Incidental finding of acquired cystic kidney disease associated renal cell carcinoma in an adolescent with kidney failure.

Acquired cystic kidney disease (ACKD) can occur in patients with chronic kidney disease and kidney failure, and its incidence increases with the duration of dialysis. In adults, ACKD is less common in the pre-dialysis group (~ 7%), but its incidence can be as high as 80% for those who are on dialysis for more than ten years. There is, however, very little information about the prevalence of ACKD in children. We report a case of malignant transformation of ACKD following a kidney transplant, highlighting the importance of surveillance of the native kidneys in paediatric patients who have been in long-term kidney replacement therapy.

Renal relapse in children and adolescents with childhood-onset lupus nephritis: a 20-year study.

OBJECTIVES: There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse. METHODS: We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001-2021 to investigate the incidence and outcomes related to renal relapse. RESULTS: Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [n = 36 (38%)] or MMF [n = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [n = 53 (54%)] or AZA [n = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s.d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3-5) and end-stage kidney disease (17.9% vs 1.8%, P < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P = 0.02), osteopenia (38.5% vs 17.9%, P = 0.04) and hypertension (30.8% vs 7.1%, P < 0.01). CONCLUSION: Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse.

Humoral and Cellular Immunogenicity of 3 Doses of BNT162b2 in Children With Kidney Diseases.

Introduction: Patients with severe kidney diseases are at risk of complications from COVID-19; however, little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated 3-dose primary series of COVID-19 vaccination among 59 pediatric patients with chronic kidney disease (CKD) (mean age 12.9 years; 30 male) with or without immunosuppression, dialysis, or kidney transplant. Dosage was 0.1 ml BNT162b2 to those aged 5 to 11 years, and 0.3 ml BNT162b2 to those aged 11 to 18 years. Results: Three doses of either vaccine type elicited significant antibody responses that included spike receptor-binding domain (S-RBD) IgG (90.5%-93.8% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6%-79.3%). There were notable T cell responses. Weaker neutralization responses were observed among those on immunosuppression, especially those receiving higher number of immunosuppressants or on mycophenolate mofetil. Neutralization was reduced against Omicron BA.1 compared to wild type (WT, i.e., ancestral) (post-dose 3 sVNT% level; 82.7% vs. 27.4%; P < 0.0001). However, the T cell response against Omicron BA.1 was preserved, which likely confers protection against severe COVID-19. Infected patients exhibited hybrid immunity after vaccination, as evidenced by the higher Omicron BA.1 neutralization response among these infected patients who received 2 doses compared with those who were uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusion: An accelerated 3-dose primary series with BNT162b2 is immunogenic and safe in young children and adolescents with kidney diseases.

Long-term outcomes with rituximab as add-on therapy in severe childhood-onset lupus nephritis.

BACKGROUND: Long-term data pertaining to rituximab as add-on therapy in childhood-onset lupus nephritis (cLN) is scarce. METHODS: A retrospective cohort study was conducted on all patients with proliferative cLN, diagnosed ≤ 18 years and between 2005 and 2021, who received rituximab for LN episodes that were life/organ threatening and/or treatment resistant to standard immunosuppression. RESULTS: Fourteen patients with cLN (female, n = 10) were included, with median follow-up period of 6.9 years. LN episodes (class III, n = 1; class IV, n = 11; class IV + V, n = 2) requiring rituximab occurred at 15.6 years (IQR 12.8-17.3), urine protein:creatinine ratio was 8.2 mg/mg (IQR 3.4-10.1) and eGFR was 28 mL/min/1.73 m2 (IQR 24-69) prior to rituximab treatment. Ten and four patients received rituximab at 1500 mg/m2 and 750 mg/m2, which were given at 46.5 days (IQR 19-69) after commencement of standard therapies. Treatment with rituximab resulted in improvements in proteinuria (ps < 0.001), eGFR (ps < 0.01) and serological parameters, including haemoglobin levels, complement 3 levels and anti-dsDNA antibodies, compared with baseline. Rates of complete/partial remission at 6-, 12- and 24-month post-rituximab were 28.6/42.8%, 64.2/21.4% and 69.2/15.3%. All three patients who required acute kidney replacement therapy became dialysis-free after rituximab. Relapse rate following rituximab was 0.11 episodes/patient-year. There was no lethal complication or severe infusion reaction. Hypogammaglobulinaemia was the most frequent complication (45%) but was mostly asymptomatic. Neutropenia and infections were observed in 20% and 25% of treatments. Upon last follow-up, three (21%) and two (14%) patients developed chronic kidney disease (stage 2, n = 2; stage 4; n = 1) and kidney failure, respectively. CONCLUSION: Add-on rituximab is an effective and safe rescue therapy for cLN patients with life-/organ-threatening manifestations or treatment-resistance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Long-Term Outcomes of Children and Adolescents With Biopsy-Proven Childhood-Onset Lupus Nephritis.

