Single-dose intravesical amikacin instillation for pyocystis in a patient with autonomic dysreflexia: A case report.

CONTEXT: Pyocystis is an infection of the epithelium of the bladder and a frequent complication of anuria. Patients with spinal cord injury (SCI) at the sixth thoracic vertebra (T6) or higher are at a greater risk for autonomic dysreflexia (AD), which can be induced by infections such as pyocystis. Cases of pyocystis treatment with aminoglycoside instillations have been reported in the literature. FINDINGS: We describe the case of a 59-year-old male with T1 American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A complete paraplegia, status post bilateral nephrectomy with recurrent episodes of AD suspected to be caused by pyocystis related to anuria. A bladder specimen culture grew Escherichia coli susceptible to amikacin with a minimum inhibitory concentration (MIC) of ≤ 8 mg/L. In the setting of anuria and with concern that intravenous antibiotics would not adequately reach the site of infection, we chose to treat the patient with a single-dose intravesical instillation of amikacin 25 mg/100 mL left to dwell for approximately 2 h. A repeat bladder culture showed no colonies. The patient remained stable with no episodes of AD and no signs or symptoms of infection one month following treatment. CONCLUSION: The purpose of this case report is to add to the current literature on intravesical aminoglycoside instillations for pyocystis to aid clinicians in treating future cases, as well as to highlight pyocystis as a potential cause of AD in SCI patients with anuria.

Effect of losartan on the recoverability of renal function in anuric and oliguric patients with a solitary obstructed kidney: a double-blind randomized placebo-controlled trial.

OBJECTIVES: To assess the role of the angiotensin receptor blocker losartan on the recoverability of renal function after de-obstruction in patients with anuria and oliguria. MATERIALS AND METHODS: This was a double-blind randomized placebo-controlled trial in anuric or oliguric patients with calcular obstruction of solitary kidney. Patients with an anomalous kidney or those with an American Society of Anesthesiology score of >3 were excluded. After relief of obstruction, patients were allocated to receive either losartan potassium 25 mg or placebo for 3 months. Serum creatinine (sCr) and renographic glomerular filtration rate (GFR) were measured at nadir and after 3 months. Changes in sCr and renographic GFR were calculated by subtracting the values at nadir from those at 3 months. Improvement, stabilization or deterioration of sCr and renographic GFR were defined as percentage increase or decrease from nadir ≥10%, while changes <10% were considered as stabilization. RESULTS: A total of 76 patients completed 3 months of follow-up. Demographics and peri-operative data were comparable in the two groups. The median (range) sCr change was -1.05 (-1.8, 0.4) and -0.5 (-1.3, 0.1) mg/dL in the losartan and placebo, groups, respectively (P = 0.07). In the losartan group, renographic GFR had improved in 26 (59.1%) and deteriorated in six (13.6%) patients, while, in the placebo group, it had improved in eight (25%) and deteriorated in 10 patients (31.3%; P = 0.01). Losartan also enhanced renographic GFR improvement vs placebo by a median (range) of 6.9 (-9, 44) vs 1.4 (-10, 32) mL/min (P = 0.004). CONCLUSIONS: In patients with anuria and oliguria, losartan treatment contributes to renal function recoverability after relief of calcular obstruction of the solitary kidney.

Utilizing physiologically based pharmacokinetic modeling to predict theoretically conceivable extreme elevation of serum flecainide concentration in an anuric hemodialysis patient with cirrhosis.

