Inge Sagel

Routine Immunohistology in Renal Diseases

Excerpt In 1907 it was suggested (1) that certain renal diseases may be caused by an immune reaction involving the glomerulus. This hypothesis has recently received renewed support. In 1951 we demo...

Occurrence and Nature of Glomerular Lesions after Group A Streptococci Infections in Children

Abstract A prospective study of renal involvement after group A streptococci infections was undertaken in 248 children who had weekly examinations for at least 6 weeks. Examination included urinaly...

Hypercalcemia in childhood renal tumors

Hypercalcemia is an uncommon complication of childhood renal tumors. It is exclusively seen in infants 6 months of age or younger with malignant rhabdoid tumor of the kidney (MRTK) or congenital mesoblastic nephroma (CMN). Secretion of parathormone or prostaglandin E2 by the tumor cells is responsible for the hypercalcemia in most of these patients. Bone metastasis has been notably absent in these patients, and the hypercalcemia completely resolves with the removal of the tumor. Hypercalcemia in itself probably does not have any prognostic significance; however, it may serve as a tumor marker in some patients. Early recognition and effective management of this complication may prevent the acute life‐threatening as well as the longstanding complications of this serious metabolic disorder.

Circulating Immune Complexes in Patients with Uncomplicated Group A Streptococcal Pharyngitis and Patients with Acute Poststreptococcal Glomerulonephritis

To investigate the role of circulating immune complexes (CIC) in the pathogenesis of acute poststreptococcal glomerulonephritis (AGN), sera were obtained serially from 13 patients with biopsy-proven AGN, 16 patients with group A streptococcal infection, and 20 age- and sex-matched controls. Samples were analysed for Clq-binding activity (Clq-BA), levels of IgG, IgA, IgM, C3 and C4, and antibody titres to streptococcal enzymes. Significant elevation of Clq-BA was observed in 11 patients (84.5%) with AGN and 7 patients (44%) with streptococcal infection alone. The data suggest that CIC do not necessarily cause glomerular damage, but rather represent a systemic inflammatory response in patients with group A streptococcal infection.

SPECIFICITY OF IMMUNOFLUORESCENCE IN EXPERIMENTAL AND HUMAN RENAL DISEASES.

Summary Severe proteinuria with considerable gamma globulin content was produced in rats by aminonucleoside injections. Sections of their kidneys at intervals between 4 and 12 days after onset of proteinuria did not show immunofluorescent staining for gamma globulin and complement. Rats made nephritic by injection of anti-rat kidney rabbit serum showed immediate morphologic damage and proteinuria with considerable gamma globulin content. Rabbit gamma globulin can be demonstrated immediately on the glomeruli while rat gamma globulin does not appear before the seventh day of disease. A kidney biopsy of a patient with multiple myeloma and advanced renal damage did not show immune staining for gamma globulin and complement, in spite of a severe proteinuria with large amounts of albumin, Bence-Jones protein and gamma globulin in the urine. Positive immune staining for gamma globulin or complement and its components in renal diseases can therefore not be attributed to trapping or unspecific transudation in the damaged kidney.

Pathology of Human Immunodeficiency Virus (HIV) Associated Nephropathy in Adults and Children

A variety of renal lesions are identified in patients infected with Human Immunodeficiency virus (HIV). A distinctive clinicopathologic entity, termed HIV-associated nephropathy (HIVAN) is noted in 7–10% of the unselected adult and pediatric hospital admissions for Acquired Immunodeficiency Syndrome (AIDS). Adult HIVAN is more common in Blacks and in intravenous (IV) drug users and is characterized clinically by acute onset of severe, often nephrotic range proteinuria with generally rapid and irreversible progression to renal failure. Histologically, focal segmental sclerosis (FGS) is frequently accompanied by a unique globally collapsing glomerulopathy with dilatation of Bowman’s space, microcystic ectasia of tubules, scant interstitial cellular infiltrate and fibrosis in the well established lesions. A combination of these distinctive clinical features and histologic findings, along with abundant tubulo-reticular inclusions (TRI) in renal vascular endothelium on electronmicroscopy, distinguishes HIVAN from heroin-associated nephropathy (HAN). A constellation of these clinicopathological findings also allows one to make a presumptive diagnosis of HIV infection with a high degree of accuracy in an asymptomatic HIV carrier. Greater frequency of multiple, budding, and complex nuclear bodies, and various cytomembranous and intranuclear inclusions, presumed to be “viral footprints,” suggest a viral etiology for HIVAN.

