Severe renal failure

Hyperoxaluria type 1 is due to functional efficiency of the liver specific peroxisomal enzyme alanine-glyoxylate aminotransferase. It leads to severe renal failure. The nervous system is not affected. 

The absorption and excretion of carbenicillin in man has been reported [396]. The antibiotic is not absorbed intact from the gut intramuscular injection (which is painful) often provides adequate serum levels (approximately 20 Mg/ntl) but infections with Pseudomonas strains having minimum inhibitory concentrations up to, or higher than, 100 Mg/ml require intravenous thbrapy to achieve such levels. No evidence of active metabolite formation has been obtained. Marked reductions in the half-life (and serum levels) of carbenicillin follow extracorporeal dialysis or peritoneal dialysis, the former producing the most striking effect [397]. These results were, of course, obtained in patients with severe renal failure. Patients with normal renal function rapidly eliminate the drug but, as with all penicillins, renal tubular secretion can be retarded by concurrent administration of probenecid. 

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). 

Tiludronate - Tiludronate is not recommended for patients with severe renal failure (Ccr less than 30 mL/min). 

In patients with severe renal failure, give 500 mg, 1 or 2 g initially. The maintenance dose should be 25% of the usual initial dose given at the usual fixed interval of 6, 8, or 12 hours. For serious or life-threatening infections, in addition to the maintenance doses, give 12.5% of the initial dose after each hemodialysis session. 

Renal function impairment WnWe caution should be used in patients with severe renal failure, therapeutic concentrations of nalidixic acid in the urine, without increased toxicity caused by drug accumulation in the blood, have been observed in patients on full dosage with creatinine clearances (Ccr) as low as 2 to 8 mL/min. Special risk Use nalidixic acid with caution in patients with epilepsy, liver disease, or severe cerebral arteriosclerosis. 

Zopiclone reduced reduced reduced in severe renal failure... 

The metabolic clearance of zopiclone is reduced in elderly patients, aged 65 years and older, resulting in increases in peak plasma concentration and ti/2 [34], The removal of zopiclone from the body is also impaired in patients with liver disease. Reductions in clearance in patients with renal impairment are significant only in severe renal failure [35] (Tab. 3). 

Fate Biotransformation of cephalosporins by the host is not clinically important. Elimination occurs through tubular secretion and/or glomerular filtration thus doses must be adjusted in the case of severe renal failure to guard against accumulation and toxicity. Cefoperazone (sef oh PER az own) and ceftriaxone are excreted through the bile into the feces and are frequently employed in patients with renal insufficiency. 

Nitrofurantoin works by inactivating bacterial ribosomal proteins and other large molecules and has a bactericidal effect. The drug is concentrated in the urine and relies on adequate renal function (glomerular filtration rate (GFR) >30 mL/min) to guarantee activity. Nitrofurantoin is ineffective for upper UTI because it does not achieve adequate concentrations in the blood. The use of nitrofurantoin in patients with moderate-to-severe renal failure (GFR <50 mL/min) is not recommended due to increased risk of peripheral neuropathy (Kucers et ah, 1997). 

ACE INHIBITORS TRIMETHOPRIM Risk of hyperkalaemia when trimethoprim is co-administered with ACE inhibitors in the presence of renal failure Uncertain at present Avoid concurrent use in the presence of severe renal failure... 

PLATINUM COMPOUNDS RITUXIMAB t risk of severe renal failure Uncertain possibly due to effects of tumour lysis syndrome (which is a result of a massive breakdown of cancer cells sensitive to chemotherapy). Features include hyperkalaemia, hyperuricaemia, hyperphosphataemia and hypocalcaemia Monitor renal function closely. Hydrate with at least 2 L of fluid before, during and after therapy. Monitor potassium and magnesium levels in particular and correct deficits. Do an ECG as arrhythmias may accompany tumour lysis syndrome... 

Moderate renal failure is defined as the situation where the GFR is 30-70 rnl/min, while severe renal failure is where the GFR is under 30 ml/min. In chroitic renal failure, the gradual destruction of nephrons is compensated by hypertrophy of the remaining nephrons. Hence, the kidney continues to excrete normal levels of salt and water even with a moderate reduction in the GFR (Martin, 1996). Eventually, however, tirea and other nitrogenous compounds (am-monia, guaitidine, urate) begin to accumulate in the bloodstream. The increase in some of these compounds produces the nausea, vomiting, and tiredness that makes the patient first aware of the renal failure. Uremia occurs when the CER fails below 20-25% the normal value (Brenner and Lazarus, 1994). 

Mobbs JP, Balant L, ReviUard C, Favre H. Effets secondaires de I acide nahdixique chez une patiente atteinte d insuffisance renale severe etude clinique et proposition d un modele pharmacocinetique. [Side effects of nahdixic acid in a patient with severe renal failure. Clinical study and proposal of a pharmacokinetic model.] Schweiz Med Wochenschr 1977 107(9) 300-6. 

Chatelain E, DeminiereC, Lacut JY, PotauxL. Severe renal failure and polyneuritis induced by foscarnet. Nephrol Dial Transplant 1998 13 2368-2369. 

Elseviers MM, De Schepper A, Corthouts R, Bosmans JL, Cosyn L, Lins RL, Lornoy W, Matthys E, Roose R, Van Caesbroeck D, Waller I, Horackova M, Schwarz A, Svrcek P, Bonucchi D, Eranek E, Morlans M, De Broe ME. High diagnostic performance of CT scan for analgesic nephropathy in patients with incipient to severe renal failure. Kidney Int 1995 48 1316-1323. 

Acute interstitial nephritis was described by Lyons et al. in four patients with idiopathic interstitial nephritis, evidenced by peripheral eosinophilia, skin rash in two patients, and moderate to severe renal failure. Biopsies in all cases revealed dense interstitial infiltrate consisting predominantly of lymphocytes, tubular degenerative changes and interstitial edema with early... 

Wlllemse PEIB, De Jong PE, Elema JD, Mulder NEI. Severe renal failure following high-dose ifosfamide and Mesna. Cancer Chemother Pharmacol, 23 329-330,1989... 

Jakobsen JA. Renal effects of iodixanol in healthy volunteers and patients with severe renal failure. Acta Radiol (SuppI) 1995 399 191-195. 

Nortier JL, Schmeiser HH, Muniz Martinez MC, Arit VM, Vervaet C, Garbar CH, Daelemans P, Vanherweghem JL. Invasive urothelial carcinoma after exposure to Chinese herbal medicine containing aristolochic acid may occur without severe renal failure. Nephrol Dial Transplant 2003 18 426-428... 

Elseviers MM, De Schepper A, Corthouts R et al. High diagnostic performance of CT scan for analgesic nephropathy in patients with incipient to severe renal failure. Kidney Int 1995 48 1316-1323. 

Irish AB, Winearls CG, Littlewood T. Presentation and survival of patients with severe renal failure and myeloma. Q J Med 1997 90 773-80. 

Serum drug concentrations should be monitored for drugs with narrow therapeutic indices and ehminated largely by the kidney (e.g., aminoglycosides and vancomycin) to optimize therapy in pediatric patients with renal dysfunction. For drugs with wide therapeutic ranges (e.g., penicillins and cephalosporins), dosage adjustment may be necessary only in moderate to severe renal failure. 

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