PURPOSE: Higher drug concentrations in complex clinical scenarios in which multiple factors such as drug-drug interactions (DDIs) and comorbidities are simultaneously present are not necessarily rationalized in prospective clinical studies. Physiologically based pharmacokinetic (PBPK) modeling and simulation of the anti-arrhythmic drug flecainide, as an example, were utilized to quantitatively rationalize the higher flecainide concentration in a complex clinical case involving end-stage renal disease (ESRD), cirrhosis, and the co-administration of mexiletine, a CYP1A2 inhibitor. METHODS: The developed flecainide PBPK model was used to evaluate the DDI effect (as measured by AUC ratio before and after inhibition) of mexiletine and the combined disease effects of ESRD and cirrhosis on flecainide exposure. RESULTS: The predicted DDI effect of mexiletine was negligible or weak in anuric hemodialysis with cirrhosis population (mean [5th/95th percentiles], 1.23 [0.97-1.67]), although it was negligible in healthy volunteers (1.03 [1.02-1.05]). The predicted flecainide concentrations after multiple flecainide doses (50 mg BID) in the anuric hemodialysis with cirrhosis population were comparable with the observed value (3602 ng/mL), which fell between the predicted concentrations in the absence and presence of mexiletine (3043 [718-8499] and 5914 [880-20,624] ng/mL, respectively). CONCLUSIONS: The PBPK simulation proposed a likely explanation that the observed higher flecainide concentration could be attributed to the combined effects of ESRD, cirrhosis, and a potential DDI with mexiletine. This approach provides quantitative insight into theoretically conceivable extremes in drug exposure occurring in complex clinical situations even if uncommon.

Thiazide increases serum calcium in anuric patients: the role of parathyroid hormone.

We evaluated the effect of hydrochlorothiazide in a sample of anuric patients on hemodialysis and found an increase in serum calcium, which occurred only in those with parathyroid hormone >300 pg/ml. This finding highlights the extra-renal effect of this diuretic and a possible role of parathyroid hormone in the mechanism. PURPOSE: Thiazide diuretics are commonly used in patients with chronic kidney disease to treat hypertension. Their effects on calcium and bone metabolism are not well established, once calciuria may not fully explain levels of calcium and parathyroid hormone (PTH) in this population. A previous study has suggested that thiazides require the presence of PTH as a permissive condition for its renal action. In anuric patients, however, the role of PTH, if any, in the thiazide effect is unknown. METHODS: To assess thiazide extra renal effect on serum calcium and whether such an effect is reliant on PTH, hydrochlorothiazide (HCTZ) 100 mg was given orally once a day to a sample of 19 anuric patients on hemodialysis for 2 weeks. Laboratories' analyses were obtained in three phases: baseline, after diuretic use, and after a 2-week washout phase. RESULTS: We demonstrated that serum calcium (Ca) increased in ten patients (52.6%) after HCTZ use, returning to previous levels after the washout period. Out of the 19 patients, ten presented PTH ≥ 300 pg/ml, and Ca has increased in eight of them, whereas in the other nine patients with PTH < 300 pg/ml, serum Ca has increased only in two individuals (RR risk of increase Ca 3.9; p = 0.012). CONCLUSIONS: HCTZ was capable of increasing serum Ca in a sample of anuric patients on hemodialysis and seems this effect is highly dependent on PTH levels. Caution is required while interpreting this result, as the small sample size might implicate in a finding caused by chance.

Point-of-Care Ultrasound to Assess Anuria in Children.

Anuria in children may arise from a host of causes and is a frequent concern in the emergency department. This review focuses on differentiating common causes of obstructive and nonobstructive anuria and the role of point-of-care ultrasound in this evaluation. We discuss some indications and basic techniques for bedside ultrasound imaging of the urinary system.

The pharmacokinetics of ampicillin-sulbactam in anuric patients: dosing optimization for prophylaxis during cardiovascular surgery.

Background The administration of antibiotic prophylaxis during cardiothoracic surgery can reduce the rate of surgical site infections. Trials of cardiothoracic antibiotic prophylaxis have found it to be beneficial in preventing postoperative wound infections. Objective To determine the more appropriate timing of repeated doses of ampicillin-sulbactam to maintain adequate antibiotic concentrations during cardiovascular surgery in anuric patients. Method Five adult anuric dialysis patients who received ampicillin-sulbactam during cardiovascular surgery at Kagoshima University Hospital, the total plasma concentrations of ampicillin and sulbactam were monitored after ampicillin (1 g)-sulbactam (0.5 g) administration. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin and sulbactam. Results The mean values for the volume of distribution, total clearance, elimination rate constant and the elimination half-life for ampicillin were 8.9 ± 2.4 L, 1.69 ± 0.93 L/h, 0.180 ± 0.059 h(-1) and 4.23 ± 1.48 h, respectively. The pharmacokinetic parameters were similar to those of sulbactam. When ampicillin (1 g)-sulbactam (0.5 g) was intravenously administered at 8, 12 and 24 h intervals, the predicted free trough plasma concentrations of ampicillin were 28.72, 12.06 and 1.25 µg/mL, respectively. Conclusion We suggest that ampicillin (1 g)-sulbactam (0.5 g) should be intravenously administered every 12 h in order to maintain a free ampicillin concentration of more than 12 µg/mL in anuric patients during cardiovascular surgery.

