Deranged renal function

Many centres prefer to avoid using NSAIDs in any patient with liver disease because of their side-effect profile. However, if the liver disorder is purely cholestatic in origin and the disease has not progressed to cirrhosis and portal hypertension, NSAIDs may be an option. Any risk-benefit assessment should consider the potential risk of hepatotox-icity, albeit rare. There are no specific contraindications in this patient because they are not cirrhotic, do not have deranged clotting, and are unlikely to be at increased risk of deteriorating renal function. If deemed necessary an NSAID could be used cautiously. 

The phase of primary respiratory alkalosis rarely is recognized in children with salicylate toxicity. They usually present in a state of mixed respiratory and renal acidosis, characterized by a decrease in blood pH, a low plasma bicarbonate concentration, and normal or nearly normal plasma PCO2. Direct salicylate-induced depression of respiration prevents adequate respiratory hyperventilation to match the increased peripheral production of CO2- Consequently, plasma PCO2 increases and blood pH decreases. Because the concentration of bicarbonate in plasma already is low due to increased renal bicarbonate excretion, the acid-base status at this stage essentially is an uncompensated respiratory acidosis. Superimposed, however, is a true metabolic acidosis caused by accumulation of acids as a result of three processes. First, toxic concentrations of salicylates displace 2-3 mEq/L of plasma bicarbonate. Second, vasomotor depression caused by toxic doses of salicylates impairs renal function, with consequent accumulation of sulfuric and phosphoric acids. Third, salicylates in toxic doses may decrease aerobic metabolism as a result of inhibition of various enzymes. This derangement of carbohydrate metabolism leads to the accumulation of organic acids, especially pyruvic, lactic, and acetoacetic acids. 

Microalbuminuria in healthy subjects is associated with atherosclerotic risk factors such as increased systolic and diastolic blood pressure (BP) decreased Apo A1 and HDL-C levels (12). Minor derangements of renal function are associated with an increase in CVD risk factors and promote progression of atherosclerosis (reviewed in ref. 14). However, in a separate study in contrast to BP, body mass index (BMl), and triglycerides (TGs), there was no relation between urinary albumin excretion and flow-mediated vasodilation in apparently healthy subjects. This suggests that the presence of atherogenic risk factors precedes the development of endothelial dysfunction in microalbuminuric but otherwise healthy subjects (75). 

Carnitine is present in biological systems as both carnitine and acylcarnitines generated in tissues (see next section). Carnitine deficiency may be a primary defect due to a genetic defect in carnitine transport systems or may be secondary to other metabolic derangements. Normal carnitine homeostasis requires reabsorption of carnitine in the renal tubule via a specific transport protein. This same transport protein is responsible for the accumulation of carnitine in heart and skeletal muscle. If this transport system is not functional, then carnitine cannot reach tissues, and primary carnitine... 

It is almost impossible to individualize the exact role of CSA-induced chronic nephrotoxicity in renal allograft outcomes. From the moment of implantation, the transplanted kidney will suffer from mechanical manipulation, ischemic injury and immunologic attack. Later on acute rejection, recurrent or de novo renal disease, hypertension, chronic viral infection, metabolic derangements (dyslipidemia, diabetes, and hyperuricemia), chronic rejection and aging may work in various combinations causing progressive structural damage and functional impairment. 

Figure 8 Slices through the median planes of 3D 300 MHz T2W images (TE = 6.5 ms, TR = 1.5 s, multiecho segmerttatlon, or RARE, factor = 32, TEeffeotive = 104 ms) of kidneys from a control rat (A), and from rats treated with an inner cortical (B) and papillary (C) toxin. Note the clear differentiation in the control kidney between cortex, medulla and papilla, and also the good definition of perirenal fat and adrenal glands. Note also the evolution of a hyperintense band in the cortical toxin-treated kidney reflecting derangement of renal tubular function and water buildup in this region. The papillary toxin evokes a loss of papillary-medullary contrast. Marked swelling of both treated kidneys is also obvious and easily quantifiable.

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