Renal function development

The rate of renal function development is species dependent. Several studies have indicated that while the calf may have nearly adult renal function by the second day of its life (57, 58), it will take up to a week in tlie lamb to reach adult function (59). As an example, the elimination half-life of sulfamethazone is 13.5 h in a 1-day-old bovine, and only 6 h in an adult (51). However, except for bob veal, renal function may not play a significant role in residue violations. 

An 82-year-old man and a 76-year-old man with normal renal function developed increased lactate concentrations (3.6 mmol/1 and 3.2 mmol/1 respectively) a few weeks after starting to take metformin (54). Both had a low bicarbonate concentration and high anion gap. The second patient was also taking ciprofloxacin for a urinary tract infection. In both patients lactate reached normal values after metformin was withdrawn. 

Acute ciclosporin-induced nephrotoxicity, causing reduced renal function, develops within the first month, and includes a dose-related rise in serum creatinine concentrations and hyperkalemia. Fatal acute tubular necrosis has also been noted after very high intravenous doses (SEDA-19, 345). Although it is clinically often difficult to differentiate from acute allograft rejection in renal transplant patients, the alteration in renal function promptly resolves on ciclosporin withdrawal or dosage reduction, and initial acute renal insufficiency is not clearly associated with the development of subsequent chronic renal dysfunction (93). Several conditions, such as pre-existing hypovolemia, concomitant diuretic treatment, or renal artery stenosis, are susceptibility factors. 

A 12-year-old girl with neuroblastoma and normal renal function developed severe hypercalcemia while receiving isotretinoin 160 mg/m /day (61). Her hypercalcemia resolved with hydration, diuretic therapy, and temporary withdrawal of isotretinoin. Despite a dosage reduction to 80 mg/m /day, severe hypercalcemia recurred during the next treatment cycle. Further treatment with isotretinoin was made tolerable by shortening the duration of the remaining cycles. 

A 46-year-old woman with a 6-year history of diabetes mellitus and previously normal renal function developed anuria, hearing loss, myoclonus, and confusion with hallucinations. She was taking lisinopril, hydrochlorothiazide, furose-mide, atorvastatin, omeprazole, salmeterol/fluti-casone and salbutamol by inhalation, metformin, insulin, oxycodone, alprazolam, ven-lafaxine, and gabapentin 300 mg tds. The gabapentin blood concentration was 17.6 mg/1. All her symptoms improved after one session of hemodialysis and had resolved at the time of discharge 4 days later. 

Urinary tract A 17-year-old patient with epilepsy and normal renal function developed interstitial nephritis and renal failure while taking levetiracetam [200 ]. 

The dosage of flucytosine is 150—200 mg/kg orally in four portions every six hours. A 1% flucytosine solution has been developed for intravenous adrninistration. In some countries, a 10% ointment is also available. In patients with normal renal function, flucytosine is seldom toxic, but occasionally severe toxicity may be observed (leukopenia and thrombocytopenia). Plasma levels should be determined and the dose in patients with impaired renal function should be checked. Liver function tests (transaininases and alkaline phosphatase) should be performed regularly. In some patients with high flucytosine plasma levels, hepatic disorders have been observed (24). 

Intestinal absorption of digoxin is less complete compared to digitoxin. In order to improve absorption, acetylated- and methylated-digoxin derivates were developed. Digitoxin is metabolised in hepatic microsomal enzymes and can be cleared independently from renal function. The therapeutical serum level of digoxin is 0.5-2.0 ng/ml and 10-35 ng/ml of digitoxin. Steady state plateau of therapeutic plasma concentrations is reached after 4-5 half-life-times using standard daily doses [5]. 

MTX is potentially toxic. Therefore, the nurse observes closely for development of adverse reactions, such as thrombocytopenia (see Nursing Alert in Gold Compounds section) and leukopenia (see discussion of adverse reactions associated with hydroxychloroquine). Hematology, liver, and renal function studies are monitored every 1 to 3 months with MTX therapy. The primary care provider is notified of abnormal hematology, liver function, or kidney function finding. The nurse immediately brings all adverse reactions or suspected adverse reactions to the attention of the primary health care provider. 

