Marius C. Florescu

Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections

Objective: Higher vancomycin concentrations are thought necessary for treatment of deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infection, yet this may result in greater risk of nephrotoxicity. We evaluated the relationship of serum vancomycin trough concentration with clinical outcomes and nephrotoxicity for patients with deep-seated MRSA infection. Methods: A retrospective cohort study evaluated adults with MRSA pneumonia, endocarditis or osteomyelitis who received vancomycin for ≥ 5 days from June 2005 to June 2007. Patients were stratified by mean vancomycin trough level [low (< 15 mg/l), high (≥ 15 mg/l)]. Outcomes were clinical response, mortality, length of stay (LOS) and nephrotoxicity. Three definitions of nephrotoxicity were used: i) rise in serum creatinine (SCr) ≥ 0.5 mg/dl; ii) 50% increase in SCr; and iii) 25% decrease in estimated creatinine clearance. Results: Fifty-five patients experiencing MRSA pneumonia (n = 28), endocarditis (n = 9), osteomyelitis (n = 20) and multiple infections (n = 2) were stratified into low (n = 39) and high (n = 16) groups. High group patients were more likely to be septic (p = 0.01) and have a higher APACHE II score (p = 0.01). After adjustment for APACHE II score, clinical response rates among survivors did not differ significantly. Risk of death was not significantly different between the high (19%) and low (5%) group patients (p = 0.1). LOS did not differ significantly between groups (p = 0.7). Nephrotoxicity occurred in the low and high groups, respectively, for 10 and 31% (p = 0.04) with definition 1, 10 and 31% (p = 0.04) with definition 2, and 13 and 25% (p = 0.1) with definition 3. After adjustment for APACHE II score, odds of nephrotoxicity based on definitions 1 or 2 were increased among the high versus low groups (OR = 3.27, 95% CI: 0.7 – 15.25, p = 0.1), although not statistically significant. Conclusions: Clinical outcomes did not differ significantly between high and low trough groups for deep-seated MRSA infections. Nephrotoxicity was consistently higher in the high trough group, regardless of the definition used.

Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault equations for dosing antimicrobials.

Study Objectives. To determine the concordance between the Modification of Diet in Renal Disease (MDRD) and Cockcroft‐Gault equations for glomerular filtration rate (GFR) estimation, the impact of using each equation on antimicrobial dosing, the difference in estimated GFR in patients with acute kidney disease (AKD) versus chronic kidney disease (CKD), and the correlation between the MDRD, Cockcroft‐Gault equation, and expert medical opinion for estimating GFR in patients with AKD.

What do we know about adenovirus in renal transplantation

Adenoviruses are common pathogens that have the potential to cause opportunistic infections with significant morbidity and mortality in immunocompromised hosts. The significance of adenoviral infection and disease is incompletely known in the setting of kidney transplantation. Reported adenovirus infections in renal transplant recipients have typically manifested as hemorrhagic cystitis and tubulointerstitial nephritis, less severe diseases than often seen in other solid organ transplant recipients (i.e. pneumonia, hepatitis and enteritis). The prevalent adenovirus subgroups associated with cystitis and nephritis are B1 and B2 with the serotypes 7, 11, 34, 35. However, disseminated or severe adenovirus infections, including fatal cases, have been described in renal transplant recipients. There is uncertainty regarding monitoring of and treatment of this virus. Although not supported by randomized clinical trials, cidofovir is used for the treatment of adenovirus disease not responding to reduction of immunosuppression.

Long-term effect of chronic intravenous and inhaled nephrotoxic antibiotic treatment on the renal function of patients with cystic fibrosis

Cystic fibrosis (CF) patients have numerous infectious exacerbations requiring prolonged antibiotic treatments, some of which are nephrotoxic. Inhaled antibiotics can reach detectable serum levels. We studied the impact of chronic nephrotoxic antibiotic exposure on kidney function in CF population. We collected data retrospectively for 113 adult CF patients followed for 8.5 years. Fifty‐seven (50.4%) were males and 56 (49.5%) females (mean age 31.7 years [SD 9.9]), of which 31% had diabetes and 9.7% had hypertension. Over 8.5 years follow up, there were no significant changes in blood urea nitrogen (BUN; P = 0.92) or creatinine (P = 0.2) in the whole group. 22% of patients had ≥1 episodes of acute kidney injury (AKI). The presence of AKI was associated with increased BUN (P = 0.002) and creatinine (P = 0.056) at the end of follow up. Use of intravenous colistin, gentamicin, tobramycin, or vancomycin did not correlate with increased BUN (P = 0.64; P = 0.49; P = 0.51; P = 0.47) or creatinine (P = 0.43; P = 0.49; P = 0.17; P = 0.2) after 8.5 years. Elevated tobramycin peak and trough levels did not correlate with increased BUN or creatinine. Inhaled colistin and gentamicin correlated with increased BUN (P = 0.009; P = 0.02) but not creatinine (P = 0.45; P = 0.46). Inhaled tobramycin did not correlate with increased BUN (P = 0.17) or creatinine (P = 0.58). Only inhaled colistin correlated with AKI episodes (P = 0.03). Chronic inhaled colistin and gentamicin are associated with an increase in BUN but not creatinine at the end of follow up. Inhaled colistin was associated with episodes of AKI. Well‐managed intravenous use of nephrotoxic antibiotics in CF population is associated with no major long‐term renal toxicity.

The effect of statin therapy on the formation of arteriovenous fistula stenoses and the rate of reoccurrence of previously treated stenoses.

