Hepatitis B Vaccination in Advanced Chronic Kidney Disease: A Quality Improvement Project at a Veteran Affairs Chronic Kidney Disease Clinic.

Hepatitis B vaccination is recommended in all patients with end-stage kidney disease (ESKD). However, only 50-60% of these patients achieve protective antibody levels if immunized after starting dialysis. Strategies to overcome this low seroconversion rate include a 6-month vaccination schedule starting earlier [chronic kidney disease (CKD) stage 4 and 5] to ensure immunity when patients progress to ESKD. We conducted a quality improvement program to immunize pre-dialysis patients. Patients who were found to have a negative baseline serology with a negative hepatitis B surface antibody level (HBsAb) were offered vaccination on a 6-month schedule (0, 1 and 6 months) with one of two available vaccines within the VA system (Recombivax™ or Engerix™). HBsAb titers were checked 3-4 months later, and titers ≥ 12 mIU/mL were indicative of immunity at VA. Patients who did not seroconvert were offered a repeat schedule of three more doses. We screened 198 patients (187 males and 11 females) with CKD 4 and 5 [glomerular filtration rate (GFR) < 29 mL/min/1.73 m2]. The median age of this cohort was 72 years (range 38-92 years). During the study period of 5 years (2015-2020), 10 patients were excluded since their GFR had improved to more than 30 mL/min/1.73 m2, 24 others had baseline immunity and 2 refused vaccination. The hepatitis B vaccination series was not started on 106 patients. Of the remaining 56, 12 patients progressed to ESKD and started dialysis before completion of the vaccination schedule, 6 expired and 1 did not come to clinic in 2020 due to the pandemic. Of the 37 patients who completed the vaccination schedule, 16 achieved seroconversion with adequate HBsAb titers, 10 did not develop immunity despite a second hepatitis B vaccination series, while 11 did not get a second series. Given the low seroconversion rate, albeit in a small cohort, vaccination should be considered in patients with earlier stages of CKD. Other options include studies on FDA approved vaccines of shorter duration. We plan to increase awareness among nephrologists, patients and nursing staff about the importance of achieving immunity against hepatitis B.

Liposuction used to treat deep vascular accesses for hemodialysis.

BACKGROUND: Oftentimes, obese dialysis patients develop a viable dialysis access but the access is too deep for cannulation and needs a superficialization procedure. METHODS: We present our 14-patient cohort in whom we performed liposuction to superficialize viable but deep vascular accesses. Out of 14 patients, 12 had arteriovenous fistulas and 2 arteriovenous grafts. The primary end points were the ability to superficialize a completely unusable access and to remove the hemodialysis catheter (3patients), or to significantly extend the useful length of a deep access in which only a very short segment was used and to continue to use the access post-surgery without the need to place a dialysis catheter (11 patients). RESULTS: The study goal was met in 13 out of 14 patients. In two of three patients, the catheters were removed and their access usable length was 14 and 13 cm, respectively. The accesses could be used immediately after liposuction in all patients in which this applied-11 patients. The usable access length increased from a mean of 5 to 12.7 cm. The access mean depth decreased from 10.8 mm pre-surgery to 7 mm post-surgery and 5.3 mm 4 weeks after surgery. The mean volume of fat removed was 43.8 cc. We had only one surgical complication: bleeding that was readily controlled with manual pressure. All patients were discharged to home the same day. Postoperative pain was mild. CONCLUSION: Liposuction is effective, safe, and seems to be the least invasive technique of superficialization.

Clinical and Regulatory Considerations for Central Venous Catheters for Hemodialysis.

Central venous catheters remain a vital option for access for patients receiving maintenance hemodialysis. There are many important and evolving clinical and regulatory considerations for all stakeholders for these devices. Innovation and transparent and comprehensive regulatory review of these devices is essential to stimulate innovation to help promote better outcomes for patients receiving maintenance hemodialysis. A workgroup that included representatives from academia, industry, and the US Food and Drug Administration was convened to identify the major design considerations and clinical and regulatory challenges of central venous catheters for hemodialysis. Our intent is to foster improved understanding of these devices and provide the foundation for strategies to foster innovation of these devices.

