Prognostic value of urinary TGF-ß1 in hemolytic uremic syndrome: A pilot study.

BACKGROUND: Transforming growth factor ß1 (TGF-ß1) is the main profibrotic cytokine. Its urinary excretion reflects intrarenal production; thus, we conjectured that it is elevated during hemolytic uremic syndrome related to Shiga-toxin-producing Escherichia coli (STEC-HUS). In this pilot study, we explored the ability of baseline TGF-ß1 excretion (exposure variable) to predict renal prognosis at 6 months (outcome variable). In a secondary investigation, we compared changes in cytokine levels during the study period between patients with opposite renal outcomes. METHODS: Urinary TGF-ß1 concentrations were measured prospectively in 24 children with STEC-HUS on admission, and at 15, 30, 60, 90, and 180 days. Normal values were obtained from 20 healthy subjects. RESULTS: Baseline TGF-ß1 concentrations predicted renal outcomes with an area under the curve of 1 (95%CI 0.85-1; sensitivity 100%, specificity 100%) with the best cutoff level >293.7 pg/mg uCr. All patients with high TGF-ß1 levels developed persistent renal impairment, unlike none with low concentrations (4/4 vs. 20/0 respectively, P = 0.0001). The latter had higher cytokine levels (P < 0.05) at each time point without reaching normal concentrations (<45 pg/mg uCr). CONCLUSIONS: Baseline urinary TGF-ß1 levels accurately predicted short-term renal outcomes in STEC-HUS children, and cytokine excretion during the first 6 months after diagnosis was higher among those with worse evolution. Larger studies are needed to validate these findings.

Levels of urinary transforming growth factor beta-1 in children with D+ hemolytic uremic syndrome.

About 25-50% of survivors of the acute phase of postdiarrheal hemolytic uremic syndrome (D+ HUS) develop chronic renal disease. Transforming growth factor beta-1 (TGFbeta-1) is the main fibrogenic growth factor in humans, and there is a significant correlation between its levels and the grade of interstitial fibrosis in chronic nephropathies. We hypothesized that increased urinary TGFbeta-1 may be an early indicator of sequelae in D+ HUS patients who show no sign of renal damage as determined by conventional diagnostic tests. We therefore compared the levels of TGFbeta-1 in urine collected from healthy controls (HC) (n = 18) with that from patients with a past history of D+ HUS (n = 39). We found that TGFbeta-1 excretion was significantly higher (p < 0.001) in the patient group (median level 73 pg/mg creatinine) than in the HC (median level 28 pg/mg creatinine). TGFbeta-1 excretion did not correlate with age, white blood cell count, length of oligoanuric period, maximum creatinine at the acute stage, or length of the follow-up. Since TGFbeta-1 excretion may reflect ongoing renal tissue damage, our results emphasize the need for the lifelong follow-up of patients with a past history of D+ HUS, even those showing apparent recovery. Long-term monitoring of this cohort is necessary to determine the clinical utility of our findings.

Síndrome hemolítica-urêmica: casuística de dez anos em um hospital universitário / Hemolytic-uremic syndrome: case of ten years in hospital

Foram analisados os pronbtuários dos pacientes internados na unidade de intenaçäo de um hospital universitário durante um período de dez anos (janeiro de 1985 a janeiro de 1995), e que tivessem o diagnóstico de Síndrome Hemolítica Urêmica. Este diagnóstico foi baseado na presença de graus variados da tríade: insuficiência renal aguda, anemia hemolítica e trombocitopenia. Desta forma, foram encontrados 13 pacientes com idades entre quatro a 84 meses com mediana de 14 meses, 11 brancos, sem predomínio de sexo. Com exceçäo de um, todos tinham peso adequado à idade...

Prognostic significance of proteinuria one year after onset of diarrhea-associated hemolytic-uremic syndrome.

We examined the prognostic value of changes in the amount of proteinuria, measured as protein/creatinine ratios in early-morning urine samples, in 40 children who had had diarrhea-associated hemolytic-uremic syndrome. One year after diagnosis, 87% of those who seemed to have fully recovered had normal urinary protein/creatinine ratios, compared with none of those with poor outcomes (p less than 0.001). None of those with poor outcomes achieved normal protein/creatinine ratios during follow-up to a maximum of 5 1/2 years, but 93% of those who made a full clinical recovery no longer had proteinuria. Measurement of the protein/creatinine ratio in an early-morning sample of urine is a simple, cost-effective, and noninvasive means of monitoring the progress of patients with diarrhea-associated hemolytic-uremic syndrome, provided that a technique sensitive at low protein concentrations is employed.

Long-term outcome and prognostic indicators in the hemolytic-uremic syndrome.

We examined 61 patients an average of 9.6 years (range 5 to 18 years) after an episode of childhood hemolytic-uremic syndrome. Twenty-four (39%) had one or more abnormalities. Seven (11%) had proteinuria and six (10%) had low creatinine clearance as solitary abnormalities. Eight (13%) had both proteinuria and reduced creatinine clearance; three (5%) had a combination of hypertension, proteinuria, and low creatinine clearance. Abnormalities sometimes appeared after an interval of apparent recovery. Logistic regression analysis showed that duration of anuria was the best predictor of disease at follow-up. No patients who had anuria lasting longer than 8 days or oliguria exceeding 15 days escaped chronic disease. However, 45% of those with disease had no anuria, and a third had no oliguria. Physicians should therefore be cautious in assuming recovery from HUS on the basis of a single evaluation and should periodically evaluate patients for an extended period.

Renal functional reserve compared in haemolytic uraemic syndrome and single kidney.

Creatinine clearance and microalbuminuria were measured before and after an oral protein load in 17 children with a history of haemolytic uraemic syndrome, 11 with a single kidney, and 15 controls, all of them normotensive and without evidence of renal damage, to look for indirect evidence of glomerular hyperfiltration. While creatinine clearance increased significantly after the protein load in controls, it did not change in patients with either haemolytic uraemic syndrome or a single kidney. Basal microalbuminuria was significantly higher in those with haemolytic uraemic syndrome when compared with those with a single kidney and controls. It increased significantly in all groups after a water load; this increase was significantly higher in haemolytic uraemic syndrome. After the protein load microalbuminuria returned to baseline. In conclusion, children with a history of haemolytic uraemic syndrome have an abnormal renal functional reserve like children with a single kidney. Only patients with haemolytic uraemic syndrome exhibited an increased microalbuminuria, however, suggesting that it may be the expression of a pathophysiological mechanism involved in haemolytic uraemic syndrome and not in single kidney, that could account for their different prognosis.