Subclinical and overt acute glomerulonephritis in children following infections with group A streptococci

Fluorescein (FIT) labelled IgG fractions from patients with acute poststreptococcal glomerulonephritis (AGN) stain parts of the basement membrane and mesangium of glomeruli from the same patients, provided renal tissue is obtained early in the disease. Staining is abolished by preabsorbing the IgG fractions with disrupted streptococci isolated from patients with AGN. Non-nephritogenic streptococci do not reduce staining. These findings were applied in an epidemiologic survey of a pediatric population with group A streptococcal infections. During a 12-month period 178 children with group A streptococcal infections were followed with weekly examinations including urinalysis and determination of serum complement (CH50) and ASLO titers. Only children in whom these parameters were normal initially were kept in the study. 2 children developed typical AGN. 21 patients were asymptomatic but showed transient urinary abnormalities and decreased CH50. Their renal tissue showed glomerular lesions ranging from mild mesangial increase and endothelial cell proliferation to the characteristic changes seen in AGN. The glomeruli showed granular staining with FIT labelled anti-human IgG and β1C. Streptococci cultured from the children were preserved. Only bacteria isolated from patients with demonstrable glomerular lesions reduced the staining capacity of FIT labelled sera from patients with AGN. Streptococci obtained from patients without evidence of renal involvement failed to preabsorb. It appears that nephritogenicity of streptococci can be predicted. This study suggests that incidence of glomerular damage following group A streptococcal infections is greater than suspected.

The Significance of Streptococcal Components as Antigens in Acute Poststreptococcal Glomerulonephritis.

Excerpt Parts of the glomerular basement membranes and the mesangium of kidney biopsies from patients with early acute poststreptococcal glomerulonephritis stain with the patients own fluorescein-...

Progression and Chronicity of Acute Post-Streptococcal Glomerulonephritis (APSGN)

In a follow-up study of 33 patients who had had overt acute post-streptococcal glomerulonephritis (APSGN), 11 patients had intermittent or persistent hematuria and/or proteinuria with or without hypertension 2–15 years after onset.

1627 ISOLATION OF A STREPTOCOCCAL ANTIGEN AND ITS POSSIBLE POLE IN THE PATHOGENESIS OF ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS

We studied the significance of a streptococcal protein (PA-Ag) in the pathogenesis of acute poststreptococcal glomerulonephritis (AGN). Purification of PA-Ag was achieved by chromatography followed by Sephadex isoelectric focusing. A single protein band at pH 4.7 was identified as PA-Ag. The molecular weight was 43000. Rabbit antisera against PA-Ag and sera of patients with AGN showed identical precipitation lines by immunodiffusion. Antibodies to PA-Ag determined by immunodiffusion were found to be present in 30 of 31 patients with AGN, in 1 of 36 patients with uncomplicated group A streptococcal upper respiratory tract infections and in 1 of 36 normal adults. These findings were confirmed by the ELISA technique. Small doses of PA-Ag injected intravenously into rabbits produced glomerular changes similar to AGN with polymorphonuclear infiltration, cellular proliferation and staining for C3 by immunofluorescence. Control rabbits injected with BSA in similar doses did not develop glomerular pathology. Following perfusion of PA-Ag into rabbit kidneys, PA-Ag was found to localize only on the glomerular basement membrane and in the mesangium. Using immunoelectrophoresis it was found that PA-Ag activates the alternate pathway of complement. Any other water soluble streptococcal fraction, used as control, did not activate the complement system. Our findings suggest that PA-Ag seems to be involved in the pathogenesis of AGN.