Varicella zoster virus serostatus before and after kidney transplantation, and vaccination of adult kidney transplant candidates

In recent years we observed 3 lethal primary varicella infections in adult kidney transplant recipients. Therefore, we wondered how many of our adult renal transplant patients were not protected against varicella zoster virus (VZV), and therefore were at risk for such a primary infection. We also studied the prevalence of VZV seronegativity in the adult patients on our waitlist for kidney transplantation. Finally, we vaccinated these seronegative patients with an attenuated live vaccine. Sera were obtained from 854 transplanted patients, and from 286 candidates on the waitlist for kidney transplantation. We observed that 2.1% of our renal transplant recipients and 3.2% of the patients on the waitlist were seronegative for VZV. We vaccinated 11 seronegative patients on the waitlist twice without side effects. In 7 of 11 patients this resulted in a positive serologic response. In conclusion, the prevalence of VZV seronegativity was low both in renal transplant recipients (2%) and in patients on the waitlist (3%). Vaccination of transplant candidates resulted in a moderate efficiency of 64%.     

Donor organ transmission of varicella zoster due to cardiac transplantation

BACKGROUND: We report a case of donor-transmitted varicella zoster viral (VZV) infection in a cardiac transplant recipient. A 15-month-old girl developed primary VZV infection 12 days after cardiac transplantation. The donor suffered from varicella 2 weeks before death from pneumococcal meningitis. METHODS: Despite treatment of the seronegative recipient with intravenous acyclovir from the time of surgery, she developed symptoms of fever, a nonspecific macular rash, and small palatal vesicles. RESULTS: After rapid diagnostic confirmation by direct immunofluorescence on vesicular fluid, high-dose intravenous acyclovir was commenced. In addition, the cyclosporine dose was reduced by 25%. The child made a quick and uncomplicated recovery. CONCLUSIONS: Donor organ transmission of VZV has not, to our knowledge, been previously reported. It occurred despite treatment with acyclovir and resulted in an atypical cutaneous eruption. It responded to an increased dose of acyclovir and a reduced level of immunosuppression.     

Prevalence of antibodies to varicella zoster virus in healthy adults

A serological study of immunity to varicella zoster was carried out using an enzyme-linked immunosorbent assay (ELISA) in 244 healthy adult laboratory staff members. The overall immunity was 90%, with a progressive increase from 81% at 20-29 years to 100% at 60 years. Approximately one-third of serologically immune individuals had no certain history of varicella. As the serological test is simple, rapid and reliable, screening for immunity should be carried out in at-risk individuals such as immunosuppressed patients, pregnant women, and laboratory and medical patients, pregnant women, and laboratory and medical personnel who come into contact with sources of virus. Definition of serological status will aid in the rational planning of intervention procedures such as epidemiological control and administration of varicella zoster immune globulin and, when it becomes available, varicella vaccine.     

Fatal varicella zoster virus encephalitis in two patients following allogeneic hematopoietic stem cell transplantation

BACKGROUND: Reduced cellular immunocompetence following allogeneic hematopoietic stem cell transplantation (aHSCT) increases susceptibility to viral infections. Varicella zoster virus (VZV) reactivation in this setting most commonly manifests as dermatomal herpes zoster but in some cases life-threatening VZV encephalitis occurs. STUDY DESIGN/RESULTS: We describe the cases of two patients who presented with shingles 3 and 18 months, respectively, after HLA-matched peripheral blood stem cell transplantation (PBSCT). Unfortunately, in the further clinical course both patients developed fatal VZV encephalitis, despite initial high-dose intravenous therapy with acyclovir and in one case with additional VZV-immunoglobulin. CONCLUSION: These two cases suggest that rapid intervention with systemic treatment is warranted and raise the question whether initial combination therapy with intravenous acyclovir and foscarnet, VZV vaccination or long-term low-dose acyclovir are needed to improve treatment and clinical outcome in immunocompromised patients, having undergone allogeneic HSCT.     

Severe acute visceral pain from varicella zoster virus

Varicella zoster virus infection often will not present in the characteristic dermatomal distribution of vesicles in patients who have undergone bone marrow transplantation. We cared for a 51-yr-old man with severe abdominal pain after bone marrow transplantation for non-Hodgkin's lymphoma. The diagnosis of varicella zoster was not entertained until he developed a diffuse vesicular rash several days after the onset of pain. We report this case to alert others who may be consulted regarding pain management options for similar oncology patients. IMPLICATIONS: We report a patient with lymphoma, prior bone marrow transplant, and acute visceral pain for whom IV opioids in large doses proved inadequate. An interventional pain management technique was considered until characteristic varicella vesicles appeared over the patient's trunk. We report this case to alert others who treat oncology patients that the diagnosis of visceral zoster should be considered when patients who have undergone bone marrow transplantation present with severe visceral pain.     