Introduction: Long-term data pertaining to childhood-onset lupus nephritis (cLN) remain extremely scarce. Methods: We conducted a retrospective cohort study of biopsy-proven cLN with onset age <18 years diagnosed from 2001 to 2020 to ascertain the long-term patient and kidney survival rates, and the incidence of advanced chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m2). Results: A total of 92 subjects (78 female; age 13.7 ± 3.3 years; all Chinese) were included, with follow-up duration of 10.3 years (interquartile range, 5.8-15.9). Of these, 83 children (90%) had proliferative lupus nephritis (LN) (Class III/IV ± V). Mycophenolate was used for induction in 36%, whereas 34% received cyclophosphamide (CYC); 55% received mycophenolate as maintenance immunosuppression. The rates of complete remission (CR) and partial remission (PR) at 6 months and 12 months, respectively, were 65% and 20% and 78% and 8%. Two patients died (mortality rate 2.1/1000 patient-years), with a standardized mortality ratio of 22.3. Three patients (3.2%) developed end-stage kidney disease (ESKD), and advanced CKD occurred in 5 patients (5.4%). Survival rates without advanced CKD, ESKD, or death were 96.7%, 94.2%, 92.7%, 83.2% and 83.2% at 1 year, 5 years, 10 years, 15 years, and 20 years, respectively. Multivariate analysis revealed that severe kidney failure necessitating dialysis at presentation (adjusted hazard ratio 37.7, 95% confidence interval [CI] 4.0-355.6, P = 0.002), nonresponse (NR) after 12 months of treatment (adjusted hazard ratio 11.2, 95% CI 2.3-54.9, P = 0.003), and multiple nephritis flares (adjusted hazard ratio 2.6, 95% CI 1.1-6.2, P = 0.03) were predictive of advanced CKD, ESKD, or death. Other adverse outcomes included infections (2.9 episodes/100 patient-years), osteopenia (32%), hypertension (17%), short stature (14%), and avascular necrosis (7%). Conclusion: The long-term outcomes of cLN appeared to have improved in the present era with effective immunosuppression, cautious drug tapering, and assurance of medication adherence. There is still an unacceptably high prevalence of adverse outcomes.

Demographics and long-term outcomes of children with end-stage kidney disease: A 20-year territory-wide study.

AIM: To evaluate the demographics and long-term patient outcomes of children with end-stage kidney disease in Hong Kong. METHODS: We conducted a cohort study at the Paediatric Nephrology Centre, the designated site providing kidney replacement therapy (KRT) for children in Hong Kong. The clinical characteristics and outcomes of all children who initiated chronic KRT before 19 years, between 2001 and 2020, were analysed. RESULTS: One hundred forty-seven children (50% male) received KRT at a mean age of 11.4 ± 5.7 years. The incidence of ESKD was 6.28 per million age-related population (pmarp). The leading cause of ESKD was congenital anomalies (33%). Ten children (7%) had pre-emptive kidney transplants, 104 (71%) and 33 (22%) patients received automated peritoneal dialysis and haemodialysis as initial KRT. The incidence of ESKD increased over time, and were 4.38, 5.07, 6.15 and 9.17 pmarp during 2001-2005, 2006-2010, 2011-2015 and 2016-2020, respectively (p = .005). Ninty-seven patients (66%) received kidney transplants and the median time to receive a kidney graft was 3.7 years (95% CI 3.1-4.3). Only 10 patients had pre-emptive kidney transplants. The mortality rate was 9.1 deaths per 1000-patient-years (95%CI 4.6-16.2). The survival probabilities at 1-, 5-, 10- and 15-year were 100%, 94.8% (95%CI 90.7-98.9%), 89.7% (95% CI 83.4%-95.9%), 87.1% (95% CI 79.3%-94.9%), respectively. Standardised mortality ratio was 54.5. 72% of deaths were due to infections. Young infants and those without kidney transplants were associated with worse survival (p < .01). Multivariate analysis demonstrated that dialysis was the only factor associated with significantly increased risk of death (HRadj 12.9, 95% CI 2.7-63.2, p = .002). CONCLUSION: We observed an increasing incidence of paediatric ESKD in Hong Kong with considerable waiting time to kidney transplant. Mortality risk is comparable to other developed countries and is highest among dialysis population. Efforts should be made to facilitate early access to paediatric kidney transplantation in Hong Kong.

A standardized technique of laparoscopic placement of peritoneal dialysis catheter with omentectomy and closure of patent processus vaginalis: A 3-in-1 minimally invasive surgical approach in children.

