Renal pathology and long-term outcome in childhood SLE.

Renal histology is increasingly used as a guide for therapy and prognosis in SLE but data in children are few and/or short-term. We assessed renal histological features in 19 children with SLE to determine whether these features are useful in predicting long-term outcome. Mean age at biopsy was 10 +/- 1.7 years old, male to female ratio was 1:2.8. Fourteen patients (73%) had diffuse proliferative lupus nephritis. Renal histology was evaluated using an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis and serum creatinine. Renal function at biopsy correlated well with AI (p < 0.001) but not CI. At short-term follow-up (30 months), 3 patients had died from sepsis and another 2 reached end-stage renal disease. CI predicted poor clinical outcome, i.e. death or renal failure (p < 0.005) but AI did not. At long-term follow-up (mean 92.1 +/- 26.8 months) only one more patient reached end-stage renal disease. In others renal function assessment showed improvement or were stable. Neither CI nor AI correlated with clinical outcome. We conclude that although AI correlates well with renal function at biopsy and CI with short-term prognosis, neither can predict long-term outcome. Treatment may have altered the natural course of disease in these patients.

Renal failure in two patients with Wolfram syndrome.

We describe a Thai family with three children, two of whom presented with Wolfram syndrome, which is a rare syndrome characterised by diabetes insipidus, diabetes mellitus, optic atrophy, deafness and urinary tract dilatation. A girl and her younger brother had insulin-dependent diabetes mellitus at 11 years old with early onset of renal impairment, proteinuria and hypertension. Urinary tract dilatation was demonstrated in both patients. Kidney biopsies were compatible with diabetic nephropathy. Both children also had bilateral sensorineural hearing loss. Optic atrophy with severe loss of vision was detected in the girl and bilateral cataract in her brother. Both patients were HLA DR2 positive. At 16 years old, her creatinine clearance was 16 ml/min/1.73 m2. Her brother's creatinine clearance was 25 ml/min/1.73 m2 at 13 years old. We conclude that renal function should be evaluated in patients with Wolfram syndrome and the cause of renal failure in these patients may be rapid and severe diabetic nephropathy.

Lupus nephritis in Thailand: clinicopathologic findings and outcome in 569 patients.

The prognosis of lupus nephritis patients in Thailand has been reported to be poorer than that in Western countries since 1978. After a great evolution in management, we re-evaluate the long-term outcome in patients who were treated and followed up at Siriraj Hospital in Bangkok from 1984 to 1991. Clinical and pathologic records were collected from 569 patients (515 females and 54 men) who were followed up for a mean period of 38.7 +/- 34.6 months. The mean age was 28 +/- 10 years and the median duration of symptoms prior to admission was 7 months. Hypertension was diagnosed in 32.4% of patients and 41.3% had serum creatinine greater than 1.5 mg/dL. Nephrotic-range proteinuria was found in 43.6% of patients and creatinine clearance less than 50 mL/min was found in 58.0%. Of the 314 patients who underwent renal biopsy, the most common histologic finding was diffuse proliferative glomerulonephritis (61.5%). The overall probability of survival was 76.5% at 60 and 90 months after diagnosis. Initial presence of hypertension, renal insufficiency (creatinine clearance < 25 mL/min), and World Health Organization histology class IV and III in the biopsied patients were the three independent factors significantly associated with lower survival probability. Neither gender nor amount of proteinuria was the predictive factor for poor outcome. During the follow-up period, 89 patients died and two patients entered a chronic dialysis program. The two leading causes of death were infection (50.5%) and uremia (28.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Presence of autoimmunity to pancreatic antigens in a patient with fibrocalculous pancreatic diabetes.

A case of fibrocalculous pancreatic diabetes (FCPD) is reported for which antibody and cellular immune characteristics were determined. The patient, a Thai woman, had serum islet cell antibodies (ICA) that were detected by both immunoperoxidase staining and an indirect enzyme-linked immunosorbent assay (ELISA). Serum anti-human insulin antibodies were negative by a displacement ELISA. Lymphoproliferation assay against pancreatic antigen prepared from a blood group O cadaveric donor was positive. Increased CD8+ lymphocytes were observed using direct immunofluorescence staining and flow cytometry. CD4+ T lymphocytes, B lymphocytes and NK cells were within normal levels. These findings provide evidence for autoimmunity to pancreatic antigens in a patient with fibrocalculous pancreatic diabetes.

Posterior polymorphous dystrophy and Alport syndrome.

Seventeen Thai patients from nine families with Alport syndrome underwent complete ocular examination and specular microscopy. Fourteen (82.3%) patients had ocular changes. Eleven (64.7%) had endothelial vesicles compatible with posterior polymorphous dystrophy. Four of these also had subepithelial opacities, a previously undescribed phenomenon. Other ocular changes included lenticonus and macular and midperipheral retinal flecks. A second group of 18 consecutive patients from 14 families with posterior polymorphous dystrophy detected during routine ocular examination underwent renal evaluation. Five had hematuria, four of whom had sensorineural hearing loss. Two of the four patients also had characteristic renal biopsy findings. Another had sensorineural hearing loss without hematuria, and renal biopsy showed a thin glomerular basement membrane. Posterior polymorphous dystrophy is a common but frequently overlooked finding in Alport syndrome. The frequent association of these two hereditary conditions suggests a common defect in basement membrane formation. Patients with posterior polymorphous dystrophy should be examined for renal abnormalities and hearing loss.

Lupus nephritis: clinicopathological study of 162 cases in Thailand.

