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Childhood membranous nephropathy (MNP) with anti-tubular basement membrane (anti-TBM) nephritis is a rare disorder that may have extrarenal manifestations. This article describes a new case to be added to the 10 previously reported. A renal biopsy specimen from a 1-year-old white boy with nephrotic syndrome, microhematuria, and hypertension showed MNP (granular global IgG, IgA and C3, and segmental IgM and C1q) associated with hypercellularity and granular deposits of IgM and C1q in the mesangium, arteriolar IgA, and linear TBM IgG, IgA, and C3. A biopsy at age 4 years showed MNP (IgG and C3) and linear IgG and C3 along the TBM. Six months later, temporary glucosuria suggested a mild tubular dysfunction. Biopsy at age 8 years showed sclerosing MNP (IgG and C3), linear TBM IgG and C3, and chronic active tubulointerstitial nephritis (TIN). Indirect immunofluorescence showed circulating anti-TBM antibodies, and the enzyme-linked immunosorbent assay (ELISA) approach verified strong reactivity with the 58-kd TIN antigen. Despite trials with steroids, chlorambucil, azathioprine, and cyclosporine, end-stage renal disease developed by the age of 9 years. At age 10 years, the patient received a cadaveric kidney transplant. With the patient now aged 12 years, the graft is still functioning well, without any clinical evidence of disease recurrence. Neurological, ocular, and abdominal symptoms, including nonbacterial diarrhea, were observed during the follow-up period. The pathophysiology of these extrarenal symptoms remains unclear. Serotyping and genotyping of HLA antigens (A2, A10, B12, B41, DR5 [1101, 1103-4, 1106 or 1108-1113], DR6 [1303, 1312, or 1413], DRB3 [*0101 and 0201-2 or 0301], DQA1 [*0501 homozygous], and DQB1 [*0301 homozygous]) did not indicate any HLA association similar to those described previously in childhood MNP with anti-TBM nephritis (HLA-B7 in four patients, HLA-DR8 in two patients). The presented case is the fifth in the literature that displays reactivity with the 58-kd TIN antigen, and for which data on HLA antigens are reported.

Renal biopsy of two children and a maternal relative, diagnosed with severe progressive tubulointerstitial nephritis, has shown the presence of distorted mitochondria. Mitochondrial DNA from the blood of these patients was analysed. No major deletions were found, but an A to G mutation was detected in position 5656. It is proposed that this mutation might play a causative role in the renal disease of the patients.

The prognostic impact of tubulitis and the phenotype of the infiltrating cells in the tubules were studied in ten percutaneous renal biopsies from six patients with acute tubulointerstitial nephritis (ATIN). The inflammatory cell subsets in the tubules and interstitium (CD3+, CD4+, CD8+, CD20+, CD45RO+, CD56+, CD57+, CD68+ and TIA-1+ cells), the expression of vimentin and the proliferation-associated antigen Ki-67 by cortical tubular cells, and the grade of tubulitis, interstitial infiltration and fibrosis were analysed. Cytotoxic injury to tubular cells in the vicinity of tubular-wall-localized lymphocytes was studied ultrastructurally. ATIN was drug-induced in three patients, related to Legionella infection in two and idiopathic in one patient. Four patients recovered, one with reduced renal function. Two patients developed end-stage renal disease. CD8+ and CD4+ lymphocytes, and a smaller number of macrophages, infiltrated the tubules. The predominant lymphocyte subset in the tubules was the same as in the interstitium. Cytotoxic injury to tubular cells was not seen electron microscopically. The tubular cells exhibited increased proliferative activity and expressed vimentin, indicating non-specific tubular damage. The cell subset, the severity of tubulitis, and the tubular expression of vimentin were not related to outcome. The main prognostic factor was the severity of the interstitial fibrosis. Tubulitis in ATIN may be a harmless non-immune reaction, mediated by tubular expression of cytokines, together with adhesion and other molecules.

A ten years old boy with severe acute renal failure was presented. The development of acute uremia was proceeded by infectious mononucleosis. Renal biopsy revealed acute tubulointerstitial nephritis. Peritoneal- and haemodialysis was completed by steroid therapy and cytostatic treatment when glomerular proteinuria was observed. Following a 2 months uremic period the patient cured completely.

In acute interstitial nephritis (AIN), mononuclear cells invade the tubules (tubulitis). The segmental localization of tubulitis is not precisely known. To clarify this question, formalin-fixed kidney biopsy specimens from 13 patients with AIN were studied stereologically by identifying cortical tubules with segment-specific markers. The periodic acid-Schiff reaction, peanut lectin, and antibodies against Tamm-Horsfall protein and epidermal cytokeratins all applied to the same section were used to identify the proximal tubules (PTs), distal convoluted tubules, distal straight tubules, and the cortical collecting system (connecting tubules and cortical collecting ducts), respectively. Morphometrically, an estimate of the relative volume of the inflammatory cell infiltrates within each category of tubular segments was obtained. Inflammatory cells were infrequently found in PTs (1.2%) but were frequently localized in distal tubules and the cortical collecting system (7.6%). There was no difference in the amount of the inflammatory cell infiltrate within these segments. Re-examination of an electron microscopic study of AIN carried out in this laboratory revealed that mononuclear cells were rarely seen in convoluted PTs but were frequently observed in straight PTs and all segments distal to them. The observations indicate that it is the distal nephron which is primarily affected by inflammatory cell infiltration in AIN.

Some basic changes in experimental pyelonephritis were studied by transmission and scanning electron microscope. Initially, bacteria settled and multiplied in capillaries and venules. Leukocytes first marginated and then escaped from the capillaries, particularly to the wide peritubular interstitium. After opening the tubular basement membrane, the infiltrating leukocytes were immediately localized in the tubular wall between epithelial cells but were never seen between the epithelial cells and the underlying basement membrane. The inflammatory cells seemed not to be able to pass through the tight junctions of the nonnecrotic tubular epithelium. As a consequence of severe inflammatory injury, the tight junctions exhibited alterations of intermediate junction type. Where circumscribed necrosis of the tubular walls occurred, leukocytes appeared in the lumen. Thus, pus casts originated from these sites, apparently as drainage of interstitial abscesses. The secondary/regressive and regenerative/tubular changes were similar to those occurring after various tubular lesions.