Surgical technique of placement of an external jugular tunneled hemodialysis catheter in a large pig model.

BACKGROUND: Currently, there is insufficient knowledge about the surgical anatomy and surgical techniques in large animals that can be used to test medical devices designed for human use. We encountered this problem in our study requiring the placement of jugular vein, tunneled, cuffed hemodialysis catheter in 70 kg pigs. Despite the operator's extensive expertise in placing tunneled hemodialysis catheters in humans, the important differences in anatomy made the procedure and choosing the appropriate catheter length challenging. METHODS: The following article describes the anatomy and our technique for the placement of tunneled hemodialysis catheter in the pig model. RESULTS: We consider our surgical technique to be sound because in all animals the catheters were placed in the desired location, the procedures were well tolerated by the animals, and there were no immediate or late complications. CONCLUSION: We present our experience to help other researchers who might encounter the same problem.

Location and structure of fibrous sheath formed after placing a tunneled hemodialysis catheter in a large pig model.

BACKGROUND AND OBJECTIVES: We evaluated the location and structure of the fibrous sheath formed after the placement of tunneled, cuffed hemodialysis catheters in large animals, 70 kg pigs. We focused on describing the location of the fibrous sheath in relation to the catheter. Its location explains the fibrous sheath's ability to cause catheter dysfunction by covering the catheter exit ports located at the catheter's tip. DESIGN: We used three animals. Each animal had a tunneled, cuffed, 15-French diameter hemodialysis catheter placed in the external jugular vein, with the tip at the junction of the superior vena cava and the right atrium. Two animals were sacrificed at 5 weeks and one animal at 17 weeks after catheter placement. The catheter and surrounding tissues were removed in one block. The fibrous sheath was dissected and longitudinally cut along the catheter to evaluate its extension in relation to the catheter. Relevant portions of the fibrous sheath were sent for pathology examination. RESULTS: The fibrous sheath covered the catheter in its entire length and circumference. It started at the entry site and continued without any interruption along the entire length of the catheter, including the tip. Its average thickness is 1 mm and has an inner cellular/inflammatory layer comprising lymphocytes, plasma cells, neutrophils, macrophages, multinucleated giant cells, and spindled cells and an outer layer comprising a mixture of collagen and fibroblasts. CONCLUSION: Our model showed that the fibrous sheath forms around all catheters and covers them in their entire length and circumference without any gaps.

Cardiac Assist Devices and Hemodialysis Catheter Procedures - What Do the Nephrologists Need to Know?

The use of ventricular assist devices (VAD) and total artificial heart (TAH) is increasing rapidly, and a large proportion of these device recipients already have or will develop severe renal dysfunction at the time of device implantation. As a consequence, nephrologists are becoming more and more involved in the care of this challenging population. As nephrologists take upon themselves many aspects of dialysis vascular access care, they need to be familiar with the special circumstances of performing hemodialysis catheter procedures in these patients. This review describes the important characteristics of these devices that have serious implications for the technique of placing or replacing dialysis catheters. These implications apply for both tunneled and nontunneled dialysis catheters and so concern all nephrologists, not only the interventionalists. We describe the important anatomical factors, anticoagulation management, device management, vascular access management and technical considerations of placing or replacing tunneled and nontunneled hemodialysis catheters from the perspective of a nephrologist establishing and maintaining lifesaving dialysis vascular access. Without a good understanding of these devices, serious consequences such as VAD rotor damage or blockage, or artificial heart valve blockage or damage can occur. These artificial devices are lifesaving, and any such complication is unacceptable. This review describes steps to minimize the risks.

Sheep Model of Hemodialysis Arteriovenous Fistula Using Superficial Veins.

