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.     

Impact of platelet transfusions in children with post-diarrheal hemolytic uremic syndrome

Background

Platelet transfusions should be avoided in children with post-diarrheal hemolytic uremic syndrome (D + HUS) because they might increase microthrombi formation, thereby aggravating the disease. As this possibility has not yet been explored, we investigated whether platelet transfusion in patients with D + HUS would lead to a worse disease course compared to that in patients who did not receive platelet transfusion.

Methods

This was a case–control study in which data from D + HUS children who received platelet transfusions (cases, n? = ?23) and those who did not (controls, n? = ?54) were retrospectively reviewed and compared.

Results

Both patient groups were similar in age (p?=?0.3), gender (p? =? 0.53), weight (p? = ?0.86), height (p? = ?0.45), prior use of non-steroidal anti-inflammatory drugs (p? = ?0.59) or antibiotics (p ?= ?0.45) and presence of dehydration at admission (p? = ?0.79). The two groups also did not differ in initial leukocyte count (p? = ?0.98), hematocrit (p? = ?0.44) and sodium (p? = ?0.11) and alanine aminotransferase levels (p? = ?0.11). During hospitalization, dialysis duration (p? = ?0.08), number of erythrocyte transfusions (p? =? 0.2), serum creatinine peak (p? = ?0.22), presence of severe bowel (p? = ?0.43) or neurologic (p? = ?0.97) injury, arterial hypertension (p? = ?0.71), need for intensive care (p? = ?0.33) and death (p? = ?1.00) were also comparable.

Conclusion

Our findings suggest that platelet transfusion does not aggravate the course of the disease. Conversely, no hemorrhagic complications were observed in the group of patients who did not receive a platelet transfusion. Until these observations are confirmed by further studies, the benefits and risk of platelet transfusion should be thoughtfully balanced on an individual case basis.     

Clustering of post-diarrheal (Shiga toxin-mediated) hemolytic uremic syndrome in families

AIMS: 1. To study the epidemiological and clinical features of Shiga toxin (Stx)-mediated (post-diarrheal) hemolytic uremic syndrome (HUS) occurring in more than 1 family member. 2. To compare familial with non-familial episodes, and concurrent familial with non-concurrent familial cases. 3. To determine the likelihood of Stx HUS occurring in a second family member. METHODS: A retrospective review from January 1970 through September 2001 of families in whom Stx HUS occurred in more than 1 family member was conducted using a computerized HUS registry. It contains information on 373 episodes that occurred in 356 families from Utah and neighboring states. Cases were categorized as being either concurrent (i.e., occurring within a month of one another) or non-concurrent, and the study was limited to those with typical (post-diarrheal) episodes. RESULTS: HUS occurred in 2 or more family members in 17 (4.8%) of the families in our registry. In 12 (3.4%) of these families episodes occurred with days to weeks of each other; in 5 families (1.4%) episodes were separated by intervals of several years. There were no statistically significant differences in demographic, seasonal, laboratory, clinical, or outcome variables between familial subsets (concurrent versus non-concurrent) or between familial and non-familial cases. CONCLUSIONS: When a child is diagnosed with D+ HUS, there is an increased risk that a second family member will also develop HUS; most often within days to weeks (i.e., within a month), but in some cases episodes may be separated by intervals of years. Non-concurrent cases suggest common environmental risk factors, or perhaps a genetic predisposition. Concurrent cases suggest a common source of infection or person-to-person transmission; a genetic predisposition cannot be excluded. These observations suggest that siblings of an index case who develop diarrhea should be kept under close surveillance.     

Duration of oliguria and anuria as predictors of chronic renal-related sequelae in post-diarrheal hemolytic uremic syndrome

Prior long-term retrospective studies have described renal sequelae in 25-50% of postdiarrheal hemolytic uremic syndrome (HUS) survivors, but the ability to predict the likelihood of chronic renal-related sequelae at the time of hospital discharge is limited. We surveyed 357 children in our HUS registry who survived an acute episode of post diarrheal HUS (D+HUS) and were without end-stage renal disease (ESRD) at the time of hospital discharge. Of the 357 patients surveyed, 159 had at least 1 year (mean 8.75 years) of follow-up. Of these, 90 individuals were identified as having had at least 1 day of oliguria, with 69 individuals having had at least 1 day of anuria. The incidences of renal-related sequelae [proteinuria, low glomerular filtration rate (GFR), and hypertension] were determined among experimental groups based on oliguria and anuria duration. One or more sequelae (e.g. proteinuria, low GFR, hypertension) was seen in 25 (36.2%) of those who had no recorded oliguria and 34 (37.8%) of those with no recorded anuria. The prevalence of chronic sequelae increased markedly in those with more than 5 days of anuria or 10 days of oliguria, with anuria being a better predictor than oliguria of most related sequelae. A particularly high incidence of hypertension was seen in patients with > 10 days of anuria (55.6%) in comparison with those with no anuria (8.9%) [odds ratio (OR) 12.8; 95% confidence interval (CI) 2.9-57.5]. Patients with > 10 days of anuria were also at substantially increased risk for low GFR and proteinuria (OR 35.2; 95% CI 5.1-240.5). These findings may help identify children who need periodic and extended follow-up after hospital discharge.     

