Renal insufficiency metabolic acidosis

Magnesium- and phosphate-containing preparations are tolerated reasonably well by most patients. However, they must be used with caution or avoided in patients with renal insufficiency, cardiac disease, or preexisting electrolyte abnormalities, and in patients on diuretic therapy. Patients taking >45 mL of oral sodium phosphate as a prescribed bowel preparation may experience electrolyte shifts that pose a risk for the development of symptomatic dehydration, renal failure, metabolic acidosis, hypocalcemic tetany, and even death in medically vulnerable populations. 

Contraindications for metformin include renal insufficiency, liver disease, alcehel abuse, cardiac insufficiency, metabolic acidosis or any hypoxia-related conditien. An additional consideration is that chronic metformin therapy can decrease oral absorption and subsequent serum concentrations of cyanocobalamin (vitamin B12) nevertheless, this effect, which is seen in approximately one in four patients, dees not appear to result in anemia. 

Potassium is contraindicated in patients who are at risk for experiencing hyperkalemia, such as those with renal failure, oliguria, or azotemia (file presence of nitrogen-containing compounds in the blood), anuria, severe hemolytic reactions, untreated Addison s disease (see Chap. 50), acute dehydration, heat cramps, and any form of hyperkalemia Potassium is used cautiously in patients with renal impairment or adrenal insufficiency, heart disease, metabolic acidosis, or prolonged or severe diarrhea. Concurrent use of potassium with... 

Metabolic acidosis In severe renal disease uncontrolled diabetes circulatory insufficiency due to shock, anoxia, or severe dehydration extracorporeal circulation of blood cardiac arrest and severe primary lactic acidosis where a rapid increase in plasma total CO2 content is crucial. Treat metabolic acidosis in addition to measures designed to control the cause of the acidosis. Because an appreciable time interval may elapse before all ancillary effects occur, bicarbonate therapy is indicated to minimize risks inherent to acidosis itself. 

Metabolic acidosis, electrolyte imbalance, transient myopia, urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity convulsions, and rarely crystalluria, renal calculi... 

In moderate metabolic acidosis which occurs in cases of mild renal insufficiency, infant diarrhoea, diabetic ketosis etc. 

Accumulation of metformin can occur in patients with renal insufficiency, and interference with pyruvate metabolism can lead to severe lactic acidosis. Lactic acidosis is more likely in situations associated with anaerobic metabolism, and metformin should not be given to patients with renal disease, liver disease, or severe pulmonary or cardiac disease predisposing to hypoxia. It is recommended to switch patients taking metformin to another oral hypoglycaemic prior to cardiac or other major surgery. 

Three stages of ethylene glycol overdose occur. Within the first few hours after ingestion, there is transient excitation followed by CNS depression. After a delay of 4-12 hours, severe metabolic acidosis develops from accumulation of acid metabolites and lactate. Finally, delayed renal insufficiency follows deposition of oxalate in renal tubules. The key to the diagnosis of ethylene glycol poisoning is recognition of anion gap acidosis, osmolar gap, and oxalate crystals in the urine in a patient without visual symptoms. 

Adefovir dipivoxil is well tolerated. A dose-dependent nephrotoxicity has been observed in clinical trials, manifested by increased serum creatinine with decreased serum phosphorous and more common in patients with baseline renal insufficiency and those receiving high doses (60 mg/d). Other potential adverse effects are headache, diarrhea, asthenia, and abdominal pain. As with other NRTI agents, lactic acidosis and hepatic steatosis are considered a risk owing to mitochondrial dysfunction. No clinically important drug-drug interactions have been recognized to date. Pivalic acid, a by-product of adefovir dipivoxil metabolism, can esterify free carnitine and result in decreased carnitine levels. However, it is not felt necessary to administer carnitine supplementation with the low doses used to treat patients with HBV (10 mg/d). 

Since iodine is eliminated by the kidneys, renal insufficiency increases the risk of toxicity, and the risk may be further increased by metabolic acidosis (44,45). 