All patients with major patterns are monitored for rhabdomyolysis and renal failure. An early sign of rhabdomyolysis is an elevated serum uric acid, associated with an increase in serum CK. Within 8 to 12 hours, the serum tests are repeated. If the uric acid falls and the CK rises, rhabdomyolysis is likely. Renal function tests may also be increased at this time. When the diagnosis of rhabdomyolysis is made, the patient is treated with 40 mg furose-mide IV once, and IV fluids. Urine myoglobin concentrations are obtained. If the patient develops renal failure, hemodialysis or peritoneal dialysis may be necessary. In all cases, multiple drug intoxication, trauma, and rhabdomyolysis are ruled out or treated. All patients are kept under observation until they are asymptomatic. 

The prototype of this class is hirudin, which was originally isolated from the salivary glands of the medicinal leech, Hirudo medicinalis. Hirudin itself is not commercially available, but recombinant technology has permitted production of hirudin derivatives, namely lepirudin and desirudin.29,38,41 Lepirudin has a short half-life of approximately 40 minutes after IV administration and 120 minutes when given SC. Elimination of lepirudin is primarily renal therefore, doses must be adjusted based on the patient s renal function. The dose should be monitored and adjusted to achieve an aPTT ratio of 1.5 to 2.5 times the baseline measurement. Lepirudin is currently approved for use in patients with HIT and related thrombosis. Up to 40% of patients treated with lepirudin will develop antibodies to the drug.29,38,41... 

Inhaled tobramycin (TOBI ) is typically administered to patients 6 years of age and older in alternating 28-day cycles of 300 mg nebulized twice daily, followed by a 28-day washout or off period to minimize development of resistance. Longterm intermittent administration improves pulmonary function, decreases microbial burden, and reduces the need for hospitalization for IV therapy.24,25 Due to minimal systemic absorption, pharmacokinetic monitoring is not necessary with normal renal function. Lower doses of nebulized tobramycin solution for injection have been used in younger children, and studies are underway using 300 mg twice daily in children under age 6. 

Several other factors also contribute to the development of anemia in patients with CKD. Uremia, a result of declining renal function, decreases the lifespan of RBCs from a normal of 120 days to as low as 60 days in patients with stage 5 CKD. Iron deficiency and blood loss from regular laboratory testing and hemodialysis also contribute to the development of anemia in patients with CKD. 

The initial dose of allopurinol is based on the patient s renal function. Patients with creatinine clearances of 50 mL/minute or less should receive a starting dose of less than 300 mg/day to minimize adverse effects. The relationship between dose of allopurinol and its most severe side effects is controversial. However, the dose can be adjusted upward as needed and tolerated. It is reasonable to reduce the dose temporarily in patients who develop reversible acute renal failure. 

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on... 

The primary goals of management of tumor lysis syndrome are (1) prevention of renal failure and (2) prevention of electrolyte imbalances. Thus the best treatment for tumor lysis syndrome is prophylaxis to enable delivery of cytotoxic therapy for the underlying malignancy. For patients who present with or develop tumor lysis syndrome despite prophylaxis, treatment goals include (1) decrease uric acid levels, (2) correct electrolyte imbalances, and (3) prevent compromised renal function. These goals should be achieved in a cost-effective manner. 

Taken together, these studies provide some evidence for the association of chronic nephropathy in occupationally exposed workers with PbB levels ranging from 60 to >100 pg/dL. It should be noted, however, that PbB levels measured at the time of renal function testing may not fully reflect the exposure history that contributed to the development of chronic nephropathy in lead workers. 

Assessment of renal function is not required prior to first administration to man or even during clinical development however, based on the potential implications of acute renal failure and the challenges in assessing it in normal healthy animals or humans, it would make sense to consider a proper assessment of renal function prior to first administration to humans. 

Renal lesions or changes in renal function in humans chronically exposed to 1,2-dibromoethane have not been identified. Following chronic inhalation exposure to 1,2-dibromoethane, rats developed toxic nephropathy (NTP 1982). 

---