#5121 IGM POSITIVE MINIMAL CHANGE DISEASE: CHARACTERIZING DISEASE SEVERITY AND OUTCOMES
Authors: Cunha Ana Cristina Santos , Braga Beatriz Gil , Sousa Sofia , Ventura Sofia , Correia Sofia , Malheiro Jorge , Campos Andreia , Santos Josefina 
Published: June 2023

Background and Aims

Minimal change disease (MCD) is the main cause of nephrotic syndrome in pediatric age and it is responsible for 10-25% of the cases in adults. It is characterized by minimal glomerular abnormalities in light microscopy, usually without immunoglobulins or complement deposits in immunofluorescence (IF). There is a subgroup of patients that presents with IgM deposition in IF, which has been described as a more aggressive disease, with frequent relapses [1], dependence of steroids [2] and worse outcomes.

Method

This is a retrospective study that analyses the follow up of 50 adult MCD patients in the nephrology consult, with diagnosis in childhood or adulthood. They had renal biopsies performed between 2009 and 2022. We did not include inappropriate biopsy samples, biopsies without IF or positive for C1q. We compared the characteristics between IgM positive (IgM+) and IgM negative (IgM-) patients at diagnosis, as well as the number of relapses per year, age of presentation and association with steroid-dependence or steroid-resistance.

Results

There were 23 (46%) patients in the IgM+ group and 27 (54%) in the IgM- group, with a mean follow-up of 10.2± 7.8 years. The IgM- subgroup was older at biopsy time (52 (30-74) years vs IgM+ 15 (13-23) years; p = 0.001) and this is probably related with the age of disease presentation, which was younger in the IgM+ group (12 (5-16) years vs IgM- 52 (73-13) years; p = 0.001). The groups were similar in sex distribution (IgM+ male n = 15 (55.6%) vs IgM- male n = 10 (44.0%); p = 0.395). There were no differences in diabetes and dyslipidemia frequencies between the two groups (Diabetes: IgM+ n = 1 (4.3%), IgM- n = 3 (11.3%), p = 0.614; Dyslipidemia: IgM+ n = 7 (30.4%), IgM- n = 7 (25.9%), p = 0.723), but the IgM- group had more patients with hypertension (IgM+ n = 2 (8.7%), IgM- n = 9 (33%), p = 0.046). The estimated glomerular filtration rate based on creatinine (eGFRcr) at biopsy time was higher in the IgM+ group (124 (104-130) ml/min/1.73 m2 vs IgM- with 96 (84-111) ml/min/1.73 m2; p = 0.003), but this happens probably due to the age as a confounding variable. In regard to the number of relapses per year, the IgM+ group had significantly more relapses than the IgM- group (IgM+ with 0.61 (0.27-1.00) relapses per year; IgM- with 0.17 (0.01-0.65) relapses per year; p = 0.011). The steroid-dependence (IgM+ n = 15 (65%); IgM- n = 11 (47%); p = 0.084) and the steroid-resistance (IgM+ n = 6 (26%); IgM- n = 3 (11%); p = 0.270) isolated outcomes were not significantly different in the two groups, but when we analyze the composed outcome of steroid-dependence plus steroid-resistance we have worse outcomes in the IgM+ subgroup (IgM+ n = 21 (91.3%); IgM- n = 14 (51.8%); p = 0.04; ORR 9.72; IC 95% 2.37-33.33). An IgM+ patient has 9.7 times the odd of being steroid-dependent or steroid-resistant of an IgM- patient. From our 50 patients, 3 evolved to stage 5 chronic kidney disease with dialysis dependency, being all of those patients IgM+. One of those patients had a recurrency of MCD after kidney transplant. There were 3 deaths with non-related to kidney disease causes, 1 in the IgM+ and 2 in the IgM- groups. Genetic test was performed in 5 of the IgM+ patients, with 4 positive results for mutations. Only 2 IgM- patients did genetic test, all without mutation´s identification.

Conclusion

This study supports the evidence that MCD patients with IgM+ biopsies have younger age MCD's presentation, more relapses per year and more steroid dependence plus resistance. Dialysis was started in 3 IgM+ patients and this group seems to have higher frequency of genetic mutations. This suggests that genetic testing could be important for future prognosis prediction and treatment options in the IgM+ patients, but further studies with a bigger study population need to be done to establish this relation.