Efficacy and safety of high dose epoetin alfa therapy in CAPD patients by cross-over study / 대한내과학회지

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is an essential and well-established treatment for renal anemia. Rcently, clinicians have moved toward administration of high dose rHuEPO to reduce the inconvenience and time efficient.We aimed to determine whether high dose subcutaneous (SC) epoetin alfa is as efficient and safe as the usual dose for treating anemia in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Twenty-four patients on CAPD were randomly assigned to a high-usual dose group (n=12) and an usual-high dose group (n=12) with a variable interval for 48 weeks. Patients received 10 times treatments by scheduled visiting during Period I lasting 24 weeks and received 4 times treatments by scheduled visiting in Period II lasting 24 weeks by cross-over. The high dose was 10,000 IU and the usual dose was 4,000 IU epoetin alfa regimen. If hematocrit was out of the targeted range, 30~39%, the interval of epoetin alfa was changed within 50% of the previous interval. RESULTS: Fifteen patients, out of 24, completed the study (8 patients in the high-usual dose group; 7 patients in the usual-high dose group). Mean hemoglobin levels at randomization and after 12, 24, 36 and 48 weeks were 10.8+/-1.1, 11.5+/-0.9, 11.5+/-1.5, 11.4+/-1.5, 11.5+/-0.8 g/dL, respectively, in high-usual dose group compared with 11.2+/-0.8, 11.4+/-1.2, 11.2+/-0.9, 11.2+/-1.4, 11.4+/-0.9 g/dL, respectively, in usual-high dose group. The mean weekly epoetin alfa dosages at randomization and after 12, 24, 36 and 48 weeks were 83.6+/-38.1, 87.1+/-35.8, 89.4+/-34.2, 60.1+/-25.1, 62.8+/-30.7 IU/kg/week, respectively, in high-usual dose group compared with 69.8+/-31.6, 64.9+/-12.2, 69.9+/-46.1, 78.8+/-29.3, 75.9+/-16.4 IU/kg/week, respectively, in usual-high dose group. No statistically significant differences between the two groups were apparent for hemoglobin levels or mean weekly epoetin alfa dosages. Treatment interval at Period I and Period II were 13.3+/-5.3, 8.2+/-4.3 days in high-usual dose group compared with 7.0+/-2.5, 13.4+/-4.0 days in usual-high dose group with statistically significant differences. Treatment interval in high dose was about two times as longer as usual dose. Adverse events were generally mild and transient, and pain on injection site following subcutaneous administration was rarely reported. CONCLUSIONS: This study demonstrates that epoetin alfa 10,000 IU is as efficient and safe as 4,000 IU with a similar weekly dose in CAPD patients. Epoetin alfa 10,000 IU administration can reduce frequency of injections by about one half.

Effect of High Dose (10, 000 IU) Epoetin Alfa (Espogen(R)) Therapy in CAPD Patients / 대한신장학회잡지

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is an established treatment for renal anemia. We aimed to determine that high dose subcutaneous epoetin alfa is as efficient and safe as usual dose for treating anemia in peritoneal dialysis patient. METHODS: Twenty four patients on CAPD were randomly assigned to either 10, 000 IU (high dose group, n=12) or 4, 000 IU (usual dose group, n=12) epoetin alfa regimen with variable interval for 24 weeks. If hematocrit was out of range (30-39%), the interval was changed within 50% of previous interval. RESULTS: Mean hemoglobin levels at randomization and after 12 weeks and 24 weeks were 11.4+/-1.3, 11.3+/-1.1, and 11.6+/-1.2 g/dL in high dose group compared with 10.8+/-0.8, 11.5+/-1.1, and 10.9+/-1.2 g/dL in usual dose group (p<0.05). The mean weekly epoetin alfa dosages at randomization and after 12 and 24 weeks were 93.2+/-45.3, 95.5+/-33.6, and 102.5+/-43.6 IU/kg in high dose group compared with 78.8+/-29.4, 75.9+/-20.6 and 75.5+/-39.7 IU/kg in usual dose group (p<0.05). But, interval in high dose group was two times as longer as usual dose group. Adverse events were generally mild and transient CONCLUSION: This study demonstrates that epoetin alfa 10, 000 IU is as efficient and safe as 4, 000 IU with similar weekly dose in CAPD patients. epoetin alfa 10, 000 IU administration reduces frequency of injections about one half.

