Tohru Nakahata

Combined therapy of enalapril and losartan attenuates histologic progression in immunoglobulin A nephropathy

Abstract Background : It has been reported that combined therapy of angiotensin converting enzyme inhibitor and angiotensin receptor blocker significantly decreases proteinuria in immunoglobulin A (IgA) nephropathy. However, histologic alterations following the therapy have not been reported.

Repeat renal biopsy in a girl with tubulointerstitial nephritis and uveitis syndrome.

Abstract. A Japanese girl aged 8 years who presented with a 2-month history of uveitis subsequently developed tubulointerstitial nephritis. A percutaneous renal biopsy revealed massive interstitial mononuclear cell infiltrates consisting of CD4-positive T cells. Despite administration of topical corticosteroids, the ocular symptoms persisted. Systemic corticosteroid therapy dramatically reduced the ocular symptoms and urinary β2-microglobulin (β 2MG) concentration. However, reducing the prednisolone dosage induced recurrence of uveitis associated with increased levels of urinary β 2MG. The CD4-positive T cell infiltration persisted in the second renal biopsy performed 6 months after the first renal biopsy. These observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Although the renal outcome of TINU has been reported to be favorable, prolonged interstitial cell infiltration may affect long-term renal outcome. Selected patients with TINU should be followed with close observation.

Interstitial cystitis and ileus in pediatric-onset systemic lupus erythematosus.

Abstract A girl aged 11 years presented with autoimmune hemolytic anemia with thrombocytopenia, and subsequently developed severe abdominal pain, vomiting, and pollakiuria. X-ray findings of her abdomen demonstrated paralytic ileus with intestinal wall thickening. Intravenous pyelography revealed bilateral hydroureter with mild hydronephrosis and contracted bladder. Pathological examination of her bladder revealed interstitial cystitis, with evidence of focal deposition of IgG and C3 in a granular pattern on small blood vessel walls. She was diagnosed as having systemic lupus erythematosus (SLE) associated with paralytic ileus and chronic interstitial cystitis. Although initiation of high-dose prednisolone therapy resulted in a gradual improvement in clinical symptoms, reducing the dosage of prednisolone caused a relapse. To our knowledge, the combination of paralytic ileus and chronic interstitial cystitis is quite uncommon in pediatric-onset SLE.

Mizoribine oral pulse therapy for a patient with severe lupus nephritis

Mizoribine (MZR) is a newly developed immunosuppressive agent in Japan. Its action has been reported to be selective inhibition of inosine monophosphate dehydrogenase and guanosine monophosphate synthetase, which results in inhibitory effects for T cell and B cell proliferation. 1 Apart from renal transplantation, recent studies proved the efficacy and safety of MZR in the treatment of childhood nephrotic syndrome (NS) 2,3 and systemic lupus erythematosus (SLE). 4

Successful treatment with leukocytapheresis in refractory Henoch-Schönlein purpura: case report.

A Japanese boy aged 7 years referred to our hospital because of steroid-resistant colicky abdominal pain and purpuric rash due to Henoch-Schönlein purpura (HSP). Since 2 weeks ago, he had been suffering from generalized purpuric rash and colicky abdominal pain associated with bloody diarrhea. The diagnosis was HSP. Although he had been treated with oral prednisolone and repeated intravenous coagulation factor XIII administration, the purpuric rash and colicky abdominal pain persisted. Because of steroid-resistant and refractory clinical pictures, leukocytapheresis (LCAP) using a granulocyte removal column was initiated thereafter. Following 3 times of treatment, his clinical symptoms completely disappeared and the increased levels of serum interleukin-6 were decreased to within the normal ranges. No adverse reaction was observed. These clinical observations suggested that LCAP might be beneficial to a proportion of patients with severe HSP. This is the first report to describe efficacy of LCAP in severe HSP.

Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

Acute renal failure with encephalopathy following Salmonella enteritidis infection.

