Unfavorable response to cyclophosphamide in steroid-dependent nephrotic syndrome.

Development of steroid dependency represents a significant therapeutic challenge in steroid-sensitive nephrotic syndrome. Previous studies have shown conflicting results concerning the benefit of a 12-week treatment with cyclophosphamide (CPO), with 24%-67% of patients achieving long-term remission. We therefore analyzed the clinical response of 20 consecutive children with steroid-dependent nephrotic syndrome (SDNS) (12 male, median age at start of treatment 5.9 years, range 3.2-14.7 years) treated at our institution with CPO (2 mg/kg per day) for 12 weeks since 1989. Median duration of follow-up was 5.8 (range 1.1-9.25) years. Only 6 of 20 children (30%) showed a long-term remission of >2 years, while 14 of 20 (70%) developed relapses again. Of these, 12 patients (86%) again developed steroid dependency, requiring further alternative treatment. Our data show that a 12-week course of CPO leads to unfavorable results in the majority of patients with SDNS. We therefore conclude that there is a need for further optimization of therapy in SDNS.

Iron homeostasis in relapsing steroid-sensitive nephrotic syndrome of childhood.

AIM: Urinary transferrin loss is a typical feature in relapse of the idiopathic nephrotic syndrome, however, the impact on serum iron homeostasis and hematological parameters has not been studied systematically so far. PATIENTS AND METHODS: Therefore, we investigated serum iron (Fe), erythropoietin (EPO), ferritin (FN), transferrin (TF), total iron-binding capacity (TEBK), transferrin saturation and the soluble transferrin receptor (sTFR) combined with hematological parameters (hemoglobin, MCV, MCH) in 42 children with relapsing, steroid-sensitive nephrotic syndrome (NS) in remission (RM, n = 26) and relapse (RL, n = 16), including 13 patients who were studied in both states. Thirty-three age-matched healthy children served as controls. RESULTS: Fe, TEBK and TF were significantly reduced in RL compared to RM in cross-sectional as well as in paired studies while ferritin, hematological parameters and EPO levels remained unchanged. A significant increase, however, of the soluble transferrin-receptor could be demonstrated in cross-sectional analysis comparing RL to RM and healthy controls (3568+/-713 mg/ml vs 2625+/-576 vs 2646+/-697; p < 0.001 respectively) as well as in paired analysis of 13 patients in RL and RM (p < 0.001). CONCLUSION: We conclude that transient transferrin and iron deficiency occurs in RL of INS but this seems to be counterbalanced by upregulation of the sTFR, a mechanism that might be important in preventing the development of iron deficiency anemia during the active nephrotic state.

Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations.

We investigated 17 children with nephrotic syndrome (NS) of early onset (14 aged < 1 year) and rapid progression to end-stage renal disease for the presence of mutations in the Wilms' tumor suppressor gene WT1 on chromosome 11. In eight children (7 genotypic males) an association with Wilms' tumor and/or ambiguous genitalia (Denys-Drash syndrome) was observed. In these eight and two additional female patients with NS only constitutional missense mutations in the WT1 gene were detected; four children presented the so-called hot spot mutation in exon 9 (R394N) and six had different mutations in exons 8 and 9 (4 not previously described). Renal biopsy showed diffuse mesangial sclerosis in eight and focal segmental sclerosis in two cases. End-stage renal disease was reached either concomitantly or within four months after onset of NS in seven of ten patients. A unilateral Wilms' tumor was found before or concomitant with NS in four children (3 males, 1 female). From the seven genotypic males with WT1 mutations, five presented ambiguous genitalia and two a female phenotype. No mutation of the WT1 gene was found in seven other children with isolated congenital or infantile NS with or without DMS who appeared to have a slower progression than the first group. It is proposed that patients with early onset, rapidly progressive NS and diffuse mesangial or focal segmental sclerosis should be tested for WT1 mutations to identify those at risk for developing Wilms' tumor.

[The treatment with levamisole of frequently recurring steroid-sensitive idiopathic nephrotic syndrome in children]. / Die Behandlung des häufig rezidivierenden steroidsensiblen idiopathischen nephrotischen Syndroms im Kindesalter mit Levamisol.

BACKGROUND AND OBJECTIVE: The treatment of frequently relapsing steroid-sensitive nephrotic syndrome in children with established immunosuppressive drugs (steroids, cyclophosphamide, cyclosporin A) sometimes presents problems because of the expected incidence of side effects. Stimulation of the immune system with the anthelminthic drug levamisole in this disease has been documented. Aim of this study was to assess in a prospective but uncontrolled series of observations its value and side effects. PATIENTS AND METHODS: 25 patients (15 boys, ten girls; median age 10 [3.5-22] years) were given levamisole, 2 mg/kg/48 h. Before this treatment was started eight of the children/adolescents (32%) had frequent relapses and 17 (68%) had become steroid-dependent. Treatment was started during steroid-induced remission and continued for 3-24 (median 6) month, while steroids were discontinued after four weeks. RESULTS: Relapse frequency per patient month was reduced from a mean of 0.5 (0.33-0.83) before to 0.31 (0-0.67) during levamisole administration (P < 0.001). In 12 patients (48%) no or considerably fewer relapses were observed. Patients with exclusively frequent relapses responded to levamisole better than those with steroid dependence (7/8 [87.5%] vs. 5/18 [27.7%], P = 0.01). Side effects were reversible leukopenia in two patients and nonspecific skin rash as well as epigastric pain in one patient. CONCLUSION: Levamisole is an efficacious addition or alternative, with a low incidence of side effects, in the treatment of frequently relapsing nephrotic syndrome, particularly so in yet steroid-dependent patients.