Mycophenolate Mofetil Therapy in Severe Membranous Nephropathy and Diffuse Proliferative Lupus Nephritis: Clinical Observation / 대한신장학회잡지

OBJECTIVE: Although cyclophosphamide (CYC) is effective for the treatment of diffuse proliferative lupus nephritis (DPLN) and severe membranous nephropathy (MN), it has serious adverse effects. Therefore, we evaluated our clinical observations with mycophenolate mofetil (MMF) for empirical treatment of DPLN and severe MN. METHODS: Seventeen patients with biopsy proven severe MN (n=8) and DPLN (n=9) received MMF for > or = 6 months as primary treatment (n=9) or subsequent maintenance therapy after CYC treatment (n=8). Treatment outcome was evaluated by random urine protein/creatinine ratio (UP/Cr) and serum creatinine (sCr) at the start and at 12 months and compared by the Wilcoxon signed-rank test. RESULTS: Overall, the mean (+/-SD) UP/Cr decreased in both MN (6.48+/-3.03 vs. 1.31+/-1.22, p= 0.016) and DPLN (3.77+/-2.34 Vs 0.83+/-0.53, p=0.043) patients. No significant change in serum Cr was detected in both MN and DPLN patients. Adverse events included nausea/abdominal discomfort (n=1) and menstrual irregularity (n=1). CONCLUSION: Short term empirical treatment with MMF in the majority of patients with severe MN and DPLN was well tolerated and effective in decrease of proteinuria and stabilization of renal function. Controlled clinical trials are necessary to define the role of MMF in the treatment of severe MN and DPLN.

Comparison of Safety and Efficiency of Hemodialysis Using Heparin-bound Hemophan with those of Saline Flushing Hemodialysis and Hemodialysis Using Low Dose Heparin in Patients at Risk of Bleeding / 대한신장학회잡지

OBJECTIVE: Although hemodialysis using heparin bound Hemophan (HBH-HD) has been reported to be a possible modality in patients at risk of bleeding, the efficiency and safety of HBH-HD is not certain. Therefore, we prospectively compared the safety and efficiency of HBH-HD with those of saline flushing HD (SF-HD) and HD using low dose heparin (LDH-HD) in 13 HD patients at risk of bleeding in a cross-over design. METHODS: The safety and efficiency were evaluated by measuring activated partial prothrombin time (aPTT) before and during HD, hemostasis time after needle removal, total blood compartment volume (TBCV) loss of dialyzer, urea clearance (K) and Kt/V. RESULTS: There was no difference in compression time needed to achieve hemostasis at puncture site after needle removal between HBH-HD, SF-HD and LDH-HD. During HBH-HD, there was a slight increase in aPTT at 15 min (50.6+/-4.5 sec), compared to predialysis levels (40.9+/-4.7 sec). In this cross- over study, aPTT during dialysis session was markedly higher in LDH-HD than those in HBH-HD or SF-HD (p<0.05). The loss of TBCV of the dialyzer was greater in SF-HD than HBH-HD or LDH-HD (17.4+/-1.9% vs. 12.4+/-1.4% vs. 10.1+/-1.8%). However, there was no difference in K (212.0+/-30.7 vs. 217.2+/-36.9 vs. 221.6+/- 29.5 mL/min) and Kt/V (1.22+/-0.12 vs. 1.24+/-0.16 vs. 1.26+/-0.18). CONCLUSION: We concluded that the safety and efficiency of HBH-HD are not different compared to SF-HD or LDH-HD and HBH-HD could an alternative hemodialysis method in patients at risk of bleeding.

