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Tubulo-interstitial kidney disease is characterized by moderate proteinuria < 1 g/day of low molecular weight proteins in range of MW 10.000-50.000. Even in the physiological proteinuria of < 150 mg/day, tubulo-interstitial kidney disease may exist. Using optimized sodium dodecyl sulfate polyacrylamid gel electrophoresis (SDS-PAGE) according to the method of Melzer, even in proteinuria of less than 150 mg/day all relevant proteins for diagnosis of glomerular or tubulo-interstitial kidney disease can be detected. This study evaluates the tubulo-interstitial kidney disease due to polychemotherapy for different types of cancer in 115 children and in 16 children with pyelo-ureteral junction obstruction. Fifty-two and 63 children were followed up during and after chemotherapy, respectively. During therapy, renal damage was recorded in 43% of patients with leukemia, 56% with nephroblastoma, and 79% with other tumors. Tubular protein patterns were seen up to three years after termination of chemotherapy (25% in acute lymphoplastic leukemia, 35% in nephroblastoma and 62% in other tumors). Patients with persistent complete tubular proteinuria or mixed glomerular/tubular proteinuria were found to have a high risk for irreversible renal failure. Children with congenital pyelo-ureteral junction obstruction could also be classified according to SDS-PAGE protein patterns. Patients without parenchymal lesions did not need surgery. Most of those with pathologic findings in SDS-PAGE exhibited partial or complete remission after surgery. The highly discriminating SDS-PAGE permits a rapid, sensitive, reproducible, and reliable analysis of urine proteins for diagnosis and follow-up of all kinds of congenital or acquired renal parenchymal kidney diseases.

Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction. In addition, we performed synchrotron x-ray analyses and immunogold labeling to detect inhibitors of calcification. Von Kossa staining revealed calcification of 53% of the arteries. The diameter of these microcalcifications ranged from 20 to 500 nm, with a core-shell structure consisting of up to three layers (subshells). Many of the calcifications consisted of 2- to 10-nm nanocrystals and showed a hydroxyapatite and whitlockite crystalline structure and mineral phase. Immunogold labeling of calcification foci revealed the calcification inhibitors fetuin-A, osteopontin, and matrix gla protein. These observations suggest that uremic microcalcifications originate from nanocrystals, are chemically diverse, and intimately associate with proteinaceous inhibitors of calcification. Furthermore, considering the core-shell structure of the calcifications, apoptotic bodies or matrix vesicles may serve as a calcification nidus.