally, medications can negatively impact the filtration units of the kidney (the glomeruli) and lead to severe protein leakage from the kidneys, causing the nephrotic syndrome.
    Some potential renal pathology and the associated drugs include:
    Minimal change disease:
    Nonsteroidal anti-inflammatory drugs
    Pamidronate and other bisphosphates
    Antibiotics (ampicillin, rifampicin, cephalosporins)
    Lithium
    D-penicillamine and tiopronin

    Sulfasalazine and 5-aminosalicylic acid derivatives
    Membranous nephropathy:
    Penicillamine
    Gold

    Nonsteroidal anti-inflammatory drugs
    Damage is minimized by recognizing the drug toxicity and discontinuing the medication.
    References
    Drug-associated glomerulopathies
    Hill GS.
    Toxicol Pathol. 1986;14(1):37-44.
    Secondary minimal change disease
    Glassock RJ
    Nephrol Dial Transplant. 2003;18 Suppl 6:vi52.
    Tubular resistance to ADH
    Water must be reabsorbed from the renal tubules to minimize urine production. The body signals the tubules to reabsorb water via a hormone called ADH. Some drugs can make the renal tubules less responsive to ADH, resulting in large production of urine, known as nephrogenic diabetes insipidus (DI).
    While the most common cause of nephrogenic DI is lithium, other possible drugs include cidofovir, foscarnet, vasopressin V2 receptor antagonists (eg tolvaptan), amphotericin, ifosfamide and orlistat.
    Reference
    Diabetes insipidus: a challenging diagnosis with new drug therapies
    Saifan C et al
    ISRN Nephrol. 2013 Mar 24;2013:797620. doi: 10.5402/2013/797620. eCollection 2013.
    Drug-induced tubular dysfunction of molecular transport
    In additional to transporting water, the kidney tubules are also needed to transport ions & molecules.
    Some drugs can impact this and lead to:
    Phosphate wasting
    Mg wasting
    Salt wasting
    Acid imbalance (renal tubular acidosis)
    Multiple problems in the proximal tubule leading to glucose, phosphate, amino acid and alkali wasting (Fanconi syndrome)

    Rickets
    References
    Drug-induced renal Fanconi syndrome
    Hall AM, Bass P, Unwin RJ.
    QJM. 2014 Apr;107(4):261-9.
    Renal rickets-practical approach
    Sahay M, Sahay R.
    Indian J Endocrinol Metab. 2013 Oct;17(Suppl 1):S35-44.
    Hypomagnesemia: an evidence-based approach to clinical cases
    Assadi F.
    Iran J Kidney Dis. 2010 Jan;4(1):13-9. Review.
    Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies
    Haque SK, Ariceta G, Batlle D.
    Nephrol Dial Transplant. 2012 Dec;27(12):4273-87.
    Pre-renal state
    Kidneys can be negatively impacted when there is decreased blood flow to the kidney. This is referred to as "pre-renal" acute kidney injury as the blood flow comes before the kidney itself (as opposed to "post-renal" problems such as blockages of the ureters or bladder).
    Drugs such as diuretics can deplete the body of salt and water. Drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) can impact kidney blood flow at the microvascular level.
    Vascular injury
    Rarely, kidney injury can occur due to damage at the level of the small blood vessels that feed the kidney. Of the various disease states that can do this, occasionally they can be drug induced.
    Examples:
    Thrombotic microangiopathy: can be induced by drugs such as ticlopidine, clopidogrel, quinine, cyclosporine, chemotherapy and valacyclovir.
    Drug-associated thrombotic microangiopathies
    Kreuter J, Winters JL.
    Semin Thromb Hemost. 2012 Nov;38(8):839-44.
    Cholesterol-emboli syndrome: can rarely be induced by drugs that disrupt atherosclerotic plaques such as warfarin or thrombolytic medication.
    Warfarin-related purple toes syndrome and cholesterol microembolization.
    Hyman BT, Landas SK, Ashman RF, Schelper RL, Robinson RA.
    Am J Med. 1987 Jun;82(6):1233-7.
    http://qxmd.com/r/3605140
    Additional reading
    A couple nice overview papers:
    Drug-induced nephrotoxicity and its biomarkers
    Kim SY, Moon A.
    Biomol Ther (Seoul). 2012 May;20(3):268-72. doi: 10.4062/biomolther.2012.20.3.268.
    Drug-induced impairment of renal function
    Pazhayattil GS, Shirali AC.
    Int J Nephrol Renovasc Dis. 2014 Dec 12;7:457-68. doi: 10.2147/IJNRD.S39747. eCollection 2014. Review.

