Hyponatremia: a new predictor of mortality in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome.

OBJECTIVES: (1) Evaluate mortality rate in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, (2) determine the leading causes of death, and (3) identify predictors of mortality at hospital admission. METHODS: We conducted a multicentric, observational, retrospective, cross-sectional study. It included patients under 18 years old with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome hospitalized between January 2005 and June 2016. Clinical and laboratory data were obtained from the Argentine National Epidemiological Surveillance System of Hemolytic Uremic Syndrome. Clinical and laboratory variables were compared between deceased and non-deceased patients. Univariate and multivariate analyses were performed. ROC curves and area under the curve were obtained. RESULTS: Seventeen (3.65%) out of the 466 patients died, being central nervous system involvement the main cause of death. Predictors of death were central nervous system involvement, the number of days since the beginning of diarrhea to hospitalization, hyponatremia, high hemoglobin, high leukocyte counts, and low bicarbonate concentration on admission. In the multivariate analysis, central nervous system involvement, sodium concentration, and hemoglobin were independent predictors. The best cut off for sodium was ≤ 128 meq/l and for hemoglobin ≥ 10.8 g/dl. CONCLUSIONS: Mortality was low in children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, being central nervous system involvement the main cause of death. The best mortality predictors found were central nervous system involvement, hemoglobin, and sodium concentration. Hyponatremia may be a new Shiga toxin-producing Escherichia coli hemolytic uremic syndrome mortality predictor.

Additive antiproteinuric effect of enalapril and losartan in children with hemolytic uremic syndrome.

BACKGROUND: Angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers decrease postdiarrheal hemolytic uremic syndrome (D + HUS) sequelar proteinuria. However, proteinuria may persist in some patients. In nephropathies other than D + HUS, an additive antiproteinuric effect with coadministration of both drugs has been observed. METHODS: To assess such an effect in D + HUS, 17 proteinuric children were retrospectively studied. After a median period of 1 year post-acute stage (range 0.5-1.9) patients received enalapril alone for a median of 2.6 years (range 0.33-12.0) at a median dose of 0.4 mg/kg/day (range 0.2-0.56). As proteinuria persisted, losartan was added at a median dose of 1.0 mg/kg/day (range 0.5-1.5) during 2.1 years (range 0.5-5.0). RESULTS: The decrease in proteinuria with enalapril was 58.0 %, which was further reduced to 83.8 % from the initial value after losartan introduction. The percentage of reduction was significantly greater with the association of both drugs (p = 0.0006) compared with the effect of enalapril exclusively (p = 0.023). Serum potassium, glomerular filtration rate, and blood pressure remained unchanged. CONCLUSIONS: Our results suggest that adding losartan to persisting proteinuric D + HUS children already on enalapril is safe and reduces proteinuria more effectively. Whereas this effect is associated with long-term kidney protection, it should be determined by prospective controlled studies.

Effect of diet, enalapril, or losartan in post-diarrheal hemolytic uremic syndrome nephropathy.

Proteinuria is the main indicator of renal disease progression in many chronic conditions. There is currently little information available on the efficacy, safety, and individual tolerance of patients with post-diarrheal hemolytic uremic syndrome (D+ HUS) nephropathy to therapies involving diet, enalapril, or losartan. A multicenter, double-blind, randomized controlled trail was conducted to evaluate the effect of a normosodic-normoproteic diet (Phase I) and the effect of normosodic-normoproteic diet plus enalapril (0.18-0.27 mg/kg/day) or losartan (0.89-1.34 mg/kg/day) (Phase II) on children with D+ HUS, normal renal function, and persistent, mild (5.1-49.9 mg/kg/day) proteinuria. Dietary intervention reduced the mean protein intake from 3.4 to 2.2 mg/kg/day. Of 137 children, proteinuria normalized in 91 (66.4 %) within 23-45 days; the remaining 46 patients were randomized to diet plus placebo (group 1, n = 16), plus losartan (group 2, n = 16), or enalapril (group 3, n = 14). In groups 1, 2, and 3, proteinuria was reduced by 30.0, 82.0, and 66.3%, respectively, and normalized in six (37.5%), three (81.3%), and 11 (78.6%) patients, respectively (χ(2)= 8.9, p = 0.015). These results suggest that: (1) a normosodic-normoproteic diet can normalize proteinuria in the majority of children with D+ HUS with mild sequelae, (2) the addition of enalapril or losartan to such dietary restrictions of protein further reduces proteinuria, and (3) these therapeutic interventions are safe and well tolerated. Whether these short-term effects can be extended to the long-term remains to be demonstrated.

Two different therapeutic regimes in patients with sequelae of hemolytic-uremic syndrome.

Renal disease is the most important long-term complication of hemolytic-uremic syndrome (HUS). A comparative study of renal function was carried out in two groups of patients. Group 1 included 19 children followed for a median of 11 years, 1960-1980, with a low-sodium diet, antihypertensive drugs, and a restricted protein intake in the end stage of renal disease. Group 2 included 26 children treated for a median of 9 years, 1988-2002, on a low-sodium diet, early restriction of protein intake according to recommendations, and angiotensin converting enzyme inhibitors (ACEi). Long-term renal function was assessed by the inverse of the plasma creatinine concentration (1/[Cr]) over time. Linear regression lines were fitted to individual values of 1/[Cr] for each child. Regression coefficients of children in group 1 were all negative, ranging from -0.031 to -0.00043; 7 were significantly different from zero, indicating a linear fall in renal function over time. In contrast, children from group 2 had 11 negative slopes (only 1 significant) and 15 positive slopes, ranging from 0.17893 to -0.3899. Fisher's exact test showed that group 1 had significantly more children with negative slopes than group 2. This comparatively better long-term outcome of renal function in children under contemporary treatment was probably associated with early restriction of protein and use of ACEi.

Nefritis lúpica / Lupus Nephritis

El pronóstico de la glomerulonefritis lúpica ha mejorado en las últimas décadas,sin embargo hay pocos estudios en pediatría con seguimiento a largo plazo.Se efetuó el análisis retrospectivo de 52 niños con diagnóstico de nefritis lúpica,seguidos en el Serviciode Nefrología del Hospital de Pediatría Juan P Garrahan entre Enero de 1988 y mayo de 1998 con el objetivo de evaluar las formas de presentación clínica y serológicas,características de la anatomía patológica,evolución posterior y sobrevida actuarial del paciente y del riñon.No observamos nefritis lúpica en menores de 6 años.50 niños fueron biopsiados y se consideró las clasificación anatomo-patológica segun la WHO.El síndrome nefrótico y la disminución del filtrado glomerular fueron las formas de presentación más frecuentes de la nefritis lúpica,La clase IV fue la norma anatomo-patológica de mayor frecuencia.El tiempo X de seguimiento fue de 49,3 meses.La sobrevida del paciente y del riñon a 5 y 10 años de seguimiento fue similar a la de otras series:88 y 86 por ciento respectivamente