Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup).

A 33-year-old Japanese man was admitted for possible kidney disease because of massive proteinuria. Laboratory findings were characterized by marked urinary protein of 4.7 g/day and high-serum triglyceride levels of 266 mg/dL. Renal biopsy revealed segmental proliferation in the mesangium and lipoprotein thrombi in the glomerular capillary. These results suggested that the diagnosis was lipoprotein glomerulopathy (LPG), although serum apolipoprotein E (apo E) levels were within normal ranges. The APOE phenotype was identified as E2/3 by isoelectric focusing polyacrylamide gel electrophoresis. Direct DNA sequencing analyses for apo E identified a duplication of amino acid 151, aspartic acid, and the gene mutation was named APOE Kanto. APOE gene mutations due to amino acid duplication are rare, and this is the first report showing that amino acid duplication among apo E gene mutations is involved in LPG. It is also noteworthy that the patient developed end-stage kidney disease after over than 10 years despite fibrate treatment.

Aldosterone Response in Severe Hypokalemia and Volume Depletion: A Case Report and Review of the Recent Research.

We report a case of severe hypokalemia and volume depletion complicated by chronic watery diarrhea resulting from chronic alcoholism in a 57-year-old man. Prompt replacement of normal saline with potassium chloride and cessation of alcohol intake resulted in a favorable outcome. We discuss the pathophysiology of the case, emphasizing the response of aldosterone in both hypokalemia and volume depletion, and provide a review of recent research.

Single low-dose rituximab for the treatment of steroid-resistant nephrotic syndrome with acute kidney injury.

The efficacy of rituximab for kidney disease, such as frequent relapsing nephrotic syndrome, has been reported recently. Herein, we report a case of a patient with acute kidney injury that was steroid-resistant nephrotic syndrome who responded to a single administration of low-dose rituximab. An 86-year-old Japanese woman with hypertension presented with severe peripheral edema within several days after onset. Due to the patient's age, renal biopsy was not performed, nephrotic syndrome was diagnosed and prednisolone was administered at 40 mg/day on the day after admission. However, anuria developed and hemodialysis was inevitably initiated on the 5th hospital day. The renal function did not recover, and the general condition gradually became aggravated. On the 50th hospital day, 100 mg rituximab was administered, which led to immediate depletion of CD20-positive cells. The urine volume gradually increased from 2-3 weeks after the rituximab administration, and the renal function recovered slightly. After 5 weeks, it became possible to wean the patient from dialysis, which had been applied for 3 months. Rituximab might be an option for the treatment of acute kidney injury due to steroid-resistant nephrotic syndrome.

Possibility of lanthanum absorption in the stomach.

Lanthanum carbonate (LC) is an orally administered phosphate binder. Its absorption is generally thought to be minimal. We report here the case of an 81-year-old woman who underwent subtotal gastrectomy for gastric cancer after receiving hemodialysis for 1 year and taking LC for 7 months. Lanthanum phosphate compounds were found histologically in the gastric mucosa and a regional lymph node and confirmed by scanning and transmission electron microscopy-energy-dispersive X-ray spectroscopy. These findings suggest that lanthanum is absorbed in the stomach and transported via lymph flow. This observation could prove helpful in future investigation of lanthanum disposition.

Correction of hyperphosphatemia suppresses cardiac remodeling in uremic rats.

BACKGROUND: Hyperphosphatemia is associated with cardiovascular disease in patients with chronic kidney disease. To examine the effects of correction of hyperphosphatemia, we investigated the association between phosphate metabolism and cardiac remodeling in uremic rats. METHODS: Four groups were studied for 8 weeks: (1) control (sham), (2) 5/6 nephrectomized (Nx) rats fed a normal phosphate regular diet (Nx + NP), (3) Nx rats fed a high phosphate (1.2 %) diet (Nx + HP), and (4) Nx rats fed a high phosphate diet containing 2 % lanthanum carbonate (Nx + HP + La). The relationship between phosphate metabolism and cardiac remodeling was analyzed. RESULTS: Nx + HP rats showed a significant increase in serum phosphate and PTH compared with Nx + NP rats, while Nx + HP + La rats showed slight decreases in these levels. Both Nx + HP and Nx + HP + La rats showed a significant increase in fibroblast growth factor-23 (FGF23) compared with Nx + NP rats. Urinary phosphate excretion showed a similar trend to that of FGF23. Nx + HP rats showed a significant increase in LV weight and matrix deposition compared with Nx + NP rats, and this increase was also significantly suppressed in Nx + HP + La rats. Serum phosphate levels and PTH were significantly correlated with LV weight and matrix deposition, but FGF23 levels did not show the correlation. FGF23 had a high correlation with urinary phosphate excretion. CONCLUSIONS: These results suggest that correction of hyperphosphatemia by lanthanum carbonate could suppress cardiac remodeling independently of changes in FGF23.

Recurrent solitary fibrous tumor of the pleura with malignant transformation and non-islet cell tumor-induced hypoglycemia due to paraneoplastic overexpression and secretion of high-molecular-weight insulin-like growth factor II.

A 41-year-old man was diagnosed with a solitary fibrous tumor (SFT) of the pleura in the posterior mediastinum. Despite two surgeries for excision, the SFT recurred and progressed with direct invasion of the chest wall and bone metastases. He was hospitalized because of cerebral infarction and presented with recurrent severe hypoglycemia fourteen years later. High-molecular-weight (HMW) insulin-like growth factor II (IGF-II) was identified in the serum and tumor using Western blotting and immunohistochemistry. These findings suggested that the cause of the recurrent severe hypoglycemia was SFT production of HMW IGF-II, a mediator of non-islet cell tumor-induced hypoglycemia (NICTH).

