Tausif Zar

Recognition, treatment, and prevention of propylene glycol toxicity.

Propylene glycol is a commonly used solvent for oral, intravenous, and topical pharmaceutical preparations. Although it is considered safe, large intravenous doses given over a short period of time can be toxic. Underlying renal insufficiency and hepatic dysfunction raise risk for toxicity. Toxic effects include hyperosmolality, increased anion gap metabolic acidosis (due to lactic acidosis), acute kidney injury, and sepsis‐like syndrome. Treatment of toxicity includes hemodialysis to effectively remove propylene glycol. Prevention is best achieved by limiting the dose of propylene glycol infused.

Reviews: Recognition, Treatment, and Prevention of Propylene Glycol Toxicity

Propylene glycol is a commonly used solvent for oral, intravenous, and topical pharmaceutical preparations. Although it is considered safe, large intravenous doses given over a short period of time can be toxic. Underlying renal insufficiency and hepatic dysfunction raise risk for toxicity. Toxic effects include hyperosmolality, increased anion gap metabolic acidosis (due to lactic acidosis), acute kidney injury, and sepsis‐like syndrome. Treatment of toxicity includes hemodialysis to effectively remove propylene glycol. Prevention is best achieved by limiting the dose of propylene glycol infused.

Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam

Background A 54-year-old male with a history of multiple admissions for alcohol intoxication was admitted to hospital with right flank pain. He received a high-dose lorazepam infusion for alcohol withdrawal during hospitalization and developed severe hyperosmolality, high anion gap metabolic acidosis, and acute kidney injury on his eighth day of hospitalization.Investigations Serum chemistries, arterial blood gas analysis, and measurement of serum propylene glycol, ethylene glycol and methanol levels.Diagnosis Propylene glycol toxicity.Management Discontinuation of lorazepam infusion, administration of fomepizole, hemodialysis for five consecutive days, hemodynamic support, and follow-up of serum osmolality as a measure of propylene glycol decay.

Paroxysmal hypertension due to baroreflex failure

CASE PRESENTATION A 78-year-old Caucasian male was referred to our hypertension clinic in February 2005 for severe blood pressure (BP) lability. He had a diagnosis of hypertension for about 10 years, but had been previously well controlled. Over the preceding 14 months, he had noticed fluctuations in BP that became progressively more severe. Based on self-monitored home BP readings, he reported systolic BP peaks of 220–240 mmHg and systolic BP nadirs of 80–90 mmHg, often happening within the same day. He also described that the rise in BP was associated with significant diaphoresis of the head and palms and facial flushing, analogous to a ‘thermometer rising inside his face and head’. Occasionally he also experienced palpitations. He had erectile dysfunction but no history of urinary incontinence or retention, or any other genitourinary complaints. He had no other cardiopulmonary, digestive, neurological or psychiatric symptoms. At the time of the initial visit, his hypertension was managed with labetalol 50 mg that he took irregularly, on average once daily. In the past, he had experienced symptomatic hypotension and fatigue with diltiazem, metoprolol, and diuretics. He did not abuse alcohol or any illicit substances and did not use any over-the-counter medications or nutriceuticals. In addition to hypertension, he had a history of squamous cell carcinoma of the left pyriform sinus (treated with extensive radiation to the neck and chemotherapy in 1998), coronary artery disease (coronary artery bypass grafting in 2000), nonproteinuric chronic kidney disease stage 3 (clinically presumed to be due to hypertensive nephrosclerosis), gastroesophageal reflux, and well-controlled hypothyroidism. In addition to labetalol, his medications included aspirin, levothyroxine, lovastatin, omeprazole, and fish oil. On examination, the patient appeared well and calm. BP averaged 184/84 mmHg in the supine position, 152/ 78 mmHg when seated, and 140/74 mmHg after 5 min of orthostasis. His heart rate was 68 b.p.m. and there were no changes with posture. Fundoscopic examination revealed arteriolar narrowing and occasional abnormal arteriovenous crossings. The skin overlying his neck was taut from previous radiation exposure. There was no jugular venous distension at 30 degrees. Bilateral carotid bruits were heard; carotid pulsations were normal. Examination of the heart, lungs, abdomen, and extremities were normal. The neurological examination showed normal focused sensory and motor examination, without any Parkinsonian or cerebellar features. Laboratory tests were significant for an elevated serum creatinine (1.9 mg dl ), with an associated estimated glomerular filtration rate of 38 ml per min per 1.73 m. Relevant laboratory tests, all of which were unremarkable, are listed in Table 1. A renal sonogram was unremarkable. A renal magnetic resonance angiogram was normal. Duplex ultrasound of the carotid arteries revealed hemodynamically significant bilateral carotid stenosis, confirmed by magnetic resonance angiography. A magnetic resonance scan of his brain was remarkable only for deep white matter ischemic lesions; there was no evidence of a brain stem lesion or infarct. Owing to the patient’s history of neck irradiation and clinical presentation, bedside evaluation of baroreflex pathway integrity was performed after he had been off antihypertensive drugs for 5 days. BP averaged 158/ 72 mmHg in the supine position, 158/64 mmHg when seated, and 156/80 in standing. The heart rate was 84 b.p.m. in all positions. The RR interval was unchanged (0.63 s) during slow deep breathing and throughout the Valsalva maneuver. We did not use a beat-to-beat monitor, so we were unable to assess the BP response to the Valsalva maneuver. The cold pressor test (hand/ forearm immersion) showed an unexpected response: he had a decline in both heart rate (93–70 b.p.m.) and BP (154/78–98/60 mmHg), both of which recovered to baseline levels after 5 min of monitoring. His 24 h ambulatory BP monitoring is displayed in Figure 1, demonstrating marked BP lability. t h e r e n a l c o n s u l t http://www.kidney-international.org

