Treatment of BK Polyomavirus-Associated Nephropathy in Paediatric Kidney Transplant Recipients: Leflunomide Versus Cidofovir.

OBJECTIVES: BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients. MATERIALS AND METHODS: Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia. RESULTS: Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy. CONCLUSIONS: Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.

Evaluation of the Claria sharesource system from the perspectives of patient/caregiver, physician, and nurse in children undergoing automated peritoneal dialysis.

BACKGROUND: Automated peritoneal dialysis (APD) is increasingly preferred worldwide. By using a software application (Homechoice with Claria sharesource system (CSS)) with a mod-M added to the APD device, details of the home dialysis treatment become visible for PD nurses and physicians, allowing for close supervision. We aimed to evaluate the perceptions of patients/caregivers, PD nurses, and physicians about the advantages and disadvantages of CSS. METHODS: Three different web-based questionnaires for patients/caregivers, nurses, and physicians were sent to 15 pediatric nephrology centers with more than 1 year of experience with CSS. RESULTS: Respective questionnaires were answered by 30 patients/caregivers, 22 pediatric nephrologists, and 15 PD nurses. Most of the nurses and physicians (87% and 73%) reported that CSS improved patient monitoring. A total of 73% of nurses suggested that CCS is not well known by physicians, while half of them reported reviewing CSS data for all patients every morning. Sixty-eight percent of physicians thought that CSS helps save time for both patients/caregivers and healthcare providers by reducing visits. However, only 20% of patients/caregivers reported reduced hospital visits. A total of 90% of patients/caregivers reported that being under constant monitoring made them feel safe, and 83% stated that the patient's sleep quality improved. CONCLUSIONS: A remote monitoring APD system, CSS, can be successfully applied with children for increased adherence to dialysis prescription by giving shared responsibility and may help increase the patient's quality of life. This platform is more commonly used by nurses than physicians. Its potential benefits should be evaluated in further well-designed clinical studies with larger patient groups. A higher resolution version of the Graphical abstract is available as Supplementary information.

Graft Survival in Patients With Lower Urinary Tract Dysfunction.

OBJECTIVES: We aimed to the determine urinary tract infection and graft survival rates in pediatric renal transplant recipients with lower urinary tract dysfunction with particular focus on neurogenic bladder, posterior urethral valve, and vesicoureteral reflux nephropathy. MATERIALS AND METHODS: Patients were grouped according to primary diseases as those with and without lower urinary tract dysfunction. Urinary tract infections during year 1 posttransplant were investigated. Estimated glomerular filtration rate was calculated using Schwartz formula. RESULTS: Our study investigated 133 kidney transplant recipients. Lower urinary tract dysfunction was found in 58 patients (43.6%): 25 with posterior urethral valve, 24 with vesicoureteral reflux nephropathy, and 9 with neurogenic bladder. Rates of posttransplant urinary tract infection were higher in patients with lower urinary tract dysfunction than in those without during both the first 6 months posttransplant (24.6% vs 10.8%; P = .037) and between posttransplant months 6 and 12 (24.6% vs 8.2%; P = .01). Patients with neurogenic bladder had the highest rate of urinary tract infections, and their estimated glomerular filtrations rates were lower compared with patients with posterior urethral valve and vesicoureteral reflux nephropathy at month 6 and years 1, 2, and 5 posttransplant (P < .001). The 5-year graft survival rates of patients without lower urinary tract dysfunction and those with vesicoureteral reflux nephropathy were similar (51.3% vs 51.6%; P = .891). CONCLUSIONS: Graft survival rates of patients with posterior urethral valve and vesicoureteral reflux nephropathy were similar to those shown in patients without lower urinary system dysfunction; however, patients with neurogenic bladder had worse graft survival and urinary tract infection rates.

Does smoking exposure affect response to treatment in children with primary monosymptomatic nocturnal enuresis?

