Single vs split dose of prednisolone in the treatment of relapses of childhood nephrotic syndrome.

Nephrotic syndrome is the commonest glomerular disease in childhood. It usually follows a relapsing and remitting course. Corticosteroids are the mainstay of treatment for both the first episode and subsequent relapses. This study was conducted at a single centre to compare the clinical response to a single dose vs. split dose of prednisolone in the treatment of relapses of childhood nephrotic syndrome. Children between the ages of 1 and 14 years admitted with a relapse of idiopathic steroid sensitive nephrotic syndrome from August 2019 to February 2020 were considered for recruitment. A block randomization method based on age was used for allocation. Patients randomised to group A received oral prednisolone at 60 mg/m2 as a single morning dose, while those randomised to group B received the same total dose as two divided doses, of which 2/3 was given in the morning and the rest in the evening. Treatment was continued until remission was achieved following which all patients were switched to alternate day prednisolone. An independent sample t test was used to compare the two groups. One hundred and four episodes of relapse occurring in 96 children were included of which 49 were treated with prednisolone as a split dose and 55 were treated with a single dose of prednisolone. The mean duration to achieve remission for the split-dose group was 8.02 days (SD 1.58) while it was 9.74 days (SD 3.72) for the single-dose group. This difference was statistically highly significant (t(102) = 3.004; p = 0.001; CI 0.58 to 2.86). There was no difference in the adverse events profile of the two groups.  Conclusion: The use of prednisolone as a split dose results in a shorter duration to achieve remission when compared to a single morning dose, resulting in a lower cumulative dose of prednisolone to achieve remission. What is Known: • Corticosteroids are the mainstay of treatment for childhood nephrotic syndrome. • Corticosteroids are given as a single dose in the morning to minimise adrenocortical suppression. What is New: • A more rapid attainment of remission can be achieved with a split dose of corticosteroids.

First experience of cadaveric renal transplantation in Sri Lanka

Objectives: To analyse the outcome of 50 consecutive cadaveric renal transplants performed in Sri Lanka. Methods: This was a single-centre longitudinal cohort study conducted in the Nephrology and Kidney Transplant Unit, Teaching Hospital Kandy, Sri Lanka. Records of 50 Sri Lankan cadaveric renal transplant recipients from 7th December 2004 to 1st September 2013 were reviewed and categorized according to early graft function, cold ischaemia time and the duration of dialysis before surgery. Results: Out of the 50 patients, twenty one (42%) had immediate graft function (IGF), 26 (52%) delayed graft function (DGF), and 2 (4%) primary non function (PNF). The average cold ischaemia time (CIT) was 8.8 hours. Out of 23 patients who died during the study period, 19 (82.6%) died although they had a functioning graft. Infection was the commonest cause of death (n=15; 65.2%). Rejection occurred in four (17.4%). Patient survival was 77.3% at one year, 63.0% at three years and 46% at five years. Graft survival was 93.2% at one year, 88.9% at 3 years and 84.6% at 5 years when death with a functioning graft was censored. Univariate analysis revealed that neither CIT nor duration of dialysis before transplant affected patient survival. There was no significant difference in patient survival between DGF and IGF. Conclusions: The events occurring in the early period following renal transplantation do not have a significant impact on long term graft outcome or patient survival. Infection is the commonest cause of death after renal transplantation and efforts should be directed to understand and prevent this complication.

Risk of relapse after meningococcal C conjugate vaccine in nephrotic syndrome.

In November, 1999, all children under age 18 years in the UK were offered immunisation with the newly introduced meningococcal C conjugate vaccine (MCCV). In a cohort of 106 patients with nephrotic syndrome, there were 63 relapses during the 12 months before vaccination, and 96 during the equivalent period postvaccination (p=0.009). The relapse rate of nephrotic syndrome increased significantly after administration of MCCV. Whether to vaccinate such children needs to be carefully considered.

Increasing the dose of prednisolone during viral infections reduces the risk of relapse in nephrotic syndrome: a randomised controlled trial.

BACKGROUND: Relapses of nephrotic syndrome are often triggered by viral upper respiratory tract infections (URTIs), possibly mediated by cytokine release. OBJECTIVE: To test, in a randomised double-blind placebo-controlled crossover trial, the hypothesis that a small short-term increase in the dose of prednisolone will reduce the release of cytokines and thereby reduce the risk of relapse. METHODS: Sequential patients receiving low-dose (<0.6 mg/kg) prednisolone on alternate days as maintenance therapy were recruited. At the first sign of a presumed viral URTI, all children were examined and randomly allocated to take medicine A or B (containing either prednisolone (5 mg) or placebo) in the first viral URTI, and vice versa in the second. If the criteria for diagnosis of a viral URTI were met, the new medicine was prescribed on alternate days for 1 week at the same dose as that of the prednisolone being taken by the patient on an alternate-day basis. A freshly voided urine sample was tested each morning. The presence of 3+ proteinuria for 3 consecutive days was diagnostic of relapse. RESULTS: 48 patients were recruited, and 40 completed the trial (29 male; 11 female). Age at entry ranged from 1.5 to 13.2 (median 5.3) years. The relapse rate after viral URTI was 19/40 (48%) in the placebo group and 7/40 (18%) in the prednisolone group (p = 0.014; two-sided probability using Fisher's exact test). CONCLUSION: Prescribing prednisolone daily for 7 consecutive days at the same dose as that taken by the patient on an alternate-day basis at the onset of a presumed viral URTI significantly reduces the risk of relapse in children with steroid-dependent nephrotic syndrome.

Treatment of steroid sensitive nephrotic syndrome.

Childhood idiopathic nephrotic syndrome (NS) is a chronic glomerular disorder, and if untreated, is associated with increased risk of life-threatening infections, thromboembolism, lipid abnormalities, and malnutrition. The aim of the management of NS in children is to induce and maintain complete remission with resolution of proteinuria and edema without encountering serious adverse effects of therapy. Over 90% of cases in children are due to minimal change disease (MCD) and a majority of them will respond to corticosteroid therapy. Steroid sensitive NS is considered to be a relatively benign condition; progression to end stage renal failure is extremely rare and over 80% achieve spontaneous remission in later childhood. The early disease is characterized by a relapsing course, placing the child at risk of acute complications. The occurrence of frequent relapses necessitates clear therapeutic strategies in order to maintain sustained remission and minimize steroid toxicity. Numerous therapeutic regimens have been proposed utilizing steroid sparing agents such as alkylating agents, principally, cyclophosphamide and chlorambucil, calcineurin inhibitors namely cyclosporin A and immunomodulatory drug levamisole with variable success and associated side-effects. It is therefore important that the benefits and risks of these agents are weighed before considering their use in the treatment of patients with NS.