The main susceptibility factor for lactic acidosis due to metformin is renal insufficiency (49). In patients taking phenformin, poor oxidative metabolism may contribute (73). 

Six experts in intensive care or metabolic disease reviewed all case reports of lactic acidosis from 1957 to 1999—37 articles reporting 80 cases (85). To be assessed the reports had to meet strict criteria, including a diagnosis of type 2 diabetes, metformin therapy before lactic acidosis, a pH of 7.35 or less, or a plasma bicarbonate concentration below 22 mmol/1 and a lactic acid concentration of at least 5 mmol/1. Because of lack of information, 33 cases were excluded. There were other susceptibility factors for lactic acidosis besides metformin in 46 of 47 cases. Only 13 of the 47 cases were classified as probably due to metformin by at least three experts. The authors suggested a rethink about the relation between lactic acidosis and metformin. However, they still recommended withdrawing therapy in acute renal insufficiency and when contrast dyes are used for radiological investigation. 

Acetazolamide can cause a metabolic acidosis in 50% of elderly patients (SEDA-11,199) occasionally (particularly if salicylates are being given or renal function is poor) the acidosis can be severe. It does this by inhibiting renal bicarbonate reabsorption. This effect is of particular use in treating patients with chronic respiratory acidosis with superimposed metabolic alkalosis. Life-threatening metabolic acidosis is rarely observed in the absence of renal insufficiency and/or diabetes mellitus. In three patients with central nervous system pathology alone conventional doses of acetazolamide resulted in severe metabolic acidosis (34). After withdrawal it took up to 48 hours for the metabolic acidosis and accompanying hyperventilation to resolve. 

A 34-year-old woman with a history of renal insufficiency induced by long-term use of cocaine developed respiratory failure and was intubated and sedated with intravenous lorazepam (65 mg, 313 mg, and 305 mg on 3 consecutive days). After 2 days she had a metabolic acidosis, with hyperlactatemia and hyperosmolality. Propylene glycol, a component of the lorazepam intravenous formulation, was considered as a potential source of the acidosis, as she had received more than 40 times the recommended amount over 72 hours. Withdrawal of lorazepam produced major improvements in lactic acid and serum osmolality. 

Nalidixic acid can cause metabolic acidosis in infants (735). This has also been seen in older children and adults with renal insufficiency and can result from disturbed lactate metabolism. Extreme overdosage can cause metabolic acidosis in subjects with normal renal function (734,736). 

Metformin has a half-life of 1.5-3 hours, is not bound to plasma proteins, is not metabolized, and is excreted by the kidneys as the active compound. As a consequence of metformin s blockade of gluconeogenesis, the drug may impair the hepatic metabolism of lactic acid. In patients with renal insufficiency, biguanides accumulate and thereby increase the risk of lactic acidosis, which appears to be a dose-related complication. 

Acid-base disorders Initial metabolic alkalosis (resulting from decreased urea synthesis with reduced bicarbonate consumption) may be superimposed by respiratory alkalosis as an outcome of disorders in lung function. During the further course, metabolic acidosis (with renal insufficiency) and respiratory acidosis (with pulmonary insufficiency) can be expected. In advanced or severe stages of the disease, lactate acidosis may develop in some 50% of all comatose patients owing to restricted gluconeogenesis. 

A 50-year-old woman with chronic renal insufficiency treated with acetazolamide for simple glaucoma developed confusion, cerebellar ataxia, and metabolic acidosis 2 weeks after starting to take aspirin for acute pericarditis (30). A diagnosis of salicylism was made despite low serum salicylate concentrations. 