BACKGROUND: There are many variables affecting the success of treatment in children with primary monosymptomatic nocturnal enuresis (PMNE). This study investigates the possible effect of cigarette smoke exposure on desmopressin treatment response in children with PMNE. METHOD: The medical records of pediatric patients with PMNE between February 2018 and December 2018 were retrospectively reviewed. Those who had moderate (3-5 wet nights/week) and severe (>5 wet nights/week) PMNE were included in the study. All patients received 120 mcg of sublingual desmopressin. After 3 months of therapy, treatment response was classified as complete response (100% dry night), partial response (between 50% and 99%) and non-responsiveness (<49% improvement). Partial response or non-responsiveness is considered as treatment failure. The relationship between treatment response to desmopressin and exposure to cigarette smoke was evaluated. Moreover, the other risk factors for treatment failure were investigated. RESULTS: A total of 81 children with the diagnosis of PMNE, with a mean age of 9.98 ± 2.62 years, were included in the study. The frequency of passive smoke exposure at home was 53.1%. Sixty-two patients (76.5%) had severe PMNE, and the response to desmopressin decreased with severity of symptoms. Non-responsiveness to treatment, partial response, and complete response were observed in 11 (13.6%), 23 (28.4%), and 47 (58.0%) of patients, respectively. Treatment failure (n = 34, 42%) was 55.8% in children exposed to smoke and 26.4% in those who were not (p = 0.001). Although univariate analysis revealed that the severity of symptoms and smoke exposure were associated with treatment failure, in multivariate analysis, the presence of smoke exposure was the only independent risk factor (OR = 3.214, 95% CI: 0.125-0.888; p = 0.024) (Summary Table 1). CONCLUSION: Exposure to cigarette smoke is a changeable and important risk factor that reduces the success of desmopressin treatment in children with PMNE.

Tacrolimus Variability: A Cause of Donor-Specific Anti-HLA Antibody Formation in Children.

BACKGROUND AND OBJECTIVES: The most important determinant of long-term graft survival in renal transplantation is adequate immunosuppression. Inadequate immunosuppression may lead to graft loss due to the presence of anti-HLA antibody. The aim of this study was to investigate the effect of variability in tacrolimus blood concentration on anti-HLA antibody development in pediatric recipients of living-donor renal transplants. METHODS: Pediatric recipients of living-donor renal transplants were retrospectively evaluated. Patients with a minimum of two years of follow-up who were administered tacrolimus were included in the study. Patients who had pretransplant anti-HLA antibody were excluded. Variability in tacrolimus blood concentration was assessed using the coefficient of variation ("tacrolimus CV") method. Tacrolimus CV was calculated separately for the first 6 months post-transplant, between 6 and 12 months post-transplant, and from the end of the first year post-transplant to the last follow-up. We constructed receiver operating characteristic (ROC) curves of the tacrolimus CV for each group to find the best cutoff value. RESULTS: A total of 67 patients (including 48 males; 72%) with a mean age of 15.16 ± 4.43 years were included in the study. Anti-HLA antibody positivity was detected in 12 patients (18%). More than three HLA mismatches and the presence of acute cellular rejection correlated with the development of anti-HLA antibody (p = 0.056, 0.009). Tacrolimus CVs for the three periods were 0.37 ± 0.11, 0.31 ± 0.18, and 0.35 ± 0.12, respectively. The cutoff value of tacrolimus CV for anti-HLA antibody development was calculated as 0.32 with a sensitivity of 90.91% and specificity of 50.94% [AUC (area under the curve) 0.713, p = 0.023]. During the second 6-month period and after a  year post-transplant, the percentage of patients with tacrolimus CV > 0.32 was significantly higher in the anti-HLA antibody positive group than in the antibody negative group (67% vs 31%, p = 0.027; 83% vs 47%, p = 0.033). The eGFR (estimated glomerular filtration rate) was similar for the anti-HLA antibody negative and positive groups (78.72 ± 2.86 vs 77.45 ± 8.08, p > 0.05). CONCLUSION: High tacrolimus concentration variability appears to be associated with anti-HLA antibody formation in pediatric recipients of living-donor renal transplants.

Eosinophilic tubulointerstitial nephritis on treatment with isotretinoin.

Drug-related acute tubulointerstitial nephritis is one of the most common causes of childhood acute renal failures which originate from kidneys. Sixteen-year old male patient with the history of isotretinoin use for the last 3 months was admitted with acute renal failure. Renal function parameters were measured as follows: blood urea nitrogen 21 mg/dL, serum creatinine 1.68 mg/dL, cystatin C 1.15 mg/L, and estimated glomerular filtration rate based on cystatin C 56.5 mL/min/1.73 m2. The patient whom pathological signs of renal biopsy sections revealed interstitial mononuclear cell and eosinophilic infiltration was diagnosed with acute tubulointerstitial nephritis. CONCLUSION: Isotretinoin is a vitamin A-derived agent which is commonly used in the treatment of acne and may cause drug-related acute tubulointerstitial nephritis. What is Known: •Drug-related acute tubulointerstitial nephritis (ATIN) is one of the most common causes of childhood acute renal failures. What is New: •Isotretinoin may cause drug-related acute tubulointerstitial nephritis.