A Case of Cryoglobulinemic Membranoproliferative Glomerulonephritis Induced by Hepatitis C Virus.

A 61-year-old man with bilateral purpura of the lower limbs and subsequent edema, was hospitalization after renal dysfunction developed. The presence of hepatitis C virus (HCV) RNA and cryoglobulin and the finding of membranoproliferative glomerulonephritis on renal biopsy led to a diagnosis of HCV-related glomerulonephritis due to cryoglobulinemia. Because of the pre-existence of nephrotic syndrome and the continuously increasing serum level of creatinine, treatment with cryofiltration, interferon, and steroids was started. After 5 cryofiltration sessions, the cryocrit level had decreased to 1% and the levels of serum creatinine and proteinuria had also decreased. However, 3 weeks after the start of treatment, nephrotic syndrome developed again and was accompanied by lower-extremity mononeuropathy and renal dysfunction. Thereafter, the patient showed disorientation, an affective disorder, and delirium, and his condition gradually deteriorated. Radiological examination of the head and examination of the cerebrospinal fluid showed no abnormalities. Despite the withdrawal of the interferon therapy and the reduction of the steroid dose, the patient's conditions remained unchanged, and the level of consciousness deteriorated. Although cryofiltration had beneficial effects and plasma exchange was continuously performed, the patient died on the 74th hospital day. Because of the significant changes due to ventilatory support and hemorrhage associated with disseminated intravascular coagulation, the autopsy findings did not allow us to definitively determine whether the symptoms had been caused by the HCV-related membranoproliferative glomerulonephritis or the interferon therapy or both. We have reported this case to provide insight into whether interferon therapy should be administered for HCV-related membranoproliferative glomerulonephritis with marked neurological symptoms due to cryoglobulinemia.

Clinical benefit of the change of dialysate calcium concentration from 3.0 to 2.75 mEq/L.

Because active vitamin D preparations and calcimimetics have been widely used to treat secondary hyperparathyroidism, maintenance of acceptable serum calcium and phosphate levels is important. A 2.75 mEq/L dialysate calcium product, which may bring the calcium balance closer to 0, has recently been launched, and we had an opportunity to examine its possible benefits. We performed a 6-month retrospective review after switching from 3.0 mEq/L to 2.75 mEq/L calcium dialysate in 85 outpatients undergoing chronic hemodialysis. We evaluated blood biochemical parameters, including predialysis and postdialysis serum calcium and phosphate levels, predialysis intact parathyroid hormone (iPTH) levels; dialysis dose (Kt/V); and doses of concomitant active vitamin D preparations, calcimimetics, phosphate binder, and erythropoiesis-stimulating agents. Postdialysis calcium levels were significantly lower and predialysis corrected calcium levels significantly decreased. The change in calcium levels before and after dialysis was smaller after switching of the dialysate than before. iPTH levels significantly increased 1 month after switching of the dialysate. No remarkable changes were observed in phosphate levels or Kt/V. The dose of alfacalcidol, one of the concomitant drugs, somewhat increased, and no remarkable changes in dosage were observed for other concomitant drugs. These results were favorable in terms of calcium balance. However, there may be limitations in interpreting the results, but the resultant calcium levels suggest that switching to 2.75 mEq/L calcium dialysate may improve the control of calcium levels. In addition, it is hoped that the treatment choice of secondary hyperparathyroidism is extended.

Effects of alogliptin in chronic kidney disease patients with type 2 diabetes.

OBJECTIVE: Diabetes is a major risk factor for chronic kidney disease (CKD). In this study, we examined the effects of alogliptin on blood glucose control and the renal function in type 2 diabetes CKD patients. METHODS: We recruited 36 CKD patients with type 2 diabetes. The patients were followed up for six months after adding alogliptin. Blood biochemical, urine test and office BP values were obtained six months before and after the start of treatment. RESULTS: The mean HbA1c value was not decreased; however, the 1,5-AG values tended to improve (p=0.1023). The mean eGFR was unchanged. There were no significant changes in the patients with an eGFR of 60 mL/min/1.73 m2 or more (25 patients) or in the patients with an eGFR less than 60 mL/min/1.73 m2 (11 patients). A total of 15 patients were identified to have rapidly declining diabetic nephropathy, with an annual reduction in eGFR of 5 mL/min/1.73 m2 or more. The slope of the regression line for eGFR (-1.296 before starting treatment with alogliptin) was positive, increasing up to 0.08786. The eGFR values appeared to stop decreasing and positively reversed. The urinary albumin-to-creatinine ratio exhibited a downward trend. The effect on the renal function was independent of the levels of blood sugar, blood pressure and lipids. CONCLUSION: We examined the ability of alogliptin to maintain the renal function in patients with CKD complicated by type 2 diabetes. Our study suggests that alogliptin can be safely administered in patients with CKD. However, although we expected alogliptin to demonstrate renal protective effects, were unable to detect statistically significant differences. One reason for this finding is that there are few registered cases.

