Clinicopathological features and outcome of secondary steroid resistant nephrotic syndrome: A retrospective analysis.

Objective: To determine the clinico-pathological features and long-term outcome of secondary steroid-resistant nephrotic syndrome treated with steroids and calcineurin inhibitors. METHODS: The retrospective cohort study was conducted at the Sindh Institute of Urology and Transplant, Karachi, in June and July 2023, and comprised data from January 1, 2008, to December 31, 2020, of children aged 1-18 years who developed steroid resistance after initial sensitivity to steroids with at least 1-year of follow-up. Demographics as well as time taken to secondary steroid response were documented. Renal biopsy of all patients with secondary steroid resistance had been performed. Eventual outcomes after treatment with calcineurin inhibitors based on the degree of proteinuria and serum albumin levels were used to categorise complete remission, partial remission and no response. Kidney function, as determined by estimated glomerular filtration rate, was recorded. Data was analysed using SPSS 22. RESULTS: Of the 1,000 patients who underwent renal biopsy for steroid resistance, 48(4.8%) had idiopathic steroid-resistant nephrotic syndrome; 32(66.7%) males, 16(33.3%) females and median age of 5 years (interquartile range: 4-7.3 years). Median age at diagnosis of nephrotic syndrome was 5 years (interquartile range: 3.6-7.3 years). The median time from nephrotic syndrome to secondary steroid-resistant nephrotic syndrome was 23 months (interquartile range: 8.75-44.5 months). Biopsy results at diagnosis showed that 27(56.3%) had minimal change disease. The mean follow-up time was 6.1±3.2 years. Of the 43(89.5%) patients who received cyclosporin for 1 year, 29(67%) obtained complete remission, 5(12%) attained partial remission and no response was seen in 9(21%) patients. Conclusion: Majority of the children had minimal change disease at the time of diagnosis of secondary steroid-resistant nephrotic syndrome. The long-term response with calcineurin inhibitors was favourable at 1 year.

Proteinuria in Asymptomatic Siblings of Children with Steroid Resistant Nephrotic Syndrome: A Screening Using Urinary Dipstick.

OBJECTIVE: To screen asymptomatic siblings of steroid-resistant nephrotic syndrome patients for proteinuria using the urinary dipstick method to determine the involvement of siblings in the familial and likely genetic cause of the steroid-resistant nephrotic syndrome. METHODS: This cross-sectional study was performed at the outpatient department of Sindh Institute of Urology and Transplantation (SIUT) from May to July 2021. RESULTS: Out of 104 patients with steroid-resistant nephrotic syndrome, siblings of 66 patients were enrolled. Mean age of primary patients with steroid resistant nephrotic syndrome was 8.7±4.3 years. Most common histopathological diagnosis was focal segmental glomerulosclerosis in 25 (37.9%) children followed by minimal change disease in 17(25.8%) of them. The majority, 48 (72.7%) patients were on immunosuppressive treatment, while 4 (6.1%) had progressed to chronic kidney disease (CKD). A total of 178 siblings were recruited in the study. There were 99(55.6%) boys and 79(44.4%) girls. Their mean age was 10.67±6.2 years. Consanguinity was high in our study population i.e. 56(84%) families. Positive proteinuria on dipstick was detected in only 5(7.5%) enrolled SRNS families. One family refused further testing. Two of the five affected siblings had nephrotic range proteinuria. Renal biopsy of one of them showed membranous nephropathy while the second showed mesangiocapillary glomerulonephritis. Both had normal renal functions. CONCLUSIONS: The frequency of proteinuria in asymptomatic siblings of children with steroid-resistant syndrome is low in our population despite a high prevalence of consanguineous marriages. Hence, familial involvement of nephrotic syndrome is low and further genetic testing for monogenic causes is required in steroid-resistant nephrotic syndrome cases.

Acquired Cystic Kidney Disease: A Hidden Complication in Children on Chronic Hemodialysis.

Objective To determine the frequency of acquired cystic kidney disease (ACKD) in children on chronic hemodialysis. Material and methods In this single-center cross-sectional study, 150 children were included who were on chronic hemodialysis for six months. Ultrasound was done to see the renal cysts. Cystic changes that could not fulfill the criteria for ACKD were also noted and analyzed. Results The mean age was 14.5 ± 3.5 years, of these 63 (42%) were males. Acquired cysts were detected in 53 (35%) of the patient and 18 patients (12%) had solitary cysts. The distribution of these entities was similar across all age groups. The underlying etiologies in the descending order were unknown 64 (43%), stone disease 31 (21%), each of the congenital anomalies of the kidney and urinary tract, and glomerulonephritis 23 (15%), and others nine (6%). A higher frequency of ACKD was detected in the children on renal replacement therapy for more than two years (33 out of 53 children, 63% with a p-value of 0.004). Conclusion The ACKD was found in one-third of our hemodialysis children and its frequency increases with the duration of hemodialysis. This percentage may not reflect the true prevalence as there is a lack of consensus on the definition of ACKD. Periodic assessment of chronic kidney disease patients for the development of ACKD especially on chronic hemodialysis is required to reduce the morbidity.

Histopathological Spectrum and Short-Term Outcome of Treatment with Cyclophosphamide in Relapsing Steroid-Sensitive Nephrotic Syndrome.

OBJECTIVE: To determine the short-term outcome of cyclophosphamide (CPO) course in children with relapsing steroid sensitive nephrotic syndrome (SSNS) with different histopathological lesions. STUDY DESIGN: Descriptive, observational study. PLACE AND DURATION OF STUDY: Pediatric Nephrology Department, Sindh Institute of Urology and Transplantation, Karachi, from January 2012 to December 2014. METHODOLOGY: All children with relapsing steroid-sensitive nephrotic syndrome, who underwent renal biopsy and received cyclophosphamide therapy, were included and followed up for 2 years. Histopathological features in renal biopsy, duration of treatment, duration of complete remission and complication frequency was noted. RESULTS: Of the total 74 patients, 47 (63.5%) were males and 27 (36.5%) females. Median age with Interquartile range (IQR) at presentation was 5 years (4-7 years). Minimal change disease (MCD) was the most common histopathological diagnosis (n=54, 73%) followed by focal segmental glomerulosclerosis (FSGS) (n=13, 17.5%), mesangioproliferative glomerulonephritis(MesPGN) (n=6, 8.1%), IgA nephropathy (n=1, 1.4%). The median number of glomeruli included in each biopsy sample was 15. The median duration of treatment with CPO was 11 weeks (9 to 13 weeks), whereas the median duration of complete remission post-therapy was 13 months (7-23 months). A median timeframe of 17 months (13-24.2 months) lapsed between establishing the diagnosis of NS and initiating CPO treatment. Leucopenia was noted in six (8.1%) patients. CONCLUSION: The short-term outcome of relapsing SSNS can be improved with CPO and steroids, with minimum short-term side effects.