acyclovir and Acute-Kidney-Injury

Acute kidney injury (AKI) is an independent risk factor for morbidity and mortality in critically ill neonates. Nephrotoxic medication exposure is common in neonates. Nephrotoxicity represents the most potentially avoidable cause of AKI in this population.. Recent studies in critically ill children revealed the importance of recognizing AKI and potentially modifiable risk factors for the development of AKI such as nephrotoxic medication exposures. Data from critically ill children who have AKI suggest that survivors are at risk for the development of chronic kidney disease. Premature infants are born with incomplete nephrogenesis and are at risk for chronic kidney disease. The use of nephrotoxic medications in the neonatal intensive care unit is very common; yet the effects of medication nephrotoxicity on the short and long-term outcomes remains highly understudied.. The neonatal kidney is predisposed to nephrotoxic AKI. Our ability to improve outcomes for this vulnerable group depends on a heightened awareness of this issue. It is important for clinicians to develop methods to minimize and prevent nephrotoxic AKI in neonates through a multidisciplinary approach aiming at earlier recognition and close monitoring of nephrotoxin-induced AKI.

Topics: Acute Kidney Injury; Acyclovir; Aminoglycosides; Amphotericin B; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Humans; Infant, Newborn; Vancomycin

An 83-year-old Japanese man had a 29-year history of well-controlled diabetes mellitus. His HbA1c level was approximately 6.0%, with no microalbuminuria and a serum creatinine level seven days before admission of 0.8 mg/dl (eGFR: 69.67 ml/min/1.73 m(2)). Five days before admission, he visited an ophthalmologist with inflammation of the right palpebra and conjunctiva and began taking valacyclovir at a dose of 3,000 mg for the treatment of herpes zoster. Two days before admission, he was prescribed loxoprofen at a dose of 180 mg for a headache. One day prior to admission, he developed dysarthria, wandering and loss of appetite. He was subsequently admitted to our hospital with progressive deterioration of consciousness (Japan Coma Scale: II-20). On admission, he exhibited renal dysfunction, with a serum creatinine level of 5.11 mg/dl (eGFR: 9.16 ml/min/1.73 m(2)). Based on his diverse symptoms and current treatment with valacyclovir, the patient was diagnosed with acyclovir-induced neurotoxicity and his symptoms rapidly improved after hemodialysis. The serum acyclovir level on admission was found to be 9.25 μg/ml. Although acyclovir-induced neurotoxicity is commonly seen in elderly patients with renal dysfunction, there are also reports of this condition in patients with a normal renal function. Valacyclovir is frequently prescribed to the elderly to treat diseases such as herpes zoster. As valacyclovir induces renal dysfunction, which raises the serum acyclovir level to the toxic range, special attention must be paid when administering this drug in elderly subjects.

Topics: Acute Kidney Injury; Acyclovir; Aged, 80 and over; Antiviral Agents; Consciousness Disorders; Diabetes Complications; Diabetes Mellitus, Type 2; Humans; Male; Valacyclovir; Valine

INTRODUCTION. Infection by the Epstein-Barr virus (EBV) -either as a primary infection, a reactivation or an active chronic infection- can give rise to several clinical forms of involvement of the central nervous system. We report a case of encephalitis due to EBV produced by viral reactivation in an immunocompetent patient which initially mimicked, from the clinical and electroencephalographic point of view, encephalitis due to type 1 herpes simplex virus (HSV-1). CASE REPORT. A 51-year-old male who had reported the presence of dorsal herpes zoster some days earlier. The patient visited the emergency department after suffering a holocranial oppressive headache and febricula for seven days; 24 hours before admission to hospital, he was suffering from drowsiness and language disorder. The neurological examination revealed stiffness in the back of the neck and dysphasia. An analysis of the cerebrospinal fluid revealed pleocytosis (422 cells/mm(3)) with 98% of mononuclear cells and normal protein and glucose concentration levels in cerebrospinal fluid. Magnetic resonance imaging of the brain and electroencephalogram readings were normal with periodic lateralised epileptiform discharges in the left temporal region. Intravenous acyclovir treatment was initiated, but renal failure meant it had to be changed to oral valaciclovir with clinical resolution and improvement of the liquoral parameters. Polymerase chain reaction in the cerebrospinal fluid was positive for EBV and negative for the other neurotropic viruses. In blood, the serology test for EBV with IgG was positive, while IgM and heterophile antibody tests were negative. CONCLUSIONS. EBV infection can give rise to acute disseminated encephalomyelitis or affect several locations in the central nervous system, especially the cerebellum. Clinical pictures mimicking HSV-1 are less frequent. When encephalitis is related to viral reactivation, precipitating factors can be detected, as in our case.. Encefalitis por el virus de Epstein-Barr: descripcion de un caso clinico y revision de la bibliografia.. Introduccion. La infeccion por el virus de Epstein-Barr (VEB) puede dar lugar –tanto como primoinfeccion, reactivacion o infeccion cronica activa– a varias formas clinicas de afectacion del sistema nervioso central. Presentamos un caso de encefalitis por VEB producido por reactivacion virica en un paciente inmunocompetente, que inicialmente simulaba, desde el punto de vista clinico y electroencefalografico, una encefalitis por virus herpes simple tipo 1 (VHS-1). Caso clinico. Varon de 51 años con antecedente de herpes zoster dorsal en los dias previos. Acudio a urgencias por un cuadro de siete dias de duracion de cefalea opresiva holocraneal y febricula; 24 horas antes de su ingreso, padecia somnolencia y alteracion del lenguaje. En la exploracion neurologica presentaba rigidez nucal y disfasia. En el liquido cefalorraquideo se evidencio pleocitosis (422 celulas/mm3) con un 98% de mononucleares, y proteinorraquia y glucorraquia normales. Resonancia magnetica cerebral normal y electroencefalograma con descargas epileptiformes lateralizadas periodicas en la region temporal izquierda. Se trato con aciclovir intravenoso; una insuficiencia renal motivo su cambio a valaciclovir oral con resolucion clinica y mejoria de los parametros licuorales. La reaccion en cadena de la polimerasa en el liquido cefalorraquideo fue positiva para VEB y negativa para el resto de virus neurotropos. En sangre, la serologia para VEB con IgG resulto positiva, y negativa con IgM y anticuerpos heterofilos. Conclusiones. La infeccion por VEB puede dar lugar a una encefalitis aguda diseminada o afectar a varias localizaciones del sistema nervioso central, principalmente el cerebelo. Menos frecuentes son los cuadros imitadores de VHS-1. Cuando la encefalitis se relaciona con reactivacion viral pueden detectarse, como en nuestro caso, factores precipitantes.

Topics: Acute Kidney Injury; Acyclovir; Antibodies, Viral; Antiviral Agents; Cerebrospinal Fluid; Drug Substitution; Electroencephalography; Encephalomyelitis, Acute Disseminated; Epilepsy; Epstein-Barr Virus Infections; Herpes Zoster; Herpesvirus 4, Human; Humans; Immunoglobulin G; Immunoglobulin M; Magnetic Resonance Imaging; Male; Middle Aged; Valacyclovir; Valine

Valacyclovir (VACV) is used increasingly to treat herpes zoster, although neuropsychiatric symptoms [VACV neurotoxicity (VAN) or acyclovir neurotoxicity], may accompany use of this drug. To promote awareness of this rare condition, we describe here two clinical cases of VAN we previously reported and review 20 cases from the literature. In all cases, chronic or acute renal failure preceded VAN. The symptoms of VAN varied, but disturbances of consciousness and hallucination occurred most commonly. When acute renal failure was due to the drug, recovery from both the disturbance of consciousness and renal failure followed within several days after discontinuation of VACV. Early recognition and diagnosis will ensure effective treatment of VAN.

