-
Atsushi Takahashi,
Tomonori Kimura,
Yoshitsugu Takabatake, Tomoko Namba,
Junya Kaimori,
Harumi Kitamura,
Isao Matsui,
Fumio Niimura,
Taiji Matsusaka,
Naonobu Fujita,
Tamotsu Yoshimori,
Yoshitaka Isaka,
Hiromi Rakugi
[show abstract]
[hide abstract]
ABSTRACT: Autophagy is a highly conserved bulk protein degradation pathway involved in cellular homeostasis. Although emerging evidence indicates involvement of autophagy in various conditions, efforts to clarify the role of autophagy in renal tubules are beginning to be elucidated. In the present study, we examined the hypothesis that autophagy guards against acute kidney injury (AKI) by modulating several deteriorative pathways that lead to tubular cell death using a cisplatin-induced model of AKI. Cisplatin treatment of GFP-LC3 (green fluorescent protein-microtubule-associated protein 1 light chain 3) transgenic mice induced autophagy in kidney proximal tubules in a time-dependent manner. Proximal tubule-specific autophagy-deficient mice exhibited more severe cisplatin-induced AKI than did control mice, as assessed via kidney function and morphologic findings. In addition, cisplatin induced more severe DNA damage and p53 activation, concomitant with an increase in apoptotic cell number, and a massive accumulation of protein aggregates in autophagy-deficient proximal tubules. Cisplatin treatment significantly increased reactive oxygen species-producing damaged mitochondria in immortalized autophagy-deficient proximal tubular cells when compared with autophagy-retrieved control cells. In conclusion, autophagy guards kidney proximal tubules against AKI, possibly by alleviating DNA damage and reactive oxygen species production and by eliminating toxic protein aggregates. Enhancing autophagy may provide a novel therapeutic option to minimize AKI.
American Journal Of Pathology 02/2012; 180(2):517-25. · 4.89 Impact Factor
-
Daisuke Mori,
Maki Shinzawa, Tomoko Namba,
Yoshito Yamaguchi,
Seiji Itano,
Natsuko Imakita,
Jun Matsuda,
Hisako Murata,
Masanobu Takeji,
Ryohei Yamamoto,
Yoshitaka Isaka,
Atsushi Yamauchi
[show abstract]
[hide abstract]
ABSTRACT: Few findings are available regarding adult-onset minimal change nephrotic syndrome (MCNS) with respect to the disease course and complications, such as acute kidney injury (AKI). We therefore performed a retrospective review to characterize the clinical presentations, steroid responsiveness and complications of adult-onset MCNS patients in our hospital.
We retrospectively reviewed 40 cases of idiopathic adult-onset MCNS who had been investigated and treated at a single center. Patients between 18 and 50 years of age (Younger group) at the time of biopsy were compared with those older than 50 years (Older group) with regard to demographic data, clinical features and treatment outcome.
Baseline characteristics of the 40 patients were: median age, 42 years (interquartile range: 28-63 years); male, 70%; mean (+/- standard deviation) systolic and diastolic blood pressures, 125 +/- 17 mmHg and 78 +/- 12 mmHg, respectively; estimated glomerular filtration rate (eGFR), 74 mL/min/1.73 m2 (range: 64-94 mL/min/1.73 m2); serum albumin, 1.8 +/- 0.3 g/dL; and urinary protein, 7.8 g/day (range: 3.9-10.4 g/day). All except for one patient received steroid pulse therapy. Time to complete response (CR) was 12 days (range: 8-21 days). Time to CR was significantly longer in the Older group (p = 0.011). The Late-responder group (time to CR > 2 weeks)was significantly older (p < 0.01), with a low eGFR (p < 0.001) and a higher prevalence of interstitial fibrosis in renal biopsy before the initiation of corticosteroid therapy (p < 0.05), compared with the Early-responder group. AKI was observed in 14 patients. Patients with an episode of AKI were significantly older (p = 0.005), with a lower eGFR (p < 0.002) and a higher prevalence of cellular casts (p < 0.05). At the follow-up, 19 patients (51%) had experienced relapses. The relapse rate was significantly lower in the Older group than in the Younger group (p < 0.05).
The present study revealed that older patients had a longer period to CR and a higher risk of AKI at follow-up.
Nippon Jinzo Gakkai shi 01/2012; 54(7):1023-30.
