Levamisole in childhood idiopathic nephrotic syndrome: new promises, and advocacy for global access.

In the current issue of Kidney International, Sinha et al. present data from an open-label, noninferior, randomized controlled trial comparing 12-months of alternate-day prednisolone, given daily during infection, versus levamisole, in children with frequently relapsing or steroid-dependent nephrotic syndrome. This study suggests that both of these strategies are efficacious and safe. Results of this study should redefine the role of levamisole in future guidelines, and a call for global availability of levamisole should be advocated.

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.

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.

Development of clinical and laboratory biomarkers in an international cohort of 428 children with lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. METHODS: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. RESULTS: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. CONCLUSIONS: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission.

A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants.

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.

Outcomes and perception of cloud-based remote patient monitoring in children receiving automated peritoneal dialysis: a prospective study.

BACKGROUND: Remote patient monitoring (RPM) for automated peritoneal dialysis (APD) may improve clinical outcomes. Paediatric data, however, remain extremely scarce. METHODS: We conducted a prospective observational study of children (0-18 years) receiving APD with cloud-based RPM over two 24-week periods (pre- and post-RPM). Primary outcomes were unplanned hospitalizations and fluid management. Children receiving APD without RPM (non-RPM) were included as control. RESULTS: Seven patients (6 females) receiving APD were enrolled in the RPM programme at 11.3 years (IQR 2.6-17.1). Main indications for RPM included history of fluid overload (n = 3) and non-adherence (n = 2). Ten children were included in the non-RPM group (6 females; 16.9 years, IQR 12.8-17.6). Four patients (57.1%, 95% CI 22.5-100%) experienced fewer unplanned hospitalizations and 5 patients (71.4%, 95% CI 34.1-100%) had shorter hospital stays during the post-RPM period. The hospitalization rates and length of stay were reduced by 45% and 42%, respectively. The higher hospitalization rates among the RPM group, compared to the non-RPM group, were no longer observed following implementation of RPM. There was a significant increase in ultrafiltration (565.6 ± 248.7 vs. 501.7 ± 286.6 ml/day, p = 0.03) and reduction in systolic blood pressure (114.1 ± 12.6 vs. 119.9 ± 11.19 mmHg, p = 0.02) during the post-RPM period. All patients demonstrated satisfactory adherence. Although quality of life (PedsQL 3.0 ESRD module) was not different pre- and post-RPM, all patients agreed in the questionnaires that the use of RPM improved their quality of life and sense of security. CONCLUSIONS: In conclusion, RPM in children receiving APD is associated with fewer and shorter unplanned hospitalizations, improved fluid management and favourable adherence to PD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute kidney injury in children with haematological malignancy: a territory-wide study.

BACKGROUND: In onco-nephrology, data on acute kidney injury (AKI) among children with haematological malignancies are scarce. METHODS: A retrospective cohort study of all patients in Hong Kong diagnosed with haematological malignancies from 2019 to 2021 before 18 years of age, was conducted to investigate the epidemiology, risk factors and clinical outcomes of AKI during the first year of treatment. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: We included 130 children with haematological malignancy at median age of 9.4 years (IQR, 3.9-14.1). Of these patients, 55.4% were acute lymphoblastic leukemia (ALL), 26.9% were lymphoma and 17.7% were acute myeloid leukemia (AML). Thirty-five patients (26.9%) developed 41 AKI episodes during the first year of diagnosis, corresponding to 32 episodes per 100-patient-year. A total of 56.1% and 29.2% of the AKI episodes occurred during induction and consolidation chemotherapy respectively. Septic shock (n = 12, 29.2%) was the leading cause of AKI; 21 episodes (51.2%) were stage 3 AKI; 12 episodes (29.3%) were stage 2 AKI; and 6 patients required continuous kidney replacement therapies. Tumor lysis syndrome and impaired baseline kidney function were significantly associated with AKI on multivariate analysis (P = 0.01). History of AKI was associated with chemotherapy postponement (37.1% vs. 16.8%, P = 0.01), worse 12-month patient survival (77.1% vs. 94.7%, log rank P = 0.002) and lower disease remission rate at 12-month (68.6% vs. 88.4%, P = 0.007), compared to patients without AKI. CONCLUSION: AKI is a common complication during treatment of haematological malignancies which is associated with worse treatment outcomes. A regular and dedicated surveillance program for at-risk patients should be studied in children with haematological malignancies for prevention and early detection of AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

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 Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study.

