Glomerular filtration impairment

In the kidney, ANG II reduces renal blood flow and constricts preferentially the efferent arteriole of the glomerulus with the result of increased glomerular filtration pressure. ANG II further enhances renal sodium and water reabsorption at the proximal tubulus. ACE inhibitors thus increase renal blood flow and decrease sodium and water retention. Furthermore, ACE inhibitors are nephroprotective, delaying the progression of glomerulosclerosis. This also appears to be a result of reduced ANG II levels and is at least partially independent from pressure reduction. On the other hand, ACE inhibitors decrease glomerular filtration pressure due to the lack of ANG II-mediated constriction of the efferent arterioles. Thus, one important undesired effect of ACE inhibitors is impaired glomerular filtration rate and impaired kidney function. 

Furosemide and ethacrynic acid preserve glomerular filtration rate and are, therefore, the diuretic agents of choice in hypertensive patients with impairment of kidney function(17,18,... 

These results suggest acute renal failure (ARF) due to tubular necrosis caused by phenol. Plasma sodium is low due mainly to impaired reabsorption in the nephron, although the slightly low albumin suggests haemodilution possibly as a result of excessive i.v. fluids. Potassium is raised due to poor exchange with sodium in the distal tubule and the acidosis (low pH and low bicarbonate concentration) arises from defective acidification of the glomerular filtrate acidosis is often associated with hyperkalaemia (raised plasma... 

Plasma volume and the extracellular fluid space have been observed to constrict 30% during reducing diets (300-600 calories per day) (B22). These changes can be accompanied by functional impairment of glomerular filtration and hepatic perfusion with transient increases up to 2 mg/100 ml in serum creatinine and BSP retention up to 40% (B22). In rare instances a significant fall in serum calcium, magnesium, or potassium was observed. Hyperuricemia was also observed, with concentrations as high as 9 mg/100 ml (B22). 

Renal function impairment No changes were observed in the pharmacokinetics of dipyridamole or its glucuronide metabolite with creatinine clearances ranging from approximately 15 mL/min to more than 100 mL/min if data were corrected for differences in age. Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10 mL/min). 

Renal function Impairment Edema may occur in the presence of renal disease with a fixed or decreased glomerular filtration rate. 

Renal function impairment In hypertensive patients with normal kidneys who are treated with hydralazine, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate. Renal function may improve where control values were below normal prior to administration. Use with caution in patients with advanced renal damage. 

Renal impairment - Some degree of renal impairment may be present in patients with gout. A daily dosage of 1 g may be adequate. However, if necessary, the daily dosage may be increased by 0.5 g increments every 4 weeks within tolerance (usually not more than 2 g/day) if symptoms of gouty arthritis are not controlled or the 24 hour urate excretion is not more than 700 mg. Probenecid may not be effective in chronic renal insufficiency, particularly when the glomerular filtration rate is 30 mL/minute or less. 

Renal function Impairment- Ceftazidime is excreted by the kidneys, almost exclusively by glomerular filtration. In patients with impaired renal function (glomerular filtration rate (GFR) less than 50 mL/min), reduce dosage to compensate for slower excretion. In patients with suspected renal insufficiency, give an initial loading dose of 1 g. Estimate GFR to determine the appropriate maintenance dose. 

Toxicity Aminoglycosides are associated with significant nephrotoxicity or ototoxicity. These agents are excreted primarily by glomerular filtration thus, the serum half-life will be prolonged and significant accumulation will occur in patients with impaired renal function. Toxicity may develop even with conventional doses, particularly in prerenal azotemia or impaired renal function. 

Concurrent immunosuppressants Sirolimus has been administered concurrently with cyclosporine and corticosteroids. The efficacy and safety of the use of sirolimus in combination with other immunosuppressive agents have not been determined. Renai function impairment Mean serum creatinine was increased and mean glomerular filtration rate was decreased in patients treated with sirolimus and cyclosporine compared with those treated with cyclosporine and placebo or azathioprine controls. Monitor renal function during the administration of maintenance immunosuppression regimens including sirolimus in combination with cyclosporine, and consider appropriate adjustment of the immunosuppression... 

Dosage adjustments - In renal transplant patients with severe chronic renal impairment (glomerular filtration rate [GFR] less than 25 mL/min per 1.73 m ) outside the immediate posttransplant period, avoid dosages of mycophenolate greater than 1 g administered twice a day. 