BACKGROUND: Omental wrapping is a common cause for catheter failure in children on peritoneal dialysis (PD). Previous studies are conflicting in the benefits of omentectomy. METHODS: We conducted a retrospective study comparing children who underwent PD catheter placement by a standardized laparoscopic three-in-one technique (lap3-in-1) from 2013 to 2018 versus a historical control cohort by open surgery without omentectomy. Lap3-in-1technique combined catheter placement with well-defined indication and extent of omentectomy, and closure of any patent processus vaginalis (PPV). RESULTS: There were 33 and 32 children in the lap3-in-1 and control cohorts respectively. 4/33(12.1%) in lap3-in-1 had reoperations for catheter failures which equated 1 reoperation per 144 catheter months. No reoperations were performed in lap3-in-1 cohort for omental wrapping or inguinal hernia, compared with 13/32 (41%; p < 0.001) and 5/32 (16%; p = 0.02) in the control cohort. Kaplan Meier survival curves showed significantly longer catheter life in the lap3-in-1 cohort (p < 0.001). In multivariate analysis by the COX proportional hazards model, the lap3-in-1 approach had significantly reduced risk of reoperation for catheter failure (HR 0.11; 95% CI: 0.04-0.31; p < 0.001). CONCLUSIONS: The lap3-in-1 technique is effective in selecting those children who would benefit from omentectomy, and avoiding a second operation for inguinal hernia which develops after PD. LEVEL OF EVIDENCE: Treatment study, level III.

Imaging studies for first urinary tract infection in infants less than 6 months old: can they be more selective?

This retrospective study aimed to evaluate the applicability of the selective approach of imaging infants < 6 months old with urinary tract infection (UTI) according to the UTI guidelines of the National Institute for Health and Clinical Excellence (NICE) 2007. Infants < 6 months old with their first UTI from January 2001 to December 2006 having undergone an ultrasound examination of the urinary tract, a micturating cystourethrogram, and a late di-mercaptosuccinic acid (DMSA) scan, were included. Their condition was evaluated against a set of risk features according to the UTI guidelines. Those having any one of these were classified as atypical and those having none as typical. There were 134 infants reviewed, with a typical (98 infants) to atypical (36 infants) ratio of 2.7 to 1. Girls were found to be relatively more represented in the atypical group [male (M):female (F) = 1.3:1] than in the typical group (M:F = 4.4:1) (P < 0.004). There were significantly more infants with abnormal micturating voiding cystourethrograms (MCUGs) (P = 0.007), more refluxing ureters (P < 0.001) and more significant vesico-ureteral reflux (VUR) (>/= grade III) (P = 0.013) in the atypical group than in the typical group; while there was no significant difference in ultrasound (US) and DMSA scan findings between the two groups. In the atypical group there was no difference in imaging studies (and, thus, the results) between the conventional practice and the NICE UTI recommendation. In the typical group, if the recommendations of the guidelines had been followed (i.e. only those with abnormal US would have been further investigated), 25 refluxing ureters and 22 scarred kidneys would have been left undiagnosed. In conclusion, application of the suggested selective imaging approach would leave a significant number of VUR and renal scars undiagnosed, and it may not be an optimal practice for infants less than 6 months old with their first UTI. The best approach remains to be clarified.

Peritonitis and exit-site infection in pediatric automated peritoneal dialysis.

We reviewed 30 patients in an automated peritoneal dialysis (APD) program from 2002 to 2006 for peritonitis. Patients were 11.6 +/- 5.5 years old at initiation of peritoneal dialysis (PD) and had a total of 976 PD months. The overall peritonitis rate was 1 episode in 54.2 patient-months, for a rate of 0.22 episode annually. The rate was considered low, which other than being an APD program, may be attributed to adherence to guidelines and in-charge nurse policy. A total of 17 episodes of peritonitis were identified in 9 patients, and the distribution of patient-specific peritonitis incidence appeared bimodal: 87% patients had no or only 1 episode of peritonitis, and 4 patients accounted for 12 episodes, with an average peritonitis rate of 1.0 annually. Causative organisms included Staphylococcus aureus, coagulase-negative Staphylococcus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, enterococci, alpha-hemolytic Streptococcus. Five episodes had concurrent exit-site infection with the same organism. During the same period in these 30 patients, 40 episodes of exit-site infection (ESI) were recorded in 23 patients. The overall ESI rate was 1 episode in 24.4 PD months. S. aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 70% of the infections. Nasal carriage of MRSA was found in 4 patients, and MRSA ESIs in 2. The ESI rate was not low as that observed in peritonitis, which may be attributed to the humid climate.

Recurrent thrombotic thrombocytopenic purpura in a young boy with systemic lupus erythematosus.

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal disease in childhood. The association of microangiopathic hemolytic anemia, schistocytes, and thrombocytopenia without fever, neurologic, and renal involvement is sufficient to suspect TTP at an early stage for prompt plasma infusion or exchange therapy. TTP has been increasingly described especially in association with systemic lupus erythematosus (SLE). We report the youngest Chinese boy who presented his SLE with TTP and subsequently experienced 9 relapses of TTP in a 2-year period. SLE disease activity index was low during his TTP relapses and therefore alertness of TTP relapse is required even in a relatively inactive period of SLE. TTP should be recognized even without renal or neurologic features and can respond to plasma therapy.

Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong.

We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.