Salmonellosis is one of the major causes of food poisoning in Japan. In general, consumption of food contaminated with non-typhi Salmonella causes acute gastroenterocolitis. However, salmonellosis has also been reported to be associated with development of severe extraintestinal multiorgan complications, including rhabdomyolysis (RM), acute renal failure (ARF), and rarely acute encephalopathy [1–5]. In this paper, we report on a patient with systemic lupus erythematosus (SLE) who developed ARF with suspected acute encephalopathy following Salmonella enteritidis infection. The patient was under treatment with immunosuppressive agents. Since patients with SLE are at an increased risk of severe infections [6], this case report may serve to emphasize the importance of prevention of food poisoning and of advocating appropriate hygienic practice in immunocompromised hosts. A 16-year-old Japanese girl with a 3-year history of SLE with WHO class IV disease was referred to our hospital because of drowsiness and disorientation. Although the SLE activity and serum complement levels were reasonably controlled under maintenance therapy with prednisolone (15 mg/day) and azathioprine (75 mg/day), the patient developed acute severe diarrhea, vomiting, and fever after eating a raw egg. She was admitted to a regional hospital with suspected food poisoning. On admission, her body weight was 36.5 kg, which represented a loss of about 1.5 kg over her previous weight recording. Her blood pressure was decreased to 70/36 mmHg. Laboratory studies revealed the following: peripheral white blood cell (WBC) count 11,200/μl, hemoglobin 13.8 g/dl, hematocrit 39.9%, platelet count 193,000/μl, blood urea nitrogen (BUN) 18.2 mg/dl, creatinine 0.9 mg/dl, and Creactive protein (CRP) 5.4 mg/dl. Despite adequate fluid replacement, the patient developed oliguria, drowsiness, and disorientation. Lumbar puncture revealed clear cerebrospinal fluid (CSF), and further examination of the CSF revealed the following: cell count 1 cell/mm, protein 22 mg/dl, glucose 71 mg/dl, and sterile culture. Emergency cranial computed tomographic and electroencephalographic findings were unremarkable. The BUN and serum creatinine increased to 41.5 mg/dl and 4.7 mg/dl, respectively. In addition, the serum level of creatinine kinase (CK) and urinary level of myoglobin also became markedly elevated to 21,307 IU/l (normal: 12–144 IU/l) and 1,073 ng/ml (normal: 0–70 ng/ml), respectively. A diagnosis of ARF caused by RM associated with some central nervous system (CNS) complication was made, and the patient was transferred to our hospital. Physical examination on admission to our hospital revealed that the patient was drowsy. Her blood pressure was 126/76 mmHg. Laboratory studies revealed the following: WBC count 10,590/μl, hemoglobin 13.9 g/100 ml, hematocrit 38.0%, platelet count 119,000/μl, serum total protein 6.6 g/dl, albumin 3.9 g/dl, BUN 63 mg/dl, creatinine 6.8 mg/dl, sodium 137 mmol/l, potassium 4.3 mmol/l, chloride 97 mmol/l, calcium 6.8 mg/dl, CRP 17.8 mg/dl, and CK 29,484 IU/l. Immunological studies revealed the following: IgG 502 mg/dl, IgA 185 mg/dl, IgM 43 mg/dl, C3 76 mg/dl (normal: 79–152 mg/dl), C4 20 mg/dl (normal: 16–38 mg/dl), and complement hemolytic activity 37.4 U/ml (normal: 23–46 U/ml). The serological test for antinuclear antibody was positive at a titer of 1:320, with a homogeneous pattern. Although the blood culture was negative, the stool culture was positive for Salmonella enteritidis. A search for endotoxin in the blood was negative. The levels of the proinflammatory cytokines, interleukin (IL)-6 and IL-8, were analyzed in the CSF specimen obtained at the onset of the salmonellosis. The CSF levels of both cytokines were significantly elevated: IL-6 328 pg/ml (measured by enzyme immunosorbent assay, normal: less than 4.0 pg/ml) and IL-8 327 pg/ml (measured by enzyme-linked immunosorbent assay, normal: less than 2.0 pg/ml). On the T. Nakahata . K. Tsugawa . H. Tanaka (*) Department of Pediatrics, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan e-mail: hirotana@cc.hirosaki-u.ac.jp

