Pre-existing Renal Impairment Research Articles

Reduced renal failure following thoracoabdominal aortic aneurysm repair by selective perfusion.

Renal failure and visceral ischemia are feared complications following thoracoabdominal aortic aneurysm (TAAA) repair, significantly contributing to mortality. This prospective study describes volume- and pressure-controlled perfusion of the renal and visceral arteries during TAAA surgery. In 73 consecutive patients (mean age 59 years), TAAA repair (27 type I, 28 type II, 8 type III and 10 type IV) was performed, using retrograde and selective organ perfusion. Sixteen patients had impaired renal function with blood creatinine higher than 100 mmol/l. During the thoracic part of the procedure, the mean distal aortic pressure was kept above 60 mm Hg by means of left-heart bypass. After opening the abdominal aorta, the renal and visceral arteries were individually perfused by means of perfusion catheters (9 French) in the first 33 patients (group I). Volume flow through each catheter was assessed with ultrasound flow meters and maintained at least at 60 ml/min. In addition to volume flow measurements, catheters with pressure sensors were used in the last 40 patients (group II), allowing pressure-controlled selective perfusion. The extent of the aneurysm was comparable in both groups. Mean cross-clamp time for the thoracic part was 46 min, including proximal anastomosis and reattachment of intercostal arteries. Mean cross-clamp time for the abdominal part was 74 min, including re-implantation of intestinal and renal arteries and selective dacron grafts to the celiac-axis arteries (n = 5), superior mesenteric arteries (n = 8) and renal arteries (n = 25), through which the catheters guaranteed continuous perfusion during the time the anastomosis was performed. Urine output was uninterrupted in all patients, irrespective of cross-clamp time. In group I, one patient (3%) developed renal failure and three patients (9%) required temporary peritoneal dialysis. In group II, no patients developed renal failure and two patients (5%) required temporary peritoneal dialysis. Thirteen patients with pre-existing renal impairment did not deteriorate. No patients developed visceral ischemia or multiple-organ failure. Total in-hospital mortality was 6/73 (8%) and was related to cardiopulmonary complications. Renal and visceral ischemia can be reduced significantly by continuous perfusion during cross-clamping in TAAA repair. Not only sufficient volume flow but also adequate arterial pressure appears to be essential in maintaining renal function.

Clinical risk associated with contrast angiography in metformin treated patients: a clinical review

Recently, concern has been expressed about the hazards of lactic acidosis following the use of intravascular iodinated contrast agents in patients taking metformin. In response the Royal College of Radiologists have issued guidelines for the management of these patients. We have reviewed the reported cases of lactic acidosis and identified that in all cases underlying renal impairment existed. To examine this further we reviewed the notes of 33 in-patients receiving metformin who underwent contrast angiography in our hospital. Twenty-nine patients had a normal serum creatinine prior to the procedure and none had a rise following angiography. Four patients had an abnormal serum creatinine prior to angiography, all four patients showed significant deterioration and all four patients died, two from unrelated causes and two from acute renal failure and acidosis. These data strongly highlight the hazards of intravascular contrast radiology in diabetic patients with pre-existing renal impairment. We have failed to find evidence in support of the Royal College of Radiologists recommendation; instead we recommend that in those patients taking metformin with evidence of renal impairment metformin should be stopped and diabetic control obtained using alternative therapy before proceeding with angiography. Patients with normal renal function taking metformin are not at risk of lactic acidosis following the use of iodinated contrast agents for angiography.

Amphotericin-B colloidal dispersion. A review of its use against systemic fungal infections and visceral leishmaniasis.