Elevated BUN and serum creatinine It is not unusual for serum creatinine and BUN levels to be elevated during cyclosporine therapy. These elevations in renal transplant patients do not necessarily indicate rejection, and each patient must be fully evaluated before dosage adjustment is indicated. These increases reflect a reduction in the glomerular filtration rate. Impaired renal function at any time requires close monitoring, and frequent dosage adjustments may be indicated. The frequency and severity of serum creatinine elevations increase with dose and duration of cyclosporine therapy. These elevations are likely to become more pronounced without dose reduction or discontinuation. 

The hemodynamic effects of diazoxide are similar to those of hydralazine and minoxidil. It produces direct relaxation of arteriolar smooth muscle with little effect on capacitance beds. Since it does not impair cardiovascular reflexes, orthostasis is not a problem. Its administration is, however, associated with a reflex increase in cardiac output that partially counters its antihypertensive effects. Propranolol and other -blockers potentiate the vasodilating properties of the drug. Diazoxide has no direct action on the heart. Although renal blood flow and glomerular filtration may fall transiently, they generally return to predrug levels within an hour. 

The major route of fluoride excretion is via the kidney and urine 40-60% of the daily intake is excreted in the urine with an elimination half-life of about 5 h [17,85]. Fluoride excretion is influenced by a number of factors, including glomerular filtration rate, urinary flow and urinary pH. The excretion of fluoride in urine is reduced in individuals with impaired renal function. Urine fluoride excretion is 0.79 mg/day in humans with normal renal function, 0.53 mg/day in those with questionable and 0.27 mg/day in those with impaired renal function [86],... 

Effect on kidney In deficiency of glucocorticoids, the glomerular filtration rate is impaired. 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

Administration of ANP produces prompt and marked increases in sodium excretion and urine flow. Glomerular filtration rate increases, with little or no change in renal blood flow, so that the filtration fraction increases. The ANP-induced natriuresis is due to both the increase in glomerular filtration rate and a decrease in proximal tubular sodium reabsorption. ANP also inhibits the secretion of renin, aldosterone, and vasopressin these changes may also increase sodium and water excretion. Finally, ANP causes vasodilation and decreases arterial blood pressure. Suppression of ANP production or blockade of its action impairs the natriuretic response to volume expansion, and increases blood pressure. 

Depending on the concentration, volatile anesthetics decrease the glomerular filtration rate and renal blood flow, and increase the filtration fraction. Since renal blood flow decreases during general anesthesia in spite of well-maintained or even increased perfusion pressures (due to increased renal vascular resistance), autoregulation of renal flow may be impaired by these drugs. 

Gastrointestinal ulceration may occur less frequently than with some other NSAIDs. A preparation combining diclofenac and misoprostol decreases upper gastrointestinal ulceration but may result in diarrhea. Another combination of diclofenac and omeprazole was also effective with respect to the prevention of recurrent bleeding, but renal adverse effects were common in high-risk patients. Diclofenac, 150 mg/d, appears to impair renal blood flow and glomerular filtration rate. Elevation of serum aminotransferases occurs more commonly with this drug than with other NSAIDs. 

Renal system Mild polyuria increased renal blood flow increased glomerular filtration rate Impaired water excretion decreased renal blood flow decreased glomerular filtration rate... 

Cortisol deficiency results in impaired renal function (particularly glomerular filtration), augmented vasopressin secretion, and diminished ability to excrete a water load. 

Flucytosine is currently available in North America only in an oral formulation. The dosage is 100-150 mg/kg/d in patients with normal renal function. It is well absorbed (> 90%), with serum concentrations peaking 1-2 hours after an oral dose. It is poorly protein-bound and penetrates well into all body fluid compartments, including the cerebrospinal fluid. It is eliminated by glomerular filtration with a half-life of 3-4 hours and is removed by hemodialysis. Levels rise rapidly with renal impairment and can lead to toxicity. Toxicity is more likely to occur in AIDS patients and those with renal insufficiency. Peak serum concentrations should be measured periodically in patients with renal insufficiency and maintained between 50 and 100 mcg/mL. 

Patients with renal diseases leading to the nephrotic syndrome often present complex problems in volume management. These patients may have reduced plasma volume in conjunction with reduced plasma oncotic pressures, especially those with "minimal change" nephropathy. In these patients, diuretic use may cause further reductions in plasma volume that can impair glomerular filtration rate and may lead to orthostatic hypotension. However, most other causes of nephrotic syndrome are associated with a primary retention of salt and water by the kidney, leading to expanded plasma volume and hypertension despite the low plasma oncotic pressure. In these cases, diuretic therapy may be beneficial in controlling the volume-dependent component of hypertension. In choosing a... 

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