[Bilharziasis as the etiology in hematuria and proteinuria in childhood]. / Bilharziose als Ursache von Hämaturie und Proteinurie im Kindesalter.

Haematuria and proteinuria are important symptoms of primary and secondary nephropathies. We report three african children presenting to our center in whom infection with S. haematobium resulted in haematuria and proteinuria. The third patient concomitantly suffered from steroid-sensitive relapsing nephrotic syndrome with the histological features of focal and segmental glomerulo-sclerosis. The diagnosis was in all cases established by light microscopy and urinary symptoms improved after treatment with praziquantel. In the third patients long term remission of the nephrotic syndrome could be maintained after 4 doses of praziquantel for recurrent bladder symptoms. We conclude that bilharziosis must be considered in the differential diagnosis of children with haeamturia and proteinuria even in Europe. The diagnosis can be established easily by light microscopy and an effective and low-risk treatment (with Praziquantel) can be offered.

Bone mineral density in pediatric patients after renal transplantation.

To evaluate the natural history of bone mineral density after successful renal transplantation (TPL) modulated by therapeutic strategies in pediatric patients we have studied peripheral and partially proximal quantitative computed radius tomography (XCT) differentiating between trabecular (TBD), cortical (CBD) and total bone density (BD) cross-sectionally in a group of 24 subjects (mean age 17.1 +/- 7.0 y, mean Scr 1.66 +/- 0.89), 66.1 months (5-260) post transplant and compared the results with 12 controls. After TPL median TBD was elevated (182.5 vs. 155.5 mg/cm3) whereas the opposite was true for CBD (361.8 vs. 437.8 mg/cm3). The physiologic age dependency of BD had got lost after TPL but could be reassumed by the measurement of proximal CBD. TBD correlated with the cumulative calcitriol dosage (r = 0.60, p < 0.05), bone alkaline phosphatase (r = 0.55, p < 0.01), the Ca x P product (r = 0.43, p < 0.05) and inversely with the time after TPL (r = -0.45, p < 0.05), but no significant correlation could be detected with the cumulative steroid dose. It was found to be higher in calcitriol treated than in vitamin D3 treated patients. Proximal CBD was inversely correlated with bone alkaline phosphatase (r = -0.71, p < 0.01) and intact PTH (r = -0.59, p < 0.05). In conclusion CBD in kidney grafted pediatric patients seems to be more or less reduced by secondary hyperparathyroidism whereas the increase of TBD appears to be induced by anticipated calcitriol treatment under dialysis regimen and gradually normalizes after TPL.

Tear fluid of hepatitis C virus carriers could be infectious.

For up to 20 to 40% of patients chronically infected with hepatitis C virus (HCV), the mode of transmission is still unknown. We demonstrate that tear fluid contains HCV RNA-carrying material with the properties of infectious virus and conclude that smear infection with tear fluid may play a role in HCV transmission.

Increased need of erythropoietin during peritonitis in children on continuous peritoneal dialysis.

Ten continuous ambulatory peritoneal dialysis (CAPD) patients experienced 23 episodes of peritonitis and were treated with intraperitoneal (IP) antibiotics as per sensitivity report. Serum ferritin was measured before and after the treatment. In 6 patients, erythropoietin (EPO) was also measured before and after the treatment. There was a significant drop in the serum EPO levels after therapy compared to the levels before, whereas serum ferritin levels did not change.

Sonographic signs of nephritis in children. A comparison of renal echography with clinical evaluation, laboratory data and biopsy.

In 40 children with histologically confirmed diagnosis of nephritis 82 sonographic examinations were performed for evaluation of echographic signs of nephritis. Increased cortical renal echointensity in comparison with the normal liver and enlarged parenchymal volume proved to be the most specific and reliable signs of nephritis, particularly if both were present. Accentuated corticomedullary differentiation was too insensitive to be of additional value. Twenty-one patients had follow up examinations in the course of their nephritis. In 15 patients sonographic signs, serum creatinine and clinical classification showed parallel changes. In two cases sonographic improvement preceded clinical and laboratory normalization by several weeks, giving valuable prognostic information.

[Results and specific problems in unrestricted indications for kidney transplantation in children]. / Ergebnisse und spezifische Probleme bei unbegrenzter Indikation zur Nierentransplantation im Kindesalter.

