Results:
Forty children were screened at enrolment. 5 children were excluded (1- diagnosed to have malignancy; 2 children- blood culture positive with DIC; 2 children- parents not giving consent). 35 children who fulfilled the inclusion criteria were enrolled and were further investigated.
Median age was 49 months with IQR of 9 to 90 months. The highest age noted was 140 months while the lowest, 1 month. Majority of patients were more than 24 months (60%). Out of 35 children studied, 62.9% were males with a sex ratio of 1.7: 1. While decreased urine output was the most common presentation, pallor was the most common clinical finding. (Table 1) Details of symptoms at presentation are described in Figure 1. Severe anemia was noted in 88.6% (31) and severe thrombocytopenia in 71.4% (25). AKI Stage 3 was seen in 80% (28) at presentation though 91.4% (32) developed it during the course. Hematuria was observed in 59.9% (21) children, among which 2 children had gross hematuria. Proteinuria was present in 27children, out of which 12 (34.3%) had nephrotic range. Six out of twelve children who showed a diarrhoea prodrome had their stools evaluated for STEC PCR to rule out STEC HUS, which were negative. Thirteen children had positive ANA (speckled pattern). Among those with positive ANA, ds-DNA was done in 3 children which were normal.
C3 and C4 levels were analyzed in all 35 patients among whom 57.1% (20) had low C3 and 25.7 % (9) had low C4 levels. Both C3 and C4 levels were low in 6 children. Five children who had low C3 and C4 were also negative for ANA, but one had speckled pattern ANA positivity. Mean C3 and C4 levels were 75 ± 26 mg/L and 22 ± 8 mg/L respectively. Three children had low FH levels with no relation to anti-FH antibody. Two children had low FI levels while 3 children had high FB levels. Anti-FH antibody levels were elevated in 44% (15) of children with a mean anti-FH titre level of 137.68 ± 50.1 AU/ml. Low CD46 expression assessed by median fluorescent index in neutrophils, monocytes and lymphocytes was noted in 8 children. (Mean δMFI - 8311 ± 1415.5) [Figure 2]
25 children had hypertension that was controlled with a mean of 3 anti-hypertensive drugs. 7 of them exhibited hypertensive emergencies requiring parenteral anti-hypertensive drugs. 62.8% (22) required dialysis support. Plasmapheresis (PEX) was offered to all children and plasma infusion was tried in the very small infants where PEX was not feasible. PEX was performed in 16 children while plasma infusion was given in 7. Immunosuppression was initiated in children where possibility of anti-FH antibody HUS was considered. Most of these children were those who had already received plasma therapy.
Seventeen children (48.6%) improved in terms of hematological remission with or without renal improvement. Eighteen children (51.4%) had a negative outcome as death or withdrawal of care (lost to follow up).
On further analysis, younger children (less than 24 months) had more negative outcome (36.8%) than those more than 24 months (63.2%) (p< 0.05). The mean hemoglobin levels were always on a higher side among children who had later attained remission compared to those who did not, however it was not statistically significant.