Formulation of amphotericin B with sodium cholesteryl sulphate alters the pharmacokinetic properties of the drug, particularly reducing its distribution to the kidneys. The antifungal activity in vitro of amphotericin B colloidal dispersion (ABCD) is similar to that of conventional amphotericin B (C-AmB) against true pathogenic organisms including Blastomyces, Coccidioides, Histoplasma and Paracoccidioides species and the opportunistic organisms such as Candida and Cryptococcus species. In animal models, ABCD was generally less effective than an identical dose of C-AmB, but overall was more effective because of its improved therapeutic index. Although ABCD appeared to be more effective than C-AmB in resolving infection and improving survival in patients with proven or probable invasive aspergillosis, the retrospective design of the study and the greater prevalence of neutropenia in patients treated with the conventional formulation necessitate cautious interpretation of the results. ABCD has been effective and seldom caused nephrotoxicity in patients with fungal infection who had previously failed to adequately respond or had developed renal toxicity with C-AmB. Similarly, ABCD was effective in patients with proven or suspected fungal infection after bone marrow transplantation. Preliminary results from a pilot study comparing ABCD and C-AmB in patients with neutropenia and persistent fever reported similar response rates with both formulations. ABCD is an effective treatment for visceral leishmaniasis in immunocompetent patients. In 1 study, about 12% of ABCD recipients discontinued the drug because of adverse events; infusion-related events were the most common cause of discontinuation. The renal tolerability of ABCD is better than that of C-AmB. ABCD appears to be an effective alternative to conventional amphotericin B in patients with invasive aspergillosis or visceral leishmaniasis and in those with proven or suspected systemic fungal infection who are intolerant of the conventional formulation or have pre-existing renal impairment. Preliminary data also suggest that ABCD is an alternative to C-AmB when used empirically in patients with neutropenia and fever. Nevertheless, the efficacy of ABCD compared with that of the conventional formulation has yet to be adequately demonstrated and the role of ABCD relative to that of liposomal and other lipid-based formulations has not been determined. ABCD, like other lipid-based and liposomal formulations of amphotericin B, has been designed to deliver the active drug to the target site, while reducing renal toxicity. The aim of increasing the therapeutic index compared with C-AmB has been achieved.

An Open Study to Assess the Safety and Tolerability of Meloxicam 15 mg in Subjects with Rheumatic Disease and Mild Renal Impairment

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has shown potent anti-inflammatory properties but good gastrointestinal (GI) renal tolerability. The safety and tolerability profile of orally administered meloxicam 15 mg given once daily over a 28 day treatment period in renally impaired patients with rheumatic disease is presented here. A total of 25 patients (aged 43-78 yr, mean age 70 yr) with rheumatic disease and mild renal impairment were enrolled in this multicentre, open-label study, with 22 patients completing the 28 day treatment period. The median estimated creatinine clearance and N-acetyl-beta-glucosaminidase/creatinine ratios (a marker of renal tubular damage) recorded at day 14, day 28 or 4-7 days after meloxicam treatment was terminated, were not statistically significantly different from baseline values. There was no evidence of accumulation of meloxicam. Overall, meloxicam was well tolerated. The most common adverse events were GI complaints of abdominal pain and dyspepsia. No adverse events related to the urinary system, or increases in serum urea or potassium were recorded. The results suggest that meloxicam, 15 mg once daily, does not further compromise renal function or result in accumulation of meloxicam over this treatment period in patients with pre-existing mild renal impairment.

Single or multiple daily doses of aminoglycosides: a meta-analysis.

To assess relative efficacy and toxicity of aminoglycosides given by single daily dose compared with multiple daily doses. Meta-analysis of 21 randomised trials identified through MEDLARS (1966 to January 1995). Data were overviewed with fixed effects and random effects models and with meta-regression analysis. Total of 3091 patients with bacterial infection, most without pre-existing renal disease. Patients were randomized to receive aminoglycosides once daily or multiple times daily with similar total daily dose. Clinical failure of treatment, nephrotoxicity, ototoxicity, and mortality. Single daily dose regimen produced a non-significant decrease in risk of antibiotic failures (random effects risk ratio 0.83 (95% confidence interval 0.57 to 1.21)). Benefit of once daily dosing was greater when the percentage of pseudomonas isolates in a trial was larger. Once daily administration reduced risk of nephrotoxicity (fixed effects risk ratio 0.74 (0.54 to 1.00)). Similar trends were noted for patients with febrile neutropenia and for children. There was no significant difference in ototoxicity between the two dosing regimens, but the power of the pooled trials to detect a meaningful difference was low. There was no significant difference in mortality. Once daily administration of aminoglycosides in patients without pre-existing renal impairment is as effective as multiple daily dosing, has a lower risk of nephrotoxicity, and no greater risk of ototoxicity. Given the additional convenience and reduced cost, once daily dosing should be the preferred mode of administration.

