Gonadal function in women treated with cyclophosphamide for childhood nephrotic syndrome: a long-term follow-up study.

The gonadal function of 18 women who were treated for childhood nephrotic syndrome at a mean age of 10.7 years with cyclophosphamide (mean dosage, 28 gm; mean duration of therapy, 354 days) was evaluated at a mean of 14.5 years after treatment by means of detailed questionnaires. Menstrual patterns were normal in all except two, who were still receiving intermittent prednisone therapy. Eight healthy children had been born to five mothers. Compared with males, there is little current evidence of gonadal toxicity in this patient group. Further follow-up is required to determine whether these women will undergo premature menopause.

Long term effects of cyclophosphamide on testicular function.

Thirty men treated in childhood with cyclophosphamide for a mean of 280 days were assessed at a mean of 12.8 years after treatment for hormone concentrations and spermatogenesis. Four were azoospermic, nine oligospermic, and 17 normospermic. There was a significant inverse correlation of sperm density with cyclophosphamide dosage and duration of treatment. After a further mean follow up of 7.2 years three patients who were previously oligospermic and one who was azoospermic had normal sperm counts. All patients had normal sexual characteristics and libido. Serum androgen and prolactin concentrations did not differ significantly between patients and controls. Raised basal and stimulated follicle stimulating hormone concentrations were in keeping with impaired spermatogenesis. All patients had significantly raised luteinising hormone responses on stimulation with luteinising hormone releasing hormone. The results suggest compensated Leydig cell failure, and patients with this condition require long term evaluation of testicular function. Potential recovery of spermatogenesis with time requires appropriate counselling and contraceptive advice.

Membranoproliferative glomerulonephritis type I in children: correlation of clinical features with pathologic subtypes.

Renal biopsies from 33 patients with membranoproliferative glomerulonephritis (MPGN) type I were reviewed to identify pathologic subtypes of this disease and assess their correlation to clinical features. The patients were divided into two groups: group A included 16 patients in chronic or end-stage renal failure and group B 17 patients with no evidence of renal insufficiency. At presentation, a nephrotic or nephritic syndrome and azotemia were equally common in both groups. The incidence of hypertension was significantly increased in group A (P less than 0.05), while recurrent gross hematuria was more common in group B. Nephrotic syndrome was more common during the course of illness in group A. Three subtypes of MPGN type I were recognized, based on whether duplication of glomerular capillary basement membranes was focal segmental (FS; 9 cases), diffuse global (DG; 18 cases), or mixed segmental and global (6 cases). Eight of nine patients showing FS MPGN type I were in group B (p less than 0.05). In contrast, 11 of 18 patients with DG MPGN type I and 4 of 6 with a segmental and global pattern were in group A (P = not significant). Therefore, FS MPGN is a good predictor of a favorable clinical outcome, whereas the other two subtypes are not. This was confirmed by a 100% actuarial kidney survival for the nine patients with FS MPGN and a 50% kidney survival of 7.5 years for patients with the other two subtypes.

Clinical features and glomerular immunofluorescence of renal biopsies from children with nephrotic syndrome due to minimal change disease and two variants of mesangial proliferative glomerulonephritis.

Response to initial course of prednisone and clinical outcome were reviewed in 82 children with nephrotic syndrome (NS) due to minimal change disease (MCD) and 2 variants of mesangial proliferative glomerulonephritis (MesPGN). Renal biopsies in Type I MesPGN showed only increased mesangial cells and matrix, whereas those in Type II MesPGN also showed interstitial fibrosis, tubular atrophy, global glomerulosclerosis and hyalinosis. Response to prednisone was complete in most cases (95% in MCD, 82% in Type I and 72% in Type II MesPGN). Remission of NS for more than 1 year while off prednisone occurred in 91% of patients with Type I MesPGN and 49% with MCD, but in only 14% with Type II MesPGN. The influence of immunoglobulins +/- complement in mesangial regions of glomeruli on initial response and outcome was assessed. Response to prednisone and outcome did not differ in IMF-positive and -negative MCD or in Type I and Type II MesPGN.

Characteristics of a benign subtype of dense deposit disease: comparison with the progressive form of this disease.