Renal artery thrombosis in a pediatric case of systemic lupus erythematosus without antiphospholipid antibodies

A 13-year-old Japanese boy with an 11-month history of systemic lupus erythematosus (SLE) without antiphospholipid antibodies (APAs) suddenly developed severe hypertension, associated with fever and generalized seizures, and mild abdominal pain. Emergency abdominal computed tomography (CT) confirmed left renal artery thrombosis, and a renal scintiscan revealed reduced blood flow to the left kidney. Promptly instituted intravenous anticoagulant therapy was not effective for controlling the infarction-reduced renal arterial blood supply. Moreover, he developed stupor due to central nervous system (CNS) lupus a week after the occurrence of the hypertensive episode. Finally, a percutaneous transluminal angioplasty successfully relieved the occlusion of the left renal artery at its origin. The CNS lupus was also successfully treated with intravenous methylprednisolone pulse therapy combined with intrathecal methotrexate and dexamethasone. Although it is well known that SLE patients with APAs have a high incidence of thrombotic complications, to date, renal artery thrombosis has rarely been reported in young patients. This APA-negative SLE patient unusually manifested renal thrombosis associated with CNS lupus.

Severe tubulointerstitial nephritis in a boy with refractory nephrotic syndrome.

urinary protein excretion, persisted during the subsequent 6 months. Five months after our first examination, the child suddenly developed acute renal failure (ARF) associated with an increase in the plasma b- d -glucan level (up to 102 pg/ml, normal <6.0 pg/ml) and serum C-reactive protein level (up to 7.1 mg/dl, normal <0.3 mg/dl). The serum creatinine and urinary sodium fractional excretion increased to 4.9 mg/dl and 5.42%, respectively. Antibiotic and antifungal therapy, as well as low-dose dopamine infusion in order to increase the glomerular blood flow [6], were promptly initiated. His daily urine output was maintained at more than 500 ml with the conservative therapy, and the ARF gradually resolved within a month thereafter. The immunosuppressive therapy for his NS, consisting of a moderate dose of PSL (20– 40 mg daily) combined with CsA at a blood trough level of approximately 100 ng/ml (except for temporary discontinuation during the episode of ARF) was continued because of refractory NS.

Childhood idiopathic membranous glomerulonephritis with isolated antinuclear antibody positivity

AbstractBackground. The occurrence of idiopathic (primary) membranous glomerulonephritis (MGN) is relatively uncommon in childhood. Although a proportion of children with idiopathic MGN may show isolated antinuclear antibody (ANA) positivity, its clinical impact remains unclear. Methods. During the past 12 years, we have treated six children with idiopathic MGN at our institution. Of these, three children with isolated ANA positivity were retrospectively evaluated. Results. The patients consisted of two boys and a girl, aged 5, 12, and 13 years at presentation, respectively. They showed proteinuria of around 1 g/day with hematuria, and isolated ANA positivity without anti-DNA antibody or hypocomplementemia. A percutaneous renal biopsy revealed MGN stage II in two of the children and stage III in one, without endothelial tubuloreticular inclusion. Two children received a 6-month course of prednisolone therapy. At the latest observation (mean interval of 42 months), all showed negative for proteinuria, and no patients had progressed to systemic lupus erythematosus (SLE). A decrease in the ANA titer with subsidence of urine abnormalities was observed in two patients. Conclusion. Although the long-term prognosis of ANA-positive idiopathic MGN in childhood remains unclear, isolated ANA postivity itself may be nonspecific, and may not indicate a subsequent progression to SLE.