The serum creatinine concentration (Cr) is typically used as a surrogate for renal function. Hence, when increased it is often a sign of acute kidney injury. However, there are circumstances in which an increase in serum creatinine may not reflect true renal pathology. Such is the case with Trimethoprim/sulfamethoxazole (Bactrim/ Septra).
In normal, healthy subjects, about 15% of the urinary creatinine is from proximal tubule secretion.
Creatinine is an organic positively charged molecule (cation) and hence is secreted by the organic cation secretory transporters (OCTs) that can be inhibited/ occupied by other organic cations.
Trimethoprim/sulfamethoxazole (organic cation) can cause a self-limited and reversible increase in serum creatinine (30 to 50 micromol/L) without affecting true renal function by occupying those transporters and preventing proximal tubular secretion.
NOTE: Trimethoprim/sulfamethoxazole contains sulfa moieties and can also acute interstitial nephritis (AIN).
Berg KJ et al. Renal effects of trimethoprim in ciclosporin- and azathioprine-treated kidney-allografted patients. Nephron. 1989;53(3):218-22.
Berglund F, Killander J, Pompeius R. Effect of trimethoprim-sulfamethoxazole on the renal excretion of creatinine in man. J Urol. 1975 Dec;114(6):802-8.
Andreev E, Koopman M, Arisz L. A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible?. J Intern Med. 1999 Sep;246(3):247-52.
Plasma Osmolality: The total solute concentration within a given fluid compartment (Mosm/kg).
Hence it is NOT dependent on temperature and pressure like OsmolaRity. See image.
An effective osmole is one that is UNABLE to cross from the Extracellular fluid (ECF) to the Intracellular fluid (ICF). Therefore it will generate an oncotic force that draws fluid across a membrane.
Effective osmoles include: Na+ and Glucose.
An ineffective osmole will contribute to total plasma osmolality but because it can freely move from the ECF to ICF, it generates no oncotic pressure. A classic example of an ineffective osmole is Urea.
NOTE: Osmolality may be increased in the setting of increased Urea (BUN); but the tonicity will not change because the increased Urea will freely equilibrate between the ICF and ECF.
Bhave G, Neilson EG. Body Fluid Dynamics: Back to the Future. Journal of the American Society of Nephrology : JASN. 2011;22(12):2166-2181. doi:10.1681/ASN.2011080865.
Post hypercapnic alkalosis (PHA) is frequently overlooked as a complication of acutely intubated & mechanically ventilated patients with COPD exacerbations.
HOW DOES IT WORK?
Post hypercapnic alkalosis refers to patients who are hypercapnic (chronic CO2 retainers) and develop a compensatory metabolic alkalosis due to renal bicarbonate (HCO3) retention. After they are intubated, their Pco2 is corrected rapidly, however their chronically elevated bicarbonate remains. This generates a metabolic alkalosis that is typically slow to fall.
B F Palmer and R J Alpern. Metabolic alkalosis. JASN. September 1, 1997 vol. 8 no. 9 1462-1469
Banga A., Khilnani GC. Post-hypercapnic alkalosis is associated with ventilator dependence and increased ICU stay. COPD. 2009 Dec;6(6):437-40.
Cortisol, the primary glucocorticoid in the body binds to glucocorticoid receptors. However, given its molecular similarity to Aldosterone (mineralcorticoid) it can also bind to mineralcorticoid receptors.
Both Aldosterone and Cortisol bind the mineralocorticoid receptors with similar affinities; however, given the vastly more abundant levels of Cortisol in the systemic circulation this could lead to over stimulating of mineralocorticoid receptors.
In order to prevent this, an enzyme, 11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) coverts cortisol to its biologically inactive metabolite cortisone (which is no longer able to bind to mineralocorticoid receptors).
However, Licorice contains glycyrrhetinic acid which inhibits 11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) and allows cortisol to over stimulate mineralcorticoid receptors resulting in mineralocorticoid excess syndrome.
Multi system disorder seen only in patients with CKD (GFR <15; rarely with a GFR of 15–29, but FDA currently warns against using gadolinium-based contrast agents in patients with a GFR <30), acute kidney injury, and after kidney transplantation.
Nephrogenic systemic fibrosis was first recognized in hemodialysis patients during the 1990s and there is a strong link to use of contrast agents containing gadolinium. Incidence is estimated around 1–4% in the highest risk (ESRD) population that has received gadolinium, and lower in patients with less severe kidney dysfunction.
Nephrogenic systemic fibrosis affects several organ systems, including: the skin, muscles, lungs, and cardiovascular system.
The most common manifestation is a debilitating fibrosing skin disorder that can range from skin-colored to erythematous papules, which coalesce to brawny patches. The skin can be thick and woody in areas and is painful out-of-proportion to findings on examination.
Several case reports and series have described benefit for patients after treatment with corticosteroids, photopheresis, plasmapheresis, and sodium thiosulfate. The true effectiveness of these interventions is still unclear.
Daftari Besheli L et al. Current status of nephrogenic systemic fibrosis. Clin Radiol. 2014 Jul;69(7):661–8.
Current Medical Diagnosis & Treatment 2017. Chapter 22: Kidney Disease. Suzanne Watnick; Tonja C. Dirkx.
Schlaudecker JD, Bernheisel CR. Gadolinium-associated nephrogenic systemic fibrosis. Am Fam Physician. 2009 Oct 1;80(7):711-4.
Hydrochlorothiazide (HCTZ) is a thiazide diuretic that acts in the distal convoluted tubule of the kidney on the Na/Cl- symporter to reduce blood pressure/ volume. However, like any medication it comes with side effects. A common mnemonic used to remember these effects is HyperGLUC.
HYPERglycemia (It occurs at higher doses of HCTZ (> 50 mg/d); Thiazides have a weak, dose-dependent, effect to stimulate ATP-sensitive K+ channels and cause hyperpolarization of beta cells, thereby inhibiting insulin release)
HYPERlipidemia (cause a 5–15% increase in total serum cholesterol and low-density lipoproteins (LDLs))