Intensive Supportive Care plus Immunosuppression in IgA Nephropathy
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Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. / Rauen, Thomas; Eitner, Frank; Fitzner, Christina; Sommerer, Claudia; Zeier, Martin; Otte, Britta; Panzer, Ulf; Peters, Harm; Benck, Urs; Mertens, Peter R; Kuhlmann, Uwe; Witzke, Oliver; Gross, Oliver; Vielhauer, Volker; Mann, Johannes F E; Hilgers, Ralf-Dieter; Floege, Jürgen; STOP-IgAN Investigators.
In: NEW ENGL J MED, Vol. 373, No. 23, 03.12.2015, p. 2225-36.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Intensive Supportive Care plus Immunosuppression in IgA Nephropathy
AU - Rauen, Thomas
AU - Eitner, Frank
AU - Fitzner, Christina
AU - Sommerer, Claudia
AU - Zeier, Martin
AU - Otte, Britta
AU - Panzer, Ulf
AU - Peters, Harm
AU - Benck, Urs
AU - Mertens, Peter R
AU - Kuhlmann, Uwe
AU - Witzke, Oliver
AU - Gross, Oliver
AU - Vielhauer, Volker
AU - Mann, Johannes F E
AU - Hilgers, Ralf-Dieter
AU - Floege, Jürgen
AU - STOP-IgAN Investigators
PY - 2015/12/3
Y1 - 2015/12/3
N2 - BACKGROUND: The outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain.METHODS: We conducted a multicenter, open-label, randomized, controlled trial with a two-group, parallel, group-sequential design. During a 6-month run-in phase, supportive care (in particular, blockade of the renin-angiotensin system) was adjusted on the basis of proteinuria. Patients who had persistent proteinuria with urinary protein excretion of at least 0.75 g per day were randomly assigned to receive supportive care alone (supportive-care group) or supportive care plus immunosuppressive therapy (immunosuppression group) for 3 years. The primary end points in hierarchical order were full clinical remission at the end of the trial (protein-to-creatinine ratio <0.2 [with both protein and creatinine measured in grams] and a decrease in the estimated glomerular filtration rate [eGFR] of <5 ml per minute per 1.73 m(2) of body-surface area from baseline) and a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) at the end of the trial. The primary end points were analyzed with the use of logistic-regression models.RESULTS: The run-in phase was completed by 309 of 337 patients. The proteinuria level decreased to less than 0.75 g of urinary protein excretion per day in 94 patients. Of the remaining 162 patients who consented to undergo randomization, 80 were assigned to the supportive-care group, and 82 to the immunosuppression group. After 3 years, 4 patients (5%) in the supportive-care group, as compared with 14 (17%) in the immunosuppression group, had a full clinical remission (P=0.01). A total of 22 patients (28%) in the supportive-care group and 21 (26%) in the immunosuppression group had a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) (P=0.75). There was no significant difference in the annual decline in eGFR between the two groups. More patients in the immunosuppression group than in the supportive-care group had severe infections, impaired glucose tolerance, and weight gain of more than 5 kg in the first year of treatment. One patient in the immunosuppression group died of sepsis.CONCLUSIONS: The addition of immunosuppressive therapy to intensive supportive care in patients with high-risk IgA nephropathy did not significantly improve the outcome, and during the 3-year study phase, more adverse effects were observed among the patients who received immunosuppressive therapy, with no change in the rate of decrease in the eGFR. (Funded by the German Federal Ministry of Education and Research; STOP-IgAN ClinicalTrials.gov number, NCT00554502.).
AB - BACKGROUND: The outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain.METHODS: We conducted a multicenter, open-label, randomized, controlled trial with a two-group, parallel, group-sequential design. During a 6-month run-in phase, supportive care (in particular, blockade of the renin-angiotensin system) was adjusted on the basis of proteinuria. Patients who had persistent proteinuria with urinary protein excretion of at least 0.75 g per day were randomly assigned to receive supportive care alone (supportive-care group) or supportive care plus immunosuppressive therapy (immunosuppression group) for 3 years. The primary end points in hierarchical order were full clinical remission at the end of the trial (protein-to-creatinine ratio <0.2 [with both protein and creatinine measured in grams] and a decrease in the estimated glomerular filtration rate [eGFR] of <5 ml per minute per 1.73 m(2) of body-surface area from baseline) and a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) at the end of the trial. The primary end points were analyzed with the use of logistic-regression models.RESULTS: The run-in phase was completed by 309 of 337 patients. The proteinuria level decreased to less than 0.75 g of urinary protein excretion per day in 94 patients. Of the remaining 162 patients who consented to undergo randomization, 80 were assigned to the supportive-care group, and 82 to the immunosuppression group. After 3 years, 4 patients (5%) in the supportive-care group, as compared with 14 (17%) in the immunosuppression group, had a full clinical remission (P=0.01). A total of 22 patients (28%) in the supportive-care group and 21 (26%) in the immunosuppression group had a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) (P=0.75). There was no significant difference in the annual decline in eGFR between the two groups. More patients in the immunosuppression group than in the supportive-care group had severe infections, impaired glucose tolerance, and weight gain of more than 5 kg in the first year of treatment. One patient in the immunosuppression group died of sepsis.CONCLUSIONS: The addition of immunosuppressive therapy to intensive supportive care in patients with high-risk IgA nephropathy did not significantly improve the outcome, and during the 3-year study phase, more adverse effects were observed among the patients who received immunosuppressive therapy, with no change in the rate of decrease in the eGFR. (Funded by the German Federal Ministry of Education and Research; STOP-IgAN ClinicalTrials.gov number, NCT00554502.).
KW - Adult
KW - Angiotensin II Type 2 Receptor Blockers
KW - Angiotensin-Converting Enzyme Inhibitors
KW - Combined Modality Therapy
KW - Critical Care
KW - Female
KW - Glomerular Filtration Rate
KW - Glomerulonephritis, IGA
KW - Glucocorticoids
KW - Humans
KW - Immunosuppression
KW - Logistic Models
KW - Male
KW - Middle Aged
KW - Proteinuria
KW - Renin-Angiotensin System
KW - Treatment Failure
U2 - 10.1056/NEJMoa1415463
DO - 10.1056/NEJMoa1415463
M3 - SCORING: Journal article
C2 - 26630142
VL - 373
SP - 2225
EP - 2236
JO - NEW ENGL J MED
JF - NEW ENGL J MED
SN - 0028-4793
IS - 23
ER -