Topics: Acute Kidney Injury; Acyclovir; Adult; Aged; Antiviral Agents; Consciousness Disorders; Female; Hallucinations; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neurotoxicity Syndromes; Valacyclovir; Valine

Several medications--notably acyclovir, sulfonamides, methotrexate, indinavir, and triamterene--are associated with the production of crystals that are insoluble in human urine. Intratubular precipitation of these crystals can lead to acute renal insufficiency. Many patients who require treatment with these medications have additional risk factors, such as true or effective intravascular volume depletion and underlying renal insufficiency, that increase the likelihood of drug-induced intrarenal crystal deposition. Acute renal failure in this setting may be preventable if it is anticipated by appropriate drug dosing, volume expansion with high urinary flow, and alkalinization of the urine when appropriate. Renal failure may be reversible if the drug is discontinued, and by volume repletion and alkalinization of the urine when appropriate. Management of established renal insufficiency includes volume repletion, dialytic support if necessary, adjustment of drug doses, and avoidance of further exposure to nephrotoxins.

Topics: Acute Kidney Injury; Acyclovir; Humans; Indinavir; Kidney; Methotrexate; Risk; Sulfonamides; Triamterene

Acyclovir nephrotoxicity has been described since the inception of the drug's use more than a decade ago. Acute renal failure mediated by this compound is characterized by abrupt elevations in serum creatinine and a gradual return to baseline renal function on discontinuation of the drug. Drug crystal formation in collecting tubules resulting in an intraparenchymal form of obstructive nephropathy has been suggested as the mechanism for acyclovir nephrotoxicity. The patient we present developed rapidly progressive acute renal failure with concomitant mental status changes in the setting of treatment with high-dose parenteral acyclovir. Acyclovir therapy was discontinued and an open renal biopsy was obtained to further evaluate our patient's diminishing renal function. Pathologic examination of the biopsy specimen revealed loss of proximal tubule brush border and dilated proximal and distal tubules with flattening of lining cells and focal nuclear loss. No crystals were noted. These changes were consistent with acute tubular necrosis with regeneration. Over the next 4 days our patient's renal and neurologic levels recovered to their prehospitalization statuses. It appears that our patient was affected by acyclovir-mediated nephrotoxicity that manifested on biopsy by acute tubular necrosis and the absence of crystalluria or crystal deposition. Intravenous acyclovir treatment can therefore produce rapidly progressive acute neurologic and renal toxicity that is usually reversible. The pathologic changes of acute tubular necrosis must now be included as part of the spectrum of renal damage associated with acyclovir therapy.

Topics: Acute Kidney Injury; Acyclovir; Aged; Humans; Kidney Tubular Necrosis, Acute; Male

Intravenous acyclovir-induced acute kidney injury (AKI) from drug crystallization in the renal tubules is described in case reports, review articles, and drug prescribing manuals. Similarly, AKI from oral acyclovir is described in case reports, but the risk in routine practice is unknown.. Retrospective population-based cohort study.. We studied a large cohort of older patients in Ontario, Canada, receiving new outpatient prescriptions from 1997 to 2011 for oral acyclovir or valacyclovir (which is metabolized to acyclovir). The comparison drug was famciclovir, an antiviral used for indications similar to acyclovir, but with no known renal toxicity.. Outpatient prescription for oral acyclovir, valacyclovir, or famciclovir.. The primary outcome was hospital admission with AKI in the 30 days after the initial prescription.. We assessed the primary outcome with health care diagnostic codes. In a subpopulation, we assessed AKI using available laboratory serum creatinine measurements.. 76,269 patients received acyclovir or valacyclovir and 84,646 received famciclovir. On average, patients were aged 76 [IQR, 71-81] years and prescription duration was 7 days. Acyclovir or valacyclovir use was not associated with a higher risk of hospital admission with AKI (209 [0.27%] events with acyclovir or valacyclovir vs 238 [0.28%] events with famciclovir [relative risk, 0.97; 95% CI, 0.81-1.17]). Results were consistent in adjusted analyses, in all subgroups, and in the subpopulation with laboratory measurements.. Diagnostic codes had high specificity but low sensitivity and underestimated the incidence of AKI. Only a limited number of patients (n = 2,729) had serum creatinine values available.. In this population-based study of older adults, oral acyclovir use was not associated with a higher risk of AKI compared to famciclovir.

Topics: Acute Kidney Injury; Acyclovir; Administration, Oral; Aged; Aged, 80 and over; Antiviral Agents; Creatinine; Female; Herpes Simplex; Herpes Zoster; Humans; Male; Ontario; Outpatients; Population Surveillance; Retrospective Studies; Risk Factors

A 72-year-old Japanese woman was treated by 3000 mg/day of valacyclovir for the herpes zoster in her left back. She had been treated as hypertension with no renal insufficiency. In two days, she visited an emergency room of a regional stroke care center with dysarthria, dexterity disorder and gait disturbance. Neither head CT nor MRI found intracranial lesions, then, laboratory tests revealed that her serum creatinine level was 4.63 mg/dL. She was transferred and admitted to our hospital on the following day and received hemodialysis under the diagnosis of AKI due to acyclovir accompanied with encephalopathy. Afterward, her serum concentration of acyclovir revealed as 44 μg/mL, which is extremely high. Her neurological symptom disappeared in parallel with the decrease of serum concentration of acyclovir. She received 3 sessions of hemodialysis and discharged on the 8th day of admission with almost normal renal function and no neurological sequela.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Female; Humans; Kidney; Stroke; Valacyclovir

Continuous venovenous hemodiafiltration (CVVHDF) is one of the treatments of critically ill children presenting severe acute liver failure. This affliction might be induced by HSV infection requiring a treatment by acyclovir. Continuous kidney replacement therapy (CKRT) can alter its pharmacokinetics, according to its physicochemical properties and CVVHDF settings.. This case describes acyclovir pharmacokinetics during CKRT in a pediatric patient treated by acyclovir. The patient was treated with adapted exposure with the usual dosing, but lower dosing should be investigated with complementary studies.. ClinicalTrials.gov NCT02539407.

Topics: Acute Kidney Injury; Acyclovir; Child; Continuous Renal Replacement Therapy; Critical Illness; Dialysis Solutions; Female; Hemodiafiltration; Humans; Infant; Liver Failure, Acute

There is limited guidance on the most appropriate dosing strategy for intravenous (IV) acyclovir in obese patients. The manufacturer's labelling suggests using ideal body weight (IBW); however, previous pharmacokinetic studies of obese patients have shown more rapid systemic clearance and lower area under the curve and peak concentrations compared with patients with a body mass index (BMI) < 30 kg/m. This was a retrospective cohort review of adult patients with a BMI ≥ 30 kg/m. In this study, 8.5% of all obese patients receiving acyclovir developed AKI. Further studies are needed to confirm dosing recommendations.

Topics: Acute Kidney Injury; Acyclovir; Adult; Body Weight; Humans; Obesity; Retrospective Studies

Topics: Acute Kidney Injury; Acyclovir; Aged; Antibodies, Viral; Antiviral Agents; Confusion; Diagnosis, Differential; DNA, Viral; Encephalitis; Encephalitis, Varicella Zoster; Exanthema; Hashimoto Disease; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Magnetic Resonance Imaging; Male; Meningoencephalitis; Neuroimaging; Recurrence

To describe the epidemiology of and risk factors associated with acute kidney injury (AKI) during acyclovir treatment in neonates and infants.. We conducted a multicenter (n = 4), retrospective cohort study of all hospitalized infants age <60 days treated with intravenous acyclovir (≥1 dose) for suspected or confirmed neonatal herpes simplex virus disease from January 2011 to December 2015. Infants with serum creatinine measured both before acyclovir (baseline) and during treatment were included. We classified AKI based on changes in creatinine according to published neonatal AKI criteria and performed Cox regression analysis to evaluate risk factors for AKI during acyclovir treatment.. We included 1017 infants. The majority received short courses of acyclovir (median, 5 doses). Fifty-seven infants (5.6%) developed AKI during acyclovir treatment, with an incidence rate of AKI at 11.6 per 1000 acyclovir days. Cox regression analysis identified having confirmed herpes simplex virus disease (OR, 4.35; P = .002), receipt of ≥2 concomitant nephrotoxic medications (OR, 3.07; P = .004), receipt of mechanical ventilation (OR, 5.97; P = .001), and admission to an intensive care unit (OR, 6.02; P = .006) as risk factors for AKI during acyclovir treatment.. Among our cohort of infants exposed to acyclovir, the rate of AKI was low. Sicker infants and those exposed to additional nephrotoxic medications seem to be at greater risk for acyclovir-induced toxicity and warrant closer monitoring.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adolescent; Child; Child, Preschool; Cohort Studies; Female; Herpes Simplex; Humans; Infant, Newborn; Male; Pregnancy Complications, Infectious; Retrospective Studies; Risk Factors