Pathologic, clinical and serum complement studies were performed on 18 patients with dense deposit disease (DDD). The patients were divided into 3 groups: group A (10 patients who developed end-stage renal failure within 2.9 +/- 1.0 years of onset) group B (3 patients who developed elevated serum creatinines within 6.8 +/- 4.8 years of onset) and group C (5 patients with no evidence of renal insufficiency after 11.0 +/- 1.4 years of follow-up). Renal biopsies from all patients showed intramembranous, electron-dense deposits in glomerular capillary basement membranes. Most group A and B patients presented with a nephritic and/or nephrotic syndrome and followed an active clinical course. In contrast, group C patients presented with either a nephrotic syndrome or asymptomatic proteinuria +/- hematuria and followed a benign course. Sera from group A and B patients contained reduced concentrations of C3 and factor B and large amounts of C3 nephritic factor (NeF) activity. In contrast, serum of group C patients contained normal amounts of C3 and factor B and low levels of C3 NeF activity. These studies show that some patients with DDD (group C) have a benign illness and that they can be identified by serum levels of C3, factor B and C3 NeF activity.

Urinary tract calculi in children.

One hundred and nine children with urinary tract calculi were reviewed and in some cases reinvestigated. Eighteen children had lower urinary tract calculi, which in all cases were associated with an underlying urodynamic abnormality. Sixty percent of 91 children with upper urinary tract calculi could be classified into 4 similarly sized etiological groups: an underlying urodynamic abnormality; urinary tract infection without a urodynamic abnormality; metabolic disorders; idiopathic hypercalciuria. An underlying abnormality was not found in 32% of cases. A painless presentation occurred in 39% of those with upper tract calculi. A family history of urinary calculi occurred in approximately one-half of children with either an idiopathic calculus or a calculus associated with cystinuria or idiopathic hypercalciuria. We conclude that urinary tract calculi, though rare in children, require extensive investigation to rule out urodynamic, infective and metabolic abnormalities. If such abnormalities are not found, the recurrence rate in the remainder is small and conservative treatment can usually be recommended.

Acute renal failure of short duration in minimal lesion nephrotic syndrome of childhood.

Two boys 12 and 8 years of age with biopsy proven minimal lesion nephrotic syndrome developed acute renal failure during the course of their illness. Renal failure developed in the first boy at the time of onset of his nephrotic syndrome while in the second boy it occurred at the time of a relapse of his disease, 5 1/2 years after onset. Both patients had a complete resolution of renal failure and nephrosis following peritoneal dialysis and oral prednisone. Acute renal failure requiring dialysis is an unexplained and rare complication of minimal lesion nephrotic syndrome in adults and children.

Hepatitis B-associated membranous glomerulonephritis in a child.

This appears to be the first reported case of membranous glomerulonephritis in a pediatric asymptomatic carrier of hepatitis B virus in North America. Routine immunofluorescent methods were used to identify the hepatitis B surface antigen in glomeruli. In addition, the glomerular immune deposits were searched for the known ultrastructural forms of the virus.

Membranoproliferative glomerulonephritis type 1: comparison of natural history in children and adults.

Clinical, laboratory and pathological data on 46 patients (29 children and 17 adult) with Type 1 membranoproliferative glomerulonephritis (MPGN) were reviewed in order to compare the natural history of the disease in two age groups. The nephrotic syndrome was the most common presenting clinical feature in both age groups. Established renal failure at time of biopsy was seen in adult males only. All the adults males, but none of the women, were either dead or in renal failure after a mean duration of diseases of 17.7 months. In contrast 43% of the children (both sexes) were in renal failure after a mean duration of disease of 51.6 months. Statistical analysis disclosed that only up to 48 months was there a significant difference in survival between the two age groups (P less than .01). Beyond this time the difference was not statistically significant. The difference in behaviour of MPGN in the two age groups is similar to that observed in other glomerulonephropathies.

Gonadal function in males treated with cyclophosphamide for nephrotic syndrome.

Analysis of semen from 16 patients treated with cyclophosphamide for nephrotic syndrome showed azoospermia in three and oligospermia in seven. Analysis was normal in the other six. Prolonged treatment, particularly with larger total dosage, was associated with a higher incidence of gonadal dysfunction. Recovery was not evident at follow-up, 2 years and 9 months to 9 years and 1 month after cessation of the therapy. Limitation of treatment with cyclophosphamide to 8 weeks/course (2.5 mg/kg/day) minimizes this side effect without greatly increasing the rate of relapse of the nephrotic syndrome in the first 2 years after therapy.