De novo diabetic nephropathy on renal allografts.

BACKGROUND: Posttransplant diabetes mellitus (PTDM) is a well-recognized clinical problem following renal transplantation. Long-term risks of PTDM are similar to those of diabetes mellitus in general population. The aim of our study was to identify de novo diabetic nephropathy (DN) in our group of patients with PTDM. METHODS: Thirty-four patients with PTDM were reviewed retrospectively. Light microscopy, immunofluorescence, and electron microscopy techniques were performed in 10 of 21 patients with graft biopsy. RESULTS: Five patients (four women, one man), aged 47.4 years (range, 29 to 58), four of whom received cadaveric grafts, were found to have de novo DN. Their serum creatinine was 211.4 micromol/L (range, 140 to 294). Three patients were slightly proteinuric (0.3 to 0.5 g/L). PTDM was diagnosed 2.4 months after transplantation (range, 1 to 6). Histologic diagnosis of de novo DN was made, on average, 52.6 months after transplantation (range, 8 to 115), and 50.2 months (range, 2 to 114) after PTDM. De novo DN presented as diffuse diabetic glomerulosclerosis in four patients and nodular diabetic sclerosis in one patient, and combined with transplant glomerulopathy in all five patients. The mean graft survival time for this group of patients was equivalent with a control group. Although the difference in slopes of serum creatinine between the studied groups was clinically relevant, it was not statistically significant. CONCLUSION: In view of our findings, when histologic de novo DN was found in 5 out of 10 patients, one could conclude that de novo DN could be a frequent complication of PTDM.

Antineutrophil cytoplasmic autoantibodies-antigen specificity and associated diseases.

Antineutrophil cytoplasmic antibodies (ANCA) are widely used as a useful diagnostic marker for small vessel vasculitides, although the test may occasionally be positive in various other conditions. The aim of this study was to assess ANCA in various clinical-pathological settings. ANCA were tested by indirect immunofluorescence and enzyme-linked immunosorbent assay and were found to be positive in 423 patients in the period from 1989-1999. Patients were grouped in accordance with their clinical-pathological setting as follows: 1. pauci-immune vasculitis confirmed by biopsy (n = 151), 2. clinically suspected vasculitis (n = 59), 3. inflammatory bowel diseases and autoimmune hepato-biliary disorders (n = 83), and 4. miscellaneous diseases (n = 130). The association of proteinase 3 ANCA with Wegener's granulomatosis (45/56) and myeloperoxidase ANCA with microscopic polyangiltis (45/54) and pauci-immune necrotising glomerulonephritis (24/28) was established. However, ANCA with other specificities were also shown to be present in these forms of vasculitides. ANCA, specific mostly for myeloperoxidase but also for other or unknown ANCA antigens, frequently revealing atypical immunofluorescence patterns, were characteristically found in other diseases. The titres of ANCA were significantly higher (p < 0.05) in patients with pauci-immune vasculitis than in those with clinically suspected vasculitis and other diseases. In conclusion, well standardised techniques for ANCA testing in conjunction with the clinical picture and histopathologic findings, if available, may significantly contribute to the diagnosis of small vessel vasculitides.

ANCA-associated vasculitis--an autopsy study.