The Safety and Efficacy of Amphotericin B Colloidal Dispersion in the Treatment of Invasive Mycoses

Amphotericin B colloidal dispersion (ABCD), a novel formulation of amphotericin B and cholesteryl sulfate in a 1:1 ratio, was developed to reduce the toxicity of amphotericin B yet retain its antifungal efficacy. In an open-label trial, ABCD at dosages as high as 6 mg/(kg.d) was administered to 168 patients with documented or presumed systemic mycoses. All patients had responded incompletely to at least 7 days' treatment with conventional amphotericin B (CAB), had experienced CAB-induced nephrotoxic effects, had preexisting renal impairment, or had experienced other CAB-related, treatment-limiting toxic effects. The clinical response to ABCD could be evaluated in 97 patients. Complete clinical response or improvement was noted in 48 (49%) of them after a mean treatment duration of 18.5 days. All 168 enrolled patients were evaluated with regard to safety of the treatment. Even at daily doses as high as 6 mg/kg, and mean and median cumulative doses of 4.0 g and 2.4 g, respectively, ABCD had little renal toxicity: the mean change in serum level of creatinine from baseline to final value was -0.02 mg/dL. Hypokalemia developed in eight patients (5%). This study provides preliminary evidence that ABCD is effective in treating invasive mycoses and lacks the dose-limiting nephrotoxicity of CAB.

The histopathology of X-ray contrast medium induced renal droplets (vacuoles)

A small but significant proportion of patients given X-ray contrast agents subsequently experience a decline in renal function. Experimental studies in rats aimed at identifying the mechanism of renal effects show vacuolation of proximal convoluted tubules. This report documents that such vacuoles normally have a proteinaceous content and that14C-radiolabelled contrast agent (iodixanol) is specifically localised within the vacuolated tubules 24 h after administration. On the basis of the persistence of some large droplets in proximal tubules, a small percentage of the administered dose of X-ray contrast agent appears to be trapped intracellularly within large proteinaceous droplets (the vacuoles) and slowly released over several weeks. Enzyme histochemistry identifies contrast-medium-induced droplets as an abnormal population of lysosomes. We propose that in the absence of pre-existing renal impairment, this slowly reversing lysosomal abnormality of proximal tubules is within the kidney's functional reserve capacity.

Aminosidine (paromomycin) in the treatment of leishmaniasis imported into the United Kingdom

We report 11 patients with leishmaniasis from different endemic areas, treated in the UK with intravenous aminosidine alone or in combination with other drugs. Clinical and parasitological cures were achieved in all 7 patients from the Mediterranean zone who had visceral disease, with one relapse. Two of 4 patients with cutaneous or mucosal disease were cured; the other 2, from Iraq and Iran, did not respond. Toxic effects were high-tone deafness in 2 patients, one of whom had pre-existing renal impairment, and transient, mild elevation of serum creatinine in 3. Aminosidine is an effective, tolerable and relatively non-toxic alternative to existing antileishmanial drugs for the treatment of visceral leishmaniasis. Further studies will be needed to assess its place in cutaneous and mucosal disease.