Febuxostat for treating allopurinol-resistant hyperuricemia in patients with chronic kidney disease.

BACKGROUND: Availability of the novel xanthine oxidase inhibitor febuxostat, which has multiple excretion pathways, enables investigation of the significance of serum uric acid control on renal function in patients with chronic kidney disease (CKD). METHODS: This was an exploratory, retrospective, observational study conducted at a single Japanese center. Serum uric acid concentrations and serum creatinine levels in the 6 months before and after the start of febuxostat treatment were collected for CKD patients switched from allopurinol after failing to achieve serum uric acid concentrations ≤6.0 mg/dL. RESULTS: Evaluable data were available for 60 patients, 67% of whom had advanced CKD (eGFR <30 mL/min/1.73 m2). Mean dose of febuxostat was 15.9 (± 8) mg/day. Mean serum uric acid concentration decreased from 8.4 (±1.4) mg/dL at baseline to 6.2 (±1.2) mg/dL at 6 months; 47.5% of patients achieved a level ≤6.0 mg/dL. The change from baseline in eGFR was positive at all time points during febuxostat treatment and the increase of 2.3 (±5.6) mL/min/1.73 m2 at 6 months was significant (p = 0.0027). Whereas the eGFR slope was negative during allopurinol treatment, it became positive after the switch to febuxostat. The change in eGFR slope before and after febuxostat treatment was significant for all patients (p < 0.01), for male patients (p < 0.05), and for patients with a baseline eGFR of <15 mL/min/1.73 m2 (p < 0.05). CONCLUSIONS: In patients with CKD, febuxostat reduces serum uric acid concentrations effectively and may suppress the progressive decline in renal function.

Comparison of once daily versus twice daily olmesartan in patients with chronic kidney disease.

BACKGROUND: The effects of olmesartan (OLM) on blood pressure and kidney function in Japanese patients with chronic kidney disease (CKD) were compared between 20 mg twice daily (BID) and 40 mg once daily (QD) treatments. METHODS: The subjects were Japanese CKD patients with concurrent hypertension who had been treated with OLM 20 mg BID for at least 3 months on an outpatient basis (n=39). After a change in the treatment regimen to 40 mg OLM QD (after breakfast), blood pressure (BP) (n=39), morning home BP (n=13), estimated glomerular filtration rate (n=39), and urinary albumin-to-creatinine ratio (n=17) were monitored for 2 months. RESULTS: No significant change in office (mean ± standard deviation [SD] [mmHg], 143.9 ± 18.8/75.7 ± 12.0 to 141.6 ± 16.1/74.7 ± 11.7, not significant [ns]) or early morning home (mean ± SD [mmHg], 133.8 ± 15.9/71.2 ± 11.5 to 133.8 ± 13.9/74.5 ± 10.5, ns) BP was observed 2 months after the change in dose. The estimated glomerular filtration rate increased significantly (mean ± SD, 49.0 ± 28.0 to 51.8 ± 27.0, P<0.05), whereas urinary albumin-to-creatinine ratio did not change significantly (mean ± SD, 0.551 ± 0.445 to 0.364 ± 0.5194, ns). CONCLUSION: High-dose OLM administered BID and QD had similar effects on outpatient and early morning home BP in CKD patients, suggesting that the BID regimen can be safely changed to a QD regimen. For CKD patients with hypertension requiring continuous long-term treatment, the possibility that the QD regimen might bring a greater therapeutic effect was suggested. However, recognizing the best blood pressure control level for a CKD patient is still a matter of debate, and should ideally be personalized.

The effects of tolvaptan on patients with severe chronic kidney disease complicated by congestive heart failure.