-
Tomonori Kimura,
Keiko Yasuda,
Yoshitsugu Obi,
Toshihiro Satoh, Tomoko Namba,
Koichi Sasaki,
Noriko Muramoto,
Akira Wada,
Hiromi Rakugi,
Yoshitaka Isaka,
Terumasa Hayashi
[show abstract]
[hide abstract]
ABSTRACT: A previously healthy black man presented with acute kidney injury wtih nephrotic syndrome. His serum creatinine and albumin concentrations were 8.0 mg/dL and 0.4 g/dL, respectively. Renal ultrasound demonstrated an enlarged kidney with an extremely high echogenic cortex. Human immunodeficiency virus (HIV) was serologically positive, and kidney biopsy revealed a collapsing variant of focal segmental glomerulosclerosis with interstitial nephritis. He was diagnosed as having HIV-associated nephropathy (HIVAN). Although there have been only a few cases with characteristic HIVAN features in Japan, the number of patients with HIVAN who need dialysis treatment is relatively high globally, and is expected to increase even in Japan. The rapid clinical course of HIVAN, along with its characteristic histology and the direct pathogenesis of HIV on podocytes, is noteworthy. We described this case with reference to some recent findings.
Nippon Jinzo Gakkai shi 01/2012; 54(2):94-8.
-
Maki Shinzawa,
Ryohei Yamamoto,
Yasuyuki Nagasawa,
Tatsuya Shoji,
Yoshitsugu Obi, Tomoko Namba,
Harumi Kitamura,
Tetsuya Kaneko,
Noriyuki Okada,
Hirotsugu Iwatani,
Atsushi Yamauchi,
Yoshiharu Tsubakihara,
Enyu Imai,
Yoshitaka Isaka,
Hiromi Rakugi
[show abstract]
[hide abstract]
ABSTRACT: Hypertension, which is affected by genetic and environmental factors, is one of the major risk factors for chronic kidney disease. Identification of the genetic factor contributing to hypertension in patients with chronic kidney disease may potentially refine a therapeutic strategy.
In the present multicenter cross-sectional study, 240 patients were eligible (aged 15-50 years with urinary protein ≥0.25 g/day) out of 429 patients who were diagnosed as having immunoglobulin (Ig) A nephropathy (IgAN) by renal biopsy between 1990 and 2005 and enrolled in our previous study, PREDICT-IgAN. The outcome was hypertension defined as ≥140 and/or ≥90 mmHg of systolic and diastolic blood pressure and/or use of antihypertensives at renal biopsy. We assessed associations between hypertension and 28 polymorphisms with the frequency of minor genotype ≥10% among 100 atherosclerosis-related polymorphisms using the Chi-squared test in dominant and recessive models. We identified polymorphisms associated with hypertension in multivariate logistic regression models.
Baseline characteristics: hypertension 36.3%. Among 28 polymorphisms, the Chi-squared test revealed that CD14 (-159CC vs CT/TT, P = 0.03) and ACE (DD vs DI/II, P = 0.03) were significantly associated with hypertension after Bonferroni correction. Multivariate logistic regression models revealed that CD14 -159CC [vs CT/TT, odds ratio (OR) 3.58 (95% confidence interval (CI) 1.66-7.63)] and ACE DD [vs DI/II, OR 4.41 (95% CI 1.80-10.8), P = 0.001] were independently associated with hypertension.
CD14 C-159T and ACE I/D contributed to hypertension in patients with IgAN.
Clinical and Experimental Nephrology 11/2011; 16(2):250-8. · 1.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In December 2008, a 69-year-old Japanese woman was admitted to the Department of Otorhinolaryngology because of hearing impairment due to bilateral exudative otitis media, and was discharged without complete recovery despite conventional treatment. Two weeks later, she was readmitted for worsened deafness, numbness, gait disturbance, and general fatigue. She was referred to our department for general investigation. On admission, laboratory examination revealed severe inflammatory signs and active nephritic urinary sediments. Cranial computed tomography (CT) revealed progressive exudative otitis media and sinusitis. Initially, Wegener's granulomatosis was suspected. Nasal cavity biopsy, however, showed no granuloma formation or vasculitis. Serology revealed high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA), suggestive of microscopic polyangitis (MPA). However, contrast CT identified stenosis of a celiac artery, and renal biopsy showed tubulointerstitial changes with minor glomerular abnormalities. Therefore, polyarteritis nodosa (PAN) was suspected and treatment with intravenous methylprednisolone was initiated. However, a lacunar infarct developed followed by cerebral hemorrhage, and the patient died 19 days after readmission. Autopsy revealed fibrinoid necrosis, neutrophilic infiltration, and giant cell reaction in small to medium-sized arteries in multiple organs. These findings led to diagnosis of systemic vasculitis anatomically compatible with PAN. This was a rare case of a patient with MPO-ANCA-positive PAN who may have developed bilateral exudative otitis media and hearing loss as the initial manifestation of PAN.