Successful renal contraction therapy in polycystic kidney patient with renal transcatheter arterial embolization prior to ABO incompatible kidney transplantation

28-year-old female received dialysis treatment due to chronic renal failure caused by polycystic kidney disease. Later, she underwent a laparoscopic splenectomy and ABO incompatible living kidney transplantation successfully following bilateral renal contraction therapy with renal transcatheter arterial embolization (renal TAE). A unilateral or bilateral native nephrectomy of a massively enlarged kidney performed at the time of renal transplantation is a common treatment in polycystic kidney patients scheduled for transplantation. On the other hand, when treated with renal TAE, such patients can avoid a laparotomy, which provides several advantages when undergoing peritoneal dialysis in the future or a laparoscopic splenectomy prior to ABO incompatible kidney transplantation. Furthermore, we consider that bilateral renal TAE is necessary for polycystic kidney patients prior to renal transplantation for a variety of reasons, including problems associated with contrast nephropathy if renal TAE for left kidney is remained after renal transplantation.     

Liver transplantation in oxalosis prior to advanced chronic kidney disease

While curative of the disease, combined kidney and liver transplantation (K/LTx) for primary hyperoxaluria type 1 (PH1) continues to carry with it a risk for patient death of 15–25%, which over time may not differ from that of kidney transplantation alone (KTx). In this editorial, survival data are reviewed as well as the limited data available for kidney graft function, which may favor K/LTx in the short term but is more uncertain in the longer term. The window of opportunity that favors preemptive K/LTx is relatively narrow and is likely even narrower for preemptive isolated LTx. Capability and experience in the medical management of such patients, and the opportunities available, as well as likely patient compliance, so far without supporting data, may be the most important determination of the best strategy for management.     

Successful kidney transplantation reduces hyperplastic parathyroid gland

INTRODUCTION: In dialysis patients, the parathyroid glands (PTGs) may increase progressively, producing abnormal bone metabolism. Changes in PTG volume among patients with hyperplastic PTGs are not well known after kidney transplantation. This study investigated PTG volume by ultrasound (US). METHODS: US of PTG was performed immediately (US-0) and 12 months after (US-12) transplantation to identify glands in all recipients. We calculated the percentage reduction in PTG volume (R%PTG). We declared it significant when it was > or =35%. Bone biochemical markers and renal function were recorded sequentially. RESULTS: Among engrafted patients, parathyroid US-0 was performed in 47 and US-0 and US-12 in 36. Some visible gland was observed upon US-0 in 13 recipients, a group that showed higher pretransplantation parathyroid hormone (PTH) levels than the remaining 34 patients with no visible glands (627 +/- 360.0 vs 280 +/- 240.9 pg/mL; P < .05). Of 36 recipients with US-0 and US-12, the baseline study identified PTGs in 12 patients (p+ group), while the remaining 24 had no identified glands (p- group). In the p+ group, no PTG, at US-12 were visible in four patients, and a significant R%PTG was observed in three at this time, representing a reduction in gland volume after transplantation among 58.3% of p+ patients. There was a progressive reduction in PTH among both groups. Patients with glandular volume reduction displayed better renal function: serum creatinine 1.7 +/- .79 versus 2.9 +/- .74 mg/dL (P < .05). CONCLUSIONS: Transplantation reversed hyperparathyroidism and PTG volume among recipients who achieved nearly normal renal function.     

Prehabilitation prior to kidney transplantation: Results from a pilot study

Prehabilitation is the process of enhancing preoperative functional capacity to improve tolerance for the upcoming stressor; it was associated with improved postoperative outcomes in a handful of studies, but never evaluated in transplantation. Kidney transplant (KT) candidates may be uniquely suited for prehabilitation because they experience a profound loss of functional capacity while waiting years on dialysis. To better understand the feasibility and effectiveness of prehabilitation in KT, we conducted a pilot study of center‐based prehabilitation for candidates; this intervention consisted of weekly physical therapy sessions at an outpatient center with at‐home exercises. We enrolled 24 participants; 18 participated in prehabilitation (75% of enrolled; 17% of eligible). 61% were male, 72% were African American, and mean age = 52 (SD = 12.9); 71% of participants had lower‐extremity impairment, and 31% were frail. By 2 months of prehabilitation, participants improved their physical activity by 64% (P = 0.004) based on accelerometry. Participants reported high satisfaction. Among 5 prehabilitation participants who received KT during the study, length of stay was shorter than for age‐, sex‐, and race‐matched control (5 vs 10 days; RR = 0.69; 95% CI:0.50‐0.94; P = 0.02). These pilot study findings suggest that prehabilitation is feasible in pretransplant patients and may potentially be a strategy to improve post‐KT outcomes.     