BACKGROUND: Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. METHODS: A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. RESULTS: A total of 346 children (age, 9.8 years; IQR, 6.6-13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3-7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P<0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01 to 0.18; P<0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P=0.05), age at first rituximab treatment (8.0 versus 10.0 years; P=0.01), and history of steroid resistance (28% versus 18%; P=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. CONCLUSIONS: Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.

Short duration of parenteral antibiotics in infants with urinary tract infections.

Objectives: Current guidelines by the Canadian Paediatric Society on treating urinary tract infections (UTIs) exclude infants ≤ 60 days old. There is considerable practice variability in this age group, especially around the optimal duration of parenteral antibiotics. The study aimed to assess local practice patterns, and the safety of a short course (≤3 days) of parenteral antibiotics in young infants. Methods: In this retrospective cohort study, 95 infants (≤60 days) with confirmed UTIs were identified at British Columbia Children's Hospital. Patients receiving short (≤3 days) and long (>3 days) duration of parenteral antibiotics were compared. Outcomes of interest included urinary tract infection recurrence within 30 days, hospital length of stay (LOS), representation, and readmission. Results: Twenty infants (21%) received a short course of parenteral antibiotics. These infants were older (median 47 days versus 28 days) and non-bacteremic. Urinary tract infection recurrence was identified in 8 patients (8%), of which 7 were treated with a long duration (P = 1.0). Patients treated with a short duration had a significantly shorter LOS, with a mean difference of 4.21 days [95% CI: 3.37 to 5.05] (P < 0.001). All five (5%) bacteremic patients were treated exclusively with parenteral antibiotics. Conclusions: In a Canadian setting, a short course of parenteral antibiotics is safe in young, non-bacteremic infants with UTIs. Despite substantial evidence, local practice patterns suggest a tendency towards prescription of long courses, providing an opportunity for quality improvement.

Epidemiology and outcomes of pediatric transplant-associated thrombotic microangiopathy in Hong Kong.

BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had increased awareness in recent years. This report summarizes the demographics and outcomes of pediatric TA-TMA in Hong Kong. METHODS: All patients aged below 18 years who underwent HSCT in the Hong Kong Children's Hospital and were diagnosed to have TA-TMA during the 2-year period from April 1, 2019 to March 31, 2021 were included. RESULTS: A total of 73 transplants (51 allogeneic and 22 autologous) in 63 patients had been performed. Six patients (four males and two females) developed TA-TMA at a median duration of 2.5 months post-HSCT. The incidence rate was 9.52%. Of the six TA-TMA patients, five underwent allogenic one underwent autologous HSCT, respectively. Three of them were histologically proven. All four patients with cyclosporine had stopped the drug once TA-TMA was suspected. Median six doses of eculizumab were administered to five out of six patients. Three patients died (two due to fungal infection and one due to acute-on-chronic renal failure) within 3 months upon diagnosis of TA-TMA. Among three survivors, two stabilized with mild stage 2 chronic kidney disease (CKD) while the other suffered from stage 5 end-stage CKD requiring lifelong dialysis. CONCLUSION: In conclusion, recognition and diagnosis of TA-TMA are challenging. Early recognition and prompt administration of complement blockage with eculizumab may be beneficial in selected cases. Further prospective research studies are recommended to improve the management and outcomes of TA-TMA.

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.

Percutaneous ultrasound-guided renal biopsies in a paediatric population: comparison of coaxial and non-coaxial techniques using 18-gauge core biopsy needles.