Clinical and Experimental Nephrology 05/2011; 15(5):754-60. · 1.37 Impact Factor
-
Tomonori Kimura,
Yoshitsugu Takabatake,
Atsushi Takahashi,
Jun-ya Kaimori,
Isao Matsui, Tomoko Namba,
Harumi Kitamura,
Fumio Niimura,
Taiji Matsusaka,
Tomoyoshi Soga,
Hiromi Rakugi,
Yoshitaka Isaka
[show abstract]
[hide abstract]
ABSTRACT: Autophagy is a bulk protein degradation system that likely plays an important role in normal proximal tubule function and recovery from acute ischemic kidney injury. Using conditional Atg5 gene deletion to eliminate autophagy in the proximal tubule, we determined whether autophagy prevents accumulation of damaged proteins and organelles with aging and ischemic renal injury. Autophagy-deficient cells accumulated deformed mitochondria and cytoplasmic inclusions, leading to cellular hypertrophy and eventual degeneration not observed in wildtype controls. In autophagy-deficient mice, I/R injury increased proximal tubule cell apoptosis with accumulation of p62 and ubiquitin positive cytoplasmic inclusions. Compared with control animals, autophagy-deficient mice exhibited significantly greater elevations in serum urea nitrogen and creatinine. These data suggest that autophagy maintains proximal tubule cell homeostasis and protects against ischemic injury. Enhancing autophagy may provide a novel therapeutic approach to minimize acute kidney injury and slow CKD progression.
Journal of the American Society of Nephrology 05/2011; 22(5):902-13. · 9.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A 76-year-old man developed fever and appetite loss, and then was referred to our hospital because of rapidly progressive renal insufficiency; his serum creatinine increased from 1.2 to 5.9 mg/dl within 1 month. On admission, his blood pressure was 166/92 mmHg, and laboratory findings showed signs of inflammation, anemia, proteinuria, and hematuria. Chest computed tomography (CT) suggested interstitial pneumonia, while a renal biopsy revealed that small arteries and arterioles were affected, and there was pauci-immune glomerulonephritis with cellular and fibrocellular crescents. In addition, an increased myeloperoxidase antineutrophil cytoplasmic antibody titer confirmed microscopic polyangiitis. Treatment with oral prednisolone was initiated and seemed to successfully resolve the vasculitis activity. On the 11th day of admission, a calcium channel blocker, azelnidipine, was added to treat hypertension. Two days later, the patient developed abdominal distension, and abdominal CT showed massive ascites. The ascitic fluid was a milky white transudate with a normal leukocyte count. Neither clinical manifestations nor laboratory findings suggestive of liver cirrhosis, malignancy, infectious peritonitis, or bowel perforation were observed. On the 18th day of admission, azelnidipine was discontinued in view of reports of calcium channel blocker-induced chyloperitoneum in patients undergoing peritoneal dialysis. Immediately, the abdominal distension disappeared, and the ascites appeared to decrease. Azelnidipine appears to have been responsible for the chyloperitoneum. Since a few cases of secondary vasculitis developing chyloperitoneum have been previously reported, vasculitis may have played a role in the development of chyloperitoneum.
Clinical and Experimental Nephrology 10/2010; 14(5):496-500. · 1.37 Impact Factor
-
Tomoko Namba,
Rie Shiba,
Takeshi Yamamoto,
Yasuhiro Hirai,
Takuma Moriwaki,
Jun Matsuda,
Hiroyuki Kadoya,
Masanobu Takeji,
Yukinori Yamada,
Harumasa Yoshihara,
Atsushi Yamauchi
[show abstract]
[hide abstract]
ABSTRACT: A 67-year-old, hepatitis C virus (HCV)-positive woman was admitted to our hospital because of proteinuria and leg edema. Laboratory examination showed decreased serum albumin and complement activity and positive cryoglobulin. The HCV RNA genotype was 1b with high viral load. Kidney biopsy showed membranoproliferative glomerulonephritis (MPGN) with capillary deposition of C3, IgM, and IgG, indicating HCV-associated glomerulonephritis. In addition to interferon (IFN) therapy, double-filtration plasmapheresis (DFPP) was performed to reduce HCV RNA blood levels in the early stage of IFN therapy. This treatment greatly reduced the viral load and induced clinical remission of MPGN, suggesting that DFPP plus IFN combination therapy may represent a potentially effective modality for refractory-type HCV-associated glomerulonephritis.