Experience with ciclosporin overdose has been reviewed by the manufacturers using published data or cases spontaneously reported (223). Accidental overdose was the most common, with doses of 20-400 mg/kg. In adults, no serious clinical consequences were observed with doses up to 100 mg/kg, and there were only minor clinical or biological effects (transient hypertension, tachycardia, headache, gastrointestinal symptoms, or slight increases in serum creatinine concentrations). However, life-threatening reactions occurred in three neonates, of whom one died after severe metabolic acidosis and renal insufficiency. Subchronic ciclosporin overdose over 8 days did not appear to cause any additional risk (224). 

In contrast, published case reports and case series have provided more insight into the potential nephrotoxicity associated with COX-2-selective inhibitors. Taken together, these case reports suggest that COX-2 inhibitors, like non-selective NSAIDs, produce similar and consistent renal adverse effects in patients with one or more risk factors that induce prostaglandin-dependent renal function (that is patients with renal and cardiovascular disease and taking a number of culprit medications, such as diuretics and ACE inhibitors). Acute renal insufficiency, disturbances in volume status (edema, heart failure), metabolic acidosis, hyperkalemia, and hyponatremia have been commonly described. The duration of treatment with COX-2 inhibitors before the development of chnically recognized renal impairment ranged from a few days to 3-4 weeks. Withdrawal of COX-2 inhibitors and supportive therapy most often resulted in resolution of renal dysfunction, but in some patients hemodialysis was required (102,108-112). 

Generalized muscle rigidity (found in 70% of the patients involved) and a progressive rise in body temperature (sometimes beyond 43°C) are the main clinical features, often associated with tachycardia, hypoxia, metabolic acidosis, cardiac dysrhythmias and, less often, disseminated intravascular coagulation, cerebral edema, and acute renal insufficiency. Diagnosis relies on the clinical signs, that is muscle rigidity and hyperpyrexia, and on raised serum activities of skeletal and cardiac muscle enzymes, for example aldolase and creatine kinase. 

Renal insufficiency and severe metabolic acidosis developed in a patient with diabetes mellitus taking metformin after recent treatment with indometacin (SEDA-22,118). 

The authors concluded that she may have been at increased risk of methemoglobinemia as a result of the metabolic acidosis associated with renal insufficiency, since impaired protein binding of prilocaine could have increased the concentrations of ionized prilocaine. Furthermore, the patient was also taking isosorbide dinitrate, which may have predisposed her to methemoglobinemia. 

Benign intracranial hypertension (pseudotumor cerebri) mainly affects babies, especially during the first 3 months of life. Occasionally even older children can be affected, especially when inordinately high doses are used (5). Very rarely, it occurs in adults with renal insufficiency. In infancy, impaired nalidixic acid elimination (due to underdeveloped glucuronidation), overdosage, or prolonged treatment may be responsible. Metabolic acidosis is usually important in adults (6). 

A 35-year-old man who regularly took paraldehyde 15-20 ml/day took 200 ml and developed a metabolic acidosis (pH 7.12) and acute renal insufficiency (12). 

A 47-year-old woman had an infusion of propofol 200 micrograms/kg/minute for 4 days. On day 2 she developed hematuria, and laboratory investigations showed renal insufficiency with hyperkalemic metabolic acidosis. She died as a result of rhabdomyolysis with cardiac involvement. 

Life-threatening hjrperkalemia secondary to the use of standard oral doses of co-trimoxazole (trimethoprim 320 mg/day and sulfamethoxazole 1600 mg/day) occurred in a 77-year-old man with moderate chronic renal insufficiency from diabetic nephropathy (71). In addition to hyperkalemia, he developed severe metabolic acidosis both resolved on appropriate medical intervention and withdrawal of co-trimoxazole. 

Hyperkalemia may occur in renal disease and adrenal insufficiency owing to impairment of normal secretory mechanisms. Metabolic acidosis, in particular diabetic acidosis, and catabolism of cellular protein in starvation or fever cause K+ release from cells. Treatment consists of correction of the acidosis and promotion of cellular uptake of K+ by administration of insulin, which enhances glucose intake. In severe cases, ion exchange resins given orally bind K+ in intestinal secretions. 

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