Topics: Acute Kidney Injury; Acyclovir; Aged, 80 and over; Drug Substitution; Encephalitis, Varicella Zoster; Female; Ganciclovir; Humans; Meningoencephalitis; Treatment Outcome

The objective of this study was to describe the incidence of acute kidney injury (AKI) in children receiving intravenous acyclovir and determine risk factors that may be associated with it.. This was a retrospective cohort study, conducted by chart review.. The study was conducted across two paediatric hospitals.. All inpatients that received intravenous acyclovir in records from January 2015 to December 2015 were reviewed. Only patients with creatinine measurements taken before and after starting acyclovir were included in the study.. The main outcome measure was the development of AKI following intravenous acyclovir administration, with AKI defined according to change in serum creatinine.. AKI following intravenous acyclovir exposure is common in children. This study raises the possibility that glomerular hyperfiltration is a previously unrecognised risk factor for acyclovir-induced AKI.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adolescent; Antiviral Agents; Child; Child, Preschool; Female; Glomerular Filtration Rate; Humans; Infant; Infant, Newborn; Male; Neoplasms; Retrospective Studies; Risk Factors

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Humans

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Crystallization; Humans; Male

Varicella zoster virus (VZV) is less susceptible than herpes simplex virus to acyclovir. The optimal acyclovir regimen during VZV encephalitis remains unknown. We report two cases of acute renal failure after an increase in acyclovir dosage from 10 mg to 15 mg/kg/8 h during the treatment of VZV encephalitis according to French guidelines.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Biomarkers; Electroencephalography; Encephalitis, Varicella Zoster; Female; Herpesvirus 3, Human; Humans; Magnetic Resonance Imaging; Male; Middle Aged

Nonsteroidal anti-inflammatory drugs (NSAIDs) are likely to be used concomitantly with acyclovir or valacyclovir in clinical practice, but the study on the safety of such combinations was seldom reported. The objective of the study was to investigate reports of acute kidney injury (AKI) events associated with the concomitant use of oral acyclovir or valacyclovir with an NSAID by using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database between January 2004 and June 2012. The frequency of AKI events in patients while simultaneously taking either acyclovir or valacyclovir and an NSAID was compared using the Chi-square test. The effect of concomitant use of acyclovir or valacyclovir and individual NSAIDs on AKI was analyzed by the reporting odds ratio (ROR). The results showed that AKI was reported as the adverse event in 8.6% of the 10923 patients taking valacyclovir compared with 8.7% of the 2556 patients taking acyclovir (p=NS). However, AKI was significantly more frequently reported in patients simultaneously taking valacyclovir and an NSAID (19.4%) than in patients simultaneously taking acyclovir and an NSAID (10.5%) (p<0.01). The results also suggested that increased risk of AKI was likely associated with the concomitant use of valacyclovir and some NSAIDs such as loxoprofen, diclofenac, etodolac, ketorolac, piroxicam or lornoxicam. The case series from the AERS indicated that compared with acyclovir, valacyclovir is more likely to be affected by NSAIDs, and the concomitant use of valacyclovir with some NSAIDs might be associated with increased risk of AKI. The drug interactions with this specific combination of medications are worth exploring further.

Topics: Acute Kidney Injury; Acyclovir; Adult; Adverse Drug Reaction Reporting Systems; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Chi-Square Distribution; Data Mining; Drug Interactions; Female; Humans; Japan; Kidney; Male; Middle Aged; Prodrugs; Risk; United States; United States Food and Drug Administration; Valacyclovir; Valine

Patients with 'suspected viral encephalitis' are frequently empirically treated with intravenous aciclovir. Increasing urea and creatinine are 'common', but rapidly progressive renal failure is reported to be 'very rare'.. To describe the clinical course and outcome of cases of aciclovir-induced acute kidney injury (AKI) encountered by the Liaison Neurology Service at AMNCH and to highlight the importance of surveillance and urgent treatment of this iatrogenic complication.. Retrospectively and prospectively collected data from the Liaison Neurology Service at AMNCH on patients who received IV aciclovir for suspected viral encephalitis and developed AKI were analysed. Aciclovir-induced AKI was defined by a consultant nephrologist in all cases as a rise in serum creatinine of > 26 μmol/L in 48 h or by ≥ 1.5 times the baseline value. Renal function, haematocrit, and fluid balance were monitored following AKI onset.. Data from 10 patients were analysed. Median time to AKI onset was 3.5 days (range: 1-6 days). Aciclovir was stopped or the dose adjusted. All patients recovered with IV normal saline, aiming for a urine output > 100-150 ml/h. The interval between first rise in creatinine and return to normal levels varied between 5 and 19 days.. Liaison neurologists and general physicians need to be aware that aciclovir may cause AKI attributed to distal intra-tubular crystal nephropathy. Daily fluid balance and renal function monitoring are essential because AKI may arise even with intensive pre-hydration. Prognosis is good if identified early and actively treated.

Topics: Acute Kidney Injury; Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Encephalitis, Viral; Female; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Young Adult

This study sought to identify the incidence of, and risk factors for, acute kidney injury (AKI) in adults treated with parenteral aciclovir.. A single-centre retrospective cohort study of prospectively acquired electronic clinical, pharmacy and laboratory data was performed with approval of the Caldicott guardian. AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria, prior to analysis of baseline patient and treatment-related risk factors.. 269 aciclovir treatment episodes were identified in 268 patients. Overall incidence of AKI was 13%. Half of AKI episodes were KDIGO grade 2/3. In univariate analysis, AKI occurred more frequently in patients with pre-existing chronic kidney disease (CKD), diabetes, and in patients treated with higher daily doses of aciclovir. There was also a trend to increased age in patients with AKI. In a binomial logistic regression model only CKD and daily dose remained significant independent factors.. AKI is an important side effect of parenteral aciclovir, the incidence of which is comparable to established nephrotoxic drugs such as aminoglycosides. Patients with pre-existing chronic kidney disease or receiving higher total doses are at greatest risk, reinforcing the clinical importance of appropriate dose adjustment for ideal body weight and baseline renal function.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Incidence; Kidney; Logistic Models; Male; Middle Aged; Retrospective Studies; Risk Factors; Young Adult

To assess the incidence, predictive factors, and prognosis of acyclovir-induced nephrotoxicity. We conducted a historical prospective cohort study of patients treated with intravenous acyclovir in North Denmark Region from 2009 to 2016. Information on baseline demographics, co-morbidities, plasma creatinine, and treatment was obtained from the medical records. The primary outcome was an increase of ≥ 40 μmol/L in plasma creatinine level from baseline. We included 276 patients treated with intravenous acyclovir of which 29 (10.5%) met the primary outcome. In 14 cases, the treating physician considered acyclovir the main reason for nephrotoxicity, whereas a potential competing cause of renal impairment was present among the 15 remaining patients. Hypertension was the only predictive factor associated with nephrotoxicity (risk ratio (RR), 2.77; 95% confidence interval (CI), 1.41-5.46), while having no co-morbidities was protective (RR, 0.32; CI, 0.16-0.63). In all cases, the nephrotoxicity was reversible following rehydration and dose reduction or discontinuation of the drug. However, the normalized plasma creatinine upon treatment was significantly higher between cases with acyclovir-induced nephrotoxicity than cases with a potential competing cause (median [interquartile range (IQR)], 93.5 μmol/L [85-108] vs 75 μmol/L [66.5-88]; p = 0.019). Acyclovir-induced, reversible nephrotoxicity was observed in 5.1-10.5% of patients. It is difficult to predict who will develop acyclovir-induced nephrotoxicity; it may occur late in treatment and hypertension was the only independent predictive factor, while the absence of co-morbidities was protective. Ensuring hydration, frequent evaluations of renal function, and corresponding dose adjustment of intravenous acyclovir treatment seem prudent.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adult; Aged; Antiviral Agents; Cohort Studies; Creatinine; Denmark; Female; Humans; Hypertension; Incidence; Kidney Diseases; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors

