Renal redox dysregulation in AKI: application for oxidative stress marker of AKI.

Oxidative stress is a major determinant of acute kidney injury (AKI); however, the effects of an AKI on renal redox system are unclear, and few existing AKI markers are suitable for evaluating oxidative stress. We measured urinary levels of the redox-regulatory protein thioredoxin 1 (TRX1) in patients with various kinds of kidney disease and in mice with renal ischemia-reperfusion injury. Urinary TRX1 levels were markedly higher in patients with AKI than in those with chronic kidney disease or in healthy subjects. In a receiver operating characteristic curve analysis to differentiate between AKI and other renal diseases, the area under the curve for urinary TRX1 was 0.94 (95% confidence interval, 0.90-0.98), and the sensitivity and specificity were 0.88 and 0.88, respectively, at the optimal cutoff value of 43.0 µg/g creatinine. Immunostaining revealed TRX1 to be diffusely distributed in the tubules of normal kidneys, but to be shifted to the brush borders or urinary lumen in injured tubules in both mice and humans with AKI. Urinary TRX1 in AKI was predominantly in the oxidized form. In cultured human proximal tubular epithelial cells, hydrogen peroxide specifically and dose dependently increased TRX1 levels in the culture supernatant, while reducing intracellular levels. These findings suggest that urinary TRX1 is an oxidative stress-specific biomarker useful for distinguishing AKI from chronic kidney disease and healthy kidneys.

Protective effects of Shichimotsu-koka-To on irreversible Thy-1 nephritis.

Oxidative stress and peritubular capillary (PTC) injury are involved in the progression of chronic kidney disease (CKD). We investigated protective effects of Shichimotsu-koka-To (SKT), a Japanese traditional Kampo prescription, against nephrosclerosis and hypertension on a CKD model due to irreversible nephritis. Six-week-old male Wistar rats were subjected to uninephrectomy, and to injection of rabbit anti-thymocyte serum. SKT treatment was continued for 15 weeks, blood pressure was measured, and then renal specimens were collected. PTC networks were detected by immunostaining for CD-31. And superoxide dismutase (SOD)-like activity in the tissue was evaluated. Blood pressure in the SKT group, as well as sham group, was significantly lower than with the vehicle. SKT markedly ameliorated renal function, which was evaluated with urea nitrogen clearance. Compared with the vehicle, SKT treatment lowered both the glomerular enlargement and hyper-cellularity by 80%, and decreased the extracellular matrix area by 75%. SKT treatment also suppressed tubular injury, and maintained PTC networks. Furthermore, SKT recovered SOD-like activity to the basal levels. These results suggest that SKT may be useful for the treatment of CKD during the progression to nephrosclerosis, through the mechanisms of anti-oxidative activity and maintenance of PTC networks.

Serial renal biopsy findings in a case of POEMS syndrome with recurrent acute renal failure.

This report describes a patient presenting with recurrent acute renal failure occurring in the course of POEMS syndrome, a multisystem disease associated with plasma cell dyscrasia. Several combined immunosuppression therapies failed to resolve recurrent acute renal failure; autologous peripheral blood stem cell transplantation was therefore applied. A renal biopsy was performed on each of four occasions when he developed renal dysfunction. The renal biopsy showed typical renal histology of POEMS, membranoproliferative glomerulonephritis-like lesions and narrowing of vessel lumina of various sizes caused by endothelial injury, which progressed to glomerulosclerosis and vessel occlusion. Recurrent acute renal failure might be caused by ischemia due to arterial occlusion. Serum levels of vascular epithelial growth factor (VEGF), which is considered to be a causative factor of endothelial lesions in POEMS syndrome, were not elevated throughout the course of this case.

Sairei-to ameliorates rat peritoneal fibrosis partly through suppression of oxidative stress.