Resolution of refractory hypotension and anuria in a premature newborn with loss-of-function of ACE.

We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most often result in fetal demise during gestation or in the first days of life and typically as a result of the Potter sequence. The premature delivery, and serendipitous early treatment with vasopressin, and then later fludrocortisone, resulted in an optimal outcome in an otherwise lethal condition.

Does the inhibition of renin-angiotensin system decrease inter-dialytic weight gain in anuric hemodialysis patients?

OBJECTIVE: Knowledge about the inhibition of centrally located angiotensin-I (AT-I) receptors by highly lipophilic AT-I receptor blockers and its' effect are limited with experimental studies. Thus, we aimed to investigate the effect of Telmisartan on Inter-dialytic weight gain (IDWG) % and echocardiographic measurements in anuric hemodialysis (HD) patients. PATIENTS AND METHODS: A total of forty-one anuric HD patients with ≥ 6 months maintenance on HD were included in this prospective, randomized and self-controlled study. Four weeks prior the study, angiotensin converting enzyme blockers and AT-I receptor blocker drugs were stopped. Patients were assessed three times during the study protocol. These are baseline, three months later (without Telmisartan period) and three months after Telmisartan therapy. RESULTS: IDWG % was significantly decreased in the period of with Telmisartan compared to period without Telmisartan (5.6 ± 1.0% vs 5.3 ± 1.0%, p = 0.03). After the administration of Telmisartan left ventricule end-diastolic diameter (LVEDD) (p = 0.001) and inferior vena cava diameter (IVCD) (19.1 ± 3.8 mm vs 17.3 ± 4.2 mm, p = 0.001) were significantly decreased compared to the period of without Telmisartan. Despite of significantly changes observed in IVCD and LVEDD measurements in a period without Telmisartan, there was no significantly difference in left ventricular mass index (LVMI) measurements in this period. However, LVMI was significantly regressed after the administration of Telmisartan (269.3 ± 82.7 g vs 256.3 ± 70.3 g, p = 0.003 respectively). CONCLUSIONS: Treatment of anuric HD patients with Telmisartan at a dose of 40 mg a day reduces IDWG%, LVEDD and IVCD measurements. Further studies investigating the long-term effect of these beneficial effects on clinical outcomes are necessary.

Aminophylline improves urine flow rates but not survival in childhood oliguric/anuric acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) morbidity and mortality rates remain high. Variable AKI outcomes have been reported in association with aminophylline treatment. This study evaluated AKI outcome in a group of Nigerian children treated with aminophylline. METHODS: This is a retrospective study of AKI in children treated with (N=9) and without (N=8) aminophylline. Studied outcome indices comprised urine flow rate (UFR), duration of oliguria/anuria, progression through AKI stages, number of patients requiring dialysis and mortality. RESULTS: Mean ages for the control and aminophylline arms were 4.6±2.7 and 4.9±2.1 years (P=0.7), respectively. All patients progressed to stage-3 AKI. Baseline median UFRs in the aminophylline and control arms were similar (0.13 Vs 0.04 ml/kg/hour respectively, P=0.5). The median UFR was significantly higher on day-5 (0.8 Vs 0.1; P=0.03), day-6 (1.0 Vs 0.2; P=0.02), and day-7 (1.2 Vs 0.2; P=0.03) in the aminophylline than the control arm, respectively. Short duration of oliguria/anuria (≤ 6 days) was more frequently observed in aminophylline- treated patients compared to controls (77.8% Vs 25.0%; odds ratio 0.09; 95% CI: 0.01-0.89; P=0.04). Only the aminophylline group maintained steady serum creatinine levels. Four out of five patients in the control group were dialyzed compared to only one out of eight patients in the aminophylline group (odds ratio 0.16; 95% CI: 0.04-0.71; P=0.03). Mortality rates were similar in aminophylline- treated and control patients (33% Vs 25%; hazard ratio 0.8; 95% CI: 0.1-5.5; P=0.8). CONCLUSION: Aminophylline therapy was beneficial for patients with AKI in terms of improved UFR and reduced need for dialysis, but failed to impact positively on survival.