Intravenous (IV) acyclovir is commonly administered medication for viral infection but is well known for its nephrotoxicity. However, there was no study for incidence, risk factors, and clinical outcomes of acute kidney injury (AKI) associated with IV acyclovir administration. We retrospectively reviewed the medical records of 287 patients who were medicated IV acyclovir from January 2008 to May 2013 in Gyeongsang National University Hospital. All had documented medical histories and underwent medical review. Demographic data, risk factors, concomitant drugs, laboratory findings and outcome were gathered from the medical records and analyzed. AKI occurred in 51 patients (17.8%). As per RIFLE classification, renal injury was graded as either at risk of renal dysfunction (62.7%), renal injury (15.6%), and renal failure (21.6%). There was no significant difference in age, sex, total dose, drug duration, and presence of hydration between AKI and non-AKI group. However, systolic pressure, underlying diabetes, concomitant vancomycin and non-steroidal anti-inflammatory drugs (NSAIDs) use was positively correlated with AKI occurrence (p = .04, p < .001, 0.01, and 0.04, respectively). Two patients underwent hemodialysis and these patients died. Higher mortality was observed in AKI patients (p < .001). Multivariate analysis also presented that presence of diabetes, concomitant NSAIDs, and vancomycin use was independent risk factor of acyclovir associated with AKI (p = .001, OR 3.611 (CI: 1.708-7.633), p = .050, OR 2.630 (CI: 1.000-6.917), and p = .009, OR 4.349 (CI: 1.452-13.022), respectively). AKI is relatively common in patients administrating acyclovir injection. Physicians should attempt to prevent, detect, and manage acyclovir associated AKI in patients prescribing acyclovir due to possible association of poor prognosis.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Adult; Aged; Antiviral Agents; Female; Glomerular Filtration Rate; Herpesviridae Infections; Humans; Incidence; Kidney; Male; Middle Aged; Prognosis; Renal Dialysis; Republic of Korea; Retrospective Studies; Risk Factors; Survival Rate

Topics: Acute Kidney Injury; Acyclovir; Aged, 80 and over; Antiviral Agents; Crystallization; Diagnosis, Differential; Diuretics; Female; Humans; Microscopy; Renal Dialysis; Urine

Alternaria species have been reported as a rare cause of fungal infection in organ and stem cell transplant recipients, but to date, no reports have been published of infection in humans caused by Alternaria rosae. Here, we report cutaneous A. rosae infection in a 66-year-old farmer with a history of primary myelofibrosis who had undergone allogeneic unrelated donor hematopoietic stem cell transplantation. Forty-nine days post transplant, he presented with a nodule on the thumb with no findings suggestive of disseminated infection. Pathology, culture, and molecular speciation showed the nodule was caused by cutaneous A. rosae. He had been on voriconazole as antifungal prophylaxis, but was found to have a subtherapeutic voriconazole level. He was switched to posaconazole based on published in vitro data showing its superior efficacy in Alternaria treatment. Susceptibility testing showed that the A. rosae isolate was indeed susceptible to posaconazole. His cutaneous lesion remained stable, but he died from respiratory failure secondary to lobar pneumonia. At lung autopsy, A. rosae was not identified in the lungs. We believe this to be the first published report, to our knowledge, of A. rosae infection in humans.

Topics: Acute Kidney Injury; Acyclovir; Aged; Alternaria; Alternariosis; Antibiotic Prophylaxis; Antifungal Agents; Drug Therapy, Combination; Fatal Outcome; Graft vs Host Disease; Hand; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Levofloxacin; Magnetic Resonance Imaging; Male; Microbial Sensitivity Tests; Paranasal Sinuses; Phaeohyphomycosis; Pneumonia; Prednisone; Primary Myelofibrosis; Respiratory Insufficiency; Spores, Fungal; Transplantation, Homologous; Triazoles; Voriconazole

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Herpes Genitalis; Humans; Male; Valacyclovir; Valine

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Birefringence; Chemical Precipitation; Deprescriptions; Encephalitis, Varicella Zoster; Humans; Male; Polymerase Chain Reaction; Urinalysis

Acyclovir (ACV) exposure is a common cause of acute kidney injury (AKI). The toxicity mechanism of ACV has always been a matter of debate. The present study investigated into the time-effect relationship and dose-effect relationship of ACV-induced nephrotoxicity in rats using metabonomics. Twenty-four rats were randomly divided into four groups: a 0.9% NaCl solution group, and 100, 300, and 600mg/kg ACV-treated groups; the ACV or vehicle solution was administered with a single intravenous injection. Urine was collected at different time periods (12h before administration, and 0-6h, 7-12h, and 13-24h after administration). Routine urinalysis was conducted by a urine automatic analyzer. Renal markers, including urine urea nitrogen, urine creatinine, and urinary N-acetyl-β-d-glucosaminidase (NAG) activity, were determined using established protocols. Urinary metabolites were evaluated using ultra performance liquid chromatography/mass spectrometry (UPLC/MS). In the ACV-treated rats, increased levels of protein (PRO), occult blood (BLD), white blood cell (WBC), and NAG activity in urine were observed, while the urine creatinine and urea nitrogen levels showed a decrease compared with the control. Moreover, urine metabolites significantly changed after the treatment with ACV, and all the effects induced by ACV were dose-time dependent. Finally, 4 metabolites (guanine, 4-guanidinobutyric acid, creatinine, and urea) were identified, which can be used for further research on the mechanism of ACV-induced nephrotoxicity.

Topics: Acute Kidney Injury; Acyclovir; Animals; Antiviral Agents; Biomarkers; Dose-Response Relationship, Drug; Kidney Function Tests; Male; Metabolome; Rats, Sprague-Dawley; Time Factors

A cluster of children receiving intravenous (IV) acyclovir for meningoencephalitis developed acute renal failure in April-May 2008, which prompted a retrospective case-control study to determine the rate of and risk factors for acute nephrotoxicity during IV acyclovir treatment in children.. The percentage decrease in glomerular filtration rate in children receiving IV acyclovir who had ≥ 1 creatinine measurement after acyclovir initiation from October 2006 to January 2009 was classified as renal risk, injury, or failure according to modified Pediatric Risk Injury, Failure, Loss, End-Stage Renal Disease criteria. Univariate and multivariate matched analyses were conducted to identify risk factors contributing to nephrotoxicity.. In the selected study group, renal dysfunction was seen in 131 of 373 (35%) treatment courses studied: 81 of 373 (22%) risk, 36 of 373 (9.7%) injury, and 14 of 373 (3.8%) failure. Most renal dysfunction occurred within 48 hours of the initiation of acyclovir. Renal function returned to the normal range but not to baseline in most cases during the follow-up period. Risk factors for renal dysfunction included acyclovir dose >15 mg/kg (OR 3.81, 95% CI 1.55-9.37) for risk; cumulative exposure greater than calculated cumulative exposure based on 500 mg/m(2)/dose (OR 6.00, 95% CI 1.95-18.46) for injury; and age >8 years (OR 21.5, 95% CI 2.2, >1000) and ceftriaxone coadministration (OR 19.3, 95% CI 1.8, >1000) for failure.. Nephrotoxicity associated with IV acyclovir is common and necessitates renal function monitoring. Risk factors include greater dose, older age, and concomitant ceftriaxone administration. Outside the neonatal period, renal dysfunction may be minimized by dosing IV acyclovir below thresholds associated with nephrotoxicity (ie, ≤ 500 mg/m(2)/dose or ≤ 15 mg/kg/dose), particularly in older patients.