BACKGROUND: Sairei-to is a herbal prescription originating from traditional Chinese medicine. We conducted an experimental study on rat peritoneal fibrosis to clarify the suppressive mechanisms of sairei-to. METHODS: Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. Peritoneal specimens were collected after 28 days of CG injection and oral administration of sairei-to. Macrophage infiltration, extracellular matrix accumulation, and angiogenesis were evaluated by immunostaining for ED-1, fibronectin, and CD-31, respectively. To observe oxidative stress in the tissue, 4-hydroxy-2-noneal (HNE) accumulation and plasma levels of superoxide dismutase (SOD) activity were detected. As a candidate of antioxidative components in sairei-to, plasma levels of baicalin were determined by high-performance liquid chromatography. RESULTS: Compared with the disease control group, serum total protein levels were significantly recovered in the sairei-to treatment group. Thickness of the submesothelial compact zone, trichrome-stained area, ED-1-positive cells, fibronectin-staining area, and HNE accumulation were suppressed in the treatment group. Concurrently, decreased plasma levels of SOD activity were recovered by sairei-to treatment. Increased CD-31-positive vessel number and area were also suppressed in the sairei-to group. Baicalin was detected in the plasma samples of the sairei-to group at 0.29 ± 0.11 µg/ml (mean±SEM). CONCLUSION: These results suggest that sairei-to ameliorates peritoneal fibrosis, partly through suppressing oxidative stress and macrophage infiltration.

Roles of coagulation pathway and factor Xa in the progression of diabetic nephropathy in db/db mice.

The active type of coagulation factor X (factor Xa) activates various cell-types through protease-activated receptor 2 (PAR2). We previously reported that a factor Xa inhibitor could suppress Thy-1 nephritis. Considering that fibrin deposition is observed in diabetic nephropathy as well as in glomerulonephritis, this study examined the roles of the coagulation pathway and factor Xa in the development of diabetic nephropathy using type 2 diabetic model mice. Diabetic (db/db) and normoglycemic (m+/m+) mice were immunohistochemically evaluated for their expression/deposition of PAR2, transforming growth factor (TGF)-ß, fibrin, extracellular matrix (ECM) proteins, and CD31 at week 20. Significantly greater numbers of PAR2-positive cells and larger amounts of fibronectin, and collagen IV depositions were observed in the glomeruli of db/db mice than those in m+/m+ mice. Next, expression of PAR2 versus deposition of collagen IV and fibronectin was compared between week 20 and week 30, and the number of PAR2-positive cells in the glomeruli decreased in contrast with the increased accumulation of ECM proteins. In an intervention study, fondaparinux, a factor Xa inhibitor, was subcutaneously administered for ten weeks from week 10 to 20. Fondaparinux treatment significantly suppressed urinary protein, glomerular hypertrophy, fibrin deposition, expression of connective tissue growth factor, and ECM proteins deposition together with CD31-positive capillaries. These results suggest that coagulation pathway and glomerular PAR2 expression are upregulated in the early phase of diabetes, together with the increase of profibrotic cytokines expression, ECM proteins deposition and CD-31-positive vessels. Factor Xa inhibition may ameliorate glomerular neoangiogenesis and ECM accumulation in diabetic nephropathy.

Churg-Strauss syndrome with severe granulomatous angiitis and crescentic glomerulonephritis, which developed during therapy with a leukotriene receptor antagonist.

A 77-year-old Japanese female developed Churg-Strauss syndrome (CSS), showing fever and numbness in bilateral hands. She was being treated for bronchial asthma with combination inhalant of corticosteroid with beta(2)-agonist, and an oral leukotriene receptor antagonist (LTRA), montelukast, for 15 months. She presented fever up to 38°C with microscopic hematuria and proteinuria, serum creatinine level of 0.7 mg/dl, and C-reactive protein of 11 mg/dl. After referral to our hospital, eosinophilia and high myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) level were observed together with hematuria and proteinuria; renal biopsy examination was performed to clarify the disorder. Renal biopsy specimens showed necrotizing crescent formation, severe granulomatous angiitis in an interlobular artery, and interstitial eosinophilic infiltration. It was noted that nearly intact glomeruli were infiltrated with eosinophils. After treatment with oral prednisolone at initial dose of 40 mg (1 mg/kg body weight), urinary findings rapidly became normal with mild elevation of serum creatinine to 1.5 mg/dl and trace level of serum C-reactive protein in 1 month. Because she was previously treated with montelukast without oral corticosteroid, linkage between CSS and LTRA was highly suspected.

Analytical and clinical validation of rapid chemiluminescence enzyme immunoassay for urinary thioredoxin, an oxidative stress-dependent early biomarker of acute kidney injury.

BACKGROUND: Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress. METHODS: A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically. RESULTS: Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria

Small animal models of kidney disease: a review.

Animal models of renal disease have provided valuable insights into the pathogenesis of acute and chronic kidney disease. Extension of these models to the mouse has become an increasingly important with the development of gene knockout and transgenic animals. In this review we discuss a range of models that can be used to mimic the mechanisms of human renal disease. While not perfect, the careful and ethical use of these models offers the opportunity to examine individual mechanisms in an accelerated time frame.

