Reversal of central nervous system involvement in hemolytic uremic syndrome by use of plasma exchanges.

A 12-year-old girl presented with weakness, diplopia, and lethargy after a prodrome of gastroenteritis. Laboratory studies were compatible with a diagnosis of hemolytic uremic syndrome. She developed seizures that were controlled by diphenylhydantoin and valium. In spite of peritoneal dialysis and fresh frozen plasma infusions, she progressed to a left hemiplegia associated with a brain scan finding of decreased blood flow in the right middle cerebral artery perfusion area. A 5 liter whole blood exchange transfusion did not improve the neurological status or low platelet count. Daily plasma exchanges with fresh frozen plasma replacement resulted in normal platelet count within 48 hours and was followed by progressive improvement in neurological status. Platelet agglutinating factor decreased to control levels. A repeat brain scan was normal.

Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children.

Streptococcus pneumoniae is an uncommon etiological organism in hemolytic uremic syndrome (HUS). Production of neuraminidase by S. pneumoniae results in exposure of red blood cell T-antigen, resulting in hemolysis, thrombocytopenia, and acute renal failure. Hepatic involvement in this form of HUS has not been described in the literature. We report in three children with S. pneumoniae-associated HUS the presence of severely elevated transaminases and conjugated hyperbilirubinemia. Increases in asparagine transaminase ranged from 11 to 46 times normal values and an increase in alanine transaminase ranged from 1.6 to 8 times normal. In all patients the rise in total bilirubin was 7-15 times normal. Biliary tree obstruction and viral causes for liver dysfunction were absent. Hepatocellular injury in S. pneumoniae-associated HUS likely results from mechanisms involved in sepsis and pneumonia-induced jaundice, combined with severely increased bilirubin production following massive hemolysis. The hepatic injury in all three patients resolved within 9, 5, and 10 days. Our experience suggests that an extensive evaluation including liver biopsy is not indicated.

Early diagnosis of Bardet-Biedl syndrome.

A 3-year-old boy presented with decreased renal function, hypertension, obesity and developmental delay. Evaluation of his kidneys revealed blunting of the calyces and multiple renal cortical cysts. Ophthalmologic evaluation showed no abnormalities on examination but electroretinography showed reduced retinal function suggesting a diffuse retinal disorder. Based on the clinical presentation with the associated abnormalities, the diagnosis of Bardet-Biedl syndrome, a form of the Laurence-Moon-Biedl syndrome was made. This syndrome should be considered and specific diagnostic efforts should be made in pediatric patients who present with renal failure and obesity.

Alport's syndrome and achalasia.

A 7-year-old boy presented with a history of postprandial vomiting, failure to thrive, hematuria, proteinuria and decreased renal function. Electron microscopy of a renal biopsy specimen demonstrated the typical glomerular basement membrane changes associated with Alport's syndrome. Audiometry revealed a moderate bilateral high-tone sensorineural hearing loss. Bilateral anterior lenticonus and a unilateral cataract were also diagnosed. Achalasia diagnosed radiologically and confirmed by biopsy was corrected by surgery. Evaluations of the parents and three siblings were negative. The patient subsequently developed end-stage renal failure. This case report and a review of the literature suggest that achalasia may be part of Alport's syndrome in some patients.

Significance of the monocyte crossmatch in living-related transplantation.

It is claimed that antibodies to the vascular-endothelial (VEM) antigen system are responsible for early renal transplant rejection. To evaluate the significance of these anti-VEM antibodies, we performed a retrospective study in 16 patients aged 14.8 +/- 5 (SD) years, who received either a living-related HLA-identical (n = 5) or haplo-identical (n = 11) transplant between 4/79 and 3/84. All patients had been transfused prior to transplantation. Lymphocyte and monocyte complement dependent cytotoxic crossmatches were performed using pre- and posttransplant recipients' sera and donor lymphocytes and monocytes. Lymphocytes were isolated with Ficoll-Hypaque; monocytes by adherence to plastic Petri dishes. Of the 16 patients studied, only 1 had a positive pre- and posttransplant monocyte crossmatch. Crossmatches using recipients' T and B lymphocytes were uniformly negative, indicating the presence of anti-VEM antibodies in the absence of anti-HLA antibodies in this 1 patient. This patient rejected the transplant in the immediate posttransplant period. Of the remaining 15 patients, 4 lost their kidneys within 16 days posttransplant, whereas 11 have good graft function. We conclude that anti-VEM antibody occurs rarely pretransplant and is an unusual cause of immediate rejection in the living-related transplant situation. However, when anti-VEM antibody is identified, transplantation should be avoided because of the likelihood of immediate early rejection.