Topics: Acute Kidney Injury; Acyclovir; Adolescent; Antiviral Agents; Case-Control Studies; Child; Child, Preschool; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Male; Retrospective Studies; Risk Factors; Young Adult

Topics: Acute Kidney Injury; Acyclovir; Aged; Attitude to Death; Delusions; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Herpes Zoster; Humans; Myoclonus; Nervous System Diseases; Neuropsychological Tests; Renal Dialysis; Risk Assessment

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Female; Humans; Male

Optimal acyclovir dosing under continuous renal replacement therapy (CRRT) in neonates is unknown. We monitored serum acyclovir levels and herpes simplex virus 1 (HSV-1) DNA levels in a neonate with disseminated HSV-1 infection and renal failure undergoing CRRT. A full-term, 5-day-old female presented with a 2-day history of lethargy and fever. She developed fulminant hepatitis and was diagnosed with HSV-1 infection by real-time polymerase chain reaction. Acyclovir was initiated at 60 mg/kg/day, which was lowered to 20 mg/kg/day because of development of renal failure. She was placed on continuous hemodialysis. Acyclovir dosing was adjusted according to serum acyclovir levels, and HSV-1 viral load was sequentially monitored. Semiquantification of serum HSV-1 levels was performed by real-time polymerase chain reaction. Acyclovir levels were measured by using liquid chromatography-tandem mass spectrometry. Acyclovir was administered at 20 mg/kg intravenously over 1 hour; peak concentration was 18.9 μg/mL. The half-life of acyclovir was estimated to be 2 to 3 h. Viral load remained high during dosing every 24 hours, with a decline of 0.17 log copies/24 hours. Acyclovir dosing was changed to 20 mg/kg/dose every 8 hours, with an average viral load decline of 0.44 log copies/24 hours. Despite the guideline recommendation of 24-hour redosing, acyclovir was dialyzed at a rate that resulted in suboptimal treatment. Individual therapeutic drug monitoring for acyclovir and dosing adjustment may be required to optimize therapy for patients undergoing CRRT.

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; DNA, Viral; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hemodiafiltration; Herpes Simplex; Humans; Infant, Newborn; Pregnancy Complications, Infectious; Real-Time Polymerase Chain Reaction; Simplexvirus

A 24-year-old female patient was admitted to the ICU with suspected meningo-encephalitis. She was treated with antibiotics and acyclovir 1500 mg/day. Forty-eight hours later she developed acute renal failure with needle-shaped crystals in the urine. Acyclovir treatment was suspended and renal function replacement therapy was initiated. After two weeks, her renal function had fully recovered. Based on the typical clinical course and the typical crystalluria, we diagnosed her with acyclovir-induced acute renal failure.

Topics: Acute Kidney Injury; Acyclovir; Female; Humans; Meningoencephalitis; Urinalysis; Young Adult

This is a case report of a 69-year-old morbidly obese woman who presented with mental status changes after she was treated with acyclovir for shingles. The predominant symptoms were word-finding difficulties and visual hallucinations. Complicating her presentation was acyclovir-induced acute renal injury causing her creatinine level to rise up to 7.4 mg/dL. Acyclovir was discontinued on the suspicion of acyclovir neurotoxicity. Even though PCR for varicella zoster virus in the cerebrospinal fluid was positive, acyclovir was not restarted and the patient continued to improve and returned to her baseline.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Cerebrospinal Fluid; Encephalitis, Varicella Zoster; Female; Hallucinations; Herpesvirus 3, Human; Humans; Obesity, Morbid; Speech Disorders

Little is known about the effects of drug-drug interactions between valacyclovir and non-steroidal anti-inflammatory drugs (NSAIDs). In this study, we analysed the adverse event 'acute kidney injury (AKI)' resulting from a possible interaction between loxoprofen (a non-selective NSAID) and valacyclovir in reports received by FDA Adverse Event Reporting System (AERS) database between January 2004 and June 2012.. Adverse event reports of elderly patients aged ≥65 years old were included in the study. Exposure categories were divided into three index groups (only valacyclovir or loxoprofen was used, and both drugs were concomitantly used) and a reference group (neither valacyclovir nor loxoprofen were used). Case/non-case AKI reports associated with these drugs were recorded and analysed by the reporting odds ratio (ROR).. In total, 447 002 reports were included in the study. The ROR, adjusted for year of reporting, age and sex, for an AKI in elderly patients who used only valacyclovir or loxoprofen compared with elderly patients who used neither valacyclovir nor loxoprofen was 4.6 (95%CI: 4.1-5.2) and 1.4 (95%CI: 1.2-1.6), respectively, while the adjusted ROR was 26.0 (95%CI: 19.2-35.3) when both drugs were concomitantly used.. Case reports in AERS are suggestive that interactions between valacyclovir and loxoprofen resulting in AKI may occur, while this association needs to be analysed by other methods in more detail in order to determine the real strength of the relationship.

Topics: Acute Kidney Injury; Acyclovir; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Drug Interactions; Female; Humans; Male; Odds Ratio; Phenylpropionates; Valacyclovir; Valine

Acute kidney injury secondary to precipitation of acyclovir crystals in the kidneys is well known and mainly observed in the setting of dehydration or pre-existing renal impairment. We describe a case of acute kidney injury secondary to intravenous administration of acyclovir in a 64-year-old female with trans-versal myelitis and no prior medical history. She developed a rapid rise in the plasma creatinine level only seven hours after the primary drug administration. Acyclovir was discontinued and a urinary flow rate was maintained at 100-200 ml/h with IV fluids. The kidney function returned to normal within five days.

Topics: Acute Kidney Injury; Acyclovir; Administration, Intravenous; Antiviral Agents; Female; Humans; Middle Aged; Myelitis, Transverse

Valacyclovir induced neurotoxicity is a life-threatening complication, usually starting 24-48 h after drug-peak serum concentrations. The elderly with impaired renal function seem to be the most susceptible group to valacyclovir neurotoxicity. Although hemodialysis is considered the best method for rapid drug removal, our case showed that intensive peritoneal dialysis regimen leads to the recovery of neurotoxicity after 3 days.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Female; Follow-Up Studies; Herpes Zoster; Humans; Kidney Failure, Chronic; Kidney Function Tests; Peritoneal Dialysis, Continuous Ambulatory; Risk Assessment; Treatment Outcome; Valacyclovir; Valine

A 23-year-old gentleman with no significant medical history other than obesity was admitted with a history of balance problems, double vision and strange behaviour following a fall from bed. Systems examination was unremarkable. The patient was given intravenous acyclovir and intravenous ceftriaxone given the suspicion of encephalitis/meningitis. Investigations including routine bloods, CT/MRI Head and lumbar puncture were unremarkable. Within 48 h of commencing intravenous acyclovir, there was a marked deterioration in renal function. On stopping acyclovir therapy, renal function improved back to baseline. No other cause for deterioration in renal function was identified. The most likely cause for acute renal failure was secondary to acyclovir therapy. This has been well documented and is due to intratubular crystal precipitation. Moreover, in this case nephrotoxicity is likely secondary to the large boluses of intravenous acyclovir that had been given as prescribed according to the total body weight.

Topics: Accidental Falls; Acute Kidney Injury; Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Ceftriaxone; Encephalitis; Humans; Male; Meningitis; Obesity; Young Adult

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Crystallization; Drug Overdose; Humans; Male; Middle Aged; Uric Acid; Valacyclovir; Valine

Meningitis or encephalitis by varicella-zoster virus (VZV) after hematopoietic stem cell transplantation (HSCT) is rarely reported. We encountered a case of meningoencephalitis with VZV re-activation 18 months after related bone marrow transplantation for recurrent acute lymphoblastic leukemia. The patient had been administered steroid and cyclosporine for chronic graft-versus-host disease. A high DNA copy number of VZV, 4.9×10(7) copies was detected in the cerebrospinal fluid. VZV also caused severe pneumonia and acute renal failure soon after the onset of meningoencephalitis. The patient was successfully treated with acyclovir, although he was left with persistent neurological sequelae. Both prompt diagnosis and early treatment of VZV reactivation are important to avoid a fatal outcome.