Current models of animal arteriovenous fistula (AVF) are swine models of femoral vein terminolaterally anastomosed to femoral artery, creating a deep AVF. This feature sets it aside from human AVFs using superficial veins. Our AVF model uses sheep superficial veins to create an AVF almost identical to human model. AVFs were created in six sheep using basilic veins sutured terminolaterally to brachial artery. Presurgery vein and artery diameters were measured. We measured AVFs and feeding arteries blood flows and diameters at 1, 3, and 5 weeks postsurgery. At 5 weeks we performed angiograms, euthanized animals, and harvested AVFs. Four animals completed the study. Three AVFs developed and were patent at 5 weeks; one thrombosed. Animal weight and presurgery vessels diameters predicted AVFs blood flows and diameters. Despite using vessels with diameters smaller than the ones recommended for human AVF, the Fistulas developed. Two animals died before the study conclusion for causes unrelated to surgery. This AVF model is anatomically almost identical to the human AVF and has a good maturation rate. It is a viable model for studying AVF maturation, devices intended to improve AVF maturation, AVF related procedures and can even support hemodialysis needles.

Cidofovir in pediatric solid organ transplant recipients: University of Nebraska experience.

BACKGROUND: Clinical experience with cidofovir in pediatric solid organ transplantation is limited. We assessed the effect of cidofovir use on renal function in pediatric solid organ transplant recipients. METHODS: Wilcoxon signed-rank tests were used to determine if changes in renal function were significant, Wilcoxon rank-sum tests to test the association between changes in glomerular filtration rate and potential confounding factors, and MacNemar tests to compare the proportions of patients at different time points. RESULTS: We included 25 patients with a mean age of 4.2 years (SD 4.6). More patients were receiving renal replacement therapy while being treated with cidofovir compared with baseline (24% vs. 4%; P = 0.03). For patients not receiving renal replacement therapy, there was no evidence of a significant median change in glomerular filtration rate from baseline to 1 month after cidofovir treatment (P = 0.32) or to the end of cidofovir treatment (P = 0.23) or in creatinine from baseline to the end of cidofovir therapy (P = 0.2). There was a marginal decreased median change in creatinine from baseline to 1 month after cidofovir treatment (P = 0.06). Fewer patients had proteinuria (72.2% vs. 27.8%; P = 0.02) and hematuria (22.2% vs. 0%) after cidofovir treatment. CONCLUSION: In our pediatric transplant cohort, cidofovir did not significantly change renal function reflected by creatinine, glomerular filtration rate, hematuria or proteinuria, but a significant number of patients required renal replacement therapy because of fluid overload.

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

BACKGROUND: 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. METHODS: Kaplan-Meier analyses were performed to estimate survival, log-rank test to compare survival distributions between groups, and Fisher's exact test to determine the association between hypogammaglobulinemia and rejection or graft loss. RESULTS: Thirty-seven solid organ transplant (SOT) recipients were included. Hypogammaglobulinemia was diagnosed at median of 5.6 months (range: 0-291.8 months) post-transplantation. Types of transplants: liver-small bowel (17); liver-small bowel-kidney (2); liver (5); small bowel (4); liver-kidney (1); kidney/kidney-pancreas (3); heart (3); heart-kidney (1); and heart-lung (1). The three-yr survival after the diagnosis of hypogammaglobulinemia was 49.5% (95% CI: 32.2-64.6%). Patients were dichotomized based upon IgG level at last follow-up: IgG ≥ 400 mg/dL (23 patients) and IgG < 400 mg/dL (14 patients). There was no evidence of a difference in survival (p = 0.44), rejection rate (p = 0.44), and graft loss censored for death (p = 0.99) at one yr between these two groups. There was no difference in survival between patients receiving or not immunoglobulin (p = 0.99) or cytomegalovirus hyperimmunoglobulin (p = 0.14). CONCLUSION: Severe hypogammaglobulinemia after SOT is associated with high mortality rates, but increasing IgG levels to ≥400 mg/dL did not seem to translate in better patient or graft survival in this cohort.

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.

