Nephrotoxicity creatinine clearance

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Q66 Methotrexate should be avoided in a patient v/ith a creatinine clearance of 12 mL/minute. Methotrexate is an antimetabolite drug that is nephrotoxic. 

Methotrexate is an antimetabolite drug that is excreted primarily by the kidney. It is contraindicated in significant renal impairment and in hepatic impairment. It is nephrotoxic and accumulation may occur in renal impairment. Dose should be reduced in renal impairment that is not severe and drug should be avoided if creatinine clearance is less than 20 mL/minute. 

Renal toxicity - Renal toxicity may be characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria, or evidence of nitrogen retention. Renal damage is usually reversible. The relative nephrotoxicity of these agents is estimated to be Kanamycin = Amikacin = Gentamicin = Tobramycin Streptomycin. 

Serious react ions may include nephrotoxicity (as evidenced by increased thirst, decreased appetite, nausea, vomiting, increased BUN and serum creatinine levels, and decreased creatinine clearance) neurotoxicity (manifested as muscle twitching, visuai disturbances, seizures, and tingiing) and ototoxicity (as evidenced by tinnitus, dizziness, and loss of hearing). 

Nephrotoxicity (as evidenced by increased BUN and serum creatinine levels and decreased creatinine clearance) may be reversible if the drug is stopped at the first sign of symptoms. 

Intravenous cidofovir is effective for the treatment of CMV retinitis and is used experimentally to treat adenovirus infections. Intravenous cidofovir must be administered with high-dose probenecid (2 g at 3 hours before the infusion and 1 g at 2 and 8 hours after), which blocks active tubular secretion and decreases nephrotoxicity. Cidofovir dosage must be adjusted for alterations in the calculated creatinine clearance or for the presence of urine protein before each infusion, and aggressive adjunctive hydration is required. Initiation of cidofovir therapy is contraindicated in patients with existing renal insufficiency. Direct intravitreal administration of cidofovir is not recommended because of ocular toxicity. 

Renal Effects. Occupational exposure to silver metal dust has been associated with increased excretion of a particular renal enzyme (N-acetyl-p-D glucosaminidase), and with decreased creatinine clearance (Rosenman et al. 1987). Both of these effects are diagnostic of marginally impaired renal function. However, the workers in this study were also exposed to cadmium, which was detected in the urine of 5 of the 27 workers studied. Cadmium is known to be nephrotoxic differentiation of the effects of the two metals in the kidney is not possible with the data presented. Therefore, no conclusion can be drawn regarding renal effects of silver based on this study. 

Unfortunately, urea and creatinine will not be outside the normal range until 60% of total kidney function is lost. Hence, creatinine clearance is a more accurate measure and is used whenever renal disease is suspected or careful dosing of nephrotoxic drugs is required. 

IFOSFAMIDE CISPLATIN t risk of neurotoxicity, haematotoxicity and tubular nephrotoxicity of ifosfamide due to t plasma concentrations of ifosfamide Cisplatin tends to cause renal damage, which results in impaired clearance of ifosfamide Do renal function tests before initiating therapy and during concurrent therapy, and adjust dosage based on creatinine clearance values. Advise patients to drink plenty of water -vigorous hydration - and consider mesna therapy for renal protection... 

Experimental exposiue of neomycin in calves has reported both nephrotoxicity and ototocity (demonstrated clinically). The clinical pathological observations included granular casts in urine, proteinuria and low specific gravity, azotemia, decreased creatinine clearance, polyuria, and polydipsia. The histopathological findings included renal tubular epithelial degeneration and necrosis (Crowell et al, 1981). 

Careful tailoring of the dose can prevent nephrotoxicity. In 89 critically ill patients with a creatinine clearance over 30 ml/minute who were treated with gentamicin or tobramycin 7 mg/kg/day independent of renal function, with subsequent doses chosen on the basis of the pharmacokinetics of the first dose, signs of renal impairment occurred in 14% in all survivors renal function recovered completely and hemofiltration was not needed (104). 

The safety and efficacy of amphotericin colloidal dispersion have been evaluated in 148 immunocompromised patients with candidemia (20). ABCD was given intravenously in a median daily dose of 3.9 (range 0.1-9.1) mg/kg for a median of 12 (range 1-72) days. In the safety analysis (n = 148 patients), nephrotoxicity occurred in 16% of the patients, with either doubling of the baseline serum creatinine concentration or an increase of 88 pmol/l (1.0 mg/dl) or a 50% fall in calculated creatinine clearance. Severe adverse events were believed to be probably or possibly related to ABCD in 36 patients (24%), including chills and fever (9.5%), hypotension and abnormal kidney function (4%), tachycardia, asthma, hypotension (3%), and dyspnea (2%). ABCD was withdrawn in 12%... 