Clinical and Experimental Nephrology 05/2010; 14(4):372-6. · 1.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Henoch-Schönlein purpura (HSP) is a systemic disorder characterized by small vessel vasculitis with the deposition of IgA immune complexes. Renal involvement is the major cause of morbidity and mortality in patients with HSP. We report here a 37-year-old female patient with HSP nephritis (HSPN) associated with steroid-resistant nephrotic syndrome and renal dysfunction despite conventional therapy. The patient was successfully treated with intravenous cyclophosphamide following treatment with intravenous pulse methylprednisolone and oral prednisolone. The combination therapy resulted in a significant decrease in proteinuria, together with improvement of renal function. The patient finally reached a stage of clinical remission.
Nippon Jinzo Gakkai shi 01/2010; 52(1):66-72.
-
[show abstract]
[hide abstract]
ABSTRACT: Although hypokalemia is a common clinical problem, symptoms generally do not become manifest unless the serum potassium (K) falls rapidly. We encountered five cases with symptomatic severe hypokalemia (K<2.0 mEq/L) hospitalized for the past 15 months at our hospital. We examined the clinical characteristics and treatment of these patients. All five patients were women, and their mean age was 77.8 (73-82)years. They suffered from hypertension. Mean K level at admission was 1.66 (1.4-1.9) mEq/L and HCO3(-) was 48.3 (33.6-56.1) mmol/L. Plasma aldosterone level was low and plasma rennin activity was suppressed. All patients developed progressive muscle weakness with elevated creatinine phosphokinase. Three of the patients had received Chinese medicine which contained licorice, one received glycyrrhizin and the other one had received both. We diagnosed these cases as pseudoaldosteronism induced by glycyrrhizin. With discontinuation of the drugs and intravenous as well as oral K supplementation, serum K were normalized and clinical symptoms improved within 12 days. For one patient who developed cardiac dysfunction, concentrated K solution (230 mEq/L) was infused into the central vein. These findings show that glycyrrhizin ingestion should be kept in mind as a cause of an extreme degree of an hypokalemia, especially in elderly patients.
Nippon Jinzo Gakkai shi 01/2010; 52(1):80-5.
-
[show abstract]
[hide abstract]
ABSTRACT: AL amyloidosis is the most common form of systemic amyloidosis. Although kidney biopsy often is the method by which the disease is identified, small amounts of amyloid in kidney biopsy specimens may be missed on routine examination unless specifically investigated. We present here a previously healthy 60-year-oldmissed on routine examination unless specifically investigated. We present here a previously healthy 60-year-old man who developed nephrotic syndrome. His first renal biopsy showed minimal change nephrotic syndromeman who developed nephrotic syndrome. His first renal biopsy showed minimal change nephrotic syndromesuggesteda subtle depost ommon formsystemicamyloidfibrilhediminationof an early lesion of renal amyloido-s (MCNS). Proteinuria remained refractory to immunosuppressive treatments. Six months later, a repeat renal biopsy clearly showed AL amyloidosis. Re-examination of the first biopsy in the light of the final diagnosis again suggested a subtle deposition of amyloid fibrils. The discrimination of an early lesion of renal amyloidosis with MCNS may often be difficult. It is necessary to maintain a high level of alertness for amyloidosis especially in aged patients with nephrotic syndrome and to consider a repeat biopsy in steroid-resistant cases.
Nippon Jinzo Gakkai shi 01/2010; 52(5):590-4.
-
[show abstract]
[hide abstract]
ABSTRACT: A 66-year-old male with scleroderma developed rapidly progressive glomerulonephritis (RPGN). Renal pathology revealed crescentic glomerulonephritis with interstitial inflammation and fibrosis. Immunofluorescent micrography showed linear deposition of IgG along the glomerular capillary wall. Both anti-glomerular basement membrane antibody (anti-GBM Ab), and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were detected by an enzyme-linked immunosorbent assay (ELISA). These findings were compatible with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation of the serum creatinine level (5.9 mg/dL), and a high titer of MPO-ANCA (530 EU) and anti-GBM Ab (21 EU). He was started on methylprednisolone pulse therapy and temporary hemodialysis. Since the immunosuppressive therapy lowered both antibody titers steadily and improved renal function, hemodialysis was discontinued 4 weeks after the therapy. It has been reported that some scleroderma patients developed rapid progressive glomerulonephritis due to ANCA-associated vasculitis in addition to the typical scleroderma renal crisis. There have been few reports of a scleroderma patient associated with RPGN, in whom both MPO-ANCA and anti GBM antibodies were detected.
Nippon Jinzo Gakkai shi 02/2008; 50(1):64-8.