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Bone Marrow Transplantation; Chronic Disease; Cyclosporine; Encephalitis, Varicella Zoster; Graft vs Host Disease; Herpesvirus 3, Human; Humans; Immunosuppressive Agents; Male; Pneumonia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Recurrence; Time Factors; Virus Activation

The human breast cancer resistance protein (BCRP/ABCG2) is widely expressed in human tissues, including the kidney. In mice, Bcrp1 (murine BCRP ortholog) mediates the transport of acyclovir into breast milk. It is plausible that acyclovir is also a substrate for the human BCRP. The objective of the study was to determine whether acyclovir is a substrate for human BCRP. Transfected human embryonic kidney (HEK293) cells (containing the wild-type ABCG2 gene) were exposed to [8-(14)C]acyclovir (1 µmol/L) in the presence or absence of the BCRP inhibitor fumitremorgin C (FTC). Intracellular acyclovir accumulation was assessed using a liquid scintillation counter. Coexposure to FTC resulted in a significant (5-fold) increase in the intracellular accumulation of acyclovir. The results suggest that acyclovir is a substrate for human BCRP. The study is the first to provide direct evidence for the role of human BCRP in acyclovir transport and its potential significance with respect to renal tubular transport of acyclovir and the direct renal tubular insult induced by the drug.

Topics: Acute Kidney Injury; Acyclovir; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Biological Transport; Cell Line, Transformed; Female; HEK293 Cells; Humans; Kidney; Kidney Tubules; Neoplasm Proteins; Transfection; Tumor Cells, Cultured

The antiviral molecule acyclovir can be responsible of severe renal dysfunction. Intratubular crystal precipitation of the drug may represent a major pathogenetic mechanism.. A 30-year old, immunocompetent woman was admitted in the neurology unit for a viral meningo-encephalitic syndrome. Intravenous acyclovir was delivered at the dose of 45 mg/kg per day. Despite a neurological improvement, she developed an acute renal insufficiency with the serum creatinine increasing from 63 to 385 micromol/L within 12 days. The urine study revealed great amounts of birefringent crystals which were typical of acyclovir derived crystals according to the spectrophotometric examination. Withdrawal of acyclovir treatment in combination with oral and parenteral hydration resulted in a complete recovery of the renal function. The conditions favouring acyclovir-induced nephrotoxicity are discussed.

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Crystallization; Female; Fluid Therapy; Humans; Infusions, Intravenous; Meningitis, Viral; Treatment Outcome

Acyclovir is an effective, frequently used antiviral agent. Adverse effects of this drug are well known and are especially seen with high doses and/or dehydration. In this article, we report a 6-year-old boy with leukemia with nonoliguric acute renal failure in normal hydration status after using acyclovir treatment. He had no preexisting renal impairment, and there were no additional symptoms. Dimercaptosuccinic acid radionucleid scyntigraphy and other laboratory findings revealed impairment of proximal tubule function, in addition to distal tubule. We emphasize that renal functions should be monitored carefully during treatment with acyclovir, and asymptomatic nephrotoxicity must be kept in mind.

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Child; Herpes Zoster; Humans; Leukemia; Male; Succimer

Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii. Recently, complicated cases have been more frequently reported, even in previously healthy patients. We describe a case of severe MSF complicated by acute renal failure and associated with herpetic oesophagitis. Acyclovir therapy resulted in remission of oesophageal symptoms within 48 h.

Topics: Acute Kidney Injury; Acyclovir; Antibodies, Viral; Antiviral Agents; Boutonneuse Fever; Esophagitis; Herpes Simplex; Herpesvirus 1, Human; Humans; Male; Middle Aged; Rickettsia conorii; Treatment Outcome

Topics: Acute Kidney Injury; Acyclovir; Chickenpox; Child, Preschool; Cyclosporine; Female; Humans; Nephrosis, Lipoid

The increasing use of oral or IV acyclovir to treat infections caused by herpesviridae family involves a rise in the number of observed adverse effects. Neuro- and nephrotoxicity are most serious observed and reported secondary effects. The monitoring of renal function is essential to detect these cases since it develops as a non-oliguric renal failure. Because of this, the outpatient and oral use of the drug can result in an underestimation of the number of cases reported. We report two patients with genital herpes and viral encephalitis that required IV acyclovir. Both inpatients developed an acute renal failure that resolved after the drug was withdrawn.

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Child; Female; Humans

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Herpesvirus 3, Human; Humans; Male; Valacyclovir; Valine

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Male; Middle Aged; Oliguria; Renal Dialysis

A 50-year-old woman developed rapidly progressive acute renal failure on the first day after the administration of intravenous acyclovir for acute left retinal necrosis. Intravenous acyclovir was stopped and replaced with intravitreal injections of ganciclovir sodium (2 mg/0.05 mL) and foscarnet (1.2 mg/0.05 mL) 3 times per week for 4 weeks. Acyclovir-induced renal impairment can be reversed if recognised early and treated with careful, timely body fluid replacement. The necrotising retinitis responded well to intravitreal antiviral agents. No complications were seen at the 6 months' follow-up. Constant vigilance is essential for avoiding acute renal failure when treating ophthalmic conditions with intravenous acyclovir. Systematic monitoring of renal function, urine output, and characteristic symptoms like loin pain is warranted.

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Eye Infections, Viral; Female; Herpesvirus 3, Human; Humans; Middle Aged; Retinal Necrosis Syndrome, Acute

Primary varicella-zoster (VZ) infection is rare in adults, but the rate of morbidity and mortality is higher than in children. Pneumonia is the most common complication of primary VZ infection in adults. Moreover, varicella pneumonia associated with acute renal failure and acute encephalopathy is very rare. This study reports on a case of disseminated VZ infection successfully treated with acyclovir. The patient was otherwise healthy and denied previous systemic or infectious disease. The initial diagnosis was varicella pneumonia. However, multiple organ involvement subsequently was found in several organs, including the kidney, brain, lung, liver, blood, and skin. The reactivation of VZ infection was strongly suspected. Abnormal renal and liver function and thrombocytopenia also were noted. The patient with chickenpox was treated successfully with acyclovir without complication. In conclusion, multiple organ involvement is a rare complication of VZ infection in adults. In the severe case presented here, adequate intravenous acyclovir administration and close observation of the general condition were essential for successfully treating disseminated VZ infection without complications.

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Chickenpox; Encephalitis, Varicella Zoster; Herpesvirus 3, Human; Humans; Male; Pneumonia, Viral

Leptospirosis is an acute generalized infectious disease, caused by spirochaetes, Leptospira interrogans. The severity of the disease ranges from an asymptomatic subclinical course to a fatal outcome. The three cases presented here were diagnosed serologically and had thrombocytopenia and acute renal failure as complication of anicteric leptospirosis. Our first case admitted with clinical presentation of pneumonia but clinical progress and laboratory findings made us to consider leptospirosis. The other two cases presented with aseptic meningitis were diagnosed as anicteric leptospirosis by the serological test results. One of the cases had fatal outcome but could not be strictly correlated with leptospirosis.

Topics: Acute Kidney Injury; Acyclovir; Adult; Aged; Agglutination Tests; Ampicillin; Anti-Bacterial Agents; Antibodies, Bacterial; Ceftriaxone; Clarithromycin; Doxycycline; Drug Therapy, Combination; Enoxaparin; Fatal Outcome; Female; Humans; Leptospira interrogans; Leptospirosis; Male; Middle Aged; Thrombocytopenia; Turkey

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Fluid Therapy; Humans; Kaposi Varicelliform Eruption; Male

Herpetic meningoencephalitis is treated with acyclovir (15 mg/kg/8 h). This higher dosage enhance the risk of acute renal failure.. We report the case of a previously healthy 42 years old man treated by intravenous aciclovir 1g/8 h for a herpetic meningoencephalitis. He presented an acute renal failure and an acute confusional state at the end of the treatment. Renal function and neurologic status improved rapidly with increased hydration and stop of the antiviral therapy.. If acyclovir is usually well tolerated, there is also a risk of acute nephropathy, especially dose-dependent. We point out the need to monitor renal function when high dosage of acyclovir is indicated.

