Carotid thromboembolism associated with nephrotic syndrome treated with dabigatran.

Nephrotic syndrome (NS) may be complicated by thromboembolism, which occasionally manifests as stroke. Although the optimal, standardized approach to the prophylaxis and management of thromboembolic complications associated with NS has not been established, anticoagulation with heparin and subsequent warfarin is the de facto standard of treatment. Dabigatran, a novel direct thrombin inhibitor, has become a substitute for warfarin and heparin for many indications, including the prophylaxis of stroke associated with nonvalvular atrial fibrillation and postoperative thromboprophylaxis in orthopedic patients. We report a 35-year-old male with NS due to membranous nephropathy (MN) that presented with carotid thromboembolism. Because the patient developed drug-induced hepatitis due to warfarin, we attempted treatment with dabigatran and were successful in continuing the medication without any complications. We also reviewed the literature on stroke associated with NS. Twenty-one prior cases have been reported, and the review of these cases revealed some interesting points. The age of onset ranged from 19 to 59 years. Most of the reported cases sustained a stroke at earlier ages than patients with atherosclerosis and atrial fibrillation, which suggests that NS may independently predispose individuals to arterial and venous thromboses. MN was the most common underlying pathology. Given that a standardized approach to the prophylaxis and management of thrombotic complications associated with NS has not been established, our experience suggests that dabigatran is a valid new treatment option for thrombotic complications of NS.

Prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD) for over 10 years.

BACKGROUND: Patients who have been on continuous ambulatory peritoneal dialysis (CAPD) for over 10 years are known to have a risk of developing encapsulating peritoneal sclerosis (EPS). However, the prognosis of patients on CAPD for over 10 years remains unclear. METHODS: To better understand the efficacy of a variety of treatments for EPS, we retrospectively reviewed 25 patients who started CAPD at Toranomon Hospital from 1981 to 1997 and continued it for longer than 10 years. RESULTS: The CAPD catheter was removed without peritoneal lavage in the initial 3 patients and they developed massive ascites. They all died of infection without resolution of the ascites. Accordingly, in the remaining 13 patients who did not undergo kidney transplantation, peritoneal lavage therapy was performed for 12 months before removing the CAPD catheter. As a result, 4 patients did not develop EPS. However, 9 patients had EPS with ascites, among whom 4 died of EPS-related diseases and 5 are alive. Five patients underwent cadaveric donor kidney transplantation. At the time of surgery, the CAPD catheter was removed without peritoneal lavage; 1 patient suffered from massive ascites immediately, although this subsided within 3 months after kidney transplantation, and 4 patients remain free from EPS-related symptoms and are doing well. CONCLUSION: Kidney transplantation may be an option for preventing EPS. This study showed that improvement of the uremic state as well as treatment with immunosuppressants including corticosteroids may contribute to preventing EPS.

Infected hepatic and renal cysts: differential impact on outcome in autosomal dominant polycystic kidney disease.

BACKGROUND: Infected cysts are a frequent and serious complication of autosomal dominant polycystic kidney disease. Such infections are classified into those affecting hepatic cysts and those affecting renal cysts. The purpose of this study was to compare the clinical course of infected hepatic cysts with that of infected renal cysts in patients with autosomal dominant polycystic kidney disease. METHODS: We analyzed 43 patients referred to us for additional treatment of severely infected cysts between January 2004 and December 2006. All patients who required further treatment in addition to antibiotic therapy were included. RESULTS: Aspiration was performed in all 28 patients with infected hepatic cysts. As a result, 17 patients were cured, 4 remain under treatment, and 6 died. One patient was cured by partial hepatectomy. Among the 15 patients with renal cysts, aspiration was performed in 4 with identifiable infected cysts, while renal transcatheter arterial embolization after appropriate antibiotic therapy was performed in 11 without identifiable infected cysts. No patient developed recurrence. CONCLUSION: In patients with infected renal cysts, aspiration or renal transcatheter arterial embolization after appropriate antibiotic therapy was effective. Although aspiration was often effective in patients with infected hepatic cysts, a good outcome was less likely than in those with renal cysts.

