Madhura Pradhan

Decline in Renal Function Following Thoracic Organ Transplantation in Children

Heart and/or lung transplantation are life‐saving treatments for end‐stage cardiopulmonary disease; however, chronic renal failure may develop. The impact of thoracic organ transplant on renal function in infants and children is not well characterized. This retrospective cohort study evaluated renal function following thoracic organ transplantation in 46 children (32 heart, 9 lung, 5 heart‐lung; median age 4.1 years) with at least 12 months of follow‐up. Glomerular filtration rate (GFR, ml/min/1.73 m2) was estimated by the Schwartz formula throughout and each GFR estimate was converted to per cent normal for age (GFR%). Changes in renal function following transplantation were analyzed using longitudinal mixed‐effects linear regression models. GFR% decreased following thoracic organ transplantation (p < 0.001). Younger age at transplant was associated with a greater decline in GFR% (p < 0.01). The decline in GFR% persisted after adjustment for nutritional status with body mass index or weight‐for‐length z‐scores. The prevalence of renal insufficiency (GFR% < 75) increased from 22% at transplant to 55% and 85% at 1 and 5 years post transplant, respectively, while 15% had a GFR% < 50 at 5 years post transplantation. Higher tacrolimus trough levels over the first 6 months correlated with a lower GFR% (p < 0.01). Renal function declined significantly following thoracic organ transplantation.

Successful deceased donor renal transplant in a sensitized pediatric recipient with the use of plasmapheresis.

Abstract:  Sensitization following renal transplant is a significant barrier to repeat transplantation in children. We report a successful DD renal transplant, with the use of PP, in an 11‐yr‐old girl who became highly sensitized following a prior failed transplant. She received PP treatments after failure of high‐dose IVIg (Gamimune®). We established the effectiveness of PP by attaining a 0% PRA and negative cross‐matches after five PP treatments. Subsequently, our patient underwent a second round of scheduled PP. When the PRA was 0%, unacceptable antigens were removed from the UNOS wait list, PP was continued, and a kidney became available within 10 days. The final flow cytometry cross‐match with the eventual donor was negative. This success demonstrates that coordination of desensitization by PP and advanced laboratory monitoring techniques with recent policies regarding allocation of organs to pediatric patients provides new opportunities for children awaiting transplantation. Since the transplant, our patient sustained a low‐titer increase of anti‐HLA antibodies. However, she has had no episodes of acute rejection and has maintained excellent graft function more than 17 months later.

Wegener granulomatosis--an atypical case.

Abstract An unusual sequence of the clinical manifestations of microvascular disease is described in a 15 year-old girl. She initially presented with acute renal failure caused by a crescentic glomerulonephritis associated with positive tests for MPO-ANCA. Eighteen months later she had pulmonary hemorrhage and respiratory failure. An open lung biopsy showed granulomas that were diagnostic for Wegener granulomatosis. We discuss the diagnostic dilemmas faced in attempts to distinguish infective causes of pulmonary granulomas, such as tuberculosis or fungi, from granulomas associated with vasculitis, in a patient previously treated with immunosuppressive therapy.

Rituximab in Steroid-Resistant Nephrotic Syndrome in Children: A (False) Glimmer of Hope?

Idiopathic nephrotic syndrome in childhood is responsive to treatment with steroids in the majority of cases. Its main causes are minimal change nephropathy (MCNS) and focal segmental glomerulosclerosis (FSGS). Approximately 10%–15% of children with idiopathic nephrotic syndrome are steroid

Neonatal atypical hemolytic uremic syndrome from a factor H mutation treated with eculizumab.

Background: Atypical hemolytic uremic syndrome (aHUS) results from an inherited dysregulation of the alternative complement pathway leading to thrombotic microangiopathy consisting of hemolytic anemia, thrombocytopenia, and renal injury. The complement inhibitor eculizumab is an approved treatment, but its reported use in neonates – who have an inherently high risk of infection – is limited. Case diagnosis/treatment: A 28-day-old female presented with gross hematuria and hypertension. aHUS was suspected based on anemia with schistocytes, thrombocytopenia, low C3, and acute kidney injury requiring peritoneal dialysis. A septic work-up initiated on day 2 for hypothermia and respiratory failure was negative. There was no improvement after 6 days of plasma therapy. Despite being < 6 weeks old she was vaccinated with pneumococcal-13 conjugate, meningococcal (groups C and Y) polysaccharide, and Haemophilus b tetanus toxoid conjugate vaccines and started on penicillin prophylaxis. After 1 dose of eculizumab 300 mg, dialysis was discontinued and her hematological parameters improved. Genetic testing revealed a complement factor H mutation. After 11 months of follow-up, she remains on eculizumab and penicillin without recurrence of aHUS or any infectious complications. Conclusions: Eculizumab is a safe and effective treatment option for aHUS even in neonates at high risk for infection.