Biocompatible characteristics of high-performance membranes.

Interactions of blood with hemodialysis membranes induce activation of blood factors that may cause adverse clinical outcomes in hemodialysis patients. The biocompatibility of a hemodialysis membrane is determined by the change in blood factors induced by blood interactions, and it is important that these interactions are mild and well tolerated by dialysis patients. Bioincompatible membranes that activate the complement system and accelerate cytokine production by monocytes may lead to chronic inflammation, dialysis-related amyloidosis, malnutrition, and atherosclerosis. Contact activation by a bioincompatible membrane may also induce an anaphylactoid reaction via bradykinin production. Thus, high-performance membranes should have both the high permeability to uremic substances shown by the glomerular basement membrane and the good biocompatibility of glomerular endothelial cells.

Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency.

The reduced expression level of the calcium-sensing receptor (CaR) is attributed to the hyposensitivity of parathyroid cells to extracellular calcium concentration [Ca2+]o, which plays a crucial role in the pathogenesis of secondary hyperparathyroidism (SHPT) in patients and rats with chronic renal insufficiency (CRI). Calcimimetic compounds have been demonstrated to improve the decreased sensitivity of CaR to extracellular calcium concentration and to suppress both parathyroid hormone (PTH) oversecretion and parathyroid cell proliferation. However, the effect of calcimimetics on the reduced CaR expression level in parathyroid cells in CRI remains unclarified. The aim of this investigation was to examine the effect of the calcimimetic compound NSP R-568 (R-568) on the CaR expression in the parathyroid cells of rats with experimental CRI. Subtotally nephrectomized rats were fed a high-phosphorus diet for 8 (n = 12; Nx-8 group) or 9 wk (n = 11; Nx-9 group) to induce severe SHPT. Another group of uremic rats were fed a high-phosphorus diet for 8 wk and then orally administered R-568 (100 micromol/kg body wt) once a day for 7 d (n = 11; Nx+R-568 group). Sham-operated rats that were fed a standard diet for 9 wk were used as controls (n = 8). R-568 treatment induced a significant reduction in plasma PTH level with significant decrease in serum calcium and without change in serum phosphorus concentration. Serum 1,25(OH)2D3 level was not affected by R-568 administration. CaR mRNA and protein levels in the Nx-8 and Nx-9 groups significantly decreased compared with those in the controls; however, no significant difference in these parameters was observed between the Nx-8 and Nx-9 groups. In the Nx+R-568 group, CaR mRNA and protein levels significantly increased compared with those in either the Nx-8 or Nx-9 group. R-568 was effective in reducing the number of proliferating cell nuclear antigen-positive cells along with parathyroid gland growth suppression in the Nx+R-568 group compared with that in the Nx-9 group. The results suggest that the calcimimetic compound R-568 upregulates decreased CaR expression, and the upregulation possibly has an enhancement effect on PTH secretion and parathyroid cell hyperplasia through the improved sensitivity of CaR to [Ca2+]o.

[Minimal change nephrotic syndrome].

In minimal change nephrotic syndrome (MCNS), selective proteinuria is associated with structural alterations of the glomerular epithelial cells, such as effacement of the foot process. Although the pathogenesis of MCNS has not been completely clarified, clinical and experimental observations suggest that it results from T cell dysfunction in the pathogenesis. Recently, it has been proposed that the occurrence of MCNS has been associated with type 2 Th (Th2) lymphocyte-dependent conditions and some vascular permeability factors, which are induced by T cell disorder. In general, MCNS has the good long-term outcome with sustained remission and preserved renal function, because almost cases are responsible for the treatment. However, some patients show frequent relapses or resistance to this treatment and need large doses of immunosuppressive agents for a long time. Therefore, we should be care for the complications associated with prolonged these therapies.

Increased 5-lipoxygenase activating protein in immune-mediated experimental nephritis.

BACKGROUND: The binding of 5-lipoxygenase (5-LO) to 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes from arachidonic acid. METHODS: We investigated the localization of FLAP in a rat model of accelerated anti-glomerular basement membrane nephritis and protein expression in cultured rat glomerular endothelial cells. RESULTS: As expected, 5-LO staining was intense and localized exclusively to perinuclear region and inside the nucleus of leukocytes and macrophages. In these cells, FLAP immunoreactivity co-localized with that of 5-LO, and was restricted to nuclear envelope. Surprisingly, intense nuclear and cytoplasmic staining for FLAP was also observed in glomerular endothelial cells in early experimental glomerulonephritis. Although 5-LO and FLAP mRNA were detected in cultured rat glomerular endothelial cells by RT-PCR, Western blot revealed only FLAP and no 5-LO protein. FLAP protein was regulated in glomerular endothelial cells by the proinflammatory cytokine, interferon-gamma, in a dose-dependent manner. CONCLUSION: The unexpected discovery of FLAP in glomerular endothelial cells in this model of glomerulonephritis, coupled with our demonstration that oral FLAP antagonist therapy reduces proteinuria in human glomerulonephritis and animal models of diabetes, provides further impetus to examine the role of this pro-inflammatory protein in glomerular immune injury.