-
[show abstract]
[hide abstract]
ABSTRACT: A 53-year-old male was admitted to our hospital for a high fever. He suffered a change in personality, memory loss and disorientation as well. The findings of cerebrospinal fluid showed monocytosis, but the titers of glucose, C1 and ADA were all normal. Although there was no bacterium in the CSF, the patient's electroencephalography finding was abnormal. We diagnosed his condition as viral meningoencephalitis and started treatment with antiviral agents. Blood chemistry showed serum sodium of 130 mEq/l and plasma osmolarity was reduced to 272 mOsm/kg, while urine osmolarity was high at 353 mOsm/kg. Two potential causes of hyponatremia in this patient were the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or cerebral salt wasting syndrome (CSWS). Physical findings revealed a contracted extracellular fluid volume, strongly suggesting the presence of CSWS. The massive urine sodium loss overcoming sodium intake supported this diagnosis. After treatment with vigorous sodium and volume replacement for over 4 weeks, hyponatremia as well as meningoencephalitis were improved without any complication. To the best of our knowledge, this is the first report on CSWS in a patient with viral meningoencephalitis.
Nippon Jinzo Gakkai shi 02/2006; 48(7):669-74.
-
Nihon Naika Gakkai Zasshi 08/2005; 94(7):1402-5.
-
[show abstract]
[hide abstract]
ABSTRACT: On April 25, 2003, a 62-year-old Japanese man had been admitted to a hospital because of heavy proteinuria and elevated serum creatinine level, and purpura on the lower extremities. On May 15, 2003, he was referred to our hospital for evaluation and treatment. Serum immunoglobulin and complements were within normal ranges. Immune serology was negative for antinuclear antibody, antiglomerular basement membrane antibody, and antineutrophil cytoplasmic antibodies. Histological examination of a percutaneous renal biopsy specimen revealed that all of the glomeruli had severe crescent formation without deposits of immunoreactants. A diagnosis of antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis was made. The patient was treated with one cycle of steroid pulse therapy (1000 mg methylprednisolone daily, given on 3 consecutive days), and subsequently with prednisolone (60 mg/day). Despite this treatment, renal failure progressed rapidly and hemodialysis was started 1 month after the acute presentation. On May 30, 2003, he suddenly developed massive hematochezia. A technetium-targeted red-blood-cell scan suggested bleeding in the small intestine. On June 11, he presented with massive melena. A bleeding ulcer was found in the third part of the duodenum, and was treated successfully with endoscopy, using a heater probe. On June 19, he presented with massive hematochezia again. Mesenteric angiography revealed active bleeding from the iliac branch of the superior mesenteric artery. He was treated with continuous intraarterial vasopressin infusion by a catheter seated in the branch artery. The majority of patients with pauci-immune crescentic glomerulonephritis, one of the most common causes of rapidly progressive glomerulonephritis, have glomerular disease as part of a systemic vasculitis. Massive gastrointestinal bleeding, although rare, should be considered one of the serious complications in these patients.
Clinical and Experimental Nephrology 07/2005; 9(2):174-8. · 1.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We examined whether thiazide diuretics could restore nocturnal blood pressure (BP) decline and reduce urinary protein excretion in patients with glomerulopathy treated with angiotensin II modulators (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers).
Twenty-five Japanese outpatients (11 men, 14 women; mean age 43 +/- 12 years) with biopsy-proven immunoglobulin (Ig)A nephropathy, preserved renal function (serum creatinine concentration </=1.2 mg/dl), stable non-nephrotic proteinuria (0.5-3 g daily), and treatment with angiotensin II modulators were studied. The patients received a diuretic, trichlormethiazide (2 mg daily) for 4 weeks after a baseline period lasting for 4 weeks.
Diuretic therapy significantly reduced conventional, 24-h, daytime and night-time blood pressures. Nocturnal blood pressure fall was significantly enhanced by diuretic therapy and a significant interaction existed between diuretic therapy and nocturnal fall in mean arterial pressure, which indicated that the degree of nocturnal blood pressure fall was affected by diuretic therapy. The urinary protein excretion rate was significantly reduced from 1.10 +/- 0.62 to 0.63 +/- 0.39 g/day by diuretic therapy. Diuretic/baseline ratio of urinary protein excretion rate was not correlated with diuretic/baseline ratio of conventional, 24-h and daytime mean arterial pressures, but with diuretic/baseline ratio of night-time mean arterial pressure (r = 0.54, P = 0.006).
Diuretics enhanced nocturnal BP decline and reduced urinary protein excretion in patients with IgA nephropathy treated with angiotensin II modulators. The combination of angiotensin II modulators and diuretics may have additional therapeutic advantages in relieving the renal and cardiovascular risks by reducing nocturnal high blood pressure.
Journal of Hypertension 04/2005; 23(4):861-5. · 4.02 Impact Factor