C1q nephropathy with acute hemolytic uremic syndrome

C1q nephropathy with hemolytic uremic syndrome (HUS) is an uncommon combination associated with rapidly progressive renal failure. We report a case of C1q nephropathy with HUS in an 18-year-old man associated with rapidly progressive renal failure. The patient did not respond to treatment with steroids and was started on maintenance hemodialysis. C1q nephropathy with HUS is rare and can lead to rapidly progressive renal failure.     

The hemolytic uremic syndrome as a complication of adriamycin nephropathy

Rats treated with two injections of adriamycin (week 0 and week 12) developed glomerusclerosis and severe tubulointerstitial lesions as described in the literature. In addition, a number ofglomerular alterations were present. These included capillary loop dilation, insudation of eosinophilic material, necrosis, duplication of the glomerular basement membrane, severe mesangiolysis with disruption of the mesangial matrix and segmental double-contours. The renal arterioles and interlobular arteries showed endothelial cell swelling. The subendothelial space was infiltrated by fibrinoid material and there was intensive fibrinoid necrosis of the wall of both arteries and arterioles extending into the glomerular tuft. These alterations were very similar to those observed in the hemolytic uremic syndrome. This observation suggests that the two injections of adriamycin, with a long interval in between them, might induce renal lesions similar to those observed in the hemolytic uremic syndrome.     

Endotoxemia in hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) was diagnosed and confirmed by renal biopsy in an 18-year-old primigravida at the 13th week of pregnancy. Circulating endotoxin was detected and the endotoxemia was progressively reduced by hemodialysis (HD) performed daily from the 3rd to the 9th day of disease. Complete normalization of the renal function was observed on day 34. The authors emphasize the importance of detecting endotoxemia in HUS in order to initiate dialysis early; at the same time they also discuss the pathogenetic role of endotoxin in this disease.     

Post-dysenteric hemolytic uremic syndrome in Bulawayo, Zimbabwe

An outbreak of dysentery in Zimbabwe was associated with a high mortality, especially in children who developed hemolytic uremic syndrome (HUS). To examine the causes of high mortality from HUS and to suggest measures that could reduce the case fatality rate, clinical and laboratory features of 91 children with dysentery were reviewed. Of these, 14 developed HUS; their findings were compared with age-matched controls with dysentery only. Persistent alteration of consciousness after rehydration, pallor, and oliguria were early clinical indicators of HUS. Leukocytosis and leukemoid reaction, microhematuria, and non-resolving hyponatremia distinguished children with HUS from those with dysentery. While Shigella dysenteriae type I was responsible for the dysentery outbreak in the community, most stool cultures of children with HUS were negative. Mortality from HUS was high. Late recognition of HUS and a lack of peritoneal dialysis could have contributed to the fatal outcome in some cases. Early recognition of HUS through close observation of children with dysentery and appropriate laboratory investigations with referral to a hospital, where peritoneal dialysis is available, should improve the outcome. Received: 24 August 2000 / Revised: 30 July 2001 / Accepted: 31 July 2001     

Steroids in the hemolytic uremic syndrome

To determine whether steroids could be of clinical benefit in the treatment of the hemolytic uremic syndrome (HUS), we conducted a randomized, double-blinded, placebo-controlled trial of methylprednisone (5 mg/kg per day in four oral doses over 7 days), in children with HUS during the acute phase. Ninety-two patients with typical HUS (47 receiving placebo and 45 receiving steroids) were investigated for neurological, hematological, and nephrological variables. There were no differences between groups in the number of convulsive episodes or transfusion requirements during the hospital stay. Serum creatinine levels were slightly increased on day 10 in the placebo group compared with the steroid group (P = 0.06) and declined significantly between days 1 and 10 only in the steroid group (P = 0.001). In the 51 patients with anuria (24 placebo, 27 steroids), median serum creatinine levels were reduced in the steroid group compared with the placebo group on the 10th day (P = 0.01). Differences in median days of oliguria [11.5 versus 8 (P = 0.28)], anuria [5 versus 7 (P = 0.20)], and dialysis [12 versus 10 (P = 0.26)] for the placebo and the steroid group respectively were not significant. Our data suggest that oral steroids are not able to modify hematological, neurological, or nephrological clinical parameters during the acute phase of childhood HUS, even though they do seem to be associated with a more rapid decline in serum creatinine levels. Received April 9, 1997; received in revised form September 8, 1997, accepted September 10, 1997     

Racial incidence of hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children and is caused by infection with verotoxin-productingEscherichai coli. There is no consensus on the relative incidence of HUS in blacks and whites. An equal racial incidence has been reported by two centers with small black populations. A series from Washington D. C. reported a low incidence in blacks. The population of Alabama is 32% black and 66% white. The Children's Hospital of Alabama admission rate has a similar racial distribution (35% black, 65% white). A record review from 1980–1992 identified 45 patients with HUS; 43 (96%) were white and only 2 (4%) were black. Based on census data for Alabama in 1980 and 1990, this gives an average annual incidence of HUS of 0.45 per 100,000 in whites and of 0.043 per 100,000 in blacks (P<0.001, Fischer's exact test). Similar results were found in the group of patients with HUS and a history of diarrhea; whites 0.39 and blacks 0.02 (P<0.001). However, in those with no history of diarrhea there was no significant racial difference: whites 0.05 and blacks 0.02. There were too few blacks to compare clinical course and outcome. We conclude that typical diarrhea-associated HUS is a relatively rare disease in blacks compared with whites. The reasons are unclear.