Tadashi Yasuda

Collagenofibrotic glomerulopathy: A systemic disease

Collagenofibrotic glomerulopathy is a recently discovered entity that is characterized by massive accumulation of spiraled and frayed collagen fibrils in mesangial and subendothelial areas, and elevated serum levels of procollagen III peptide. We report the autopsy of a patient who received continuous ambulatory peritoneal dialysis (CAPD) therapy for 7 years. Autopsy disclosed that massive accumulation of peculiar collagen fibers was found not only in the kidney, but also in many organs including spleen, liver, myocardium, and thyroid gland. Although the possibility remains that CAPD for 7 years might change or aggravate the deposition of abnormal collagen, the current case suggests a possibility that collagenofibrotic glomerulopathy is a systemic disorder with abnormal metabolism of type III collagen.

Sclerodermatous Renal Crisis in a Patient With Mixed Connective Tissue Disease

We report a patient with mixed connective tissue disease who developed accelerated hypertension, acute renal insufficiency, and microangiopathic hemolytic anemia. A renal biopsy specimen showed marked vascular changes in small arteries consisting of laminated endothelial cell proliferation and luminal thrombosis, which were similar to those of scleroderma renal crisis. This patient was successfully treated with an angiotensin-converting enzyme inhibitor as well as analogues of prostaglandin E1 and prostaglandin I2. In patients with mixed connective tissue disease, a fatal complication like scleroderma renal crisis should be considered when the blood pressure rapidly increases. The combined administration of angiotensin-converting enzyme inhibitors and analogues of prostaglandin E1 and prostaglandin I2 may be an effective treatment for this complication.

Effects of tumour necrosis factor α and interleukin 1 β on the proliferation of cultured glomerular epithelial cells

Rat glomerular epithelial cells were cultured with human monocyte supernatant or with recombinant cytokines. A primary glomerular culture and a glomerular epithelial cell culture were made; supernatant from monocyte cultures derived from healthy humans, and recombinant tumour necrosis factor α (TNF α) or recombinant interleukin 1 β (IL-1 β) were added. Cell proliferation rates were assayed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. In serum-free media, consistent proliferation of glomerular epithelial cells (GEC) was observed throughout the 3 week culture period. Significant growth-stimulatory effects were induced by lipopolysaccharide-treated monocyte conditioned medium and by 1–50 ng/ml of TNF α, growth being up to 400% more than in the control culture. The effect of TNF α depended mainly on its interaction with epidermal growth factor (EGF). In contrast to TNF α, IL-1 β inhibited GEC proliferation; this was due to the early appearance and proliferation of mesangial cells, despite the culture being serum-free. This study showed that activated monocytes secrete growth factors for GEC in vitro, and that interaction between both TNF α and IL-1 β and between TNF α and EGF can modulate GEC proliferation. These findings suggest that, under pathological conditions, monocytes or macrophages affect GEC proliferation, probably being involved in crescent formation.

Mesangiolytic glomerulonephritis associated with Takatsuki's syndrome: An analysis of five renal biopsy specimens

Renal biopsy specimens from five patients with Takatsukis syndrome were studied. Proteinuria and hematuria were modestly positive in four cases and three cases, respectively. One case demonstrated early azotemia, while four cases revealed normal serum creatinine levels. All cases displayed glomerular enlargement and lobulation, mesangial cell proliferation, and double contour structure, simulating membranoproliferative glomerulonephritis. It is noteworthy that mesangial loosening was also detected in the renal biopsy specimens of this study. This change was present diffuse-globally in the well-developed cases and focal-globally or segmentally in the developing cases. In addition, various morphologic expressions were observed, ie, microaneurysms congested with RBCs, tentatively termed mesangial hyaline thrombi, nodule-like lesions, and tiny to small-sized mesangiolytic lesions. Since all these features could be explained by low-grade mesangiolysis, the renal alteration associated with this syndrome was termed mesangiolytic glomerulonephritis. Humoral factor(s) also toxic to the mesangium were implicated.

Expression of 90-kDa Heat Shock Protein Within Regenerative Tubular Cells in a Patient with Acute Oliguric Renal Failure Due to Malignant Hypertension

A 29-year-old man developed acute oliguric renal failure with severe hypertension and microangiopathy. He was treated with hemodialysis and anti-hypertensive drugs, but oliguria was prolonged. A renal biopsy was performed on the 29th hospital day. Small arteries and arterioles were characterized by marked intimal thickening, and most of the glomeruli showed ischemic changes. Although there was extensive tubular loss and atrophy, regenerative changes were occasionally observed in some tubules, in which 90-kDa heat-shock protein was induced. He was diagnosed as having malignant nephrosclerosis, and was treated with a prostaglandin I2 analog, in addition to anti-hypertensive drugs. Thereafter, his renal function recovered gradually, and hemodialysis was discontinued on the 49th hospital day. Functional recovery lasts more than five years. We suggest that the expression of HSP90 in regenerative tubular cells is a useful histological indicator for predicting recovery from acute oliguric renal failure due to malignant hypertension.

Pan-nephritis (glomerulonephritis, arteriolitis, and tubulointerstitial nephritis) associated with predominant mesangial C1q deposition and hypocomplementemia: a variant type of C1q nephropathy?