Lipopolysaccharide-triggered acute aggravation of mesangioproliferative glomerulonephritis through activation of coagulation in a high IgA strain of ddY mice.

BACKGROUND: The high IgA (HIGA) strain of ddY mice represents an inbred model of IgA nephropathy that shows mesangioproliferative glomerulonephritis with mesangial IgA deposition. In this study, aggravation of glomerulonephritis in HIGA mice through lipopolysaccharide (LPS)-triggered activation of coagulation was investigated. METHODS: Twelve-week-old HIGA and BALB/c mice were intraperitoneally injected with LPS twice at an interval of 3 days, and kidney specimens were collected 7 days after the second LPS injection. In an intervention experiment, the factor Xa inhibitor danaparoid was injected intraperitoneally every day for 7 days after the first LPS injection. RESULTS: LPS injection induced macrophage infiltration and cellular proliferation in the mesangium together with fibrin deposition and monocyte chemoattractant protein 1 mRNA expression, as well as antigen deposition of tissue factor, factor V, factor X, and protease-activated receptor 2. These phenomena were obvious in HIGA mice when compared to BALB/c mice. Interestingly, toll-like receptor 4 was intensely expressed in HIGA mice before LPS injection and subsequently decreased. Danaparoid treatment significantly ameliorated proteinuria, cellular proliferation, and fibrin deposition. CONCLUSIONS: The present data suggest that tissue factor and factor V induction by LPS may in part accelerate mesangioproliferative glomerulonephritis through activation of factor X and downstream proinflammatory and procoagulant mechanisms.

Tissue factor and factor v involvement in rat peritoneal fibrosis.

OBJECTIVE: Fibrin deposition on the peritoneum has been frequently observed in peritoneal fibrosis induced by long-term peritoneal dialysis. The present study was conducted to clarify the contribution of factor Xa through tissue factor and factor V expression in peritoneal fibrosis. METHODS: Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. For the interventional study, the factor Xa inhibitor fondaparinux was subcutaneously administered. After 28 days of CG injection, peritoneal specimens were examined by immunohistochemical analyses and in situ hybridization. RESULTS: The peritoneal submesothelial compact zone was observed to be markedly thicker in the CG-injected groups than in the normal group, and that thickness was dose dependent. Immunohistochemical study revealed massive fibrin, fibronectin, and type IV collagen depositions in the CG-injected groups, which was markedly higher than that in the normal group. Macrophage infiltration and staining for tissue factor, factor V, factor X, and protease-activated receptor-2 were intense in the CG-injected groups and negative/trace in the normal group. Tissue factor and factor V mRNAs were abundant in cells in the thickened peritoneum. A double-labeling experiment revealed that tissue factor was observed mainly in macrophages, and factor V was abundantly distributed in the fibrotic tissue together with macrophages. Fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue, and size and number of CD31-positive vessels. CONCLUSION: These results suggest that expression of tissue factor and factor V in infiltrated macrophages, together with factor X deposition, may progress angiogenesis and accumulation of extracellular matrix components, partly via profibrotic and procoagulant mechanisms in the peritoneum after inflammatory stimulation.

[Case of kidney failure with thrombotic microangiopathy lesions in renal biopsy caused by accelerated hypertension in young adult].

A 19-year-old male was admitted to our hospital for the treatment of severe hypertension with renal dysfunction. Two years before admission, his hypertension had been diagnosed as essential hypertension based on a series of examinations when his renal function was not impaired. Visits to his primary physician ended when he developed severe hypertension of 210/140 mmHg, at which time renal dysfunction and serum creatinine of 2.25 mg/dL were discovered. Renin and antidiuretic hormone were slightly elevated, but renal artery stenosis or other abnormalities were not detected by magnetic resonance imaging and computer tomography. After the hypertension was controlled by medication, a renal biopsy was performed to assess renal impairment. Histology demonstrated lesions compatible with thrombotic microangiopathy (TMA) and ischemic lesions, including fibrinoid necrosis, intimal thickening, occlusion in the small arteries, wrinkling and duplication of the glomerular basement membrane with microthrombi, and focal interstitial fibrosis. Renal function ameliorated after the hypertension was controlled. This case suggests that severe and accelerated hypertension can cause TMA with renal impairment even in young people.

