Nishio Honda

Renal involvement in mixed connective tissue disease. Report of 5 cases.

5 cases with the compatible serological criteria of mixed connective tissue disease described earlier are presented. In 1 of them with a moderate degree of proteinuria, the renal biopsy disclosed membranous nephritis. However, despite the absence of overt clinical renal disease in the other 4 cases, biopsies disclosed membranous nephritis in 1 and mild mesangial proliferative glomerulonephritis in the remaining 3 cases. In the follow-up of these 4 cases, 2 subsequently developed abnormal urinalysis. Electron microscopic examinations demonstrated electron-dense deposits in glomeruli, and 4 of these patients also had microtubular structures in the endothelial cytoplasm. Contrarily to the original concept, our findings suggest that mixed connective tissue disease also induces immune complex disease.

Erythropoietin production in patients with chronic renal failure

Studies were performed to reexamine the response of erythropoietin (Epo) production to acute hypoxic stimuli in patients with end-stage renal disease (ESRD). In the absence of acute bleeding or hypoxia, the serum Epo level in ESRD was similar to that of normal subjects despite severe anemia. In 11 dialysis patients with acute bleeding, the decrease in the Hb level from 8.9 to 5.8 g/dL provoked a significant increase in serum Epo up to 52.2 times the normal value. The increase in serum Epo was associated with a significant increase in corrected reticulocyte. Systemic hypoxemia (PaO2 < 65 mm Hg) in 8 dialysis patients provoked a significant elevation in the serum Epo level up to 24.6 times the normal level. There was an inverse relationship between serum Epo and arterial PaO2 (r = -0.715). The serum Epo level in these patients declined to or near the normal value after recovery from acute hypoxic stress. These data suggest that the ability of the Epo production is well preserved in ESRD, indicating that acute hypoxic stimuli provoke a significant increase in serum Epo.

Interstrain Differences in Murine Daunomycin-Induced Nephrosis

Examining 8 inbred murine strains [A/J, BALB/c, SM/J, C3H/J, SWR/J, C57BL/6J (B6), DBA-2, B10D2/old (B10D2/o)] for urinary albumin excretion after a single daunomycin (DM) injection (20 mg/kg), we found strain specificity in susceptibility to DM nephrosis. This specificity did not relate to the serum disappearance rate of this drug. A/J and BALB/c were highly susceptible to the nephrosis while C57BL/6J, DBA-2 and B10D2/o were completely resistant to it. Chronological observation revealed that A/J mice had significant proteinuria at 2 weeks after injection, and it persisted for the remaining 4 weeks of this experiment, while C57BL/6J showed no increase over the experimental period. Using segregants obtained from an A/J and B6 backcross, it has been shown that susceptibility is inherited as an autosomal recessive trait and involves approximately three genes. Neither a C5 deficiency, H-2 type nor coat color gene (c-locus) was related to this susceptibility. This strain difference in nephrotoxicity would be a promising way to investigate its subcellular mechanism.

Ulcerative colitis complicated by idiopathic central serous chorioretinopathy with bullous retinal detachment

SummaryA 44-year-old woman, hospitalized with severe diarrhea due to ulcerative colitis, was found to have a rare ocular complication, idiopathic central serous chorioretinopathy with bullous retinal detachment. The ocular symptom started with the flare-up of the ulcerative colitis. Steroid therapy was not effective on the ocular disorder, while her ulcerative colitis became dormant. Relationship between the two disorders is discussed.

Suppression of Proteinuria by Dipyridamole in Rats with Aminonucleoside Nephropathy

Nephrosis was induced by single injections of puromycin of aminonucleoside to rats which were divided into two groups; the experimental group receiving dipyridamole in addition to aminonucleoside and the control group receiving aminonucleoside alone. 24-hour urinary albumin increased in rats of both groups after aminonucleoside injections. However, the experimental rats excreted significantly less albumin than controls. On the contrary, there was no significant difference in urinary IgG between the two groups. The stainings of anionic sites of glomerular basement membrane using ruthenium red revealed the reduction of anionic charge in the glomerular basement membrane of both groups, but the decrease of anionic charge was suppressed in lamina rara interna of the experimental rats. Considering the role of charge barrier in the glomerular basement membrane, it is concluded that the maintenance of anionic charge in experimental rats is causally related to the suppressed excretion of albumin.

Renal Hemodynamics in Oliguric and Nonoliguric Acute Renal Failure of Rabbits

The role of renal hemodynamic alterations in the curtailment of renal functions was studied in uranyl acetate-induced oliguric (ORF) and nonoliguric (NORF) renal failures of rabbits. 5 days after drug injection, renal functional and morphological changes were most remarkable. A depression of Cin and elevation of serum creatinine concentration were more marked in ORF than in NORF. Renal blood flow was high as compared to controls. Cortical blood flow redistributed to the inner cortex. There was no significant difference in renal blood flow or cortical flow distribution between renal failure models. The findings suggest the minor roles of renal blood flow and cortical flow distribution in maintaining renal failure in these nephrotoxic models. Prominent tubular necrosis was found in ORF but not in NORF. Arterial inulin concentration during retrograde ureteral infusion of 14C-inulin solution was significantly high in ORF as compared to controls and NORF. However, this inulin leakage was too small to explain severely curtailed inulin clearance.