Risk of serious opportunistic infections after solid organ transplantation: interleukin-2 receptor antagonists versus polyclonal antibodies. A meta-analysis.

BACKGROUND: We aimed to evaluate and quantify the risk of serious opportunistic infections after induction with polyclonal antibodies versus IL-2 receptor antagonists (IL-2RAs) in randomized clinical trials. METHODS: PRISMA guidelines were followed and random-effects models were performed. RESULTS: 70 randomized clinical trials (10,106 patients) were selected: 36 polyclonal antibodies (n = 3377), and 34 IL-2RAs (n = 6729). Compared to controls, polyclonal antibodies showed higher risk of serious opportunistic infections (OR: 1.93, 95% CI: 1.34-2.80; p < 0.0001); IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.80, 95% CI: 0.68-0.94; p = 0.009). Polyclonal antibodies were associated with higher risk of bacterial (OR: 1.58, 95% CI: 1.00-2.50; p = 0.049) and viral infections (OR: 2.37, 95% CI: 1.60-3.49; p < 0.0001), while IL-2RAs were associated with lower risk of cytomegalovirus (CMV) disease (OR: 0.73, 95% CI: 0.56-0.97; p = 0.032). Adjusted indirect comparison: compared to polyclonal antibodies, IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.41, 95% CI: 0.34-0.49; p < 0.0001), bacterial infections (OR: 0.51, 95% CI: 0.39-0.67; p < 0.0001) and CMV disease (OR: 0.58, 95% CI: 0.34-0.98; p = 0.043). Results remained consistent across allografts. CONCLUSION: The risk of serious opportunistic infections, bacterial infections and CMV disease were all significantly decreased with IL-2RAs compared to polyclonal antibodies.

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.

How I do it: endovascular treatment of arteriovenous graft pseudoaneurysms-watch out for the mouth.

We present a case of arteriovenous graft pseudoaneurysms treated endovascularly with stent grafts and make suggestions regarding the technique of evaluating the pseudoaneurysms and choosing the proper location to deploy the stent grafts to maximize the outcomes and minimize the length of the graft covered by the stent. We also comment on the selection of lesions that are suitable to be treated with this technique.

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.

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.

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.

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.

Staphylococcus aureus infections in kidney transplantation: a matched case controlled study.

BACKGROUND: Data are lacking on the risk factors and outcomes of Staphylococcus aureus infections in kidney transplant recipients. METHODS: Kidney recipients with S. aureus infections (n = 20) were retrospectively identified and compared to age- and transplant-type-matched (1:2) non-S. aureus-infected controls (n = 40). Risk factors for S. aureus infections were identified by conditional logistic regression analysis. RESULTS: Methicillin-resistant S. aureus (MRSA) was the cause of 32.1% of infections. Localizations of the infections were as follows: skin 42.9%, intra-abdominal 35.7%, blood stream 7.1%, and pulmonary 10.7%. The infections developed at a median time of 29 days (range 0-358 days) after transplantation. By univariate analysis, variables significantly associated with infection were steroid administration 4 weeks prior to infection (odds ratio (OR) 4.2, 95% confidence interval (95% CI) 1.1-15.8; p = 0.03) and the presence of a central venous catheter 7 days prior to infection (OR 5.6, 95% CI 1.1-27.8; p = 0.03). By multivariate analysis, subjects with steroid treatment during the previous 4 weeks had a 6.13-times higher risk of developing S. aureus infection (95% CI 1.5-25.7; p = 0.01), and the risk of infection decreased by a factor of 0.65 for every 1-y increase in age (95% CI 0.44-0.97; p = 0.03); these results were adjusted for matched criteria. Post-infection outcomes (cases vs controls) included graft loss (10% vs 0%; p = 0.11) and 12-month mortality (0% vs 2.5%; p = 0.99). CONCLUSIONS: Younger age and steroid treatment were significant independent risk factors associated with S. aureus infections after kidney transplantation. Graft and patient survival were not affected, but the study was not powered for these outcomes.