One hundred and sixty two cases of lupus nephritis biopsied over three years in Thailand were studied. A pattern of clinical and histological renal disease very similar to that seen in the United States or Europe emerged. The predominant histological type was World Health Organisation class IV (diffuse proliferative; 58.6%). Patients with renal insufficiency (creatinine greater than or equal to 2 mg/100 ml) or hypertension at the time of biopsy had a considerably worse three year survival. Certain features such as sclerotic glomeruli, tubular atrophy, and an interstitial mononuclear cell infiltrate were significantly associated with a worse outcome (0.05 greater than p greater than 0.01), and patients who died with poor renal function had significantly higher chronicity scores than those in other groups (p less than 0.05). These findings emphasise the importance of chronic renal damage in the morbidity and mortality of patients with lupus nephritis.

Blood leucocyte infiltration after intravenous injection of ferritin in the rat.

Monocytes infiltrate glomeruli during mesangial deposition of ferritin, and during experimental glomerulonephritis. To determine whether this is solely a local phenomenon, leucocyte infiltration in other organs has been studied following intravenous ferritin injection. Lewis rats received an i.v. injection of 150 mg ferritin/100 g body weight. At 24 h there was a peripheral blood leucocytosis (ferritin-treated rats 26.32 +/- 13.7, control rats 8.54 +/- 2.41 X 10(6) cells/ml) due to increase in polymorphs and monocytes. Bone marrow cell counts fell (ferritin-treated rats 49 +/- 7, control 80 +/- 11 X 10(6)/100 g body weight). Cell counts on cell suspensions of perfused, enzyme-digested lung, liver and spleen, and lung lavage showed major significant increases in total cell counts: lung 250 +/- 36 (89 +/- 16), lung lavage 2.6 +/- 0.8 (1.4 +/- 0.5), liver 140 +/- 37 (60 +/- 11), spleen 306 +/- 38 (200 +/- 27) X 10(6)/100 g body weight (control values in parentheses). Cytospin preparations of these suspensions, stained for non-specific esterase showed that the increase in cell numbers was due to increases in non-specific esterase-positive cells (monocytes) and polymorphs. These results demonstrate a generalized leucocyte mobilization, sequestration, and tissue infiltration after i.v. ferritin. The renal glomerulus therefore is not the only site of leucocyte accumulation. These findings may have relevance for studies on inflammation mediated by leucocytes in models of experimental immune complex glomerulonephritis.

Monocyte infiltration in human glomerulonephritis: alpha-1-antitrypsin as a marker for mononuclear phagocytes in renal biopsies.

Alpha-1-antitrypsin detected by immunoperoxidase has been used as a marker for infiltrating monocytes on formalin-fixed, paraffin-embedded sections of 75 renal biopsies. Patients were classified on the basis of glomerular hypercellularity on light microscopy. Monocytes increased with increasing glomerular hypercellularity, most being in diffuse proliferative GN (DPGN) and severe mesangiocapillary GN (MCGN-S). Monocytes were reduced by 48-95% in repeat biopsies of DPGN, mesangial proliferative GN and focal GN, but not in MCGN. In electron micrographs (70 biopsies) monocytes were identified but less frequently than by alpha-1-antitrypsin. Highest numbers were found with subepithelial or subendothelial deposits and lowest numbers in biopsies without deposits. The results show monocytes are detectable in human proliferative GN, numbers increasing with increasing glomerular hypercellularity, and subendothelial and subepithelial deposits.

Accumulation of silicone elastomer in regular dialysis.

A retrospective autopsy study of 78 patients treated by some form of dialysis for chronic renal failure in Newcastle 1964-1981 showed that: 1) Particles resembling silicone elastomer were present in 48 per cent of 61 patients haemodialysed with the use of silicone rubber pump inserts but in none of the 11 treated by haemodialysis with other pump inserts or of the six treated by peritoneal dialysis alone; 2) The prevalence of these particles and their density increased with time on haemodialysis; 3) There was little evidence of a tissue reaction to the particles and no association between their presence and histological evidence of liver disease; 4) There was a higher incidence of clinical and biochemical evidence of liver disease in patients with silicone deposits than in those without. Although there are other possible explanations for this higher incidence of hepatic dysfunction it would be safer to assume that silicone particle spallation is not innocuous.

Pulmonary artery obstruction in thalassaemia.

A new feature has been encountered in review of a large species of autopsy materials of beta-thalassaemia/Hb E disease. Among 43 patients pulmonary arterial obstructive lesions were found in 19 (44%), of which 17 were splenectomised cases. The pulmonary arterial thromboembolism may have been due to circulating platelet aggregates. This newly discovered pathology may be an additional factor contributing toward dyspnoea and heart failure in thalassaemia besides anaemia and cardiac iron deposition. If it is proven that this pulmonary arterial thromboembolism is indeed due to circulating platelet aggregates, preventive measure by administration of drugs reducing platelet aggregation such as aspirin and Persantin may be indicated, especially after splenectomy.

Immunoproliferative disease of the gastrointestinal tract: a report of five cases.

Five patients with immunoproliferative disease of the gastrointestinal tract are presented. The main pathological feature was dense diffuse lymphoplasmacytic and immunoblastic infiltration of the mucosa and submucosa, of the proximal small bowel in 3 cases and the stomach in 2. Four of the five patients had concomitant immunoblastic sarcoma. The clinical presentation and pathological findings are compared and contrasted with those of "Mediterranean abdominal lymphoma" and alpha chain disease, and the possible role of ethnogeographical and environmental factors in the pathogenesis are discussed.