In Hamburg 22 children had 33 renal transplantations in the time from 1976 till 1982. 58% of all children in this area with end-stage renal disease have now a functioning graft compared to only 11% of the adult patients. This is the result of preferred transplantation in children whenever possible. Retransplantation was more frequent in children (32%) than in adults (19%). 5 years function rate of renal allografts is significantly worse in children than in adults. Growth and degree of rehabilitation are described in 12 pediatric renal allograft recipients who survived with a functioning graft for at least 3 years. Good rehabilitation as indicated by attendance of school and employment was reached in 83% of these patients. Different growth patterns occurred. Clinical factors associated with growth performance include graft function and age at the time of transplantation.

[Severe course of a hemolytic-uremic syndrome]. / Schwerer Verlauf eines hämolytisch-urämischen Syndroms.

After an upper respiratory tract infection an eight months old infant developed a severe hemolytic uremic syndrome with anemia, thrombocytopenia and anuria. Remarkable was a lesion of the erythrocytes by neuraminidase producing microorganisms. By early hemodialysis, blood transfusions and accurate fluid therapy the acute stage could be managed. The proceeding course was complicated by hypertension, seizures, coma, abdominal pain attacks and a fibrinous hemorrhagic pericarditis, which made an incomplete pericardectomy necessary. Although it came again to diuresis a severe chronic renal failure with its concluding effects as anemia, acidosis, hypertension and inanition resulted. After a four months period the patient died of biventricular congestive heart failure.

[Sonography for monitoring kidney transplants]. / Sonographie bei transplantierten Nieren.

Ultrasonography is very useful for judging the position and course of renal transplants. With this method extra- and intrarenal complications can be detected very accurately. The sonographic examination is quite harmless and puts little strain on the patient. It can be carried out a few days after the operation. This initial sonogram, obtained as early as possible, makes it easier to recognize and to interpret later changes more promptly and correctly. The results of sonographic examinations in 18 patients with renal transplants are presented. They show that a normal sonogram reliably excludes extrarenal complications such as fluid collection or obstruction as well as rejection of the transplant. All cases of rejection correlated to clearly abnormal sonographic findings.

[Flow sheets of urine samples in haemolytic uraemic syndrome. Examinations by analytic isotachophoresis (author's transl)]. / Ubersichtsspektren von Urinproben im Ablauf von hämolytisch-urämischen Syndromen. Untersuchungen mittels analytischer Isotachophorese.

In 29 urinary fractions of six children with haemolytic uraemic syndrome (HUS) a specific substance could be demonstrate during the acute phase of the disease by means of isotachophoresis. Urine tests in six patients with other kidney diseases and with uraemia and in seven healthy persons did not show this substance. From this, we assume that the substance demonstrated in the isotachogram has a direct correlation to the HUS.

[Treatment of severe haemolytic-uraemic syndrome by dialysis (author's transl)]. / Dialysebehandlung des schweren hämolytisch-urämischen Syndroms.

Since 1973 haemodialysis was performed on 30 children with severe haemolytic-uraemic syndrome. Serial measurements were made of blood pressure, blood picture, renal function, complement values, excretion of fibrinogen split-products and beta2-microglobulin in urine. Of 22 children in the acute severe stage two died, in one case treatment having been started too late, in the other as a result of fulminating pneumococcal pneumonia. Twenty children survived without residual symptoms and with normal renal function. Of six children with severe progressive haemolytic-uraemic syndrome two developed terminal renal failure. In one child a renal transplantation has since been performed. One child requires chronic dialysis after nephrectomy. Three children died as a result of arterial hypertension, one of yeast septicaemia. Of two children with recurrent haemolytic-uraemic syndrome one developed terminal renal failure which was successfully treated by renal transplantation. One child died in a hypertensive crisis. The overall death rate of the group was 23%, in the group with the acute severe haemolytic-uraemic syndrome it was 9%. The results suggest that haemodialysis significantly improves the prognosis of severe haemolytic-uraemic syndrome.

[Prevention of HBs antigen-positive serum hepatitis with hyperimmune-globulin anti-HBs]. / Prophylaxe der HBs-Antigen-positiven Serumhepatitis mit Hyperimmunglobulin Anti-HBs. Untersuchungen zur Plasmaelimination von HBs-Antikörpern

Selection of donors to prevent HBs-antigen positive serum hepatitis has been only partially successful. For this reason the attempt was made to prevent the disease by passive immunisation with anti-HBs antibodies. A prerequisite for the systematic use of such immunisation is the determination of antibody threshold which would still provide protection. Plasma elimination of transmitted. HBs antibodies was serially measured in five children with terminal renal failure and ten normal subjects after intensive contact with HBs antibodies. Half-life values indicated marked individual variations which have to be taken into account with long-term prophylaxis. In the children they were 28.5, 25.9, 16.6, 11.7 and 7.8 days, respectively. In the healthy subjects the half-life averaged 20.3 days. The long-term programme developed by the authors appears to be suitable for revealing the value of hyperimmune-globulin anti-HBs in the prevention of HBs-antigen positive serum hepatitis.