BACKGROUND: Tolvaptan, a diuretic with a new mechanism of action, selectively binds to the vasopressin V2 receptor and inhibits reabsorption of water. Its effect on heart failure is proven, but its benefit for patients with chronic kidney disease (CKD) has not been not confirmed. In this study, we examined the effect of tolvaptan on patients with severe CKD. METHODS: We analyzed patients with stage 4 or higher CKD who had congestive heart failure that was resistant to existing diuretics. The patients were administered an initial tolvaptan dose of 7.5 mg/day. We assumed urine volume and urine osmolality to be the main effective endpoint and recorded free water clearance, serum osmolality, serum creatinine (Cr) level, and adverse events. RESULTS: There was no instance of clinically significant hypernatremia. The urine volume increased significantly (P < 0.0001), as did the urine osmolality (P = 0.0053). Free water clearance showed a tendency to increase, although the difference was not statistically significant. The serum creatinine level did not change significantly, and there was no clear effect on renal function. However, in patients with stage 5 CKD, the serum creatinine level decreased significantly (n = 5, P = 0.0435). There were no adverse events. CONCLUSION: We confirmed that tolvaptan has a diuretic effect in patients with both severe CKD and congestive heart failure without causing either clinically significant hypernatremia or an adverse effect on renal function. Tolvaptan is an effective diuretic for patients with CKD.

Proliferative glomerulonephritis with monoclonal IgG2κ deposit successfully treated with steroids: a case report and review of the literature.

A novel form of glomerular injury with monoclonal immunoglobulin (Ig) IgG deposition, termed "proliferative glomerulonephritis (GN) with monoclonal IgG deposits" (PGNMID), is a recently described entity. PGNMID presents with various histological patterns, such as membranoproliferative GN, endocapillary proliferative GN and membranous nephropathy (MN). The deposits are composed of monoclonal immunoglobulin, most commonly IgG3 and occasionally IgG2. At present, the clinical significance of each IgG subclass and the morphological patterns of glomerular injury have not been fully investigated due to the limited number of PGNMID cases reported. The patient was a 27-year-old woman presenting with a mild degree of proteinuria and no other physical or serological abnormalities. Monoclonal Ig could not be identified in her serum or urine. Renal biopsy found features of MN with deposition of monoclonal IgG2κ. Electron microscopy examination revealed non-organised electron-dense deposits predominantly in subepithelial locations. Based on a diagnosis of PGNMID, she was treated with prednisolone and proteinuria significantly decreased in less than 4 weeks. Although the clinical outcomes of PGNMID remain to be defined, MN features may possibly be a sign of favourable prognosis-a hypothesis supported by recent reports. The absence of advanced chronic damage in the kidney, such as glomerulosclerosis or tubulointerstitial fibrosis, may also have contributed to the favourable outcome in the present case. Further studies on additional PGNMID cases that allow the correlation of morphological features and IgG subclasses with clinical outcomes are needed in order to confirm our findings and further solidify the clinical aspects of this new disease entity.

History and current practice of blood purification therapy in nippon medical school musashi kosugi hospital: 31 years of practice.

INTRODUCTION: Renal replacement therapy was established in Japan approximately 40 years ago, and a blood purification unit was established in our hospital 31 years ago. With an eye toward the future, we reviewed and analyzed the practice of blood purification therapy in our hospital to date. METHODS: Patients were selected from 3 decades when therapy was performed: from October 1979 through December 1989, from January 1990 through December 1999, and from January 2000 through December 2010. RESULTS: The total number of patients was 1,115. The numbers of patients with stage 5D/T chronic kidney disease, with acute kidney injury, and undergoing therapeutic apheresis has increased with each decade. Diabetic nephropathy, chronic glomerulonephritis, and nephrosclerosis are the most frequent primary causes of stage 5D/T chronic kidney disease. The percentage of patients with diabetic nephropathy at our hospital has increased markedly and has recently been more than 50% and has exceeded the national average. The trends observed in our study for mean age at the start of dialysis therapy were similar to national trends. Peritoneal dialysis was started in 1999, and the percent of patients undergoing peritoneal dialysis greatly exceeded the national average. Various pathophysiologies were found to be associated with acute kidney injury and therapeutic apheresis. CONCLUSION: The number of patients requiring renal replacement therapy continues to increase with the development of the hospital, especially in the Department of Nephrology. Progress in blood purification therapies is remarkable as well. To successfully address these challenges, we must strive for continued self-assessment.

Efficacy of aliskiren in Japanese chronic kidney disease patients with hypertension.

