ESPN 50th Annual Meeting

ESPN 2017


 
IS RAAS BLOCKADE EFFECTIVE IN NPHS2 GLOMERULOPATHY?
AGNES TRAUTMANN 1 FATIH OZALTIN 2 ALEXANDRA ZUROWKSA 3 HELENA HELENA 4 BASSAM SAEED 5 MARTA AZOCAR 6 ALEV YILMAZ 7 ALI ANARAT 8 AYSE BALAT 9 SALIM CALISKAN 10 RAFAEL T. KRMAR 11 PAULINE ABOU-JAOUDE 12 BEATA S. LIPSKA-ZIńôTKIEWICZ 13 KATHARINA HEES 14 FRANZ SCHAEFER 1

1- DIVISION OF PEDIATRIC NEPHROLOGY, UNIVERSITY CENTER FOR PEDIATRICS AND ADOLESCENT MEDICINE, HEIDELBERG, GERMANY
2- DEPARTMENT OF PEDIATRIC NEPHROLOGY, NEPHROGENETICS LABORATORY AND CENTER FOR BIOBANKING AND GENOMICS, HACETTEPE UNIVERSITY, ANKARA, TURKEY
3- DEPARTMENT OF PEDIATRIC NEPHROLOGY, MEDICAL UNIVERSITY OF GDANSK, GDANSK, POLAND
4- DEPARTMENT OF PEDIATRIC NEPHROLOGY, CENTRE HOSPITALAR, PORTO, PORTUGAL
5- DEPARTMENT OF PEDIATRIC NEPHROLOGY, KIDNEY HOSPITAL OF DAMASCUS, SYRIA
6- PEDIATRIC NEPHROLOGY, HOSPITAL LUIS CALVO MACKENNA-FACULTAD DE CHILE, SANTIAGO DE CHILE
7- DEPARTMENT OF PEDIATRIC NEPHROLOGY, ISTANBUL MEDICAL FACULTY, ISTANBUL, TURKEY
8- PEDIATRIC NEPHROLOGY DEPARTMENT, CUKUROVA UNIVERSITY MEDICAL FACULTY, ADANA, TURKEY
9- DEPARTMENT OF PEDIATRIC NEPHROLOGY, GAZIANTEP UNIVERSITY MEDICAL FACULTY, GAZIANTEP, TURKEY
10- PEDIATRIC NEPHROLOGY DEPARTMENT, CERRAHPASA MEDICAL FACULTY, ISTANBUL UNIVERSITY, ISTANBUL, TURKEY
11- DIVISION OF PEDIATRICS, DEPARTMENT OF CLINICAL SCIENCE, INTERVENTION AND TECHNOLOGY, KAROLINSKA UNIVERSITY HOSPITAL, STOCKHOLM, SWEDEN
12- DIVISION OF PEDIATRIC NEPHROLOGY, NOTRE DAME DE SECOURS UNIVERSITY HOSPITAL, BYBLOS, LEBANON
13- DEPARTMENT OF BIOLOGY AND GENETICS, MEDICAL UNIVERSITY OF GDANSK, GDANSK, POLAND
14- INSTITUTE OF MEDICAL BIOMETRY AND INFORMATICS, UNIVERSITY OF HEIDELBERG, GERMANY
 
Introduction:

Antiproteinuric therapy with renin-angiotensin-aldosterone system (RAAS) antagonists is an accepted pharmacological approach in hereditary nephropathies. Partial responsiveness to calcineurin inhibition (CNI) has anecdotally been reported. Here we explored changes in albuminemia during RAAS blockade with and without intensified immunosuppression (IIS) in a cohort of children with NPHS2 glomerulopathy.

Material and methods:

We performed a longitudinal PodoNet registry analysis of 40 children with steroid resistant nephrotic syndrome (SRNS) caused by NPHS2 mutation and documented periods of RAAS antagonist therapy with and without co-treatment with intensified immunosuppression (IIS; 79% CNI) administered before the genetic diagnosis was made. Serum albumin and estimated (e)GFR were assessed before IIS and/or RAAS blockade, during combined RAAS/IIS treatment and during RAAS blockade after IIS discontinuation.

Results:

RAAS blockade was started shortly after first disease manifestation (median 2.4 (IQR 0.9-6) months). In 16 patients RAAS antagonists were initiated simultaneously with IIS, whereas in 24 patients RAAS antagonists were added after an average IIS treatment duration of 2.8 (1.2-5.3) months. Combined IIS/RAAS blockade did not change serum albumin significantly (mean 19.7±6.2 -> 20.2±5.6 g/l; p=0.19). Within 12 months after IIS discontinuation but continued RAAS blockade serum albumin increased slightly to a mean of 21.6±6.2 g/l (p=0.02). eGFR decreased by 7 ml/min*1.73m2 during this period. During subsequent follow-up under continued RAAS blockade (total duration 4.0 (IQR 2.8-5.6) years) serum albumin increased further to a mean of 22.5±5.8 g/l (p=0.06), paralleled by a median eGFR loss by 18 (6-36) ml/min per year. The changes in serum albumin and eGFR were weakly correlated (r=-0.14). 

Conclusions:

Neither IIS nor RAAS blockade nor the two interventions combined appear effective in increasing serum albumin to a relevant degree in patients with NPHS2 glomerulopathy. Rather, serum albumin gradually increases over time as eGFR deteriorates.