Historical and pharmacological studies on rehmannia root processing- Trends in usage and comparison of the immunostimulatory effects of its products with or without steam processing and pretreatment with liquor.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Rehmannia glutinosa (RR) is a crude drug used in traditional Japanese Kampo medicine and traditional Chinese medicine (TCM). Sometimes, the crude drug is subjected to additional processing before use. AIM OF THE STUDY: To determine the effects of steam processing and pretreatment with liquor of RR through historical investigation, analytical chemistry, and pharmacological experiments. MATERIALS AND METHODS: We inspected TCM literature from the Later Han Dynasty to the present day. Dried RR steamed for 3, 6, 9, or 12 h (steamed RRs, SRRs), dried RR soaked in yellow rice wine (liquor) (liquor-RR), and dried RR steamed for 6 h pretreated with liquor (liquor-SRR) were prepared. These samples were extracted using boiling water, and the inducible effects of the extracts on granulocyte colony-stimulating factor (G-CSF) secretion in cultured enterocytes and the content of their marker compounds were evaluated by using HPLC. RESULTS: The effect of processing using both steaming and the pretreatment using liquor described in TCM literature over different eras was to enhance the warming effect and tonifying qi (energy) of RR. We found that SRR, processed by pretreatment with liquor, became mainstream since the Qing Dynasty. In SRR, stachyose content was decreased and fructose and manninotriose contents were increased with steaming time. However, the content of these compounds was not altered by pretreatment with liquor. RR extract induced G-CSF secretion in cultured enterocytes; moreover, the SRR extract steamed for more than 6 h had significantly stronger effects than that RR. Pretreatment with liquor did not cause any significant differences in the effects of RR or SRR. CONCLUSIONS: The aim of processing for RR by both steaming and pretreatment with liquor in TCM literature over different eras was to enhance the tonifying effect on qi and its immunostimulatory effect. Although the effect of RR on the induction of G-CSF secretion in intestinal epithelial cells was enhanced by steaming, this enhancement was not enhanced by the pretreatment with liquor. These results provide scientific support for steaming, but could not elucidate a reason for pretreatment with liquor in TCM theory.

Angiotensin II receptor blockade ameliorates mesangioproliferative glomerulonephritis in rats through suppression of CTGF and PAI-1, independently of the coagulation system.

BACKGROUND: Previously we observed that the coagulation system promotes matrix protein accumulation through transforming growth factor (TGF)-beta and connective tissue growth factor (CTGF) expression in rat mesangioproliferative glomerulonephritis (MsPGN). Angiotensin II receptor blockers (ARBs) are known to suppress matrix accumulation in experimental MsPGN. In the present study, we investigated whether ARB suppresses MsPGN through inhibition of these profibrotic cytokines, and in relation to coagulation and fibrinolytic systems. METHODS: MsPGN was induced in Wistar rats by intravenous injection of anti-Thy-1.1 monoclonal antibody, OX-7. As an ARB, olmesartan was orally administered in rat feed from the day of OX-7 injection (day 0) to day 8, when rats were sacrificed and kidney specimens were collected. The degrees of cellular proliferation, matrix production, coagulation factors, and inhibitory factor of fibrinolysis were evaluated. RESULTS: Although blood pressure did not change in the normal, disease control, or treatment groups, the amount of urinary protein was significantly decreased in the ARB-treated groups, compared with the disease control group (p < 0.05). alpha-Smooth muscle actin expression was suppressed significantly in the treatment groups (p < 0.001). Blue-staining areas of trichrome, the number of proliferating cell nuclear antigen (PCNA)- or ED-1-positive cells, fibronectin and plasminogen activator inhibitor type 1 in glomeruli significantly decreased in the treatment groups (p < 0.05, respectively); however, fibrin-related antigen and factor V depositions were not suppressed in the treatment groups. CONCLUSIONS: These results suggest that the ARB drug would ameliorate MsPGN in vivo, at least partly through CTGF and plasminogen activator inhibitor type 1 suppression, and independently of the local coagulation system in glomeruli.

Comparison of peroxidase response to mental arithmetic stress in saliva of smokers and non-smokers.