Radiologically Placed Tunneled Hemodialysis Catheters: A Single Pediatric Institutional Experience of 120 Patients

PURPOSE To report the outcome of tunneled dialysis catheter insertion in 120 patients. MATERIALS AND METHODS A retrospective review of the interventional radiology database and electronic medical records of 120 patients who had tunneled dialysis catheters inserted from April 1997 to July 2010 was performed with institutional review board approval. There were 61 female patients and 59 male patients, with a mean age of 13.3 years (range, 0.2-28.5 y). A total of 193 primary insertions and 330 salvage procedures were performed. RESULTS The technical success rate for primary catheter insertions was 100%. Immediate complications included self-limiting tract bleeding and air embolism in two of 193 insertions each (1.03%). Mean indwell duration for primary insertions was 66 catheter-days (range, 1-765 d), compared with a total mean of 159.4 catheter-days (range, 1-1,034 d). Rates of infection and mechanical complications were 0.21 and 0.9 per 100 total catheter-days, respectively. Mechanical and infections complications were increased in children younger than 9 years of age and weighing less than 20 kg. The catheter removal rates for infection and mechanical complications were 0.084 and 0.081 per 100 catheter-days, respectively. Medical salvage procedures, ie, intracatheter thrombolytic agent use or antibiotic therapy (52.1%) and interventional radiologic catheter salvage procedures (47.1%), increased catheter survival by an average of 54.8 days (range, 0-959 d). CONCLUSIONS Radiologic placement of tunneled hemodialysis catheters is a safe and technically successful procedure in pediatric patients. However, there is a high rate of infectious and mechanical complications, particularly in younger and smaller patients.

A quality improvement initiative to increase pneumococcal vaccination coverage among children after kidney transplant.

Pneumococcal vaccination rates among children receiving a kidney transplant remain suboptimal. Current practice guidelines in the United States recommend giving the PPSV23 after priming with the PCV13. We conducted a QI initiative to increase pneumococcal vaccine rates in our kidney transplant recipients by developing an age‐based vaccine algorithm, obtaining vaccine records, and generating reminders for patients and clinicians. A monthly report from the EHR tracked outcomes. The process metric was missed vaccine opportunities, and the overall objective was to improve coverage with both the PCV13 and PPSV23. Over the first six months, we increased the percentage of visits where the vaccine was given from a baseline of 4% to 33%. However, by the end of the 12‐month period, the percentage of eligible visits where the vaccine was given decreased to 8.7%. Nevertheless, over the 12‐month observation period, we were able to increase the percentage of transplant patients receiving the PCV13 and PPSV23 from 6% to 52%. Utilizing an age‐based algorithm and the electronic medical record, vaccine champions can track both missed visit opportunities and the number of vaccinated patients to improve pneumococcal immunization coverage for these high‐risk patients.

Claudin 19-based familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a sibling pair

BACKGROUND Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare, autosomal recessive condition caused by mutations in CLDN16 or CLDN19, which encode for tight junction proteins, claudin-16 and claudin-19, respectively. This condition often has a delayed diagnosis in patients with no prior family history due to a lack of specific clinical symptoms. Description of case, diagnosis, and treatment: A 4-year, 10-month-old Caucasian boy presented with failure to thrive, developmental delay, and ocular findings consisting of horizontal nystagmus, bilateral macular staphylomas, and high myopia. Laboratory studies revealed hypercalciuria, hypomagnesemia, and renal insufficiency. Renal ultrasound showed bilateral small kidneys with medullary nephrocalcinosis. Candidate gene sequencing performed at age 7 years identified a novel, homozygous, frameshift mutation c.140_141delAT (p.Tyr47Stop) within CLDN19, confirming the molecular diagnosis of FHHNC. Due to rapid renal progression, the proband underwent renal transplant at age 10 years, 10 months. FHHNC was prenatally diagnosed in the probands sister, who was found at birth to have ocular findings and hypomagnesemia. In addition, she had feeding intolerance and persistent hypoglycemia with hyperinsulinism that has required chronic diazoxide therapy. CONCLUSIONS Although rare, FHHNC should be suspected in patients who present with nephrocalcinosis in the setting of congenital eye anomalies..

Heart Retransplant Recipients Have Better Survival With Concurrent Kidney Transplant Than With Heart Retransplant Alone

Background Heart retransplant (HRT) recipients represent a growing number of transplant patients. The impact of concurrent kidney transplants (KTs) in this population has not been well studied. We tested the hypothesis that recipients of HRT with concurrent KT (HRT‐KT) would have worse survival than recipients of HRT alone. Methods and Results A retrospective analysis of the United Network of Organ Sharing database was performed for all patients undergoing HRT from 1987 to 2011. There were 1660 HRT patients, of which 116 (7%) received concurrent KT. Those who received HRT‐KT had older age, longer wait‐list time, worse kidney function, and more known diabetes. Survival among recipients of HRT‐KT was significantly better than that of recipients of HRT alone (P=0.005). A subgroup of 323 HRT patients with severe kidney dysfunction (estimated glomerular filtration rate <30 mL/min per 1.73 m2 or on dialysis) was studied in more detail, and 76 (24%) received concurrent KT. Those on dialysis at the time of HRT had better survival with versus without concurrent KT (P<0.0001). On multivariable analysis, concurrent KT was independently associated with better outcomes for all patients with HRT and for the subgroup of patients with severe kidney dysfunction. Conclusions Recipients of HRT‐KT have better survival than recipients of HRT alone. Further research is needed to determine which HRT patients may benefit the most from concurrent KT.

Urinalysis interpretation for pediatricians.

CME EDUCATIONAL OBJECTIVES: 1.Cost-effectively evaluate microscopic hematuria and proteinuria.2.Recognize important conditions associated with isolated microscopic hematuria.3.Review important conditions associated with asymptomatic proteinuria.