  2. Leah Pritchett

    disclaimer: I'm writing this late at night, in bed, on my cell phone. My answer is therefore going to be largely based on what I can remember from class. If I misremembered something, feel free to correct me. Also, OP, if you would like actual references, examples, etc, feel free to comment and I'll find some at a more convenient time/location.
    Now, on to the answer...
    From what I can remember, there are two major ways that a drug can damage the kidneys.
    Firstly, the drug could be directly toxic to the cells of the kidney, damaging them in some way. With fewer kidney cells to share the work, the kidneys become more stressed and start to fail.
    Secondly, and I believe this is the more common mechanism, the drug interferes with blood supply to/from the kidney. Since I can't get a lovely picture right now, I'm going to hope that you have a basic working knowledge of nephron anatomy. If not, here's the Reader's Digest version: the kidney filters the blood through small units called the nephron. A blood vessel leads into each individual nephron, which then goes through the glomerulus (a sort of blood vessel meshwork), and then out a collecting blood vessel into the rest of the nephron. The glomerulus acts as the main filter of the blood, and the rest of the nephron mostly controls salt/water balance between the blood and the urine.
    The glomerulus needs a good amount of blood pressure coming in to be able to filter effectively, so to help with that, the blood vessel leading into the glomerulus is much larger in diameter than the one leading out of it. This means a larger blood volume is rushing into the glomerulus than is leaving it. My personal favorite analogy is to imagine a large river running up into a dam of some sort, with only a small stream on the other side. Keeping up the blood pressure allows the glomerulus to do it's job.
    However, the glomerulus is very delicate. Changes in the blood pressure leading into the glomerulus can have huge effects on how well it works. If the blood pressure leading into the glomerulus increases, the delicate blood vessels may experience trauma (imagine our river becoming swollen and flooded, and overwhelming the dam). Alternatively, if the blood pressure leading into the glomerulus is too low, it won't have enough pressure to work properly (imagine our river drying up so that it's about half it's original size, then imagine that the stream on the other side of the dam is now also smaller).
    Because of this, drugs that affect the amount of blood pressure leading into the glomerulus can damage it over time, eventually causing the majority of the filtering units, the nephrons, to fail, which leads to kidney failure.
    An example of this is with NSAID drugs, such as ibuprofen or naproxen. These drugs work by blocking the production of a molecule called prostaglandin in the body. Since prostaglandins contribute to pain and swelling, these drugs are effective pain relievers. However, prostaglandins also contribute to the expanding of blood vessels leading into the kidney. When these drugs block their production, they cause the blood vessels leading into the kidney to be smaller, thereby decreasing the blood flow to the glomerulus. This is bad for kidney function, as we described above. This is why people taking very high doses of these medications over long periods of time have to be careful about monitoring their kidney function.
    It is also important to note that certain medical conditions can exacerbate the nephrotoxic effects of some medications. For example, uncontrolled diabetes can lead to damage of kidney blood vessels over time, which can compound the risk of using drugs which may damage the kidney.
    As far as I know, there really isn't anything we can do to stop it. Some kidney issues are reversible if the drug is stopped, but some are not. This is why clinicians are very careful when selecting and combining drugs that may harm the kidneys, and closely monitoring their function when the need for these drugs is there.

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