الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
This study included 280 patients with idiopathic nephrotic syndrome, aged from 1 to 15 years, 180 males and 100 females, diagnosed and followed at pediatric nephrology unit, Sohag University Hospital in the period from January 2000 to December 2014. This work included both retrospective and prospective parts. The retrospective part included 203 patients, diagnosed in the period from January 2000 to January 2010 and followed till the end of the study with their data collected from patients’ medical records. The prospective part included 77 new patients diagnosed and followed in the period from January 2010 to December 2014. Patients with less than one year follow up or with incomplete data were excluded.
Idiopathic nephrotic syndrome was diagnosed depending on the presence of nephrotic range proteinuria >40 mg/h/m2 or protein/creatinine ratio (uPCR) >2 g/g and hypoalbuminemia <25 g/l with or without edema in the absence of systemic or extrarenal disorders. In addition to full medical history and detailed physical examination, the following investigations were done for all patients at presentation: urine analysis by dipsticks and microscopy, urine 24-hours proteins or first morning protein/creatinine ratio, serum total protein and albumin, blood urea nitrogen, serum creatinine, total serum cholesterol and triglyceride, full blood count, serum electrolytes, Complement 3 (C3) and abdominal sonography. Antinuclear antibodies (ANA) test was done for patients more than 10 years old at disease onset.
The patients were divided into 3 age groups: preschool age (1-6 years), school age (6-12 years) and adolescence (12-15). Steroid (prednisone) was given to all patients in a dose of 2mg/kg/day, for 4-6 weeks, followed by 1.5 mg/kg on alternate days for 4-6 weeks then gradually withdrawn over 2-5 months. The following definitions were used to categorize the steroid response patterns in our patients: complete remission (proteinuria <4 mg/h/m2, 0-trace on Albustix or protein/creatinine ratio <0.2 g/g); partial remission (proteinuria reduction of 50% or greater from the presenting value and absolute protein/creatinine ratio between 0.2 ̶ 2 g/g); steroid response (remission with steroid therapy); relapse (nephrotic range proteinuria for 3 consecutive days after having been in remission); frequent relapses (≥2 relapses within 6 months of initial response or ≥4 relapses within a period of 12 months); steroid dependence (2 consecutive relapses during steroid therapy or within 14 days after cessation of successful steroid therapy); steroid resistance (failure to achieve remission after 8 weeks of steroid therapy); initial steroid resistant (steroid resistance during the first episode); late steroid resistance (persistent proteinuria during ≥ 4 weeks of steroid following one or more remissions).
Renal biopsy was indicated at presentation for patients with atypical features (age >10 years, persistent hypertension, gross hematuria, renal impairment not attributable to hypovolemia or low C3) and following therapy initiation for patients with initial or late steroid resistant nephrotic syndrome and those with steroid dependent or frequently relapsing nephrotic syndrome before treatment with cyclosporine. Informed written consent was taken from the parents before the procedure and the specimens were examined by the same pathologist using light microscopy.
For patients with steroid dependent or frequently relapsing nephrotic syndrome who failed to maintain remission on low dose steroid; one of the alternative therapies (levamisole, cyclophosphamide, cyclosporine or mycophenolate mofetil) was used. Patients with steroid resistant nephrotic syndrome were treated with one or more of the immunosuppressive medications (cyclophosphamide, cyclosporine and mycophenolate mofetil) in addition to steroid. The patients’ demographic and clinical profiles, steroid response patterns, the underlying histopathological spectrum and disease outcome were studied.
The results of this study showed that a total of 280 patients with idiopathic nephrotic syndrome (203 in the retrospective group and 77 in the prospective group) were included. The mean age of patients at disease onset was 4.60±2.58 (range 1-15) years. There were 180 males and 100 females with male/female ratio 1.8/1. Mean follow up duration was 4.44±3.24 (range 1-15) years. Initial hypertension and initial hematuria were present in 16.4 and 12.9% of patients respectively. Ninety percent of patients were steroid sensitive, while 10% were steroid resistant. About 50% of steroid sensitive patients had no or infrequent relapses, while about 48% of them were either steroid dependent or frequently relapsing and 2% developed late steroid resistance. Significant rise in steroid resistance in the prospective study relative to the retrospective study was detected (P=0.00).
Renal biopsy was done in total 62 (22.1%) patients (36 patients in the retrospective study and 26 patients in the prospective study). Indications for renal biopsy were steroid resistance (early and late) in 46.9%, frequently relapsing and steroid dependent nephrotic syndrome before cyclosporine use in 41.9% and atypical features at presentation in 11.2%. The biopsy results revealed that minimal change disease was present in 48.4%, focal segmental glomerulosclerosis in 30.6% and mesangioproliferative glomerulonephritis in 21% of biopsied patients. Steroid resistance was present in about 79%, 46%, and 17% of patients with focal segmental glomerulosclerosis, mesangioproliferative glomerulonephritis and minimal change disease respectively. There was a rise in the frequency of focal segmental glomerulosclerosis and a decline in frequency of minimal change disease in the prospective study relative to the retrospective study. By the end of the study about 7.1% of total patients were with persistent proteinuria (no or partial remission). End stage renal disease developed in 1.4% of patients, all were multi-drug resistant, and with focal segmental glomerulosclerosis. Death occurred in 1.8% of patients, 60% of them were with focal segmental glomerulosclerosis who developed end stage renal disease and 40% were with minimal change disease that developed massive sepsis, but all of them were resistant to steroid and other immunosuppressive medications.
Conclusions: The demographic features of idiopathic nephrotic syndrome in our locality were comparable to those worldwide with its predominance in young age and in male sex. Inspite of high steroid response rate in ninety percent of patients, about half of steroid sensitive patients developed either steroid dependent or frequently relapsing course. Steroid resistance showed increasing rate in the recent years. Steroid resistance (early and late) was the main indication for renal biopsy. Minimal change disease was the most common underlying pathology in idiopathic nephrotic syndrome, but there was decline in its frequency over years, with increase in the frequency of focal segmental glomerulosclerosis. Focal segmental glomerulosclerosis carried the highest steroid resistance rate. Resistance to steroid and other immunosuppressive therapies and the presence of focal segmental glomerulosclerosis histopathology carried the worst prognosis and the highest rate of progression to end stage renal disease.