Glomerular Alterations in Experimental Oliguric and Nonoliguric Acute Renal Failure

Studies were performed in oliguric and nonoliguric forms of uranyl acetate (UA)-induced and ischemic acute renal failure (ARF) to examine whether a reduction in GFR is correlated with glomerular morphologic alterations. UA-induced nonoliguric and oliguric ARF were induced in rabbits by i.v. injections of 0.9 and 2 mg/kg, respectively. A 60-min renal artery clamping produced nonoliguric ARF in previously uninephrectomized rats, but oliguric ARF in the clamped kidneys of sham-nephrectomized animals. A decline in the whole-kidney CIn rate was more marked in oliguric ARF kidneys of both models than in nonoliguric ARF kidneys. Also, tubular damage was more pronounced in oliguric kidneys when compared with nonoliguric kidneys. Scanning electron microscopic observations revealed glomerular alterations in oliguric and nonoliguric kidneys in both models, evidenced by a flattening and spreading of podocyte cell bodies associated with loss of epithelial foot processes and a reduction in the density and diameter of endothelial fenestrae. There was no significant difference in these glomerular changes between oliguric and nonoliguric kidneys. The findings suggest that less reduction in the whole-kidney GFR in nonoliguric ARF kidneys is ascribed largely to less pronounced tubular damage rather than to less severe glomerular morphologic alterations.

Intraglomerular fibronectin in rat experimental glomerulonephritis.

SummaryTo clarify the mechanisms of glomerular pericapillary fibronectin deposition in human membranous nephropathy and mesangial proliferative glomerulonephritis, intraglomerular fibronectin distribution was examined by light and electron microscopy using the experimental rat models of Heymann and nephrotoxic serum nephritis. As previously demonstrated by immunofluorescence microscopy (Pettersson and Colvin 1978; Ikeya et al. 1985, 1986), fibronectin was distributed in the mesangial areas and occasionally on percicapillary walls of normal glomeruli, while in nephrotoxic serum nephritis and Heymann nephritis, fibronectin was diffusely located along glomerular capillary walls as well as in the mesangium. By immunoelectron microscopy using the immunogold technique, fibronectin was also noted in the mesangial areas and the lamina densa of the glomerular basement membrane (GBM) in normal glomeruli. In nephrotoxic serum nephritis, fibronectin was seen around mesangial cells situated between endothelial cells and the GBM, suggesting that pericapillary fibronectin in nephrotoxic serum nephritis reflects mesangial extension. However, in Heymann nephritis, it was found uniformly in the lamina rara interna, lamina densa and lamina rara externa of the GBM, indicating no specific relation to glomerular cells. When sections of normal and both experimental nephritis kidneys were incubated with fluorescein isothiocyanate conjugated with rat plasma fibronectin, a linear pattern of fluorescein staining along the glomerular capillary walls was observed in Heymann nephritis but not in normal or nephrotoxic serum nephritic rats. The GBM in Heymann nephritis would thus appear to have an affinity for plasma fibronectin. Based on the above findings, fibronectin in the GBM of rats with Heymann nephritis may reasonably be concluded to originate from the plasma.

Incomplete tubular duplication of esophagus with heterotopic gastric mucosa

Esophageal diverticula are classified as congenital or acquired. In congenital diverticula, a few cases that are regarded as the result of incomplete duplication of the esophagus have been reported (1, 2). The epithelium of an esophageal diverticulum is usually stratified, but in duplication it is not infrequently ciliated columnar epithelium, similar to bronchial epithelium (3). We present a case that we consider to be a duplication of the esophagus, the mucosa of which was fully lined with heterotopic gastric mucosa comprising both pyloric and fundic glands.

Effects of Desoxycorticosterone Acetate (DOCA) Plus Saline Drinking on Gentamicin-Mediated Nephropathy in Rats

Studies were performed to examine the effect of desoxycorticosterone acetate (DOCA) treatment plus isotonic saline drinking on gentamicin (GM)-mediated nephropathy in rats. GM, 40 mg/kg/day, was subcutaneously injected for 13 days following a 5-week treatment with water drinking or DOCA (10 mg/kg/week) plus saline drinking. Twenty-four hours after the last injection of GM, renal blood flow (RBF) and Cin decreased to approximately 69% and 52% of the control values in water-drinking GM-treated rats, respectively, but was well maintained in DOCA plus saline-drinking GM-treated animals. There was no significant difference in morphologic tubular injury or the renal cortical GM content between GM-treated groups. Saline drinking alone (1% saline, 5 weeks) lessened neither GM-induced reduction in GFR nor tubular damage. Body weight loss occurred following GM injection in the water-drinking group but not in the DOCA plus saline-drinking and saline-drinking-alone groups. DOCA plus saline drinking significantly suppressed the plasma renin activity (PRA) but saline drinking alone did not. A significant inverse correlation was found between PRA and Cin in water-drinking GM-treated and untreated rats. The data suggest that the beneficial effect of DOCA plus saline drinking is associated with renin-angiotensin suppression rather than with the renal GM content or well-maintained hydration.