A 35-year-old man showed acute nephritic syndrome manifested as proteinuria, hematuria, and hypocomplementemia after upper respiratory infection. A renal biopsy showed mild to moderate mesangial proliferative glomerulonephritis with an accumulation of mononuclear cells in the capillary loop and with the deposition of C1q (graded as 3+), immunoglobulin (Ig) G, C3 (2+), IgA, IgM, and fibrinogen (weak to 1+), and mononuclear cell infiltration of the glomerular hilus, arterioles, and proximal tubules, which was a peculiar form of renal lesion. The mesangial deposition of C1q has been well documented in lupus nephritis, membranoproliferative glomerulonephritis, and endocapillary glomerulonephritis. The clinical signs and laboratory data in our patient ruled out these diseases. Although an immunofluorescence study showed these similarities to Clq nephropathy, the histopathological features of the peculiar arteriolitis and tubulointerstitial nephritis and laboratory findings of hypocomplementemia, as well as the good response to oral steroid therapy, differed from typical C1q nephropathy. The current patient appears to be a very rare phenotype of nephritis, being the only 1 case in almost 2,800 renal biopsies.

Case report : nephrotic syndrome associated with a total hydatidiform mole

The authors describe a 51-year-old Japanese woman who developed nephrotic syndrome in association with a total hydatidiform mole. The nephrotic syndrome remitted completely following hysterectomy. A renal biopsy performed before the operation showed diffuse mesangial cell proliferation of a moderate degree, and thickened capillary walls with focal and segmental subendothelial deposits, as well as circumferential mesangial interposition. Occasional foci of the mesangiolysis were also observed. Immunofluorescence microscopy revealed granular staining of IgM along the glomerular capillary walls in a fringe pattern. A review of the literature revealed that this patient appears to be the first case of nephrotic syndrome associated with a total mole, although there have been two cases of nephrotic syndrome due to preeclamptic nephropathy associated with a partial or transitional mole.

A combination of livedo racemosa, occlusion of cerebral blood vessels, and nephropathy: Kidney involvement in sneddon's syndrome

A 59-year-old woman with retinal vein thrombosis and livedo racemosa had hematuria (4+) and proteinuria (1.7 g/day). Skin biopsy showed swollen blood vessel walls with infiltration of mononuclear cells, which were compatible with livedo racemosa (vasculitis). Magnetic resonance imaging (MRI) of the brain demonstrated multiple lacunar infarctions in the basal ganglia and white matter. Renal biopsy showed that small round cells had infiltrated into the interstitium, and a reticular structure was observed in the glomerular hilus. An amorphous substance composed of a single cell was present in the glomerular capillary lumen. Immunofluorescent study demonstrated the deposition of only IgA, in a segmental pattern differing from the diffuse global mesangial pattern seen in IgA nephropathy. After combined therapy including 40 mg/day prednisolone, 50 mg/day cyclophosphamide, antiplatelet drug, and anticoagulant was started, proteinuria and hematuria improved to 0.5 g/day and 2+, respectively, at the time of discharge. Sneddons syndrome is a rare entity characterized by livedo racemosa and cerebrovascular lesions. In our patient with livedo racemosa, occlusion of cerebral blood vessels, and nephropathy with segmental immunoglobulin A (IgA) deposition, no antiphospholipid antibodies were detected on routine examination. Dermatologists, neurologists, psychiatrists, and nephrologists should be aware of the existence of Sneddons syndrome with nephropathy (LI-O-N).

Significance of fibrils in the formation of the Kimmelstiel-Wilson nodule

The pathogenesis of the nodular lesion in diabetic glomerulosclerosis is described in association with fibrils. Thirteen diabetic patients with glomerular nodular lesions and 9 diabetics without the nodules were examined by electron microscopy using periodic acid-thio-carbohydrazide-silver proteinate staining. In cases of nodular glomerulosclerosis, abundant fibrillar structures mixed with electron-dense material were detected within the nodule and the mesangial matrix. They were also occasionally observed along the subendothelial space of the glomerular capillary walls. On the cross-section, these fibrils, including the lucent periphery, were 34 nm wide. Immunohistologically, collagen V and collagen VI were detected in nodular lesions. In contrast, in cases of the diffuse type of glomerulosclerosis, the widened mesangium was composed of dense material, which resembled the original mesangial matrix. The above fibrils were not detected in the mesangium. These findings suggest that the accumulation of the peculiar fibrils in the glomerular mesangium is a major pathogenic factor in the formation of Kimmelstiel-Wilson nodules.

Kappa Light Chain Nodular Glomerulosclerosis with Conspicuous Crescent Formation and Tubulointerstitial Injury

We describe a 39‐year‐old man who developed kappa light chain nodular glomerulosclerosis with superimposed conspicuous crescent formation and extensive tubulointerstitial injury. The clinical picture was characterized by nephrotic syndrome and rapidly progressive glomerulonephritis. Incessantly progressive loss of renal function culminated in irreversible renal failure 7 weeks after initial manifestation of renal insufficiency. The patient has since been maintained on thrice weekly hemodialysis with chemotherapy for five years. At the time of pathologic diagnosis by renal biopsy, there was no evidence of multiple myeloma, and no serum M‐component or Bence‐Jones proteinuria was detected. An initial bone marrow aspirate revealed the presence of 0.6% atypical lymphocytes as the sole abnormality, although these were later identified as atypical plasma cells. These cells had also infiltrated the renal interstitium. Crescentic kappa light chain nodular glomerulosclerosis lacking evidence of plasma cell dyscrasia should be included in the differential diagnosis of rapidly progressive glomerulonephritis.