Predictable removal of anticardiolipin antibody by therapeutic plasma exchange (TPE) in catastrophic antiphospholipid antibody syndrome (CAPS).

Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare life-threatening variant of antiphospholipid antibody syndrome (APS), with an associated mortality rate of > 50%. Treatment recommendations are aggressive and consist of intravenous heparin, steroids, immunoglobulins and/or therapeutic plasma exchange (TPE). At present, insufficient data exist to make precise recommendations regarding the most effective therapy for CAPS. Accumulating evidence over recent years is encouraging and may lead to future guidelines. We report predictive and effective removal of pathological anticardiolipin antibody (aCL AB) in a patient with CAPS. The case report and discussion provide valuable insight into aCL AB production and its removal by first- order kinetics using TPE.

Focal Segmental Glomerulosclerosis Associated Seronegative Antiphospholipid Syndrome

Secondary Focal Segmental Glomerulosclerosis (FSGS) from thrombotic microangiopathies including Antiphospholipid Antibody Syndrome (APS), is well documented. We present a case with clinical features of APS but consistently negative serologies, suggesting ‘Seronegative APS (SNAPS)’. The patient was evaluated at the Division of Nephrology, University of Connecticut Health Center for progressive Chronic Kidney Disease (CKD). A renal biopsy exhibited thrombotic microangiopathy and associated FSGS. Systemic thrombophilia can be primary or secondary and has an extensive list of differential diagnoses. Distinct clinical features and serologic markers characterize a particular etiology. Antiphospholipid Syndrome (APS) is the most common acquired thrombophilia. Serologic evidence of APS is the presence of commonly recognized antibodies to phospholipids in this syndrome i.e. anticardiolipin (aCL) antibodies, Lupus Anticoagulant (LA) and β2-glycoprotein 1 (β2GPI) antibodies. Rarely a patient with classic clinical features of APS does not exhibit any of the above antibodies, suggesting ‘Seronegative APS (SNAPS)’.