BACKGROUND: Percutaneous ultrasound-guided biopsy is performed in paediatric patients for evaluation of diffuse renal parenchymal disease. When compared with the non-coaxial technique, the coaxial technique has the advantages of obtaining multiple tissue cores via a single capsular puncture and post-biopsy tract embolisation. OBJECTIVES: To compare the coaxial and non-coaxial techniques of percutaneous ultrasound (US)-guided biopsy of native kidney parenchyma in children and adolescents with renal disease. MATERIALS AND METHODS: We retrospectively identified consecutive patients who underwent percutaneous US-guided renal biopsy using an 18-gauge core biopsy needle from July 2019 to July 2021 in a single tertiary paediatric nephrology centre. Focal renal tumour biopsy and transplant kidney biopsy were excluded. The total glomerular yield, specimen adequacy, complication rate and procedural time between the coaxial and non-coaxial groups were compared. RESULTS: There were 34 percutaneous US-guided renal biopsies: 22 using a coaxial technique and 12 using a non-coaxial technique. The total median glomerular yield obtained was higher in the coaxial group (coaxial=37.9; non-coaxial=22.2; P=0.02). No statistically significant difference was noted between specimen adequacy (coaxial=100%; non-coaxial=91.7%; P=0.35). While no statistically significant difference was detected for overall complication rates (coaxial=13.6%; non-coaxial=41.7%; P=0.09), the coaxial group had a lower rate of haemorrhagic complications (coaxial=4.5%; non-coaxial=41.7%; P=0.01). One patient in the non-coaxial group had post-biopsy haemorrhage requiring embolisation. The procedural time was shorter in the coaxial group (coaxial=26.3 ± 7.0 min; non-coaxial=51.3 ± 11.5 min; P<0.001). CONCLUSION: Percutaneous US-guided renal biopsy in children using the coaxial technique has significantly higher total glomerular yield, shorter procedural time and fewer haemorrhagic complications, compared to biopsies using the non-coaxial technique.

Rituximab in children with steroid sensitive nephrotic syndrome: in quest of the optimal regimen.

Rituximab has emerged as an effective and important therapy in children with complicated frequently relapsing and steroid-dependent nephrotic syndrome to induce long-term disease remission and avoid steroid toxicities. The optimal rituximab regimen is not totally well defined, and there are many varying practices worldwide. We will in this review describe how patient factors, rituximab dose, and use of maintenance immunosuppression affect treatment outcomes. Specifically, low-dose rituximab without concomitant immunosuppression is associated with shorter relapse-free duration while other regimens have comparable outcomes. Patients with more severe disease generally have worse response to rituximab. Although rituximab appears to be generally safe, there are growing concerns of chronic hypogammaglobulinemia and impaired immunity especially in young children. Reliable prognostications and biomarkers for guiding subsequent treatments to avoid excessive treatments are yet to be identified. In this review, we will outline the, as we see it, best approach of rituximab in childhood steroid sensitive nephrotic syndrome at the present state of knowledge.

When should we start and stop ACEi/ARB in paediatric chronic kidney disease?

Renin-angiotensin-aldosterone inhibitors (RAASi) are the mainstay therapy in both adult and paediatric chronic kidney disease (CKD). RAASi slow down the progression of kidney failure by optimization of blood pressure and reduction of proteinuria. Despite recommendations from published guidelines in adults, the evidence related to the use of RAASi is surprisingly scarce in children. Moreover, their role in advanced CKD remains controversial. Without much guidance from the literature, paediatric nephrologists may discontinue RAASi in patients with advanced CKD due to apparent worsening of kidney function, hyperkalaemia and hypotension. Current data suggest that this strategy may in fact lead to a more rapid decline in kidney function. The optimal approach in this clinical scenario is still not well defined and there are varying practices worldwide. We will in this review describe the existing evidence on the use of RAASi in CKD with particular focus on paediatric data. We will also address the use of RAASi in advanced CKD and discuss the potential benefits and harms. At the end, we will suggest a practical approach for the use of RAASi in children with CKD based on current state of knowledge.

A Chinese Boy With Lupus Anticoagulant-hypoprothrombinemia Syndrome: A Case Report and Review of the Literature.