A case of primary hyperparathyroidism with severe bone and renal changes.

We report a 79-year-old Japanese woman who had primary hyperparathyroidism (HPT) with end-stage renal disease and severe bone changes. In 2004, she began to experience pain in her shoulders and knees, as well as muscle weakness and anorexia. She already had renal failure with a serum Cr of 4.7 mg/dl, while serum calcium was 9.6 mg/dl, PTH was 2,710 pg/ml, and serum alkaline phosphatase was 923 mU/ml. Multiple fractures of the pelvic bones and lumbar spine, osteoporosis, and subperiosteal bone resorption were detected. Although hemodialysis (HD) was started in February 2005, her symptoms became more severe. Total parathyroidectomy (PTX) and right iliac crest bone biopsy were performed. Histomorphometric analysis of the cancellous bone indicated a diagnosis of osteitis fibrosa, but a reduction of cortical bone and near absence of cancellous bone were also apparent. This showed that bone resorption by osteoclasts was predominant over bone formation by osteoblasts. Soon after PTX, her pain subsided completely. We conclude that primary HPT should be detected and treated early enough to avoid renal damage, since renal dysfunction markedly accelerates bone changes in patients with primary HPT.

Changes in the activities of daily living (ADL) in relation to the level of amputation of patients undergoing lower extremity amputation for arteriosclerosis obliterans (ASO).

BACKGROUND: The relationship between the level of amputation and the activities of daily living (ADL) in Japanese patients with arteriosclerosis obliterans (ASO) is unclear. METHODS AND RESULTS: In the present study 81 patients with ASO who underwent lower extremity amputation and were discharged from hospital after rehabilitation we evaluated. The patients were classified into 4 groups: toe amputation group (Toe), heel-preserving amputation group (Heel), below-knee amputation group (BK), and above-knee amputation group (AK). ADL at discharge and factors affecting the length of hospitalization were determined. Patients were walking at discharge in 94.5%, 94.0%, 59.0%, and 0.0% of the Toe, the Heel, BK, and AK group, respectively. However, the ratio of patients able to walk independently was 68% in the Toe group and 19% in the Heel group. In addition, the length of hospital stay was significant shorter in the Toe group than in the other groups. Factors affecting the length of hospital stay were the amputation level, cerebrovascular disease, reoperation, and diabetes. CONCLUSIONS: ADL are less affected and the length of hospital stay is shorter for patients undergoing toe amputation than other levels of lower extremity amputation. However, heel-preserving amputation maintains a comparable level of ADL in terms of ambulatory discharge.

Induction of anti-carbonic-anhydrase-II antibody causes renal tubular acidosis in a mouse model of Sjogren's syndrome.

BACKGROUND/AIM: We recently reported that renal tubular acidosis (RTA) in Sjogren's syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. METHODS: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. RESULTS: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. CONCLUSION: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.

Quality of life improvement and long-term effects of peripheral blood mononuclear cell transplantation for severe arteriosclerosis obliterans in diabetic patients on dialysis.

BACKGROUND: Severe arteriosclerosis obliterans (ASO) can be intractable, especially in diabetic patients on hemodialysis (HD). Recently, the transplantation of autologous peripheral blood mononuclear cells (PBMNCs) has been reported to have beneficial effects, but the long-term effects and impact on quality of life (QOL) have not been studied. METHODS AND RESULTS: Autologous PBMNCs were transplanted into 7 diabetic patients on HD who had severe ASO (5 cases with Fontaine IV and 2 with Fontaine III) after administration of 5 microg/kg granulocyte colony stimulating factor; QOL and degree of ischemia was assessed by measuring skin temperature, skin perfusion pressure (SPP), ankle-brachial index (ABI), and ulcer size, and from angiographic findings. At 4 weeks after the procedure, skin temperature was significantly improved, and SPP and ABI also were increased. These beneficial effects persisted for up to 24 weeks. Angiographic findings and ulcer size improved in 3 of 7 and 3 of 4 patients, respectively. SF-36v2 analysis revealed significant improvements in pain scores. No serious complications were detected. CONCLUSION: Transplantation of PBMNCs resulted in improvement in pain and leg ischemia for over 6 months without serious complications. This therapy is safe and effective for severe ASO in diabetic patients on HD.

