Takatoshi Matsuo

Effect of 22-oxacalcitriol on bone histology of hemodialyzed patients with severe secondary hyperparathyroidism

To examine the effectiveness of 22-oxacalcitriol (OCT) injection on the improvement of severe osteitis fibrosa, we studied 10 hemodialyzed patients (age, 59 +/- 12 years). The initial OCT dose was 5 microg and was administered three times weekly at the end of each hemodialysis session. OCT doses (1, 3, 5, 10, 15, and 20 microg) were changed in subsequent weeks to maintain serum calcium levels at less than 11.5 mg/dL. Administration of OCT significantly suppressed serum intact parathyroid hormone (PTH) from an initial level of 1,193 +/- 584 to 775 +/- 552 pg/mL in the 24th week (n = 10). OCT increased PTH levels again to 857 +/- 635 pg/mL in the 48th week (n = 7). Among the 10 patients, 5 patients (high responders) showed more than a 50% suppression of serum intact PTH levels at the end of the study. The rest of the patients had hypercalcemia and did not receive increased OCT doses (low responders). At the start of the treatment, the only difference between high and low responders was serum calcium level. Serum calcium levels (adjusted for serum albumin level) increased from 9.7 +/- 0.7 mg/dL (n = 10) at the beginning to 10.5 +/- 0.6 mg/dL (n = 10) in the 24th week and to 11. 1 +/- 0.7 mg/dL (n = 7) in the 48th week. Six patients (1 to 6) agreed to undergo a second bone biopsy in the 24th week of OCT administration. In bone histomorphometric measurements, OCT significantly changed bone marrow fibrosis, mineralization (labeled mineralizing surface and bone formation rate), and osteoid formation (osteoid volume and thickness). In conclusion, intravenous OCT effectively suppressed PTH secretion and improved the bone histological characteristics of severe osteitis fibrosa, especially in patients with initial serum calcium levels less than 10 mg/dL. With concerns about OCT causing adynamic bone, additional bone histological data are needed to ensure the long-term safety of OCT.

Acute Respiratory Failure due to ‘Pulmonary Calciphylaxis’ in a Maintenance Haemodialysis Patient

Calciphylaxis is a rapidly developing, fatal process of vascular calcium deposition with prominent cutaneous manifestation. We treated a long-term haemodialysis patient who developed an analogous disorder limited to the lungs. A 57-year-old man was admitted for initiation of peritoneal dialysis because limited cardiac reserve precluded further haemodialysis. He was treated successfully for pneumonia until hypoxia and progressive hypercalcaemia developed. 99mTc-methylene disphosphonate scintigraphy showed diffusely increased pulmonary uptake. Death supervened despite aggressive and successful treatment of hypercalcaemia. Autopsy studies included immunohistochemistry and morphometric studies of bone. Alveolar capillary walls showed diffuse calcium deposition. Both gross and microscopical findings differed from those of typical metastatic calcification in dialysis patients. Immunoreactivity for parathyroid hormone-related protein was present in the lesions. Bone histomorphometry indicated mild osteitis fibrosa. Pneumonia is believed to have caused local synthesis of parathyroid hormone-related protein that, along with high calcium × phosphorus product, contributed to calcium deposition. By analogy with the cutaneous process we termed the deposition ‘pulmonary calciphylaxis’.

Effective Antibiotic Treatment of Methicillin-Resistant Staphylococcus aureus-Associated Glomerulonephritis

Background: A new type of glomerulonephritis following a methicillin-resistant Staphylococcus aureus (MRSA) infection has been reported. The purpose of this study is to elucidate the clinicopathological features and the responsiveness to treatment of the disease. Methods: We studied the treatment of 8 patients with glomerulonephritis related to MRSA infection. We observed the eight cases and analyzed clinical features, laboratory findings and histopathological data. Results: On admission, all patients had no renal abnormalities. One to four months after suffering from MRSA infection, severe proteinuria and hematuria developed. Renal biopsy specimens revealed moderate to severe mesangial proliferative glomerulonephritis with various degrees of crescent formation. Immunofluorescence studies showed IgA and C3. Antibiotic therapy was performed in six cases, resulting in successfully reducing the proteinuria in parallel with the decreased activity of MRSA infection in five cases. The other 2 cases received corticosteroid treatment after complete cessation of MRSA infection, but they had a relapse of MRSA infection and later died from sepsis. Conclusions: These results suggested that MRSA-associated glomerulonephritis might respond to antibiotic treatment in most cases. This also indicated that special care must be taken in the application of steroid therapy for the glomerulonephritis with crescents, even though the MRSA infection has gone into an inactive state.

A nephrotic case of vesicoureteral reflux representing focal segmental glomerulosclerosis associated with podocytic infolding lesions

The case was a 54-year-old woman who had suffered from occasional incontinence of urine after a craniotomy for subarachnoid hemorrhage in 1991. In June 1998 she was admitted for nephrotic syndrome without hematuria. Intravenous pyelography and voiding cystourethrography revealed bilateral hydronephrosis, atonic bladder, and vesicoureteral reflux (VUR). Renal biopsy demonstrated the presence of focal segmental glomerulosclerosis with cellular lesions. However, periodic-acid methenamine silver (PAM) staining revealed bubbling and spike appearance in the diffuse peripheral loops, although immunofluorescence microscopy showed negative findings in the glomeruli. Electron microscopy revealed diffuse thickening of the glomerular basement membrane (GBM) accompanying diffuse podocytic infolding lesions into the GBM and numerous spherical microstructures in the GBM. No findings of dense deposits were observed in the GBM and mesangium. Her urinary protein excretion decreased and renal function improved after placement of an urethral catheter for one year. A second renal biopsy revealed a remarkable decrease in podocytic infolding lesions, although microstructures in the GBM remained. Although mechanisms of the occurrence of these peculiar podocytic infolding lesions are unclear, it is speculated that podocyte damage due to hydronephrosis may have caused the lesions.

Crescentic glomerulonephritis with antimyeloperoxidase antibodies developing during the course of IgA nephropathy in a patient with rheumatoid arthritis

Abstract Glomerulonephritis, such as membranous nephropathy, IgA nephropathy, and p-antineutrophil cytoplasmic autoantibody (ANCA)-related crescentic glomerulonephritis, has been shown to occur in rheumatoid arthritis (RA). However, the occurrence of two types of glomerulonephritis in a patient with RA is rarely observed. Here, we describe a patient with RA who developed crescentic glomerulonephritis with antimyeloperoxidase (MPO) antibodies during the course of IgA nephropathy. This case indicates that crescentic glomerulonephritis and IgA nephropathy may occur together in association with p-ANCA in RA.