We herein report an unusual case of lupus with bleeding diathesis in a Chinese adolescent boy. In the presence of lupus anticoagulant and hypoprothrombinemia, the diagnosis of lupus anticoagulant-hypoprothrombinemia syndrome was made. He responded promptly to immunosuppressive agents and achieved disease remission.

Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes.

Rituximab is an effective treatment for steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) in children. However, the optimal rituximab regimen remains unknown. To help determine this we conducted an international, multicenter retrospective study at 11 tertiary pediatric nephrology centers in Asia, Europe and North America of children 1-18 years of age with complicated SDFRNS receiving rituximab between 2005-2016 for 18 or more months follow-up. The effect of rituximab prescribed at three dosing levels: low (375mg/m2), medium (750mg/m2) and high (1125-1500mg/m2), with or without maintenance immunosuppression (defined as concurrent use of corticosteroids, mycophenolate motile or calcineurin inhibition at first relapse or for at least six months following the rituximab treatment) was examined. Among the 511 children (median age 11.5 year, 67% boys), 191, 208 and 112 received low, medium and high dose rituximab, respectively. Within this total cohort of 511 children, 283 (55%) received maintenance immunosuppression. Renal biopsies were performed in 317 children indicating the predominant histology was minimal change disease (74%). Without maintenance immunosuppression, low-dose rituximab had a shorter relapse-free period and a higher relapse risk (8.5 months) than medium (12.7 months; adjusted hazard ratio, 0.62) and high dose (14.3 months; adjusted hazard ratio, 0.50; all significant). With maintenance immunosuppression, the relapse-free survival in low-dose rituximab (14 months) was similar to medium (10.9 months; adjusted hazard ratio, 1.23) and high dose (12.0 months; adjusted hazard ratio, 0.92; all non-significant). Most adverse events were mild. Thus, children receiving low-dose rituximab without maintenance immunosuppression had the shortest relapse-free survival. Hence, both rituximab dose and maintenance immunosuppression have important effects on the treatment outcomes.

Vertical gaze palsy and intraoral numbness in a patient with neuro-psychiatric systemic lupus erythematosus: A case report and literature review.

We report, to the best of our knowledge, the first case of neuropsychiatric systemic lupus erythematosus with clinical presentation of bilateral upward gaze palsy and intraoral numbness. Magnetic resonance imaging of the brain was able to identify the pathogenic lesion at the left side of midbrain, involving the vertical gaze center and sensory pathways for innervating the buccal and hard palate mucosa. A course of aggressive immunosuppressive treatment resulted in prompt resolution of gaze palsy and the midbrain lesion.

Left ventricular stiffness in paediatric patients with end-stage kidney disease.

BACKGROUND: We tested the hypothesis that myocardial stiffness is altered in paediatric patients with end-stage kidney disease (ESKD) and explored its association with clinical parameters of chronic kidney disease (CKD). METHODS: Thirty-five patients with ESKD (16 males) aged 17.5 ± 3 years old, 18/35 of whom were receiving dialysis and 17 post kidney transplant, were studied. Left ventricular (LV) myocardial stiffness was determined by measurement of diastolic wall strain (DWS) and stiffness index (SI), while LV diastolic function was interrogated by pulsed-wave and tissue Doppler echocardiography. RESULTS: Compared with available literature data, both dialysis and transplanted patients had significantly lower DWS and greater SI, reduced transmitral early (E) to late diastolic velocity ratio and septal and lateral mitral annular early (e') diastolic velocities, and greater septal and lateral E/e' ratios (all p < 0.05). Multivariate analysis revealed that z score of diastolic blood pressure (ß = 0.43, p = 0.004) and the duration of renal replacement therapy (ß = 0.55, p < 0.001) were significant determinants of LV SI. Subgroup analysis in post-transplant patients showed z score of diastolic blood pressure (ß = 0.54, p = 0.025) remained as a significant determinant of LV SI. CONCLUSION: Increased LV myocardial stiffness is evident in paediatric dialysis and transplanted patients with ESKD, and is associated with blood pressure and duration of renal replacement therapy.