Sudesh P. Makker

Tubular Basement Membrane Antibody-Induced Interstitial Nephritis in Systemic Lupus Erythematosus

Interstitial nephritis characterized by linear staining for human immunoglobulin G (IgG) along the tubular basement membrane of proximal renal tubules is described in a child with systemic lupus erythematosus (SLE). Autoantibodies reacting with the tubular basement membrane of the proximal renal tubules and Bowman capsule of glomeruli were present in serum. The autoantibodies were specific and could be absorbed with a normal human renal cortical fraction. The findings suggest that in addition to the well-known, immune complex-mediated injury, autoantibody-induced interstitial nephritis can also rarely occur in SLE.

Urinary excretion of Hageman factor (factor XII) and the presence of nonfunctional Hageman factor in the nephrotic syndrome

Acquired deficiencies of functional Hageman factor (factor XII) and prekallikrein, proteins involved in the plasma kinin-generating system, have been previously reported in the nephrotic syndrome. The basis for these changes, however, is not fully understood. We have examined the levels of Hageman factor and prekallikrein by functional and radioimmunoassays in plasmas and urines of 11 patients with the nephrotic syndrome. All 11 patients had decreased titers of plasma Hageman factor activity (mean +/- standard deviation (SD), 0.29 +/- 0.15 U/ml), but essentially normal titers of immunoreactive Hageman factor (0.68 +/- 0.23 U/ml). The ratio of immunoreactive Hageman factor to functional Hageman factor (2.63 +/- 0.86) was significantly higher than that in nine control patients (1.08 +/- 0.17). Since no circulating anticoagulants against Hageman factor were detected, these data suggest the presence of nonfunctional (altered) Hageman factor in plasmas of patients with the nephrotic syndrome. Urinary excretion of Hageman factor was present in six patients but did not appear to account for the reduced plasma Hageman factor activity. Urinary Hageman factor in one patient had the same size as plasma Hageman factor as assessed by gel filtration and sucrose density gradient centrifugation. The titers of plasma prekallikrein were within the normal range. These studies indicate urinary excretion of Hageman factor and alterations in the functional sites of plasma Hageman factor molecules in the nephrotic syndrome. Whether these changes are related to the pathogenesis of the nephrotic syndrome remains to be determined.

Evidence that the antigen of autologous immune complex glomerulonephritis of rats is a mannose- or glucose-containing glycoprotein.

Summary Chemical nature of the brush border antigen (BBAg) of the autologous immune complex glomerulonephritis (AIC) of rats was investigated by a histochemical method utilizing indirect immunofluorescence. Fresh frozen rat kidney sections, a specific antibody to BBAg (BBAb), purified lectins (concanavalin A, Ricin II, wheat germ hemagglutinin) and a specific sugar, α-methyl-D-mannopyranoside were used. The reaction of the specific antibody BBAb to its antigen BBAg on tissue sections was blocked by concanavalin A but not be Ricin II and wheat germ agglutinin. This blockade was reversed by α-methyl-D-mannopyranoside. These results suggest that the antigen of AIC of rats is a mannose or glucose containing glycoprotein. Identification of the chemical nature of the antigen of AIC is of considerable importance because AIC has a striking clinical, histological, and immunohistological similarity to the idiopathic membranous glomerulonephritis in humans. This work was supported by research grants from The Kidney Foundation of Ohio, Inc., and NIH Grants RR 05410-14 and AM 25782. The author is indebted to Mrs. Sharon Monahan for her excellent technical assistance.

Identical progression of juvenile hereditary nephronophthisis in monozygotic twins

A pair of monozygotic twins with juvenile hereditary nephronophthisis was studiedfor nearly ten years. Astonishing similarity was observed in the clinical course, progression, and histopathology of the disease. In a review of the natural history of various diseases in identical twins it was noted that diseases of infectious or immunologic pathogenesis usually do not follow identical courses. Diseases due to inborn errors of metabolism are more likely to do so. It is suggested that juvenile hereditary nephronophthisis might be due to an inborn error of metabolism.

Pregnancy in patients who have had the idiopathic nephrotic syndrome in childhood

Ten women who had had the idiopathic nephrotic syndrome but who had been in remission from 8 months to 19 years (mean 8.42 years) prior to the onset of pregnancy were studied during pregnancy. Seven of ten had no problems pertaining to their previous renal disease. One patient had an overt relapse of the nephrotic syndrome, another had aggravation of proteinuria only, and another developed mild azotemia with aggravation of proteinuria. A total of 18 pregnancies were observed; of these 17 resulted in the births of live newborn babies. Only one infant had a congenital malformation. It is suggested that pregnancy in patients who are in remission of the nephrotic syndrome usually does not lead to reactivation of the nephrotic syndrome in the mother and probably does not carry an increased risk of fetal illness and death.