Saliva is the first body fluid to encounter exogenous materials or gases such as cigarette smoke (CS). The aim of this study was to examine whether smoking affects oral peroxidase (OPO) reactivity to mental stress. The subjects were 39 non-smokers and 10 smokers. In the experiment, the Kraepelin psychodiagnostic test as a psychological stressor and saliva was sampled 30 min before, just before, immediately after, and 30 min after the beginning of the test. OPO reactivity to the test between smokers and non-smokers was measured in addition to uric acid concentration, flow rate, IgA, thiocyanate (SCN-) concentration, amylase activity as a salivary stress marker, and ultra-weak chemiluminescence (UCL) level, which is indicative of salivary antioxidative and antibacterial abilities. Moreover, we studied the effect of smoking on the response of salivary peroxidase (SPO) and myeloperoxidase (MPO) activity to mental stress, respectively. The results showed that the IgA concentration, amylase activity, SCN(- concentration, and UCL level are higher in the non-smoking group than smoking group and the IgA concentration and UCL level increased in the non-smokers significantly just after the Kraepelin test. The levels of SCN-) were higher in smokers than in non-smokers and OPO activity was greater in the non-smoking group in all sessions. Furthermore, only the non-smokers had significantly increased MPO activity just after the test. MPO may play a crucial role in the response to acute psychological stress besides inflammation, and CS suppresses this response significantly.

Clinical efficacy of intravenous immunoglobulin for patients with MPO-ANCA-associated rapidly progressive glomerulonephritis.

BACKGROUND: To determine whether intravenous immunoglobulin (IVIg) can control disease activity in patients with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated rapidly progressive glomerulonephritis (RPGN). METHODS: Twelve patients with serologically and histologically confirmed MPO-ANCA-associated RPGN (7 men, 5 women; mean age 71 +/- 3 years) received IVIg (400 mg/kg/day) alone for 5 days. The effects of IVIg were evaluated by white blood cell counts, serum C-reactive protein levels, Birmingham Vasculitis Activity Score, rate of change in reciprocal creatinine (1/Cre), and plasma tumor necrosis factor-alpha levels after IVIg administration. Corticosteroids with or without cyclophosphamide were commenced after IVIg. RESULTS: After IVIg treatment, a significant decrease was observed in white blood cell count (p < 0.05), C-reactive protein values (p < 0.001), and Birmingham Vasculitis Activity Score (p < 0.001) concomitant with the amelioration of systemic symptoms. The rate of change in 1/Cre significantly improved (p < 0.05). Plasma tumor necrosis factor-alpha levels that were significantly elevated in patients before IVIg compared with normal controls (p < 0.0001), rapidly declined after IVIg with a significant reduction (p < 0.05). Three months post-treatment with IVIg, all patients showed improvement of disease without serious infectious complications. CONCLUSION: IVIg is a potential component of remission induction therapy for patients with MPO-ANCA-associated RPGN.

Suppressive mechanisms of Sairei-to on mesangial matrix expansion in rat mesangioproliferative glomerulonephritis.

BACKGROUND: Sairei-to (TJ-114) is a Japanese herbal medicine of standardized quality, originating from traditional Chinese medicine. In the present in vivo study, we investigated the suppressive effects of TJ-114 and related drugs, Shosaiko-to (TJ-9), and Saiboku-to (TJ-96), on mesangioproliferative glomerulonephritis (MsPGN) in rats. TJ-9 is a basal prescription of TJ-96 and TJ-114. We evaluated the efficacy of these drugs on proteinuria, extracellular matrix (ECM) accumulation, and superoxide dismutase (SOD)-activity. METHODS: MsPGN in Wistar rats was induced by intravenous injection of rabbit anti-rat thymocyte serum (ATS). TJ-114, TJ-9, TJ-96 (500 mg/kg/day), or prednisolone (PSL, 2 mg/kg/day) was orally administered to the rats as drinking water from the day of ATS injection (day 0) to day 8, when rats were sacrificed and the kidney specimens were collected. Macrophage infiltration was evaluated by immunostaining for ED-1. ECM was measured by trichrome-staining, and fibronectin immunostaining. Northern blotting was performed to clarify the mRNA expression of cytokines and fibronectin. SOD-activity in the homogenate of renal cortex was also evaluated. RESULTS: The amount of urinary protein was significantly decreased only in the TJ-114-treated group compared with the disease control group (p < 0.05). The number of ED-1-positive cells was significantly decreased in all the treatment groups (p < 0.05, respectively). Decreases in the trichrome-stained area were observed moderately in the TJ-114-treated group (66% of control, p < 0.001) and mildly in the PSL-treated group (76% of control, p < 0.001). The staining area of fibronectin in the glomerulus was significantly decreased in all the treated groups except PSL, and was especially suppressed in the TJ-114-treated group (45% of control, p < 0.001). Transforming growth factor (TGF) and connective tissue growth factor (CTGF) expression significantly decreased in the TJ-114-treated group to the control level (p < 0.05). TGF-beta, CTGF, and fibronectin mRNA were upregulated in the disease control group, and TJ-114 suppressed these mRNA expressions in glomeruli. The SOD-activity of renal cortex-homogenate was significantly augmented in all the treated groups except PSL, markedly in the TJ-96- and TJ-114-treated groups. CONCLUSION: These results suggest that TJ-114 ameliorates ECM accumulation in experimental rat MsPGN, partly suppressing TGF-beta and CTGF expression through the recovery of SOD-activity.