BACKGROUND: Aliskiren, a novel direct renin inhibitor, is hypothesized to inhibit the renin-angiotensin- system. This study attempted to provide insight into this mechanism by examining the antihypertensive and renoprotective effects of aliskiren in hypertensive chronic kidney disease (CKD) patients. METHODS: After recruitment, 43 hypertensive CKD patients (mean age, 53.7 years) began treatment of aliskiren. The patients were classified into high (over 30 mL/min/1.73 m(2)) estimated glomerular filtration rate (eGFR) group or low (under 30 mL/min/1.73 m(2)) eGFR group for comparison of measurements of various parameters over the 6-month observation period. RESULTS: Systolic blood pressure/diastolic blood pressure of 150 mg/day group decreased to an average of 126.8 ± 21.6 mmHg/69.3 ± 15.1 mmHg (average decrease: -7.4/-8.3 mmHg) over the 6-month observation period, while that of 300 mg/day group significantly decreased to an average of 133.5 ± 14.0 mmHg/71.5 ± 11.7 mmHg (average decrease: -21.1/-14.6 mmHg). Urinary protein of all patients decreased slightly and insignificantly to 1.1 ± 1.7 g/gCr from 1.4 ± 2.5 g/gCr. The serum creatinine (Cr) level of all patients decreased from 1.81 ± 1.10 mg/dL to 1.78 ± 0.82 mg/dL. Although the serum Cr level of the high eGFR group decreased from 1.28 ± 0.45 mg/dL to 1.27 ± 0.57 mg/dL, that of the low eGFR group slightly but insignificantly increased from 2.49 ± 0.64 mg/dL to 2.69 ± 1.11 mg/dL. CONCLUSION: Administration of aliskiren exerts an antihypertensive effect on hypertensive CKD patients that may lead to a decrease in urinary protein and an improvement in renal functioning.

Efficacy of high-throughput leukocytapheresis for rheumatoid arthritis with a reduced response to infliximab.

Infliximab (INF), a tumor necrosis factor-alpha (TNF-alpha) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high-throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS-180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28-joint disease activity score with C-reactive protein (DAS28-CRP) and with the erythrocyte sedimentation rate (DAS28-ESR). DAS28-CRP decreased significantly from 5.8 +/- 0.6 before LCAP to 3.9 +/- 0.7 (P = 0.0182) at 1-2 weeks after completion of five sessions of LCAP, and DAS28-ESR decreased significantly from 6.4 +/- 0.6 to 4.6 +/- 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF.

[QT dispersion increases during hemodialysis procedures in patients undergoing maintenance dialysis: association with an RA system and holter electrocardiogram].

BACKGROUND: Patients undergoing maintenance dialysis have been associated with a high incidence of arrhythmias, which increases with hemodialysis (HD) procedures. In recent years, QT dispersion (QT-d), which is defined as the difference between the maximum and minimum QT intervals (QTmax, QTmin) on an electrocardiogram (ECG), has attracted attention as a useful tool for predicting and evaluating ventricular arrhythmias. AIM: To determine the QT interval and QT-d before and after HD in stable subjects on maintenance dialysis. Further, to analyze the association of changes (Delta) in the QT interval and QT-d with the fluid removal ratio and changes in laboratory data. PATIENTS AND METHODS: We selected 82 patients undergoing maintenance dialysis who were less than 80 years of age. QT intervals before and after HD were obtained, and laboratory data including neurohumoral factors and the RA system were carried out. Of all the patients, 63 underwent a 24-hour holter-monitoring ECG. RESULTS: QTmax was significantly prolonged with QTmin remaining unchanged, and QT-d was significantly increased. DeltaQT-d demonstrated a significant correlation with DeltaQTmax, DeltaQTmin and Deltaaldosterone, but showed no correlation with the fluid removal ratio and changes in laboratory data. Results of the holter ECG revealed that in the grade 0 (Lown's classification) group, no change was obtained in DeltaQTmax, DeltaQTmin and DeltaQT-d, and in groups 1 to 5, significant increases were noted in DeltaQTmax and DeltaQT-d. CONCLUSIONS: The increase in QT-d has a possible link with arrhythmia inducibility during HD, and the results of the holter ECG suggest that an increase in QT-d may predict the frequency of arrhythmias. Change in the RA system appeared to have an impact on QT-d, but there was no impact of this parameter on the fluid removal ratio or changes in the laboratory data.