Hiroyuki Tochimaru

Renal tubular involvement mimicking Bartter syndrome in a patient with Kearns-Sayre syndrome

A 10-year-old boy had short stature, external ophthalmoplegia, atypical retinal pigmentary degeneration, and sensorineural hearing loss (Kearns-Sayre syndrome). In addition to ragged-red fibers observed on modified Gomori trichrome staining, there were scattered fibers exhibiting no cytochrome c oxidase activity, indicating a focal deficiency. Cytochrome c oxidase and other respiratory chain enzyme activities were normal biochemically. The patient also had renal tubular dysfunction, including isosthenuria, decreased urine-concentrating ability, and excessive excretion of potassium and magnesium. In addition, he had hyperreninemia and hyperaldosteronism but no hypertension. The renal dysfunction was thought to have resulted from a primary defect in the thick ascending limb of the loop of Henle, mimicking Bartter syndrome. In contrast to previously described cases of cytochrome c oxidase deficiency with de Toni-Fanconi Debré syndrome, the patient had less intensive muscle abnormalities. A renal biopsy specimen showed ultrastructural changes in mitochondria that were similar to those seen in biopsy specimens of muscle. A large-scale deletion (8.8 kilobases) in mitochondrial DNA was found in biopsy specimens of muscle and kidney.

Identification and immunohistochemical localization of macrophage migration inhibitory factor in human kidney

Macrophage migration inhibitory factor (MIF) was the first lymphokine identified in activated T‐lymphocytes. MIF can induce proinflammatory cytokines, such as interleukin‐1 and tumor necrosis factor‐α. In this study, we identified MIF expression in a tissue specimen of a normal portion of a nephrectomized human kidney by reverse transcription‐polymerase chain reaction (RT‐PCR) and Western blot analysis. Furthermore, immunohistochemical study using an anti‐human MIF polyclonal antibody demonstrated that MIF was mostly present in the renal tubule epithelial cells and, to a lesser extent, in Bowmans capsular epithelial cells. We also carried out immunohistochemistry on cultured human renal proximal tubule epithelial cells, which showed that MIF was present in the cytoplasm of the epithelial cells. These results suggest the possibility that MIF takes part in the mechanism of inflammation and immunological events in the human kidney.

Glomerular Deposition of C4 Cleavage Fragment (C4d) and C4-Binding Protein in Idiopathic Membranous Glomerulonephritis

Renal biopsies from 12 patients with idiopathic membranous glomerulonephritis (IMGN) were investigated by immunofluorescence microscopy for the localization of C4d and C4-binding protein (C4bp). Although Clq and C4 deposits were found in only 2 of 12 cases (16%), C4d and C4bp deposits were identified in 11 cases (92%) in close association with IgG deposits in the glomeruli. The results suggest that complement activation through the classical pathway usually occurs in IMGN. The detection of C4d and C4bp in the glomeruli appears to be a sensitive indicator of the classical pathway activation in IMGN.

4q33–qter deletion and absorptive hypercalciuria: Report of two unrelated girls

We report on two unrelated girls with multiple malformations, each of whom had a der(4)t(4;?)(q33;?) chromosome--an unbalanced translocation chromosome with deletion of the 4q33-qter segment and addition of a segment of an unknown chromosome. One of the two girls had asymptomatic kidney stones. Both had excess urinary calcium excretion (0.53 and 0.84 mg/mg creatinine, respectively), exaggerated excretion on oral calcium load, and reduced but excessive excretion on restricted calcium intake. The urinary calcium excretion of their parents was normal. Both girls were thus diagnosed to have sporadic absorptive hypercalciuria. It was deduced that the 4q33-qter segment contains the putative gene for absorptive hypercalciuria.

Urinary Excretion of Terminal Complement Complexes in Glomerular Disease

To evaluate renal terminal complement activation in patients with glomerular diseases, we measured terminal complement complexes (TCCs) in plasma and urine with sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against a C9 neoepitope expressed on TCC and a polyclonal antihuman C7 antibody. TCCs were detectable in plasma but not in urine in most of normal controls. In plasma, TCC levels were elevated in 4 of 22 patients with lupus nephritis and in 6 of 12 with membranoproliferative glomerulonephritis. However all patients with IgA nephritis, focal glomerulosclerosis, idiopathic membranous nephritis and idiopathic minimal change nephrotic syndrome (MC) showed normal values. In urine, TCCs were detectable in almost all patients with heavy proteinuria (greater than or equal to 100 mg/ml) except MC. The TCCs present in urine were partially purified by gel filtration using Sepharose 6B and were found to contain C5, C6, C7, C8, C9 and S protein by ELISA. Although the molecular weight of TCC is similar to that of IgM, the fractional excretion rate of TCC was about 100 times higher than that of IgM. These results suggest that TCCs detectable in urine contain SC5b-9 complexes and are mostly of renal origin.

Hypercalciuria and nephrolithiasis in Wilson disease

nation with a cineloop technique allows the immediate judgement of the coronary vessels over a certain distance, whereas M-mode echocardiography provides a small section only. Irrespective of this, the M-mode-beam should cross the vessel in a perpendicular fashion in order to obtain reliable measurements. In our opinion, this may carry a risk of increased errors in distance measurements, especially for the right coronary artery which is difficult to visualize. Unfortunately, Muscumeci et al. do not report their experience with the right coronary artery. In summary, we would like to recommend the use of twodimensional echocardiography in combination with cineloop techniques for quick and reliable measurements of coronary arterial diameters.

Progressive Renal Failure despite Discontinuation of Mefenamic Acid

NSAID-induced Renal failure was excepted to be reversed with the discontinuation of mefenamic acid. However, the renal failure progressed. This progression may be due to the progression to extensive interstitial fibrosis

Acute Tubular Necrosis in LEC Rats with Hereditary Hepatic Failure — A New Animal Model of Hepatorenal Syndrome

It has been reported that LEC rats are a useful animal model for spontaneous fulminant hepatitis [1] and liver cell carcinoma [2]. At 16–20 weeks of age, 80%–90% of LEC rats spontaneously develop severe hepatic disease, but its etiopathogenesis has not yet been clarified. The clinical features of these LEC rats are marked jaundice, ascitis, subcutaneous bleeding, and oliguria, and their low urinary output suggests the presence of an accompanying renal lesion. In this paper, we present the laboratory data and histopathological findings in the liver and kidney of LEC rats — hepatocellular lipid degeneration and acute renal failure due to acute tubular necrosis — and suggest that LEC rats can serve as an animal model for human hepatorenal syndrome.

Current topics in childhood lupus nephritis

Lupus nephritis is a major predictor of the prognosis of systemic lupus erythematosus (SLE). The present paper discusses lupus nephritis from clinical and immunopathological points of view.