Failure to demonstrate contrast nephrotoxicity

We tested the hypothesis that there is no difference in the change in serum creatinine level following computed tomography (CT) between those given high osmolality contrast, low osmolality contrast and those not receiving contrast material. Patients were assigned according to current radiological practice to receive one or other type of radiocontrast material or to have a scan without intravenous contrast (plain scan). The CT unit of Royal Newcastle Hospital, a tertiary referral institution. Of 3188 inpatients having a CT scan between June 1988 and December 1989, 1041 patients were eligible (having a first scan in "office hours" outside holiday periods, not due for imminent discharge, aged 18 years or more and not presenting to the Intensive Care Unit or with acute trauma). Twenty-five patients were excluded as baseline measures of renal function were missing and 132 subjects were lost to follow-up, leaving 884 study subjects. CT scans using high osmolality, low osmolality or no contrast (plain scan). Renal impairment as defined by a maximal increase in the serum creatinine level of greater than or equal to 50% or greater than 0.04 mmol/L from the baseline level on at least one of the subsequent four days. Renal impairment was seen in 4% (12 of 292), 12% (23 of 187) and 4% (16 of 405) of patients given high osmolality, low osmolality or no contrast respectively. Age and the baseline level of serum creatinine were independent predictors of the development of renal impairment (P = 0.04 and 0.02 respectively) and those given low osmolality contrast were 3.2 times (95% confidence interval, 1.6-6.3) more likely to develop renal impairment than those given no contrast. There was no excess risk with the use of high osmolality contrast compared to no contrast (odds ratio, 1.06; 95% confidence interval, 0.5-2.3). Selection factors (sicker patients being given low osmolality contrast) are likely to have accounted for the excess risk in the low osmolality group as mortality in hospital was higher in this group than in the others. The 51 patients who developed renal impairment (cases) were matched for age, sex, type of contrast and pre-existing renal impairment with up to three controls (150 patients in total). Cases were more likely to have had a blood transfusion (odds ratio, 6.40; 95% confidence interval, 2.18-22.63) or surgery (odds ratio, 3.22; 95% confidence interval, 1.19-7.65) than controls. Confounding by other factors which impair renal function is likely to explain previous suggestions of an effect of radio-contrast material on renal function. There does not appear to be a risk of renal impairment from the use of high osmolality radiocontrast material (although a small effect or an effect in particular subgroups cannot be excluded by our study). Fear of causing or exacerbating renal damage should not be a reason to use low osmolality contrast material, nor should it be a reason for with-holding contrast studies.

High-dose intravenous IgG treatment and renal function

In an open trial of high dose intravenous IgG (IVIG) treatment in nephrotic patients with glomerulonephritis, the first six patients so far studied showed a transient rise in plasma creatinine. This increase was not associated with any symptoms and the urinary deposit remained unchanged. Two other patients with pre-existing renal impairment but without nephrotic syndrome had a transient and reversible rise in plasma creatinine immediately after IVIG. These observations suggest that high-dose IVIG infusion can produce short-lived disturbances in renal function in patients with kidney diseases.

Sulfate homeostasis. III. Effect of chronic naproxen or sulindac treatment on inorganic sulfate disposition in arthritic patients with renal impairment.

The purpose of the present investigation was to examine the influence of chronic naproxen (500 mg twice daily) or sulindac (200 mg twice daily) therapy on the disposition of inorganic sulfate in arthritic subjects with impaired renal function. Subjects were studied during a control period (after a 7-day NSAID washout) and after 14 days of treatment with either naproxen or sulindac. During the control period subjects in this investigation exhibited higher serum sulfate concentrations and lower sulfate renal clearance values than reported for younger subjects with normal renal function. Treatment with either sulindac or naproxen significantly decreased creatinine clearance. Sulindac therapy also increased the serum sulfate concentration and decreased the clearance of sulfate; a similar trend was observed after naproxen therapy but the average change was smaller and not statistically significant. There were significant correlations between the creatinine and the sulfate clearances or serum concentrations. The glomerular filtration rate of inorganic sulfate was not altered by drug treatment and there was no impairment of reabsorption. The serum concentrations and renal clearance of other electrolytes (sodium, potassium, magnesium, calcium, phosphorus) were largely unaffected. Therefore, chronic treatment with naproxen or sulindac decreases the renal clearance of endogenous sulfate in humans: this appears to be a consequence of the decrement in renal function observed in subjects with preexisting mild renal impairment.