Prophylactic eculizumab prior to kidney transplantation for atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) in childhood is a rare disease associated with high morbidity and mortality. Most cases progress to end-stage renal failure. In approximately 50% of affected patients, mutations in genes encoding complement proteins are causative of the impairment in the regulation of the complement alternative pathway. This leads to deficient host cell protection and inappropriate complement activation on platelets and endothelial cells, particularly in the kidneys. Complement factor H (FH) heterozygosity induces unregulated activation of the membrane attack complex (MAC) C5b-9. Present therapeutic strategies for aHUS include lifelong plasmapheresis and renal dialysis. Unfortunately, kidney transplantation is frequently an unsatisfactory intervention due to the high rate of post-transplantation HUS recurrence, particularly in patients with FH mutation. Combined liver-kidney transplantation is also associated with poor outcome, mostly as a result of premature liver failure secondary to uncontrolled complement activation. Eculizumab is a complement C5 antibody that inhibits complement factor 5a (C5a) and the formation of the MAC. Thus, this antibody may be a promising new agent for patients with an aHUS undergoing kidney transplantation. We present the first case of a young patient with aHUS who received eculizumab as prophylactic treatment prior to a successful kidney transplantation.     

Successful living-related kidney transplantation in hereditary renal hypouricaemia

Sir, Hereditary renal hypouricaemia (MIM: 220150 [OMIM] ) is a syndrome thatinvolves a defect in urate transporter1 (URAT1) for urate reabsorptionat the brush border membrane of the proximal tubule in the kidney[1]. A G774A mutation in      

Native nephrectomy prior to pediatric kidney transplantation: biological and clinical aspects

Background

Pre-transplant nephrectomy is performed to reduce risks to graft and recipient. The aims of this study were to evaluate (1) indications, surgical approach, and morbidity of native nephrectomy and (2) the effects of kidney removal on clinical and biological parameters.

Methods

This study was designed as a single-center retrospective cohort study in which 49 consecutive patients with uni- or bilateral native nephrectomies were identified from a total of 126 consecutive graft recipients in our pediatric kidney transplantation database between 1992 and 2011. Demographic, clinical, and laboratory details were extracted from charts and electronic records, including operation reports and pre- and post-operative clinic notes.

Results

Of the 49 nephrectomized patients, 47% had anomalies of the kidneys and urinary tract, 22% had cystinosis, 12% had focal segmental glomerulosclerosis, and 6% had congenital nephrotic syndrome. Nephrectomy decisions were based on clinical judgment, taking physiological and psychosocial aspects into consideration. Nephrectomy was performed in patients with polyuria (>2.5?ml/kg/h) and/or large proteinuria (>40?mg/m²/h), recurrent urinary tract infection or (rarely) hypertension. Urine output decreased from (median) 3.79 to 2.32?ml/kg/h (?34%), and proteinuria from 157 to 100?mg/m²/h (?40%) after unilateral nephrectomy (p?=?0.005). After bilateral nephrectomy, serum albumin, protein and fibrinogen concentrations normalized in 93, 73, and 55% of nephrectomized patients, respectively. Clinically relevant procedure-related complications (peritoneal laceration, hematoma) occurred in five patients.

Conclusion

In summary, we demonstrate quantitatively that native nephrectomy prior to transplantation improved serum protein levels and anticipated post-transplant fluid intake needs in select children, reducing the risk of graft hypoperfusion and its postulated consequences for graft outcome.     

Normothermic ex vivo kidney perfusion for graft quality assessment prior to transplantation

Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30‐kg pigs were recovered in a model of heart‐beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days. After transplantation, renal function measured based on peak serum creatinine differed significantly among groups (P < .05). Throughout NEVKP, intrarenal resistance was lowest in group A and highest in group C (P < .05). intrarenal resistance at the initiation of NEVKP correlated with postoperative renal function (P < .001 at NEVKP hour 1). Markers of acid‐base homeostasis (pH, HCO₃^–, base excess) differed among groups (P < .05) and correlated with posttransplantation renal function (P < .001 for pH at NEVKP hour 1). Similarly, lactate and aspartate aminotransferase were lowest in noninjured grafts versus donation after circulatory death kidneys (P < .05) and correlated with posttransplantation kidney function (P < .001 for lactate at NEVKP hour 1). In conclusion, assessment of perfusion characteristics and clinically available perfusate biomarkers during NEVKP allows the prediction of posttransplantation graft function. Thus, NEVKP might allow decision‐making regarding whether grafts are suitable for transplantation.