Renée Habib

Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein-Henoch purpura nephritis

Abstract. Between 1980 and 1994, 38 children with severe forms of Schönlein-Henoch purpura glomerulonephritis were entered into a prospective study to evaluate methylprednisolone pulse therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and/or had 50% or more crescentic glomeruli. Initial renal biopsies were obtained from all patients and revealed diffuse proliferative endocapillary glomerulonephritis in 2, focal and segmental glomerulonephritis in 4, and endo- and extracapillary glomerulonephritis in 32, 21 of whom had 50% or more glomeruli with crescents. Patients were treated with intravenous pulse methylprednisolone (3 days) followed by oral prednisone (3.5 months). At the latest follow-up, 1–16 years after initiation of therapy, 27 children had clinically recovered, 3 showed minimal urinary abnormalities, 4 persistent nephropathy, and 4 had progressed to end-stage renal failure. Sequential renal biopsies were obtained from 30 patients, 7–25 months after initiation of therapy. The clinical outcome correlated well with of the activity (hypercellularity, cellular and fibrocellular crescents, and interstitial edema with mononuclear cell infiltrates) and the chronicity (fibrous crescents, glomerular sclerosis, tubular atrophy, and interstitial fibrosis) indexes of post-therapy biopsies. Of particular interest were the post-therapy biopsies of the 18 patients who clinically recovered. They showed a significant decrease of the activity index from 5.1±1.1 to 0.4±0.8 with a decrease or even a disappearance of IgA deposits, while the chronicity index remained low (0.4±0.8 compared with 1.4±1). Although uncontrolled, our study suggests that methylprednisolone pulse therapy is effective in those patients at risk of progression of their nephropathy, especially if started early during the course of the disease before the crescents become fibrous.

Glomerular Lesions in the Transplanted Kidney in Children

The glomerular pathology of 634 transplant specimens (526 biopsies and 108 transplantectomies) from 410 children was studied. Three types of glomerulopathies were observed: (1) recurrent glomerulonephritis (GN) (40 of 142 patients with glomerular nephropathy), (2) de novo GN (52 grafts), and (3) transplant glomerulopathy (29 grafts). The study of recurrent GN is considered of great interest because of the possible insight into the nature of the original disease and the opportunity to observe the evolution of the disease in sequential biopsies of the transplant. The two major forms of de novo GN were membranous GN and IgG linear deposits along glomerular and tubular basement membranes. Transplant glomerulopathy, although distinctive morphologically, may resemble membranoproliferative GN (MPGN) or thrombotic microangiopathy.

Chronic Renal Failure in Children

Among the 2,052 children with renal disease admitted to a Pediatric Department during a period of 10 years, 270 developed chronic renal failure (CRF). Of these 270 patients, 147 (54%) were under 5 yea

Immunopathological findings in idiopathic nephrosis: clinical significance of glomerular "immune deposits".

Idiopathic nephrosis (IN), which includes minimal change (MCD), diffuse mesangial proliferation (DMP) and focal segmental glomerular sclerosis (FSGS), is classically characterized by the absence of significant deposits by immunofluorescence microcopy (IF), except for the focal lesions of segmental sclerosis and/or hyalinosis of FSGS, which fix IgM and C3 antiserums. Since IF is available in most centres, an increasing number of unexpected findings has been reported. In order to evaluate the clinical significance of the glomerular deposits revealed by IF in some instances, we reviewed the renal biopsy findings of 222 consecutive children presenting with IN and in whom IF microscopy was available. By light microscopy, 122 patients showed MCD, 10 DMP, and 90 FSGS with DMP (11 cases) or without (79 cases). By IF, 125 specimens were negative and served as controls; 54 showed mesangial IgM deposits, 24 mesangial IgG deposits (associated with Clq deposits in 16), 15 scattered granules of C3 and 4 predominant deposits of mesangial IgA. We correlated these findings with initial response to steroid therapy and outcome and could find no significant difference between the various categories defined by IF and the control group. Repeat biopsies, performed in 21 cases, showed the persistence of deposits in 11 and their transformation in 10. The particular problem raised by the patients who present with IN and mesangial IgA deposits is discussed. Our results demonstrate that patients presenting with IN and “positive IF”, whether showing IgM, IgG and Clq, C3 or IgA, do not represent distinct clinicopathological entities.

Infantile chronic tubulo-interstitial nephritis with cortical microcysts: variant of nephronophthisis or new disease entity?

Over a 15-year period we observed seven children (four girls, three boys) who presented within the first months of life with severe renal failure and acidosis, associated with hypertension in five patients and polyuria in four. In addition, one patient had a severe cholestatic liver disease. In two families, a similarly affected sibling had died previously. Four patients were referred with the clinical diagnosis of polycystic kidney disease because of moderate enlargement of kidneys, but renal imaging (intravenous pyelography and ultrasonography) did not confirm this diagnosis. A renal biopsy, performed in all patients, showed similar features characterized by a diffuse chronic tubulo-interstitial nephritis (TIN) and particularly by the presence of microcystic dilatation of proximal tubules and Bowmans space. Liver pathology was normal in two patients, including one with hepatomegaly. However, in the patient with cholestasis there was inflammatory portal fibrosis with mild duct proliferation. Progression of the renal disease was extremely rapid and all patients reached end-stage renal failure (ESRF) before the age of 2 years (11–22 months). Two children had successful renal transplants. Although this chronic TIN shares some features with nephronophthisis, we suggest that it represents a distinct entity both on clinical and morphological grounds. The specific clinical features of this disease are its early onset and rapid progression to ESRF. Pathologically, it differs from nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes and by the presence of cortical microcysts.