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Humans; Male

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Drug Administration Routes; Glomerular Filtration Rate; Humans; Male

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Coma; Confusion; Female; Humans; Middle Aged; Valacyclovir; Valine

Topics: Acute Kidney Injury; Acyclovir; Aged; Central Nervous System; Cerebrospinal Fluid; Encephalitis, Varicella Zoster; Herpesvirus 3, Human; Humans; Magnetic Resonance Angiography; Male; Skin; Virus Activation

We report a case with microscopic polyangiitis (MPA) complicated by varicella zoster encephalitis. A 60-year-old woman caught a common cold and had acute otitis media in April 1998. Proteinuria and hematuria with hyaline cast were noted at the routine medical check in May, and she was referred to our hospital because of high fever and chest pain. MPA was diagnosed with acute progressive renal failure, pleuritis and elevated anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA). Corticosteroid therapy was administered under hemodialysis but MPA was flared several times with various symptoms including interstitial pneumonitis, alveolar hemorrhage and erythema multiforme exudativum. During the course of the disease she developed disseminated varicella zoster and encephalitis. Positive polymerase chain reaction to varicella zoster in cerebrospinal fluid helped to differentiate her encephalitis from central nervous system symptoms due to microscopic angiitis and herpes simplex encephalitis. Combination of corticosteroid and acyclovir therapies for MPA and varicella zoster encephalitis under hemodialysis were successful. The diagnostic process and therapies to these complicated contexts were thought to be very important.

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Diagnosis, Differential; Drug Therapy, Combination; Encephalitis, Varicella Zoster; Female; Herpes Zoster; Humans; Immunocompromised Host; Methylprednisolone; Middle Aged; Polyarteritis Nodosa; Pulse Therapy, Drug; Renal Dialysis; Severity of Illness Index; Treatment Outcome

Topics: Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Coma; Encephalitis, Viral; Humans; Male

We present a critically ill patient with severe renal failure and anuria who underwent hemodialysis (HD), continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF) at different occasions, with 2 commonly used high-efficiency dialyzers (F-8 and CA-210), while receiving i.v. acyclovir. We estimate that during 24 hours of CVVHD with F-8 dialyzer approximately 18% and during 24 hours of CVVHDF with CA-210 dialyzer approximately 65% of the daily administered acyclovir is removed. This is comparable to the amount removed during 4 6 hours of HD, as reported previously. The percentage acyclovir extraction was 84% and 60% during CVVHD and CVVHDF with F-8 and CA-210 dialyzers, respectively. Acyclovir clearance during CVVHD was 14 ml/min and during CVVHDF was 17 ml/min, with F-8 and CA-210 dialyzers, respectively. Acyclovir half-life was 22.5 and 25.5 hours in 2 occasions off any type of renal replacement therapy, and it was 19.5 hours during CVVHDF with CA-210 dialyzer.

Topics: Acute Kidney Injury; Acyclovir; Anuria; Female; Hemofiltration; Humans; Kidney Transplantation; Middle Aged; Renal Dialysis; Transplantation, Homologous

Several published reports have suggested that oral acyclovir can cause renal insufficiency, but baseline renal function was either abnormal or unclear in those reports. We describe a patient with oral acyclovir-induced acute renal failure and a normal serum creatinine level documented just before exposure to the drug. Conceivably, competition with a cephalosporin for renal tubular elimination predisposed our patient to nephrotoxic serum levels of acyclovir. In addition, the patient had sickle cell trait, which might have contributed to a disproportionate degree of hyperkalemia and acidosis seen early in the patient's clinical course.

Topics: Acidosis, Renal Tubular; Acute Kidney Injury; Acyclovir; Adult; Antiviral Agents; Creatinine; HIV Infections; Humans; Hyperkalemia; Male; Sickle Cell Trait

We report the case of a 65-year-old man treated with intravenous acyclovir and amoxicilline for meningoencephalitis. Six days later, he suddenly developed acute renal failure, associated with central nervous system symptoms. The high acyclovir concentration in plasma and spinal fluid confirmed the hypothesis of acyclovir toxicity. Continuous haemofiltration resulted in a rapid amendment of neurologic and renal symptoms. Despite the high therapeutic index of acyclovir, manifestations of neurotoxicity and nephrotoxicity are not a rare event. The risk is increased in the elderly and in patients with renal insufficiency. Rapid intravenous injections are contraindicated. Continuous haemofiltration is rapidly efficient. The value of acyclovir concentration determination in plasma and spinal fluid are stressed.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Brain Diseases; Humans; Male; Meningoencephalitis

Whole-kidney function and glomerular hemodynamics were evaluated after acute (50 mg/kg, iv, in bolus) and short-term chronic (50 mg mg/kg, ip, 5 days) acyclovir (ACV) and short-term chronic ganciclovir (Gan; 30 mg/kg, ip, 5 days) treatment in envolemic Munich-Wistar rats. The evaluation of whole-kidney function of the ACV groups showed a significant reduction in total GFR (0.96 +/- 0.10 to 0.28 +/- 0.02 mL/min in the acute group, P < 0.05, and 1.04 +/- 0.09 to 0.33 +/- 0.04 mL/min in the chronic group, P < 0.05) with a marked increase in total renal vascular resistance (TRVR) (33 +/- 5 to 122 +/- 26 mm Hg.min/mL in the acute group and 28 +/- 3 to 74 +/- 18 mm Hg.min/mL in the chronic group, P < 0.05) and a reduction in RPF (2.29 +/- 0.25 to 0.81 +/- 0.15 mL/min in the acute group and 2.57 +/- 0.36 to 1.30 +/- 0.40 mL/min in the chronic group, P < 0.05). Conversely, urinary flow (V') was unchanged (3.6 +/- 0.4 to 3.6 +/- 0.2 microL/min in the acute group) or elevated (3.7 +/- 0.6 to 6.6 +/- 1.4 microL/min in the chronic group, P < 0.05). The evaluation of glomerular hemodynamics after ACV treatment showed a reduction in single-nephron GFR (SNGFR) (46.4 +/- 5.3 to 26.2 +/- 3.4 nL/min in the acute group and 38.7 +/- 5.7 to 21.1 +/- 5.7 nL/min in the chronic group, P < 0.05), a significant elevation in total arteriolar resistance (RT) (2.90 +/- 0.44 to 4.94 +/- 0.77 x 10(10) dyn.s.cm-5 in the acute group and 3.72 +/- 0.45 to 9.00 +/- 2.40 x 10(10) dyn.s.cm-5 in the chronic group, P < 0.05) and a severe reduction in glomerular plasma flow rate (QA) (152.6 +/- 29.5 to 103.8 +/- 27.8 nL/min in the acute group and 149.1 +/- 29.8 to 68.5 +/- 10.0 nL/min in the chronic group, P < 0.05). However, the glomerular ultrafiltration coefficient, Kf, was changed only in the chronic group (0.1002 +/- 0.0165 to 0.0499 +/- 0.0090 nL/(s.mm Hg), P < 0.05). After Gan treatment, no changes were observed in GFR (1.04 +/- 0.09 to 0.96 +/- 0.08 mL/min, with the maintenance of RPF (2.57 +/- 0.36 to 2.66 +/- 0.34 mL/min) and a nonsignificant reduction in TRVR (28 +/- 3 to 20 +/- 3 mm Hg.min/mL. The short-term Gan treatment also showed a different pattern in glomerular hemodynamics by inducing an elevation in SNGFR (38.7 +/- 5.7 to 50.3 +/- 2.8 nL/min, P < 0.05) with no changes in QA (150 +/- 30 to 135 +/- 22 nL/min) and a mild vasodilation, RT (3.7 +/- 0.5 to 2.7 +/- 0.3 x 10(10) dyn.s.cm-5, P < 0.05) associated with an increment in Kf (0.1002 +/- 0.0165 to 0.2400 +/- 0.0700 nL/(s.mm

Topics: Acute Kidney Injury; Acyclovir; Animals; Antiviral Agents; Ganciclovir; Glomerular Filtration Rate; Hemodynamics; Kidney; Kidney Glomerulus; Male; Rats; Rats, Wistar; Renal Circulation; Vascular Resistance

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Coma; Drug Overdose; Herpes Zoster; Humans; Male; Sleep Stages

A 9-year-old boy developed acute renal failure following intravenous acyclovir (30 mg/kg per day) administered for 6 days to treat herpetic encephalitis. Physical findings and urine output were normal, except for increasing blood urea nitrogen (BUN), serum creatinine and mild proteinuria. Acyclovir was discontinued. However BUN and serum creatinine continued to increase and peaked on the following day at 8.6 mmol/l of urea (24 mg/dl) and 194 mumol/l (2.2 mg/ml), respectively. Conservative treatment and hydration were carried out. The kidney function returned to normal within 1 week. The use of acyclovir when necessary in renal failure patients is discussed.