Statins reduce inflammation in end‐stage renal disease patients and improve endothelial function beyond cholesterol lowering. Despite this, statins do not improve the maturation rate, primary patency rate, and the cumulative survival of arteriovenous fistulas (AVFs). It is unknown if statins decrease the number of stenoses developing in AVFs or prolong the intervals between angioplasties needed to treat recurring stenoses. We conducted a retrospective chart review of our 265 active dialysis patients. The statin group was significantly more likely to be diabetic (64% vs. 43.6%) and treated with aspirin (64% vs. 40%) when compared to those not treated with statins (P = 0.04 and 0.01). The mean time to first intervention (primary patency) was 16.5 months in statin users and 15.8 months in the nonstatin group (P = 0.49) with standard deviations of ±18.5 and 16.6 months, respectively. Statin use was not associated with a significant decrease in the number of stenoses diagnosed (P = 0.28). The mean time between recurrent stenoses’ angioplasties was 8.9 months in statin users and 7.3 months in the nonstatin patients (P = 0.25). Aspirin users were more likely to have a decreased primary patency (rate ratio = 1.65, P = 0.03) compared with nonaspirin users. Patients who were prescribed aspirin developed 1.6 (P 0.01) times more stenoses than those not treated with aspirin. We report for the first time that statin therapy does not decrease the number of stenotic lesions developing in the AVF or prolong the interval between procedures required to treat recurrent stenoses.

Accidental extravascular insertion of a subclavian hemodialysis catheter is signaled by nonvisualization of catheter tip

Subclavian hemodialysis (HD) catheter placement under fluoroscopy with perforation of the superior vena cava (SVC) is a rare complication that needs to be recognized and treated appropriately. We report the case of a 47‐year‐old black woman under treatment for end‐stage renal disease secondary to HIV‐associated nephropathy who sustained an extravascular insertion of fluoroscopy‐guided subclavian catheterization for HD. Subsequent successful removal of the extravascularly placed catheter along with repair of the lacerated SVC were effected by open thoracic surgery.

Endovascular treatment of arteriovenous graft pseudoaneurysms, indications, complications, and outcomes: A systematic review

There are limited data regarding endovascular treatment of arteriovenous graft (AVG) pseudoaneurysms using stent grafts. We performed a comprehensive literature review on the use of stent grafts in the treatment of AVG pseudoaneurysms. We included 10 studies (121 patients). The mean AVG age was 3.1 years (95% confidence interval [CI]: 2.2–4) and pseudoaneurysm mean diameter was 34 mm (95% CI: 23–46). The majority (71%) of the pseudoaneurysms were located on the arterial limb of the AVG and 77% presented with venous anastomosis stenosis requiring angioplasty. The mean number of stents used to treat one lesion was 1.4 (95% CI: 1.3–1.5). The technical success rate of pseudoaneurysm isolation was 100% in all studies and 100% of patients received hemodialysis using the AVG after pseudoaneurysm treatment without the need for catheter placement. The primary patency rates for 1, 3, and 6 months were 81%, 73%, and 24%. Secondary patency was 80%, 77%, and 74% at 1, 3, and 6 months. Arteriovenous graft thrombosis occurred in 12% of patients. Arteriovenous graft infection developed in 35% of cases. Arteriovenous graft pseudoaneurysm treatment using stent grafts is effective in managing even large pseudoaneurysms and has acceptable primary and secondary patency rates. Graft infection was a relatively frequent complication.

Does increasing immunoglobulin levels impact survival in solid organ transplant recipients with hypogammaglobulinemia

Severe hypogammaglobulinemia (IgG < 400 mg/dL) has adverse impact on mortality during the first year post‐transplantation. The aim of the study was to determine whether increasing IgG levels to ≥400 mg/dL improved outcomes.

Calcium supplementation after parathyroidectomy in dialysis and renal transplant patients

Background Data on the risk factors and clinical course of hungry bone syndrome are lacking in dialysis and renal transplant patients who undergo parathyroidectomy. In this study, we aimed to assess the risks and clinical course of hungry bone syndrome and calcium repletion after parathyroidectomy in dialysis and renal transplant patients. Methods We performed a retrospective review of parathyroidectomies performed at The Nebraska Medical Center. Results We identified 41 patients, ie, 30 (73%) dialysis and eleven (27%) renal transplant patients. Dialysis patients had a significantly higher pre-surgery intact parathyroid hormone (iPTH, P<0.001) and a larger iPTH drop after surgery (P<0.001) than transplant recipients. Post-surgery hypocalcemia in dialysis patients was severe and required aggressive and prolonged calcium replacement (11 g) versus a very mild hypocalcemia requiring only brief and minimal replacement (0.5 g) in transplant recipients (P<0.001). Hypophosphatemia was not detected in the dialysis group. Phosphorus did not increase immediately after surgery in transplant recipients. The hospital stay was significantly longer in dialysis patients (8.2 days) compared with transplant recipients (3.2 days, P<0.001). Conclusion The clinical course of hungry bone syndrome is more severe in dialysis patients than in renal transplant recipients. Young age, elevated alkaline phosphatase, elevated pre-surgery iPTH, and a large decrease in post-surgical iPTH are risk factors for severe hungry bone syndrome in dialysis patients.

Statin Therapy and Hemodialysis Vascular Access—Were We Bringing a Knife to a Gunfight and Were Hoping to Win?

Vascular access dysfunction is a major contributor to end stage renal disease patient morbidity, and the cost of maintaining it is staggering. Any intervention able to improve the vascular access maturation rate and/or patency would be significant progress. Based on the anti‐inflammatory and vascular beneficial effects demonstrated in non‐end stage renal disease patients, we were hoping that statin use might provide the much needed improvement in the hemodialysis vascular access outcome. The reality proved disappointing. The statins failed to improve every aspect of hemodialysis vascular access studied. The present editorial discusses the current data regarding the effect of statins on vascular access and attempts to explain their lack of success.