Pseudotumor cerebri with vision impairment in two children with renal transplantation.

The syndrome of pseudotumor cerebri consists of headaches, difficulty with vision and papilledema associated with raised intracranial pressure (ICP) without localizing neurological mass lesions. Recently, an association of pseudotumor cerebri and renal insufficiency, chronic dialysis or renal transplantation has been noted. Loss of vision remains a serious threat in children with pseudotumor cerebri. We report two children who developed pseudotumor cerebri with impairment of vision 5 years after renal transplantation. An awareness of this association should prompt the nephrologist to investigate and treat the symptoms of raised ICP to prevent visual loss.

Focal segmental glomerulosclerosis in desquamative interstitial pneumonia.

Renal involvement in desquamative interstitial pneumonitis (DIP) manifesting as chronic renal failure has been reported only once. An uncommon disorder in children, DIP has been associated with a variety of systemic disorders and has an immune-mediated pathogenesis. A 16-year-old Black male was diagnosed to have DIP on lung biopsy at the age of 10 months. He was first noted to have proteinuria at age 5 which progressed to nephrotic syndrome by age 13 when the laboratory tests showed elevated IgG, normal serum complement, increased circulating immune complexes and absent anti-GBM antibodies. A percutaneous renal biopsy specimen performed at age 13 revealed focal segmental glomerulosclerosis. Despite prednisone treatment of 2 mg/kg/day for 12 weeks, renal failure progressed requiring hemodialysis. Pulmonary functions, although reduced, remained stable.

Failure of fresh frozen plasma infusions to alter the course of hemolytic uremic syndrome.

The hemolytic uremic syndrome (HUS) is characterized by thrombocytopenia, anemia, and acute renal failure. Fresh frozen plasma (FFP) infusions have been claimed to shorten the course of HUS. However, no long-term follow-up is available. Hence, we analyzed the effects of FFP infusions on acute resolution and long-term sequelae of HUS in 12 children (5 boys, 7 girls, mean age 4.5 years, range 7 months to 9 years) and compared to a historical control group of 31 children (13 boys, 18 girls, mean age 3 years, range 8 months to 9 years). The patient population, severity of HUS, and other modes of therapy except FFP were similar in the two groups. There was no statistically significant difference between the groups in the acute resolution of HUS as evaluated by recovery of anemia, thrombocytopenia, and return of renal functions. Long-term sequelae of HUS such as hypertension, end-stage renal disease, and CNS residual abnormalities were also similar in two groups. One child died in the FFP group and 2 children died in the control group. We feel that FFP infusions have no significant effect on the course of HUS and its use should be questioned.

Acquired cystic kidney disease in children undergoing long-term dialysis.

Acquired cystic kidney disease (ACKD) occurs in adult patients undergoing long-term dialysis. Early detection is important because clinically significant hematuria and malignancies are associated with ACKD. We evaluated by magnetic resonance imaging (MRI) and ultrasonography (US) the incidence of ACKD in 15 patients aged 7.3-21.6 years (mean 15.9 years) with non-cystic primary renal disease. Nine patients had been treated with peritoneal dialysis only, and 6 with both hemodialysis and peritoneal dialysis for 24-73 months (mean 37 months). Three patients (20%) had no cysts. In 5 patients (33%) with bilateral multiple cysts, the diagnosis of ACKD was made by MRI and US. In another 5 patients, solitary cysts were localized to one kidney by MRI, and in 2 patients solitary cysts were seen in both kidneys. This study documents that ACKD is not limited to older patients with end-stage renal disease. Early detection of these cysts can be accomplished by MRI and is warranted since 1 patient developed neoplastic tubular changes which can precede tumor formation.

Renal transplantation in a child with primary oxalosis.

Primary hyperoxaluria (oxalosis) is an autosomal recessive disorder due to an inherited deficiency of the peroxisomal alanine:glyoxylate aminotransferase characterized by increased production and urinary excretion of oxalate and glycolate resulting in renal failure due to oxalate deposition. Because of the risk of continuing oxalate deposition in the transplanted kidney, oxalosis had been considered a contraindication for transplantation. A 5-year-old boy with oxalosis, maintained on peritoneal dialysis, received a haploidentical qiving-related transplant. The preoperative management included donor-specific transfusions and daily hemodialysis to remove a maximum amount of oxalate. The immunosuppression consisted of azathioprine and prednisone. Aggressive fluid management including noncalciuric diuretics (hydrochlorothiazide) kept urine output high. Pyridoxine, magnesium, neutral phosphate and sodium benzoate were used to prevent deposition of oxalate in the transplanted kidney. Two acute rejection episodes responded to steroid boluses. A kidney biopsy during the second rejection episode confirmed the diagnosis but also revealed oxalate deposits in the transplanted kidney. More than 4 years after transplantation, the patient has catch-up growth and his serum creatinine is 1.4 mg/dl. In conclusion, oxalosis is not an absolute contraindication to renal transplantation. Transplantation can be performed successfully utilizing living-related donor kidneys and aggressive medical management. The risks of deterioration of function and oxalate deposition in the transplant kidney are offset by improvement in quality of life.

