Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria.

Alport syndrome (ATS) and benign familial hematuria (BFH) are type IV collagen inherited disorders. Mutations in COL4A5 are generally believed to cause X-linked ATS, whereas mutations in COL4A3 and COL4A4 genes can be associated with the autosomal-recessive and -dominant type of ATS or BFH. In view of the wide spectrum of phenotypes, an exact diagnosis is sometimes difficult to achieve. This study involved screening each exon with boundary intronic sequences of COL4A3, COL4A4, and COL4A5 genes by optimized polymerase chain reaction-single-stranded conformational polymorphism analysis in 17 families with ATS and in 40 families diagnosed as having BFH. Twelve different mutations were found in the COL4A5 gene in ATS patients, comprising nine missense mutations, a splice site mutation, a mutation causing frameshift, and a nonsense mutation. One of the missense mutations (p.G624D) was present not only in one family with ATS but also in five families with suspected BFH. Three heterozygous mutations in the COL4A3 gene (two missense and one frameshift) and four heterozygous mutations in COL4A4 (two splice site, one in-frame deletion, and one missense) were identified in patients with BFH. Sixteen mutations are to the best of our knowledge new and private.

Xanthogranulomatous pyelonephritis in nonfunctioning transplanted kidney.

Xanthogranulomatous pyelonephritis in native and allografted kidneys is a rare variant of severe chronic infection of the renal parenchyma. In a native kidney the diagnosis may sometimes be established by ultrasonography and computed tomography. In the renal allograft, the diagnosis could only be established by histologic evaluation of the transplant biopsy or nephrectomy. The reported case presents a febrile patient with a failing renal graft, in whom xanthogranulomatous pyelonephritis was established by histologic evaluation of transplantectomy specimens. Xanthogranulomatous pyelonephritis should therefore be included in the list of possible etiologies of the fever in patient with nonfunctioning transplanted kidney.

Interstitial capillary in normal and in transplanted kidneys: an ultrastructural study.

Knowledge about the normal structure and pathology of interstitial capillary is limited. Splitting and multilayering of the basal membrane (BM), as a marker of chronic rejection, has been published in association with transplant glomerulopathy. The authors investigated the ultrastructural features of the interstitial capillary basal membrane in normal (15 biopsies) and in transplanted kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8 biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6 patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8 patients). All biopsies were fixed in 1% OsO4, embedded in Epon, and examined by electron microscope. Measurements of the interstitial capillary BM were made. The BM of interstitial capillary of intact kidney was a homogenous continuous structure, 88 nm in width on average. Thickening with diffuse multilayering of BM was most intensive in patients with transplant glomerulopathy, and much less intensive in patients with acute tubulointerstitial rejection and in patients with recurrent or de novo glomerulonephritis. These findings may provide the first information about the morphology of the normal basal lamina of interstitial capillary and support the diagnostic value of interstitial capillary changes in chronic rejection.

Mildly elevated serum creatinine concentration correlates with the extent of coronary atherosclerosis.

Mildly elevated serum creatinine concentration was proposed to be a marker for increased risk of cardiovascular disease mortality. The aim of our prospective study was to evaluate a possible association between serum creatinine concentration and extent of coronary atherosclerosis together with conventional risk factors for atherosclerosis. Serum creatinine concentration was measured in 40 male patients without overt renal or ischemic renal disease (mean age 53 +/- 7 years) with stable or unstable angina undergoing routine coronary arteriography. The extent of coronary atherosclerosis was assessed by Gensini score. In univariate linear regression analysis Gensini score significantly correlated with serum concentrations of apolipoprotein AII (r=-0.3242, P<0.05) and creatinine (r=+0.3194, P<0.05), but not with serum concentrations of lipids (total, low- and high-density lipoprotein cholesterol, triglycerides), other apolipoproteins (apo B, apo AI), lipoprotein(a), autoantibodies to oxidatively modified low-density lipoprotein or age, weight and status of smoking, diabetes or hypertension. Multivariate linear regression analysis revealed that elevated serum creatinine was associated with the extent of coronary atherosclerosis independently of conventional risk factors for atherosclerosis. Mildly elevated serum creatinine was probably the marker of generalised vascular disease denoting early nephrovasculopathy in correlation with established atherosclerotic risk factors.

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.

Operative treatment of destructive spondyloarthropathy of the lumbar spine in a patient on chronic dialysis.

We present a patient with end-stage renal disease treated by chronic dialysis, in whom progressive destructive spondyloarthropathy of the lumbar spine was successfully managed by fusion with internal fixation, resulting in relief of pain and restoration of activity.

Magnesium hydrogen carbonate natural mineral water enriched with K(+)-citrate and vitamin B6 improves urinary abnormalities in patients with calcium oxalate nephrolithiasis.

The influence of drinking magnesium hydrogen carbonate natural mineral water enriched with potassium citrate on urinary metabolic abnormalities was prospectively studied in 27 patients with recurrent calcium oxalate nephrolithiasis. The mean 24-hour urinary pH shifted from 6.34 to 6.93 (p < 0.01), the mean urinary magnesium/urinary creatinine ratio rose from 0.47 to 0.67 (p < 0.01), the mean urinary citrate/urinary creatinine ratio increased from 0.26 to 0.35 (p NS), and the mean 24-hour urinary calcium decreased from 7.98 to 6.05 mmol (p < 0.05). The effects of magnesium hydrogen carbonate natural mineral water enriched with potassium citrate were found to be favorable on urinary calcium, urinary magnesium/urinary creatinine ratio and urinary pH in patients with calcium oxalate nephrolithiasis.

Captopril renography and duplex Doppler sonography in the diagnosis of renovascular hypertension.

BACKGROUND: The purpose of this prospective study was to determine the clinical usefulness of captopril renal scintigraphy and duplex Doppler sonography in detecting haemodynamically significant renal artery stenosis (> or = 60%) and predicting cure or improvement of hypertension following revascularisation. METHODS: Twenty-eight patients with moderate or high index of clinical suspicion of renovascular hypertension underwent both captopril renal scintigraphy and duplex Doppler sonography before undergoing renal angiography. Patients with angiographically proved (> or = 60%) RAS were treated by percutaneous transluminal renal angioplasty unless it was contraindicated. RESULTS: The results of captopril renal scintigraphy and duplex Doppler sonography were compared by renal angiography of 45 renal arteries in 28 patients. Eleven renal arteries were excluded from further comparison, because no accurate Doppler signal could be obtained. The sensitivity and specificity of captopril renal scintigraphy in the identification of RAS (> or = 60%) was 78% and 81% respectively. The sensitivity of duplex Doppler sonography was 83% and the specificity was 81%. Positive predictive values of both tests for blood pressure cure or improvement after PTRA were 86% for CRS and 85% for DDS. CONCLUSIONS: Captopril renal scintigraphy and duplex Doppler sonography are comparable tests for detection of patients with haemodynamically significant renal artery stenosis (> or = 60%). Positive predictive values of both tests for cure or improvement of hypertension after percutaneous transluminal renal angioplasty are good and comparable.