Hepatitis C virus-associated tubulointerstitial injury.

BACKGROUND: Tubulointerstitial damage is recognized as a determinant of the prognosis of kidney disease. Various types of viral infection have been reported to induce tubulointerstitial lesions; however, that caused by hepatitis C virus (HCV) remains unclear, although glomerular lesions caused by this viral infection have been well documented. METHODS: To identify any association, we retrospectively investigated 320 patients who underwent renal biopsy and did not have extrarenal diseases causing tubulointerstitial nephritis. RESULTS: Of these patients, 13 patients had HCV infection and 307 patients did not. In a case-control study, HCV infection showed a significant association with the prevalence of tubulointerstitial injury. To offset the secondary tubulointerstitial change caused by advanced glomerulopathy, we performed a glomerular stage-matched comparison of patients with membranous nephropathy (MN). Nine patients with MN among the 13 HCV-infected patients and 18 HCV-negative patients with electron microscopic glomerular stage-matched MN were randomly selected from the overall pool of patients. Comparing areas of interstitial fibrosis and inflammatory cell infiltration, both were greater in HCV-infected than HCV-negative patients. In biopsy tissues from HCV-infected patients, positive signal for HCV was observed in the perinuclear area of tubular epithelial cells and infiltrating cells on immunohistochemistry and in situ hybridization. By a strand-specific reverse-transcription polymerase chain reaction for HCV, both genomic- and replicative-strand RNA were detected in renal tissues. CONCLUSION: These results suggest that HCV infection is a potent pathogenic factor of tubulointerstitial injury.

Renal tubular regeneration by bone marrow-derived cells in a girl after bone marrow transplantation.

Recent studies have indicated that bone marrow cells can contribute to regeneration of the kidney in experimental models. However, renal regeneration by apparent bone marrow-derived cells has not been shown previously in humans. The authors here report on a 7-year-old girl who received whole bone marrow transplantation from a male donor, and the contribution of bone marrow cells to the regeneration after renal damage was shown by in situ hybridization for the Y chromosome on autopsy specimens of the kidney. This observation suggests the clinical potential of bone marrow cells as a therapeutic option for renal injury.

Sarcoidosis complicated with IgA nephropathy.

Though IgA nephropathy (IgAN) and sarcoidosis have been reported simultaneously in patients occasionally, it remains controversial whether there is any association between the two. In this report we describe our experience with one definite and two subclinical cases of IgAN diagnosed during the clinical course of sarcoidosis. Our findings suggest a possible association between these disorders, and a higher incidence of subclinical IgAN among sarcoidosis patients than among the general population. We also discuss the common immunological background shared by these two diseases.

Intravenous immunoglobulin (IVIg) therapy in MPO-ANCA related polyangiitis with rapidly progressive glomerulonephritis in Japan.

For 30 myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) related rapidly progressive glomerulonephritis patients (male 17, female 13, average age of 68 +/- 11.8 years old), intravenous immunoglobulin (IVIg) (400 mg/kg/day) was administered for 5 consecutive days before or along with conventional immunosuppressive therapy in Japan. Twenty patients were treated with IVIg before the start or newly increase of conventional therapy and evaluated the independent effect of this therapy. In these patients, just after IVIg, significant decrease of CRP from 8.61 +/- 5.77 to 5.47 +/- 4.50 mg/dl (P < 0.001) was noted with improvement of elevated serum creatinine in 12 out of 19 patients (63%). In the analysis of the overall outcome of 30 patients, at 3 months after IVIg and following conventional therapy, no patients showed renal death except 4 for whom hemodialysis had been started before IVIg. At 6 months, renal survival rate were 92% (newly renal death 2 out of 26) and 2 patients died due to cerebral bleeding (survival rate was 93%). No fatal infection was noted. IVIg might be the potent inducible therapy which can be promoted before the beginning of conventional immunosuppressant treatment for relatively aged and lower immunopotent MPO-ANCA patients in Japan.