Increased incidence of HLA-B40 group antigens in children with hemolytic-uremic syndrome.

Hemolytic uremic syndrome (HUS) develops in 25-30% of children infected with Escherichia coli strains that produce Shiga-like toxins, also known as verocytotoxins. Mild HUS also occurs in 1 in 4 of the other family members, suggesting a familial predisposition to HUS. To understand the possible genetic predisposition, the frequency of HLA antigens was evaluated in 30 children (12 boys, 18 girls; mean age 3.8 years) with HUS following a prodrome of bloody diarrhea. When compared to a blood donor population from the same geographic area and ethnic background, no significant differences were noted in the frequency of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. However, the frequency of HLA-B40 and its splits (B60, 61, 41, 47) was significantly higher in the study population (corrected p < 0.005). The relative risk of developing HUS was 6.04 when HLA-B40 and HLA-B40 split products were present, and the risk increased to 8.5 when the analysis was extended to include the cross-reactive antigens B44 and B13. These HLA-B antigens share common amino acid sequences at positions 41-45 and 67-74 on the alpha-1 domain of the HLA class I molecule. Our data suggest that the inheritance of HLA-B40, its splits, and cross-reactive antigens increases the risk of developing HUS.

Outcome of renal transplantation in children aged 1-5 and 6-18 years.

Results of renal transplantation in younger children have not been very encouraging in the past. We therefore studied the effect of newer immunosuppressive regimens on the outcome of renal transplantation of 5 children aged 2.9 +/- 1.3 years (range 1.6-5.0), and compared it to 10 children of an older pediatric patient group aged 11.4 +/- 4.4 years (range 6.0-18.5). All patients with the exception of 1 underwent dialysis. The percentage of cadaveric and live-related transplants was similar in both groups. Recipients of a cadaveric transplant had at least 3 blood transfusions; recipients of live-related transplants had donor-specific transfusions with azathioprine. Posttransplantation immunosuppression consisted of prednisone and azathioprine; recipients of cadaveric transplants received also ciclosporin. Rejection episodes and side effects (hypertension, hirsutism) were comparable in both groups. In the younger patient group, 1 patient died of a congenital lung abnormality but had a functioning graft. In the older patient group, 1 patient lost his graft 16 months posttransplantation due to reduction of his immunosuppressives, necessitated by a severe CMV infection. Growth and development improved in the younger patient group, but was stable in older patients. Renal transplantation is a suitable option in younger pediatric patients. Graft survival rates are comparable to those of older patients.

Postpartum renal failure in a patient with membranoproliferative glomerulonephritis type II.

The previously reported detrimental effects of pregnancy on the course of membranoproliferative glomerulonephritis type II (MPGN type II) are limited and are usually considered to be mild. Based on these reports, a 19-year-old female with the diagnosis of MPGN type II who had stable renal function (creatinine 0.9 mg/dl) and a mild nephrotic syndrome with hypertension for 5 years of close follow-up was advised to complete her pregnancy. After a full-term pregnancy, complicated only by moderate nephrotic syndrome, a healthy female infant was born. Two weeks after delivery, the patient presented with acute renal failure and malignant hypertension, without evidence of hemolysis of hepatic failure. Immunologic parameters, including, C3, C4, antinuclear antibodies, circulating immune complexes as well as antibodies to glomerular basement membrane antigen and tubular basement membrane antigen were negative. Peritoneal dialysis was initiated and a renal biopsy was performed which showed MPGN type II with 50% crescents. Despite pulse therapy with methylprednisolone, renal function did not improve, resulting in the need for chronic dialysis. Although no specific nephritogenic mechanism was shown, the course of this patient should be considered when counseling female patients with MPGN type II, regarding the possibility of pregnancy exacerbating their disease, or resulting in rapidly progressive renal failure.

Peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis.