Cyclosporin in the treatment of idiopathic nephrotic syndrome in children

Thirty-five children (12 girls, 23 boys), aged from 1 year and 5 months to 14 years at the onset of idiopathic nephrotic syndrome, received cyclosporin A (CyA) because of steroid toxicity or failure to respond to steroids. The initial oral dose was 6 mg/kg per day and this was adjusted to obtain trough plasma levels of 50–150 ng/ml. The duration of treatment was between 2 and 8 months. In patients who responded to CyA treatment, the dosage was tapered off; treatment was stopped if found to be ineffective. Of the 35 children, 20 were frequent-relapsing steroid responders who suffered serious side-effects from steroid therapy. Seventeen of them either went into remission or did not relapse despite the withdrawal of prednisone. Prednisone doses could be lowered but not stopped in 1 patient and the remaining 2 patients relapsed when prednisone was tapered off. At the final examination, 10 of the 12 children in whom CyA was tapered off and who had initially responded to CyA had relapsed. A second course was given to these 10 patients and 3 failed to respond. Five children were partial steroid responders and CyA induced a remission in 1 and a partial remission in another. Among the 10 children who were steroid resistant, only 1 responded to CyA, 2 had a partial response and 7 failed to respond to CyA. A reduction of glomerular filtration rate occurred in 8 patients, 7 of whom had either persistent nephrotic syndrome or were in relapse, which suggests that factors other than CyA nephrotoxicity may have been operative. Complete reversal occurred in only 4 patients. Significant histological changes, likely to be related to CyA, were seen in 2 repeat renal biopsies out of the 11 performed.

Collagen type III glomerulopathy: a new type of hereditary nephropathy

A new type of hereditary glomerulopathy was observed in ten children presenting with early and progressive glomerular symptoms, often associated with hypertension. Light microscopy showed a diffuse increase in the mesangial matrix and generalized widening of the capillary walls. Electron-microscopic examination of renal tissue, after phosphotungstic acid treatment, revealed the presence of fibrillar collagen within the mesangial matrix and the subendothelial aspect of the glomerular basement membrane, adjacent to normal lamina densa. Immunohistochemical studies identified the fibrillar collagen not usually present within the glomerular extracellular matrix as type III collagen. Clinical and family studies ruled out the diagnosis of nail-patella syndrome, an autosomal dominant disorder with typical extrarenal symptoms, which is also characterized by the presence of fibrillar collagen within the glomerular basement membranes. The poor renal outcome, the possible extrarenal haematological and pulmonary involvement and the transmission as an autosomal recessive trait strongly suggest that collagen type III glomerulopathy is a new type of hereditary disease. From the high incidence of superimposed haemolytic uraemic syndrome in patients or their siblings, it may be hypothetized that collagen type III glomerulopathy is the underlying defect in some of the familial cases of haemolytic uraemic syndromes.

Haemolytic uraemic syndrome: prognostic factors in children over 3 years of age*

Previous studies have shown that age at onset of primary haemolytic uraemic syndrome (HUS) is a feature of prognostic significance, the disease being of much better outcome in paediatric patients younger than 3 years than in older children. In an attempt to find an explanation for such a difference, we analysed the clinical and pathological features of 42 children over 3 years of age who presented with HUS between 1955 and 1990 in our department. On the basis of the presence of a prodromal diarrhoea, we divided our patients into two groups: 21 children presented with the diarrhoea-associated (typical or D+) form of HUS, whereas 21 had the non-diarrhoea-associated (atypical or D-) form. Of the 42 children, 20 (47.5%) progressed to end-stage renal failure. However, our study shows that age at onset of HUS is not a prognostic feature per se. The difference in outcome between children and infants is most likely related to the high incidence of the atypical subset of HUS in children over 3 years, a subset that is very uncommon in infants. The ominous features which characterise this form of the disease are: (1) the absence of a diarrhoeal prodrome, (2) normal urine output, (3) marked proteinuria, (4) hypertension, (5) the occurrence of relapses or recurrences and (6) the presence of widespread and severe arteriolar changes on renal biopsy. The poor prognosis of the atypical form of HUS warrants the use of fresh-frozen plasma infusions and/or plasma exchange as early as possible in the course of the disease.

Immunopathology of membranoproliferative glomerulonephritis with subendothelial deposits (Type I MPGN)

Abstract Immunofluorescence microscopy (IF) studies were carried out in 36 patients with Type I MPGN and showed the constant presence of deposits containing C3. Based on the presence or the absence of immunoglobulins (Ig), two main patterns were observed. Complement profiles (30 patients) and C3NeF activity (20 patients) were studied in the two groups defined by IF. Our findings indicate an activation of the complement system through the classical pathway even in the group characterized by the absence of Ig. Such an activation suggests the role of immune complexes in the pathogenesis of the disease. Because of the presence of C3NeF activity in occasional patients, a superimposed activation through the alternative pathway is not unlikely. In two additional patients, one with predominant IgA within the deposits and one with C2-deficiency, the complement system is probably activated through the alternative pathway.

Le syndrome hémolytique et urémique de I’enfant

Les auteurs rapportent 27 observations anatomo-cliniques, chez I’enfant, de «syndrome hemolytique et uremique» caracterise par la survenue simultanee d’une anemie hemolytique, d’une atteinte renale, d