Liposomal amphotericin B (AmBisome) in the treatment of fungal infections in neutropenic patients

The use of high-dose chemotherapy and the subsequent prolonged neutropenia in patients with haematological diseases has resulted in an increased incidence of fungal infections. The diagnosis and treatment of these infections in neutropenic patients pose major therapeutic problems. The only drug with proven efficacy in the treatment of deep-seated fungal infections, including invasive aspergillosis, is amphotericin B. Unfortunately, this drug has adverse side effects, most importantly dose-dependent nephrotoxicity; furthermore, some patients fail to show a response to amphotericin B. We have treated 20 patients undergoing myeloablative chemotherapy and/or bone marrow transplantation for haematological diseases with liposomal amphotericin (AmBisome) for proven or suspected aspergillosis. Eighteen patients had diffuse interstitial pneumonitis and two patients had suspected fungal liver abscesses. Five patients had mycologically proven fungal infection and of these, three patients (60%) showed a complete response to liposomal amphotericin. Eleven patients received liposomal amphotericin because of the failure of conventional amphotericin B to eradicate proven or suspected fungal infection. Five of these 11 patients (45%) showed a complete clinical response to liposomal amphotericin. Eight patients received liposomal amphotericin because of pre-existing renal impairment or nephrotoxicity caused by conventional amphotericin B. Four of these patients (50%) showed a response to liposomal amphotericin. Recovery from probable fungal infection in this group of patients occurred when there was complete remission of underlying disease and recovery of neutrophil counts, when they were concurrently treated with liposomal amphotericin.

Cephalosporin-Induced Nephrotoxicity: Does it Exist?

The literature has been reviewed to determine whether cephalosporins have been implicated in causing nephrotoxicity and to assess the influence of concomitant aminoglycoside therapy. Animal and human data have implicated cephaloridine and cephalothin in causing nephrotoxicity, both alone and in combination with aminoglycosides. There are few data implicating other cephalosporins in causing nephrotoxicity. Cefazolin, which is nephrotoxic in animals, has not been reported to produce nephrotoxicity in humans. Two studies have documented nephrotoxicity due to ceftazidime, especially in patients with preexisting renal impairment. Such patients should have their dosage adjusted to minimize ceftazidime-induced renal impairment. Finally, cephalosporins other than cephaloridine and cephalothin have not been documented to increase the risk of nephrotoxicity when used in combination with aminoglycosides compared with aminoglycosides alone.

Renal Hemodynamic Consequences of Angiotensin-Converting Enzyme Inhibition in Congestive Heart Failure

Angiotensin-converting enzyme (ACE) inhibitors are of benefit in the management of heart failure. In some studies in patients with heart failure, a decline in renal function occurred more frequently in patients treated with enalapril maleate, a longer-acting agent, than in those treated with captopril, a shorter-acting drug. Patients experiencing a decline in renal function had a number of predisposing hormonal and hemodynamic factors. In one report, these factors included an initial fall in blood pressure that was sustained, lower cardiac output, and a relatively high fixed dose of enalapril that contributed to renal impairment. In a second study, the decline in renal function was most severe in patients with a lower systemic arterial pressure in whom glomerular filtration may have been dependent on angiotensin II. In a third study, intravascular volume depletion and an activated renin-angiotensin system led to reduced renal function. Reduction of angiotensin II level in plasma and tissues by ACE inhibitors decreases systemic vascular resistance and efferent arteriolar tone, which tends to decrease glomerular filtration rate. If compensatory increases in cardiac output are inadequate or preexisting renal impairment or volume depletion is present, renal function will deteriorate. Long-acting ACE inhibitors prolong the decreased efferent arteriolar tone and may compromise cardiac muscle response to catecholamines. The use of shorter-acting agents in patients who exhibit deterioration in renal function may be preferable.