Reviews: Recognition, Treatment, and Prevention of Propylene Glycol Toxicity: PROPYLENE GLYCOL TOXICITY

Propylene glycol is a commonly used solvent for oral, intravenous, and topical pharmaceutical preparations. Although it is considered safe, large intravenous doses given over a short period of time can be toxic. Underlying renal insufficiency and hepatic dysfunction raise risk for toxicity. Toxic effects include hyperosmolality, increased anion gap metabolic acidosis (due to lactic acidosis), acute kidney injury, and sepsis‐like syndrome. Treatment of toxicity includes hemodialysis to effectively remove propylene glycol. Prevention is best achieved by limiting the dose of propylene glycol infused.

CANDIDEMIA‐INDUCED ACUTE INTERSTITIAL NEPHRITIS

Common causes of acute interstitial nephritis (AIN) include infections and medications. We present a rarely reported case of AIN associated with Candida albicans fungemia. A 44-year-old woman with history of Crohn’s disease and hypertension was admitted with partial small bowel obstruction. She was taking amlodipine and mesalamine at home. During hospitalization, she was prescribed bowel rest, intravenous fluids, prednisone, levofloxacin and metronidazole. A peripherally inserted central catheter (PICC line) was placed for hyperalimentation. During the next week, the patient improved steadily. On the ninth day, she developed a high-grade fever (103.8° F). The laboratory workup revealed severe acute kidney injury (AKI), with an increase in creatinine from 0.8 to 3.5 mg/dL over a 3-day period (Fig. 1). The patient was non-oliguric and remained haemodynamically stable. Urinalysis showed multiple white blood cells, but the urine culture was negative. Two sets of peripheral blood cultures grew C. albicans. The patient was started on caspofungin (50 mg i.v. daily after a loading dose of 70 mg i.v.). The PICC line was removed on the same day. Culture of the catheter tip revealed C. albicans. No obvious aetiology of the AKI was identified except the coinciding candidemia. A renal ultrasound was unremarkable. The fractional excretion of sodium and urea were 2% and 56% respectively, suggesting renal parenchymal injury (acute tubular necrosis or AIN). In Crohn’s disease, hyperoxaluria can cause AKI and has been identified as a cause of AIN; however, the patient’s 24 h urine oxalate level was within reference range (31 mg/day). Proteinuria was 456 mg/day. Urine microscopy performed by the nephrologist revealed several white blood cell casts, suggestive of interstitial inflammation. A gallium-67 scintigram showed moderately intense tracer uptake in both kidneys at 48 h, consistent with AIN (Fig. 2). No peripheral eosinophilia or rash was noted. The temporal relationship between the candidemia and the AKI was compelling. The only significant intervention was the treatment of candidemia. As floroquinolones have been reported to cause AIN, levofloxacin was stopped temporarily. The patient, however, had received levofloxacin in the past, and she was again treated for pneumonia 1 month later with levofloxacin, without any adverse effects. Mesalamine is also a known aetiology of AIN, but the patient was taking it for months prior to admission and was continued on it during the current hospitalization. Given the rapid improvement in serum creatinine, a renal biopsy was considered unlikely to change management. The patient was continued on caspofungin during her hospital stay. Repeated blood cultures were negative. She was switched to oral fluconazole upon discharge. Her renal function continued to improve (Fig. 1) and returned to baseline (0.8 mg/dL) in the next 3 months. Candida species are reported to posses a tropism for the kidneys; in two autopsy series of fatal systemic candidiasis, renal involvement was reported to be 52–82%. There is, however, a paucity of case reports of candidemia-induced AIN in the literature. This can be attributed to the lack of pathologic (renal biopsy) evidence, presumably either due to the recovery of renal function with treatment of fungemia and/or due to the fact that the renal biopsy in septic patients is considered high risk. A Pubmed search revealed only two case reports. Both cases developed candidemia and AKI in somewhat identical situations to our patient (i.e. a hospitalized, immunocompromised patient receiving broad-spectrum antibiotics and parenteral nutrition). Renal biopsies revealed cortical microabscesses and intense