Topics: Acute Kidney Injury; Acyclovir; Child; Encephalitis, Viral; Humans; Infusions, Intravenous; Male

We are presenting the case of a seventy-six year old male infected with Herpes zoster of the trigeminal nerve. He had no previous nephropathology, but developed acute renal failure following the administration of an intravenous bolus of Acyclovir. The existing literature was reviewed. Possible pathogenic mechanisms are discussed, and precautions against nephrotoxicity are emphasized.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Cranial Nerve Diseases; Herpes Zoster; Humans; Male; Trigeminal Nerve

Two children who developed acute renal failure in the immediate post-renal transplantation period are presented. Each was immunosuppressed with cyclosporin and was also receiving oral acyclovir for prophylaxis against cytomegalovirus infection. Renal biopsy findings suggested drug toxicity. Discontinuation of acyclovir coincided with reversal of renal impairment. As cyclosporin levels were at the lower end of the therapeutic range, we believe acyclovir to be the likely causative agent.

Topics: Acute Kidney Injury; Acyclovir; Administration, Oral; Adolescent; Biopsy; Child; Cytomegalovirus Infections; Female; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Premedication

To report a case of acute renal failure and neurotoxicity following administration of oral acyclovir.. Medical record of the patient, case reports identified by MEDLINE.. Data were abstracted from relevant published data by Johnson and reviewed by the remaining authors.. A 69-year-old woman was diagnosed with herpes zoster and oral acyclovir was prescribed by her local physician. After approximately two days the patient was taken to the emergency department of a local hospital with signs of acute confusion and acute renal failure. Medications included oxycodone/acetaminophen, alprazolam, prazepam, and digoxin. Pertinent laboratory abnormalities included serum digoxin 4.1 mumol/L, white blood cell count 17.6 x 10(9)/L, blood urea nitrogen (BUN) 24 mmol/L of urea, and serum creatinine 305 mumol/L (patient baseline is 11 mmol/L of urea and 91.5 serum creatinine mumol/L, respectively). Because of increasing lethargy and a focal seizure, she was transferred to our institution. Despite an extensive workup, no organic cause of her altered mental status and acute renal failure was identified. Four days after discontinuation of the acyclovir, without specific intervention, the patient's mental status improved and her BUN and serum creatinine concentrations had decreased to 21 mmol/L of urea and 190.6 mumol/L, respectively. On day 5, the patient was alert and oriented to name, place, year, and month. On day 9, her renal function and mental status had returned to baseline and she was discharged.. Acute renal failure and neurotoxicity are usually associated with intravenous acyclovir. The temporal relationship between the initiation of oral acyclovir therapy and the onset of adverse events, supported by published data of a few similar cases, strongly implicate oral acyclovir as the cause of this patient's acute renal failure and neurotoxicity. This case suggests that elderly patients with mild increased serum creatinine concentrations may be at increased risk and should be monitored closely for signs and symptoms of acute renal failure and neurotoxicity.

Topics: Acute Kidney Injury; Acyclovir; Administration, Oral; Aged; Blood Urea Nitrogen; Confusion; Creatinine; Female; Humans; Seizures; Substance-Related Disorders

Severe neurotoxicity and acute renal failure developed in a patient with newly diagnosed AIDS while receiving high-dosage intravenous acyclovir for disseminated herpes zoster. Hemodialysis resulted in a rapid resolution of neurologic symptoms and was associated with a reduction in plasma acyclovir concentration. Acute hemodialysis therapy should be considered in cases of serious neurotoxicity secondary to acyclovir, especially when accompanied by renal failure.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Acyclovir; Humans; Male; Middle Aged; Nervous System Diseases; Neurotoxins; Renal Dialysis

Topics: Acute Kidney Injury; Acyclovir; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antineoplastic Agents; Cisplatin; Humans; Methotrexate; Penicillins

Topics: Acute Kidney Injury; Acyclovir; Administration, Oral; Glomerulonephritis; Herpes Zoster; Humans; Male; Middle Aged

Of 19 children treated with high-dose intravenous acyclovir, 7, all of whom had encephalitis, also had a restricted fluid intake. Of these, 3 experienced non-oliguric renal insufficiency (plasma creatinine up to 176, 250 and 351 mumol/l, respectively) which resolved within 1 week of discontinuing acyclovir. Renal function was stable in the remaining 4 patients in this group and in the 12 children treated with acyclovir but without fluid restriction. We suggest the decreased renal function resulted from intratubular acyclovir crystalluria.

Topics: Acute Kidney Injury; Acyclovir; Adolescent; Child; Female; Humans; Male; Risk Factors

The occurrence of anuria and stupor in a patient treated with acyclovir afforded the opportunity to discuss the renal and neurological toxicity of this drug. Acute renal insufficiency by crystallization of acyclovir and intratubular obstruction is a not infrequent side effect. The risk depends on the dose, the administration mode, the patient's state of hydration and preexisting renal failure. The evolution is typified by a rapid onset (after 24-48 h) and a prompt recovery after ending the treatment. The demonstration in urinalysis of crystals within leukocytes helps to establish the diagnosis. Neurological involvement can vary from confusion to coma. The cerebrospinal fluid is normal and the electroencephalogram shows diffuse slowing. A favorable outcome after ending treatment is the rule. Awareness of the risk factors associated with renal and neurological toxicity should lead to a reduction of its frequency.

Topics: Acute Kidney Injury; Acyclovir; Aged; Aged, 80 and over; Akathisia, Drug-Induced; Cognition Disorders; Herpes Zoster; Humans; Male

Topics: Acute Kidney Injury; Acyclovir; Encephalitis; Herpes Simplex; Humans; Infusions, Intravenous; Male; Middle Aged

Topics: Acute Kidney Injury; Acyclovir; Charcoal; Exchange Transfusion, Whole Blood; Female; Herpes Simplex; Humans; Infant, Newborn; Infusions, Intravenous

Topics: Acute Kidney Injury; Acyclovir; Adult; Humans; Infusions, Intravenous; Male

Four patients with a chronic fatigue syndrome experienced five episodes of acute renal insufficiency associated with high-dose (500 mg/m2) intravenous acyclovir administered intravenously as one-hour infusions. Nephrotoxicity developed despite precautions to avoid volume contraction. Examination of the urinary sediment of three patients by polarizing microscopy showed birefringent needle-shaped crystals within leukocytes. In the most severely affected patient, a serum creatinine concentration of 8.6 mg/dl developed and the patient underwent percutaneous renal biopsy that revealed foci of interstitial inflammation without tubular necrosis. Urine, blood, and renal tissue levels of acyclovir were high. One patient was rechallenged with low-dose intravenous acyclovir and the four patients later received oral acyclovir, all without adverse effect. The combined data from these patients support crystalluria and obstructive nephropathy as a mechanism of acyclovir-induced renal failure in humans. This experience emphasizes the importance of maintaining adequate hydration during high-dose acyclovir therapy.

Topics: Acute Kidney Injury; Acyclovir; Adult; Crystallization; Humans; Infusions, Intravenous; Kidney

Topics: Acute Kidney Injury; Acyclovir; Coma; Female; Humans; Middle Aged

Topics: Acute Kidney Injury; Acyclovir; Adult; Female; Herpes Simplex; Herpes Zoster; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Neoplasms; Pregnancy; Pregnancy Complications; Virus Diseases