Tonsillectomy and corticosteroid therapy with concomitant methylprednisolone pulse therapy for IgA nephropathy.

IgA nephropathy (IgAN) is the most common chronic kidney disease in Japan, but the optimum treatment remains controversial. Our objective was to evaluate the effect of tonsillectomy and corticosteroid therapy combined with methylprednisone pulse therapy in patients at our hospital who had IgAN. Tonsillectomy plus pulse therapy was evaluated in 72 patients (33 men and 39 women) with a diagnosis of IgAN based on renal biopsy who were followed up for more than 1 year. The mean age of the patients was 35.2 +/- 10.9 years (range: 20-58 years) and the mean observation period after tonsillectomy was 20.3 +/- 9.7 months (range: 12-36 months). After tonsillectomy, steroid pulse therapy was administered (methylprednisolone at 500 mg daily for 3 days) 1-3 times and was followed by oral prednisolone from an initial dose of 30 mg on alternate days that was tapered gradually over one year. At 2 years after tonsillectomy, serum creatinine was unchanged or improved in the majority of patients, but worsened in 5 patients. Hematuria (erythrocytes/HPF) improved from Grade 3.76 (11-30/HPF) to Grade 1.94 (1-5/HPF) on average (we defined the grade of hematuria). None of the patients experienced exacerbation of hematuria. Proteinuria decreased from 1.32 g/day to 0.86 g/day (65% of the pretreatment value), and only 4 patients showed an increase of proteinuria. Mean protein loss decreased to less than 0.5 g/day in patients with creatinine clearance > or =90 ml/min and/or patients with initial protein excretion < or =1.0 g/day.

Percutaneous transcatheter hepatic artery embolization for liver cysts in autosomal dominant polycystic kidney disease.

BACKGROUND: We have achieved renal contraction therapy in patients with autosomal dominant polycystic kidney disease (ADPKD) by means of renal transcatheter arterial embolization (TAE) using intravascular coils, decreasing renal size and improving quality of life in almost all patients. We presently perform hepatic TAE in patients with intractable symptomatic polycystic liver. STUDY DESIGN: Uncontrolled trial. SETTING & PARTICIPANTS: 30 patients with ADPKD referred for arteriography to an academic medical center. 22 patients had kidney failure treated by means of dialysis. INTERVENTION: We embolized arteries supplying hepatic segments replaced by cysts that were associated with well-developed hepatic arteries, but obstructed intrahepatic portal veins. OUTCOMES & MEASUREMENTS: Various volumes before and after TAE were compared by using computed tomography and National Institutes of Health Image software in 30 patients with follow-up computed tomography 18 to 37 months after therapy. RESULTS: Total liver volume and total intrahepatic cyst volume decreased from 7,882 +/- 2,916 and 6,677 +/- 2,978 to 6,041 +/- 2,282 and 4,625 +/- 2,299 cm(3), respectively (P < 0.0001 for both). Fractions of remaining (FR) total liver volume and FR of intrahepatic cyst volume were 78.8% +/- 17.6% and 70.4% +/- 20.9%, respectively. Hepatic parenchyma increased from 1,205 +/- 250 to 1,406 +/- 277 cm(3) (P = 0.0004). In 29 of 30 patients, both total liver volume and intrahepatic cyst volume decreased; in 1 patient, total liver volume increased from 5,755 to 7,069 cm(3), whereas cysts enlarged from 4,500 to 5,531 cm(3). No serious complications were experienced. In 24 patients, the post-TAE course was favorable. TAE failed to benefit 6 patients because of unrelated hepatic infection, peritonitis, hepatic failure, acute leukemia, or pelvic fracture. LIMITATIONS: Absence of a control group. CONCLUSIONS: TAE may be an option for patients with ADPKD with symptomatic polycystic liver who are not candidates for surgical treatment.

Systemic AA-amyloidosis related to MPO-ANCA microscopic polyangiitis: a case report.