Effect of eplerenone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric chronic hemodialysis patients - a pilot study.

INTRODUCTION AND AIMS: Recent studies have suggested that aldosterone has many effects in addition to its ability to cause the kidney to retain sodium. To test the hypothesis that aldosterone can cause hypertension in a manner that does not involve renal sodium retention, we administered eplerenone, a specific aldosterone antagonist, to oligo-anuric chronic hemodialysis patients who had HTN. METHODS: 220 chronic hemodialysis patients underwent initial screening. Of these, 8 patients were followed for 8 weeks and their blood pressure, weight, plasma potassium, aldosterone levels and plasma renin activity were recorded. After a 4 week run in period, each patient received eplerenone 25 mg twice daily for another 4 weeks. RESULTS: Administration of eplerenone for 4 weeks decreased predialysis systolic blood pressure from 166 ± 14 to 153 ± 10 mmHg (p < 0.05). Eplerenone had no effect on diastolic blood pressure, potassium, predialysis weight, intradialytic weight gain, plasma aldosterone or PRA. CONCLUSION: Eplerenone significantly reduces systolic blood pressure in oligo-anuric hypertensive hemodialysis patients without effect on plasma aldosterone concentrations or plasma renin activity. Plasma potassium increases minimally after 4 weeks of therapy, a finding that raises some concern for long-term eplerenone use in chronic hemodialysis.

Effect of spironolactone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric hemodialysis patients.

BACKGROUND: Through its actions on nonepithelial tissues, including brain, blood vessels, and heart, aldosterone may mediate hypertension, cardiac hypertrophy, and fibrosis. Whether aldosterone has a direct pathogenic role in the development of cardiovascular complications in patients with end-stage renal disease is unknown. Oligo-anuric dialysis patients provide a clinical setting to study the effects of the mineralocorticoid receptor blocker spironolactone that are independent of the diuretic properties of the drug. We performed a randomized, double-blinded, placebo-controlled, crossover study to assess the effect of spironolactone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric hemodialysis patients. METHODS: Eight hemodialysis patients were administered either spironolactone, 50 mg, or placebo orally twice daily for 2 weeks, followed by a 3-week washout period, after which patients crossed over in their treatment arms for 2 more weeks. RESULTS: Administration of spironolactone for 2 weeks decreased predialysis systolic blood pressure from 142.0 +/- 19.6 to 131.4 +/- 18.2 mm Hg (P < 0.05). Compared with placebo, a 2-week course of spironolactone had no effect on predialysis and postdialysis plasma potassium or aldosterone concentrations or renin activity. CONCLUSION: When administered for 2 weeks, spironolactone, 50 mg twice daily, reduced predialysis systolic blood pressure, but did not produce hyperkalemia in oligo-anuric hemodialysis patients.

Glycyrrhetinic acid decreases plasma potassium concentrations in patients with anuria.

ABSTRACT. Licorice-associated hypertension is thought to be due to increased renal sodium retention. The active compound of licorice, glycyrrhetinic acid (GA), inhibits renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and by that mechanism increases access of cortisol to the mineralocorticoid receptor that causes renal sodium retention and potassium loss. In addition, a direct vascular effect of 11beta-HSD activity has recently been incriminated to promote hypertension, a contention based on in vitro observations. This investigation was designed to establish whether this extrarenal effect of 11beta-HSD is relevant for BP regulation and potassium concentrations in plasma. In a prospective, double-blind, cross-over study, seven patients with anuria on chronic hemodialysis were randomly assigned after a baseline period of 2 wk to placebo or GA (1 g/d) for 2 wk, separated by a washout phase of 3 wk. The ratio of plasma cortisol/cortisone, determined by gas chromatography-mass spectrometry, increased in all patients after GA intake (F = 9.705; P < 0.004), which indicates inhibition of 11beta-HSD. Twenty-four-hour BP values did not change throughout the study. The increase of the plasma cortisol/cortisone ratio was paralleled by a decline in the plasma potassium concentration in every patient. The mean +/- SD plasma potassium concentration decreased from 5.5 +/- 0.6 mM/L at baseline to 4.9 +/- 0.7 and 4.5 +/- 0.8 mM/L after 1 and 2 wk on GA, respectively (F = 9.934, P < 0.003). Extrarenal 11beta-HSD activity influences serum potassium concentrations but does not regulate BP independently of renal sodium retention.