A Case of Concomitant Interstitial Nephritis by BK Virus with Acute Rejection in a Renal Allograft Recipient / 대한신장학회잡지

Polyomavirus BK viral allograft nephritis is a great challenge in posttransplant management and graft survival because of difficulty in diagnosing and treatment. Initial treatment usually involves reducing immunosuppressive medications. However if concomitant acute rejection exist, it is more challenging in managing these patients, because acute rejection requires increase in immunosuppression. We present a case of a 35-year-old man who developed BK viral allograft nephritis and concomitant acute rejection 3 months after transplantation. BK viral allograft nephritis was missed in diagnosis and only pulse steroids for anti-rejection therapy was done. Initially, renal function was improved, but 4 months later, he presented with deterioration in renal function. Second renal biopsy showed BK allograft nephritis without rejection. BK viral DNA in plasma by PCR and urinary decoy cell were also positive. Reduction in immunosuppression by discontinuing mycophenolate mofetil stabilized the deterioration in renal function, however it failed to clear viremia.

Estimation of GFR Using Iohexol Plasma Clearance in Korean without Renal Disease / 대한신장학회잡지

BACKGROUND: Plasma clearance of iohexol (Omnipaque(r)) which used widely in radiologic procedure is considered as useful method for estimation of GFR because iohexol is neither reabsorbed nor secreted from tubule after filtered as inulin and its extrarenal clearance is negligible. Plasma clearance of iohexol can be calculated from two compartment model or one compartment model with Brochner-Mortensen (B-M) modification which convenient and reliable. But there were controversies about sufficient sampling numbers and times for B-M modification of iohexol clearance. METHODS: Nineteen healthy Korean without renal disease underwent measurement of iohexol clearance. Iohexol was given as a single iv dose, and 14 blood sample were drawn up to 300 min. A reference GFR was iohexol clearance calculated from two-compartment model using 14 samples (CL-T). From 8, 3 and 2 samples clearances were calculated by B-M modification (CL-M8, 3 and 2 respectively). The accuracy of estimates was evaluated as percent of estimates falling within 10% above or below the reference GFR. Accuracy of CCr and equations for GFR estimation were also compared. RESULTS: CL-T, CL-M8, CL-M3 and CL-M2 were not different (101.9+/-24.0, 101.9+/-18.7, 101.7+/-18.6, 101.9+/-19.5 mL/min/1.73 m2 respectively). Accuracy of CL-M8, 3 and 2 were not different (74%, 84% and 79% respectively, p>0.05). MDRD equation had higher accuracy (47%) compared with other equations. CONCIUSION: These results indicate that sampling number for measuring iohexol plasma clearance using simplified method might be reduced to only two without accuracy loss in Korean without renal disease.

Randomized Trial of Tacrolimus Versus Cyclosporine in Steroid Withdrawal in Living Donor Renal Transplant Recipients / 대한신장학회잡지

BACKGROUND: The introduction of new immunosuppressants has prompted several trials of steroid withdrawal immunosuppression. However, several groups have reported a higher incidence of rejection. METHODS: We conducted a randomized two-arm, parallel group, open label, prospective study to compare steroid withdrawal (at 6 months post-transplant) regimens: tacrolimus+mycophenolate mofetil (MMF) (FK group) vs cyclosporine+MMF (CyA group). Entry criteria were: first living donor transplant recipient, no diabetes mellitus (DM), no congestive heart failure, no chronic liver disease, and no acute rejection by 6 months post-transplant. The primary endpoint was a biopsy-proven acute rejection episode or treatment failure within 1 year post- transplant. RESULTS: While eighty-seven recipients were assigned to FK (n=43) and CyA group (n=44) before transplantation, seventy-six recipients (FK 39, CyA 37) could taper off steroid at 6 months post-transplant since eleven were excluded due to acute rejection within 6 months post-transplant (FK 2, CyA 3), protocol violation (FK 2, CyA 1), drug change due to side effect (CyA 2) and follow-up loss (CyA 1). After steroid withdrawal, acute rejection episode was 0% in FK group and 13.5% in CyA group (p0.05 in every variable). CONCLUSION: These data suggest that steroid withdrawal are successful in first living donor renal transplant recipients and tacrolimus may be more effective than cyclosporine significantly in preventing acute rejection after steroid withdrawal.