We report autopsy findings in an 83-year-old woman with myeloperoxidase-type anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive microscopic polyangiitis and systemic AA amyloidosis. With a diagnosis of MPO-ANCA-related microscopic polyangiitis, the patient was treated with corticosteroids, but she died of intractable enteritis. Autopsy showed inactive vasculitis affecting small arteries in kidney, lung, intestinal tract, and skeletal muscle. Gastrointestinal viscera were thickened, and AA-amyloid was demonstrated in arterioles and surrounding tissues. Amyloidosis also involved heart, kidney, gallbladder, pancreas, salivary gland, and subcutis. ANCA-positive microscopic polyangiitis appears to have been the likely cause of this patient's AA-amyloidosis.

Successful renal transcatheter arterial embolization in three patients with symptomatic hydronephrosis due to ureteral obstruction.

BACKGROUND: Conventional treatments for symptomatic enlargement of a nonfunctional hydronephrotic kidney caused by obstructive uropathy include surgical treatments. METHODS: Patients included a 67-year-old woman whose obstruction was caused by a lower urinary tract stone complicating spinal tuberculosis (patient 1); a 52-year-old man with compressive complete congenital obstruction crossing the ureteropelvic junction from an aberrant renal artery (patient 2); and a 19-year-old woman with essentially complete idiopathic congenital obstruction at the ureteropelvic junction (patient 3), who required antibiotics for pyelonephritis before embolization. The renal artery was embolized using platinum microcoils. RESULTS: Although the sensation of abdominal fullness diminished within approximately two week after TAE, it took one to two years until the embolized kidney size shrank from 1377+/-634 cm3 (range, 829 to 2072) to 43+/-46 cm3 (42 to 94) by the evaluation of computed tomography. Fever after embolization persisted for 5 days in patient 1, 3 in patient 2, and 9 in patient 3. Flank pain resolved within 5 days in all. Pyelonephritis and complications of treatment have not occurred. CONCLUSION: Embolization for this indication was safe and effective.

[Case of autosomal dominant polycystic kidney disease associated with pelvic insufficiency fracture].

We experienced a case of A-59-year-old woman having autosomal dominant polycystic kidney disease with renal insufficiency associated with pelvic insufficiency fracture. On admission the pelvic bone compressed by the enlarged kidney and liver due to polycystic disease was demonstrated on the pelvic CT. Her bone mineral density was not significantly decreased contrary to our expectation. The prominent bone absorption in the endosteal and exosteal surface of the cortical bone was demonstrated in the bone specimen form iliac bone although the state of the cancellous bone and bone formation rate was normal. We performed the transcatheter embolization (TAE) to the kidney and liver to diminish their sizes. The fracture was rapidly improved and she could walk 6 months later after the TAE. In this case, we considered that the longstanding compression to the pelvic bone by the enlarged liver and kidney made the cortical and the binding of muscle/tendon and cortical bone fragile and it led to the pelvic insufficiency fracture.

Pelvic insufficiency fracture related to autosomal dominant polycystic kidney disease.

We report the case of a patient with autosomal dominant polycystic kidney disease (ADPKD) and an insufficiency-type fracture of the pelvis. A 60-year-old Japanese woman was admitted because of pain in the right ischium and pubis that began suddenly with no precipitating cause. Computed tomography showed the bony pelvis to be compressed by enlarged dependent kidneys and an enlarged liver. We relieved compression on the pelvic bones by means of transarterial embolization (TAE) to the kidneys and liver after initiation of hemodialysis therapy. The fracture healed gradually after TAE, and the patient could walk 4 months later. In an iliac bone specimen obtained before TAE, cancellous bone was intact, but periosteal and endosteal surfaces of cortical bone showed marked resorption and were irregular. Normally, many ligaments are connected tightly to the periosteal surface, supporting the cortical bone. However, because of extensive surface resorption associated with pressure from enlarged kidneys, connections between ligaments and the periosteal surface presumably became fragile, promoting an insufficiency fracture from unapparent external forces. Thus, ADPKD is a potential cause of insufficiency fracture owing to abnormalities of cortical bone.