We present a report on peritoneal kinetics in children undergoing continuous ambulatory/cycling peritoneal dialysis (CAPD/CCPD). The effect of long-term treatment with CAPD/CCPD, peritonitis episodes, and dialysate inflow volume on peritoneal kinetics in children was evaluated. Peritoneal kinetic studies (PKSs) were performed in 47 pediatric patients at different times following initiation of CAPD/CCPD. In 18 of these patients, PKSs were repeated up to four times with an unchanged dialysate inflow volume after up to 55 months of CAPD/CCPD treatment. The PKS consisted of a 120-minute dwell with a 1.5% dextrose dialysate solution. Peritoneal clearance, dialysance, and dialysate to plasma (D/P) concentration ratios were calculated after 30, 60, and 120 minutes. The results of the serial PKSs demonstrate stable peritoneal creatinine and urea-N clearance, dialysance or D/P concentration ratios. Furthermore, there was no adverse effect of 32 peritonitis episodes. Finally, inflow volumes correlated directly with clearances of creatinine (P less than .01), urea-N (P less than .001), and potassium (P less than .001), and there was an inverse relationship to the D/P concentration ratios of creatinine (P less than .01), urea-N (P less than .01), potassium (P less than .01), and uric acid (P less than .01). Thus, CAPD/CCPD is a useful and effective long-term treatment modality for pediatric patients. Maximal dialysate inflow volumes should be provided to enhance peritoneal kinetics.

Experience with renal transplantation in children undergoing peritoneal dialysis (CAPD/CCPD).

For children with end-stage renal disease, renal transplantation is the ultimate goal because it offers the potential of maximum rehabilitation. In order to evaluate the infectious risk of renal transplantation in patients previously maintained on continuous ambulatory peritoneal dialysis (CAPD) and/or continuous cycling peritoneal dialysis (CCPD), we retrospectively evalauted the clinical course of 44 pediatric patients (mean age 12.0 +/- 5.7 [SD] years) who received 32 cadaver and 16 live-related donor renal grafts after being maintained on peritoneal dialysis for 756 patient-months (mean 17.1 +/- 11.5 months). In the posttransplant period, 25 patients (57%) required dialysis because of acute tubular necrosis or acute rejection. Peritonitis developed in five patients (11%) following transplantation; two were being dialyzed at the time. Exit-site and tunnel infections occurred in nine patients (20%). In all instances, antibiotic treatment and/or catheter removal was curative. Posttransplant ascites developed in 12 patients (27%) and was alleviated by catheter drainage. The catheters were left in situ at the time of transplantation and electively removed when stable graft function was present. The 1- and 2-year actuarial graft survival rate was 65% and 55%, respectively. One patient died in the immediate posttransplant period, which was unrelated to peritoneal dialysis. In conclusion, pediatric patients maintained on CAPD and/or CCPD can be safely transplanted. The potential infectious risks related to peritoneal dialysis can be managed with appropriate management of the catheter and prompt antibiotic therapy. The patient and graft survival rates are comparable to those with patients receiving hemodialysis prior to transplantation. There is no need to limit access to transplantation in children undergoing CAPD and/or CCPD.

Peritoneal clearances with different dialysis regimens in children undergoing continuous cycling peritoneal dialysis.

Peritoneal clearances and dialysate protein losses occurring in paediatric patients undergoing different continuous cycling peritoneal dialysis (CCPD) regimens have not been well defined. We, therefore, evaluated 10 children aged 15.8 +/- 2.5 (SD) years who were maintained on home peritoneal dialysis for 20.5 +/- 10 months. All patients had at least 3 months of CCPD. The patients were admitted to the Clinical Research Center for 48 hours and allocated to five different dialysis protocols. In protocol I, the frequency of exchanges was 10 per 10 hours; in Protocol II it was 5 per 10 hours; and in Protocol III it was 3 per 10 hours. Protocol II D and III D had, in addition, a daytime dwell of one-half the night-time volume. A 1.5% glucose dialysate solution was used for night-time dialysis, and 4.25% glucose dialysate solution for the daytime dwell. The mean inflow dialysate volume per exchange was 36.7 +/- 5.6 ml/kg body weight and was constant in each patient for each study protocol. BUN and creatinine clearances for each protocol were calculated and dialysate protein losses were measured. The data indicate that hourly night-time dialysis (Protocol I) provides best solute clearance. A daytime dwell further enhances the total solute clearance and should be used preferably in anuric patients. Residual urine output contributes significantly to the total solute clearance. Protein losses are maximum with low-frequency exchanges and a daytime dwell. No significant differences in the serum albumin concentrations were found during the different protocols; however, the long-term effect of the protein loss on the nutritional status of the patients requires further evaluation.