A Case of Spontaneous Renal Artery Dissection Secondary to Fibromuscular Dysplasia and Treatment by Renal Arterial Stenting / 대한신장학회잡지

Isolated spontaneous renal artery dissection (SRAD) associated with fibromuscular dysplasia (FMD) is a rare condition that can result in renal infarction. Treatment and long-term management of patients with this condition is controversial. We report the case of a patient with SRAD secondary to FMD who was treated by renal arterial stenting. A previous healthy 50-year-old white male presented to the emergency department with acute right flank pain. Blood pressure was 150/90 mmHg and serum creatinine was 1.6 mg/dL. A CT scan of the abdomen showed multifocal right renal infarction. The patient was started on anticoagulant regimen of heparin. Renal angiography showed the dissection of right renal artery and stenosis of mid-segment of right main renal artery and intrarenal branches. We decided to perform percutaneous balloon angioplasty and stenting for the purpose of dilating the stenotic renal artery, preventing recurrence of the disease and controlling hypertension and elevated creatinine. A dissected intimal flap was closed successfully by renal artery stenting and stenotic renal artery was dilated by stenting and balloon angioplasty. Five days after the procedure, he was discharged with warfarin. Three months later, he had normal renal function and blood pressure without antihypertensive medication was mildly elevated at 145/104 mmHg. Conclusively, stent implantation to renal artery dissection can be effective, reliable and feasible and can be an alternative to surgical treatment.

A Case of Systemic Vasculitis with Intraperitoneal Aneurysmal Rupture / 대한신장학회잡지

Though systemic vasculitidis are a group of diseases with extremely low incidence and prevalence, vessels with diverse size from aorta to capillaries are involved. It has been argued how to classify and define systemic vasculitidis, especially how to discriminate poly arteritis nodosa (PAN) and microscopic polyangiitis (MPA). Since there are lots of overlapping between them, clinical manifestations, antineuclear cytoplasmic antibody (ANCA) and angiographic findings besides pathologic findings should be considered altogether. We report a case of systemic vasculitis in which crescentic necrotizing glomerulonephritis with positive perinuclear-type ANCA occurred with intraperitoneal aneurysmal rupture simultaneously. Our case can be a typical one that shows definite overlapping between PAN and MPA.

Primary Sjogren's Syndrome with Renal Pseudolymphoma Featuring Interstitial Nephritis / 대한신장학회잡지

A 65 year-old woman with Sjogren's syndrome was found to have renal mass and acute renal failure. Immunopathologic analysis of renal biopsy specimens showed polyclonal lymphocytic interstitial infiltration. Gene rearrangement study of T cell receptor showed a polyclonal pattern. The degree of azotemia and the size of pseudolymphoma diminished dramatically with steroid therapy. This is a case of proven pseudolymphoma that was found as renal mass in Sjogren's syndrome.