Pharmacokinetics of cefpirome during continuous venovenous hemofiltration: rationale for an 8-hour dosing interval.

OBJECTIVE: Cefpirome is a new semisynthetic cephalosporin, primarily eliminated by the kidneys, that requires dosage adjustment in patients with kidney failure. The optimal dosing regimen of cefpirome in patients with continuous veno-venous hemofiltration (CVVH) is unknown. METHODS: Pharmacokinetic properties of cefpirome were investigated in eight anuric patients with acute kidney failure treated by CVVH. All patients received a dosage of 2 g cefpirome every 8 hours after starting the hemofiltration with high-flux polysulfone membranes. Concentrations of cefpirome in plasma and ultrafiltrate were measured by HPLC. RESULTS: Total clearance and hemofiltration clearance of cefpirome were 589.1 +/- 164.5 mL/min and 43.3 +/- 7.8 mL/min, respectively. Serum elimination half-life was 2.36 +/- 0.59 hours. The highest plasma drug concentration was 14.8 +/- 3.2 microg/mL, and it declined to trough levels of 3.1 +/- 0.8 microg/mL at the end of the dosing interval. CONCLUSION: On the basis of previously published pharmacodynamic characteristics of cefpirome and the pharmacokinetic parameters obtained in this study, we calculated a required total daily dose of 2 g every 8 hours to achieve sufficient plasma antibiotic levels to cover the majority of target pathogens. However, this dosage may be insufficient during CVVH for intermediate resistant strains of Pseudomonas aeruginosa.

[Anuria after abdominal surgery in 2 newborn infants. Beneficial effect of noradrenaline]. / Anurie après chirurgie abdominale chez deux nouveau-nés. Effet bénéfique de la noradrénaline.

BACKGROUND: Abdominal surgery in neonates may be complicated by acute renal failure that is sometimes due to increased intra-abdominal pressure. Correction of the decreased renal perfusion may be difficult. CASE REPORTS: Case no 1. A girl weighing 3,000 g was operated on at 3 hours of life for congenital omphalocele. Closing the defect induced increased intra-abdominal pressure and decreased systemic pressure. Despite dopamine, dobutamine, followed by furosemide, anuria persisted without manifestations of heart failure. Noradrenaline (0.1 to 0.7 micrograms/kg/min intravenously) given 24 hours after surgery resulted in normalization of systemic pressure and diuresis. Case no 2. A boy was born at gestational week 30, weighing 1,450 g. At 8 days of age, he was suffering from shock that was attributed to perforation of the bowel due to necrotizing enterocolitis. Surgery was complicated by acute circulatory and renal failure that did not respond to dopamine, dobutamine or furosemide. Infusion of noradrenaline, (0.2 to 0.6 micrograms/kg/min intravenously) induced diuresis within 3 hours. CONCLUSIONS: Noradrenaline can be useful in patients with postoperative increased intra-abdominal pressure. It should only be given after correction of hypovolemia, control of myocardial function, and when dopamine remains ineffective.

Efficacy of low-dose dopamine infusion.

Urine output following administration of a low-dose dopamine infusion was assessed in 20 very immature infants (median gestational age 27 weeks). Prior to the infusion, all infants had had a period of anuria. Urine output improved significantly during the second 24 h after commencing the infusion but, at that time period, urine output was greater than 2 ml/kg/h (designated a good response) in only 13 infants. There was no significant difference in gestational age, birth weight, period of anuria or fluid input of infants who had a good or a poor response to dopamine. Although the baseline blood pressure did not differ significantly between these two groups, the increase in blood pressure resulting from dopamine administration was significantly greater in those infants with a good response in urine output (p < 0.02). We conclude that low-dose dopamine infusion can improve urine output in very immature infants. Our results suggest that there may be inter-individual variation in the sensitivity to dopamine.