The purpose of the study was to analyse the autopsies of 31 patients (20 female, mean age 67 years, range 28-87 years; and 11 male, mean age 66 years, range 47-80 years) with antineutrophil cytoplasmic antibodies (ANCA)-positive vasculitis, which was clinically confirmed in 25 patients and suspected in 6 patients, who had been treated and had died between 1989 and 1999. Kidney biopsy was performed in 22 patients on average 33 months (range, 1-132 months) prior to death. Biopsy and autopsy tissue specimens were examined by standard light and immunofluorescence microscopy techniques. Pauci-immune extracapillary glomerulonephritis was found in nearly the same percentage of 22 renal biopsies and 31 autopsies, namely in 91% and 84%, respectively. Active necrotising extracapillary glomerulonephritis was the prevailing lesion in 75% of biopsies, while advanced sclerosing glomerular lesions prevailed in 69% of autopsies. In the biopsies, necrotising lesions predominated in patients with ANCA of proteinase 3 specificity, while sclerotic lesions were more often associated with myeloperoxidase-ANCA. In the autopsies, florid necrotising systemic vasculitis coexisted in 2 patients with advanced sclerosing glomerulonephritis. Autopsies revealed the actual expansion of vasculitic disease, disclosed clinically silent vasculitic involvement of unusual locations and, in 3 patients, confirmed the clinically suspected vasculitis. The final diagnoses in 31 patients were as follows: Wegener's granulomatosis (5 men, 2 women), microscopic polyangitis (10 women, 2 men), pauci-immune crescentic glomerulonephritis (4 women, 3 men), a single case each of polyarteritis nodosa and isolated cutaneous vasculitis. In 3 patients, suspected vasculitis was not confirmed at autopsy. Nineteen of 31 patients died from septic infections or necrotising pneumonias, and 6 patients from progressive or recurrent vasculitis with complications, altogether nearly 80%. Cardiovascular failure, including pulmonary thrombembolism, caused death in 6 patients.

Effect of intrauterine growth retardation on the clinical course and prognosis of IgA glomerulonephritis in children.

Intrauterine growth retardation (IUGR) resulting in a reduced number of nephrons is one of the nonimmune mechanisms that have been recently proposed as contributing to the progression of renal diseases. The purpose of our study was to determine whether IUGR has any effect on the clinical course and prognosis of IgA glomerulonephritis (IgA GN) in children. Fifty children with biopsy-proven IgA GN, who were followed for at least 3 years, were included. Six of the 50 children (12%) had signs of IUGR at birth, defined as birth weight below the 10th percentile for gestational age. There were no significant differences in initial clinical presentation between children with IUGR and those without IUGR. However, in kidney biopsy specimens, we found a significantly higher mean percentage of sclerotic glomeruli in children with IUGR than in those without IUGR (33 vs. 13%, p < 0.015). At the end of the follow-up period, we observed a significantly higher incidence of arterial hypertension in children with IUGR than in those without IUGR (50 vs. 11 %, p < 0.05). Other differences between the two groups of children were not statistically significant. In conclusion, our study demonstrated an increased risk of the development of arterial hypertension and glomerulosclerosis in children with IgA GN who had suffered from IUGR with a birth weight below the 10th percentile for gestational age. IUGR may therefore help to identify early in the course of IgA GN those children who are at higher risk of an unfavorable course.

Acute renal failure due to hemorrhagic fever with renal syndrome.

The aim of our study was to analyze the clinical course and outcome of acute renal failure (ARF) in patients with hemorrhagic fever with renal syndrome (HFRS). From 1983 to 1995, we treated 33 patients (27 males, 6 females) aged from 16 to 71 years. Half of patients were connected with work at a farm or in a forest. The disease was confirmed serologically with indirect immunofluorescence test (IFT) and enzyme-linked immunosorbent assay (ELISA). In 18 patients percutaneous kidney needle biopsies were analyzed. In 85% of the cases, the disease broke out from June to October. The most frequently expressed clinical signs and symptoms were fever, nausea/vomiting, headache, backache, abdominal pain, myalgia, diarrhea, conjunctival injection, and hemorrhages. Four patients had concomitant pancreatitis. In 25 patients, oliguria was present, and transient hemodialysis treatment was needed in 19 patients. Infection with Hantaan virus was established in 20 patients and with Puumala virus in 13 patients. At renal biopsy, acute interstitial nephritis accompanied with hemorrhages and necrosis was found, and at a later biopsy there were also signs of interstitial fibrosis. All patients were cured, but renal function was not completely recovered in some. We conclude that ARF is a serious complication in patients with HFRS. Although not lethal in our group of patients, many of them showed severe signs and symptoms of illness. Transient hemodialysis was necessary in two-thirds of the patients. Some degree of functional defects and morphological changes might persist.