Treatment of gram-negative infections in patients with renal impairment: new alternatives to aminoglycosides.

Aminoglycosides have become an indispensable component in the armamentarium against serious gram-negative infections. In spite of the availability of effective guidelines for prevention, the frequency of toxic side effects associated with aminoglycoside therapy is an impetus for the substitution of safer and equally efficacious alternatives, particularly in the setting of renal impairment. Recently, three new classes of antibiotics with potent gram-negative activity have become available. These are the monobactams, the carbapenems, and the fluorinated 4-quinolones. The antimicrobial spectrum of aztreonam, a monobactam, closely resembles that of aminoglycosides. Imipenem, a carbapenem, is a broad spectrum antibiotic with activity against gram-negative aerobes as well as gram-positive aerobes and many anaerobes. Ciprofloxacin, an orally active quinolone, has gram-positive and gram-negative coverage against aerobes but not anaerobes. These agents offer an alternative therapeutic option to aminoglycosides and, in the setting of pre-existing renal impairment, are particularly attractive in view of their safety.

Effects of intravenous infusion of urographic contrast agents on glomerular filtration rate, serum concentration and urinary excretion of uric acid in subjects with normal renal function.

The utilization of modern triiodinated radiocontrast agents for intravenous urography (IVU) is widely considered as a very safe procedure in patients free of currently well defined risk factors, amongst which the prominent ones are preexisting renal disease and diabetes mellitus complicated by deteriorated renal function (1,2,3). Whereas the incidence of nephrotoxicity accidents is extremely low in patients with no preexisting renal insufficiency, the risk of an acute, and sometimes definitive, deterioration of renal function following administration of radiocontrast agents has been evaluated as high as 90 % in insulin dependent diabetic patients with severe preexisting renal impairment (1).

Oral-pharyngeal histoplasmosis

Histoplasmosis is a rare disease in India. We are reporting this disease in a middle-aged non-Caucasian male who has never travelled outside India. Successful treatment was achieved with the nephrotoxic anti-mycotic drug (Amphotericin B), despite a pre-existing renal impairment.

Renal function during cefoperazone treatment

Renal function was studied in 19 patients with varying degrees of renal impairment during treatment with cefoperazone in doses from 43 to 75 mg/kg body weight. Cefoperazone showed a low degree of nephrotoxicity. Increasing levels of alanine aminopeptidase or β2-microglobulin in the urine related to the cefoperazone treatment was not seen in any patient. A decrease in glomerular filtration rate, as measured by 51Chrome-EDTA clearance, was seen in two patients one of whom had a pre-existing liver derangement and renal impairment and was treated for 3 weeks with a relatively high dose.

Evaluation of amikacin dosage regimes in the low and very low birthweight newborn.

The recommended neonatal dosage regime for amikacin of 15 mg/kg/day was found to be unsatisfactory in four neonates and a loading dose of 10 mg/kg did not improve levels in two further newborns with normal renal function. Fourteen neonates on 20 mg/kg/day regime achieved satisfactory levels; peak values were 21.5 +/- 4.5 microgram/ml and trough levels 3.34 +/- 2.05 microgram/ml. Peak time ranged from 17 to 60 minutes and varied with the dose given. The half-life was related to plasma creatinine, urea, post-natal age and weight. Thirteen neonates with pre-existing renal impairment were managed by alteration of dosage interval or quantity given. Side-effects were confined to eosinophilia in six infants, and no definite nephrotoxicity or gross eighth nerve damage was demonstrated.

Renal function during cefuroxime treatment in patients with pre-existing renal impairment.

Renal function during cefuroxime treatment in patients with pre-existing renal impairment.