Rajiv Sinha1,2, Anil Vasudevan3, Indira Agarwal4, Sidharth Kumar Sethi5, Abhijeet Saha6, Subal Pradhan7, Sudha Ekambaram8, Nilam Thaker9, Manoj Matnani10, Sushmita Banerjee11, Jyoti Sharma12, Jyoti Singhal12, Shazia Ashraf13, Kausik Mandal14. 1. Division of Paediatric Nephrology, Institute of Child Health, Kolkata, India, rajivsinha_in@yahoo.com. 2. Department of Paediatrics, Apollo Gleneagles Hospital, Kolkata, India, rajivsinha_in@yahoo.com. 3. Department of Paediatric Nephrology, St. John's Medical College Hospital, Bengaluru, India. 4. Division of Paediatric Nephrology, Christian Medical College Hospital, Vellore, India. 5. Pediatric Nephrology, Kidney Institute, Medanta, The Medicity, Gurgaon, India. 6. Department of Paediatrics, Lady Hardinge Medical College, New Delhi, India. 7. Department of Paediatrics, SVPPGIP and SCB Medical College, Cuttack, India. 8. Mehta Multispeciality Hospitals India Pvt Ltd., Chennai, India. 9. Children Nephrology Center, Department of Paediatric Nephrology, Ahmedabad, India. 10. KEM Hospital and Jehangir Hospital, Pune, India. 11. Calcutta Medical Research Institute, Kolkata, India. 12. Department of Medical Genetics, KEM Hospital, Pune, India. 13. Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 14. Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Abstract
BACKGROUND: There is a paucity of information on epidemiology, diagnosis, and treatment outcomes of congenital nephrotic syndrome (CNS) in developing countries. METHODS: Retrospective (2012-2017) review of case records undertaken across 12 Indian pediatric nephrology centers. RESULTS: Sixty-five children (58% male, median birth weight 2.4 kg [interquartile range (IQR) 2.1-2.86]) were identified with CNS. Nearly half (45%) were preterm with previous history of fetal loss/sibling death in 22% and history of consanguinity in a third. No infective etiology was confirmed. Genetic reports available for 15 (23%) children identified causal mutations in 10 (8 in NPHS1 [1 novel variant], 1 in WT 1 [novel variant], and 1 in PLCE-1 gene). In addition, 1 child was clinically diagnosed as Galloway Mowat syndrome. Next-generation sequencing showed 80% yield and Sanger sequencing 20%. Albumin infusion and angiotensin-converting enzyme inhibitors were used initially in around two-third of cohort, while only 12% of children received indomethacin. Totally, 22 (34%) children were lost to follow-up after initial visit, and among the rest median follow-up was 69 days (IQR 20-180) with 18 (42%) deaths. Eight children showed partial response (including 2 with NPHS1 compound mutation), 1 complete response, and all of them were alive at last follow-up in contrast to 53% mortality among nonresponders, p = 0.004. CONCLUSION: This largest reported series on CNS from India revealed suboptimal management with poor outcome as well as low number of CNS being subjected to genetic evaluation.
BACKGROUND: There is a paucity of information on epidemiology, diagnosis, and treatment outcomes of congenital nephrotic syndrome (CNS) in developing countries. METHODS: Retrospective (2012-2017) review of case records undertaken across 12 Indian pediatric nephrology centers. RESULTS: Sixty-five children (58% male, median birth weight 2.4 kg [interquartile range (IQR) 2.1-2.86]) were identified with CNS. Nearly half (45%) were preterm with previous history of fetal loss/sibling death in 22% and history of consanguinity in a third. No infective etiology was confirmed. Genetic reports available for 15 (23%) children identified causal mutations in 10 (8 in NPHS1 [1 novel variant], 1 in WT 1 [novel variant], and 1 in PLCE-1 gene). In addition, 1 child was clinically diagnosed as Galloway Mowat syndrome. Next-generation sequencing showed 80% yield and Sanger sequencing 20%. Albumin infusion and angiotensin-converting enzyme inhibitors were used initially in around two-third of cohort, while only 12% of children received indomethacin. Totally, 22 (34%) children were lost to follow-up after initial visit, and among the rest median follow-up was 69 days (IQR 20-180) with 18 (42%) deaths. Eight children showed partial response (including 2 with NPHS1 compound mutation), 1 complete response, and all of them were alive at last follow-up in contrast to 53% mortality among nonresponders, p = 0.004. CONCLUSION: This largest reported series on CNS from India revealed suboptimal management with poor outcome as well as low number of CNS being subjected to genetic evaluation.