Arterial embolization of renal allograft to control hemorrhage secondary to percutaneous nephropyelostomy.

AbstractPercutaneous nephropyelostomy is an accepted method for relieving obstruction of the upper urinary tract. We report a case of massive renal hemorrhage following removal of the percutaneous nephropyelostomy catheter. Treatment with angioinfarction of the bleeding branch of the renal artery was successful.

Brush Border Antibodies of Heymann Nephritis of Rats in Normal Human Serum

Summary Brush border antibody of Hey-mann nephritis of rats was detected in 36.0% of normal human sera by indirect immunofluorescence technique. Persons with blood group B were less likely to develop this antibody. Its existence in the serum may or may not be related to the genesis of idiopathic membranous glomerulo-nephropathy in humans. Many investigators are looking for BB Ab in the sera of patients with renal disease; thus, it is important to know that BBAb can exist in the sera of normal human controls who do not have any clinical evidence of renal disease. Further studies on this subject will be needed to understand the significance of this observation. Possibilities to explain this observation are presented. I thank Ms. Barbara Schiffauer and Ms. Rebecca Turinic for technical assistance. This work was supported by the Kidney Foundation of Ohio, Inc., and General Research Support Grant No. RR-05410-14, NIH.

TREATMENT OF HIGH RENIN REFRACTORY HYPERTENSION IN CHILDREN WITH MINOXIDIL (A NEW HYPERTENSIVE DRUG NOT PREVIOUSLY USED IN CHILDREN)

Hypertension developed in a 10 yr. old girl following a renal transplant with blood pressure (BP) between 160/120 and 200/160, and elevated peripheral vein renin (15.2 to 35.5 ng/ml/hr, normal 0.53 ± 0.4). Before transplantation her kidneys had been removed and no stenosis was evident at the site of the anastomosis by angiography. While hypertensive, she developed cardiomegaly and deterioration of renal function [serum creatinine (Cr) from 0.8 to 2.1 mg2]. BP was uncontrollable with daily dosages of Methyldopa 2.5 gm, Hydralazine 300 mg, Guanethidine 200 mg, Propranolol 100 mg, Furosemide 120 mg, and only transient relief was achieved by Diazoxide (300 to 600 mg/day). A transplant nephrectomy was contemplated. Minoxidil given 2.5 mg/6 hrs orally reduced her BP to normal (130/80) within 12 hrs. Other antihypertensives except Propranolol and Furosemide were discontinued. With normalization of BP the heart size decreased and the renal function improved (Cr 0.9 mg%). Five months later on Minoxidil (10 mg/6 hrs) her BP is 130/90, her transplant function is excellent (Cr 0.8 mg%), but the renins remain elevated (13.9 to 24.5). A side effect of generalized hirsutism has occurred. It is felt that high renin refractory systemic hypertension can be controlled by Minoxidil and offers an alternative to transplant nephrectomy.

Demonstration of a Tubular Basement Membrane Antibody in the Pathogenesis of Autoimmune Nephrosis in Rats

Summary Another humoral autoantibody tubular basement membrane antibody (TBMAb) has been demonstrated in the immune sera of Lewis rats in whom autoimmune nephrosis was produced by repeated intraperitoneal injections of a mixture containing complete Freunds adjuvant and a kidney tubular fraction obtained from normal Sprague-Dawley rats. The antibody, by indirect immunofluorescent technique, localized in a linear pattern along the normal tubular basement membrane and Bowmans capsule, but not along the glomerular basement membrane. Also the antibody (TBMAb) could be eluted from the immune deposits in the glomeruli of the diseased animals. These studies suggest the nephritogenicity of this antibody (TBMAb) and point out that at least two antigens (BBAg and TBMAg) may be nephritogenic in this form of experimental autoimmune nephrosis. Addendum: It has been noted that TBM Ab develops only when Lewis rats are injected with Sprague-Dawley rat kidney and not vice versa.

Growing Up with Renal Failure

For the past 10 years, we have been caring for children and adolescents with renal failure (RF) and their families in an evolving program of comprehensive pediatric care that features attention to psychosocial development, involvement of child and family in treatment decisions, and family-oriented intervention concerning psychological crises which arise in the course of physical treatment.1–3