The safety and efficacy of ABCD have been stndied in 220 bone marrow transplant recipients enrolled in the same five phase I or phase II stndies (23). The median dose in this population was 4 (range 0.4—8.0) mg/kg, and the median duration of treatment was 16 (range 1-409) days. Overall, 37 (19%) of the patients had nephrotoxicity, defined as a doubling of serum creatinine from baseline, an increase of 88 pmol/l from baseline, or at least a 50% fall in calculated creatinine clearance. There were no significant changes in hepatic transaminases, alkaline phosphatase, or total bilirubin. Fever and chills were reported by 12 and 11% of patients respectively. Other acute, severe, infusion-related adverse events were hypoxia (4.1%), hypertension (2.7%), and hypotension (2.7%). 

Amphotericin-associated nephrotoxicity has been studied in a retrospective analysis of 69 recipients of blood stem-cell transplants with multiple myeloma who received at least two doses of amphotericin deoxycholate during 1992-95 (111). Nephrotoxicity occurred in 30 patients (43%) and developed rapidly. Patients who developed nephrotoxicity were similar to those who did not in many aspects associated with their treatment. However, baseline-estimated creatinine clearance, ciclosporin therapy, nephrotoxic drug therapy within 30 days of starting amphotericin, and the number of concomitant... 

Alterations in creatinine clearance or acute renal insufficiency occur in 10-20% of patients with AIDS receiving intravenous foscarnet (11), due to acute tubular damage. Severe renal insufficiency can be prevented in most cases by careful hydration before and during therapy (12). To minimize the residual incidence of nephrotoxicity, the dose of foscarnet should be frequently recalculated, based on the estimated creatinine clearance. 

A full course of gentamicin therapy causes nephrotoxicity in 1-55% of patients. Two types of gentamicin-induced nephrotoxicity are recognized (1) a gradual reduction in creatinine clearance, occurring after about 2 weeks, in about 5-10% of patients receiving the drug in full doses. 

The clinical and biological tolerance of iobitridol (Xenetix, a non-ionic medium, osmolality 915 mosmol/ kg at an iodine concentration of 350 mg/ml) has been assessed in a placebo-controlled study in 21 patients with chronic renal insufficiency (glomerular filtration rate less than 60 ml/minute) (170). Serum creatinine and creatinine clearance remained stable 24 and 48 hours after the procedure. No patient had a nephrotoxic reaction or acute oliguria. Only one patient given iobitridol had an increase in serum creatinine of more than 15% from baseline the serum creatinine normalized within 4 days of contrast administration. One patient given placebo had... 

The protective effects of intravenous hydration alone (0.45% isotonic saline, 1 ml/kg/hour for 12 hours before and 12 hours after contrast administration), fenoldopam (0.1 microgram/kg/minute for 4 hours before and 4 hours after the procedure), and acetylcysteine (600 mg bd 24 for hours before and 24 hours after the procedure) have been compared in preventing contrast nephrotoxicity after intravascular administration of low-osmolar non-ionic contrast medium (199). The incidence of nephrotoxicity was 15% in the hydration group, 16% in the fenoldopam group, and 18% in the acetylcysteine group. AU the groups were comparable and basehne creatinine clearance was about 60 ml/minute in aU the patients who received a similar dose of the contrast medium (1.5 ml/ kg). The authors concluded that fenoldopam and acetylcysteine do not offer extra protection against contrast nephrotoxicity over hydration alone. 

There was a profonnd rednction in renal fnnction associated with very long-term parenteral nntrition (continning for periods longer than 10 years) in 29 of 33 patients stndied a rednction in estimated creatinine clearance of 0.6-15.4% per year (110). Tnbnlar fnnction, as determined by the tnbnlar reabsorption of phosphate, was impaired in 52%. Althongh nephrotoxic dmg nse, bacteremia, fnngemia, age, and infection rate acconnted for part of the dechne in renal fnnction, most of it was nnexplained. 

Because of nephrotoxicity (oliguria, cylindruria, and reduced creatinine clearance, with crystal deposits in renal tubules and interstitial tissue) (4) phenazopyridine should not be used in patients with suspected renal disease and insufficiency, or in patients with glucose-6-phos-phate dehydrogenase deficiency. Bladder stones have also been described (5). 

Cisplatin-induced nephrotoxicity can be detected by a rise in blood urea or by a fall in creatinine clearance. Tubular dysfunction can cause hyponatremia (72), hypokalemia, hypomagnesemia (173), and hjrpophosphatemia. Inappropriate ADH secretion may be partly responsible for hjrponatremia (191). 

---