Hemodialysis Using Heparin Bound Hemophan Hemodialysis in ESRD Patients at High Risk for Bleeding: A Seven-Year Experience / 대한신장학회잡지

OBJECTIVE: Positively charged N, N-diethyl-aminoehtyl groups on Hemophan enable negative charged heparin to be bound with the dialyzer membrane and hemodialysis using heparin bound Hemophan (HBH- HD) could be a hemodialysis modality in patients at risk of bleeding. We designed simplified heparin binding technique and evaluated the bleeding risk and efficiency of HBH-HD in chronic renal failure patients at risk of bleeding. METHODS: During the period from April 1995 through April 2002, 159 patients at high bleeding risk received 1057 HBH-HD (dialyzer: GFS plus 11, Gambro). The duration of each HBH-HD was standardized to 4 hours at blood-flow rate of 200-250 mL/min. To evaluate safety of HBH-HD, we measured serum heparin concentration (HC) and activated partial thromboplastin time (aPTT) at baseline, 15, 60, 120 minutes and endpoint (240 minutes) (n= 40). To evaluate the dialysis efficiency, HBH-HD and routine hemodialysis with systemic heparinization (R-HD) were compared for total blood compartment volume (TBCV) loss, dialyzer urea clearance (K) and Kt/V in same study group patients (n=20). RESULTS: Clotting of dialyzer necessitating termination of dialysis occurred in 11 (1.0%) out of 1, 057 dialyses at 150 minutes, and clotting requiring change of blood line occurred in 64 dialyses (6.1%) between 150 and 230 minutes. There was a slight increase in the aPTT (mean+/-SD, 49.8+/-10.5 sec) and HC (0.14+/-0.06 U/mL) at 15 min, compared to predialysis levels of 44.3+/-12.9 sec and 0.11+/-0.06 U/ mL, respectively (p>0.05). But no increase in aPTT, HC was observed in measurements at 60 min, 120 min, and at the endpoint. TBCV loss was significantly higher in HBH-HD (mean+/-SD, 17.2+/-9.6%), compared to R-HD (2.8+/-1.2%) (p0.05). CONCLUSION: HBH-HD could be a safe and efficient HD technique in patients at high risk of bleeding. Extracorporeal clotting, however, should be observed carefully during HBH-HD.

A Case of Postinfectious Glomerulonephritis Following Meningococcal Meningitis / 대한신장학회잡지

A 21-year-old male was presented with sudden headache, fever, petechiae and neck stiffness. The diagnosis of meningococcal meningitis was confirmed by examination of cerebrospinal fluid. The clinical symptoms of the illness were improved after treatment of antibiotics. However the patient developed generalized edema, oliguria, azotemia, and heavy proteinuria in the recovery phase of illness. Low serum C3 level was also noted. A kidney biopsy was performed and showed the features of postinfectious glomerulonephritis and typical subepithelial humps on electron-microscopic examination. His symptoms and laboratory findings were improved, and C3 level returned to normal range after conservative treatment. We suggest that a complement deficiency should be ruled out in patients of glomerulonephritis developed during the recovery phase of meningococcal meningitis. C3 nephritic factor detection and renal biopsy should be carefully considered in these patients.

A Case of Light Chain Deposition Disease without Significant Proteinuria / 대한신장학회잡지

A 67-year-old male was admitted to the hospital for evaluation of incidentally detected anemia and mild azotemia. Urinalysis showed no abnormal finding and 24 hr urine protein amount was clinically insignificant (270 mg/day). Urine and serum protein electrophoresis were negative for a monoclonal spike. However, urine and serum immunoelectrophoresis demonstrated the presence of monoclonal free kappa light chains. Renal biopsy showed the features of chronic tubulointerstitial disease and on the immunofluorescence studies, kappa light chain was in a linear pattern in basement membranes of glomeruli and tubules. Work-up for multiple myeloma including bone marrow biopsy showed results compatible with multiple myeloma. Treatment was started with vincristine, adriamycin and doxorubicin at monthly interval for three months followed by autologus peripheral blood stem cell transplantation. At follow-up 5 months after autologus peripheral blood stem cell transplantation, the patient is well with a serum creatinine of 2.3-2.6 mg/dL and 24 hr urine protein of 200-350 mg.

Peritoneopleural Leakage in Continuous Ambulatory Peritoneal Dialysis : Successful Treatment with Video-Assisted Thoracoscopic Talc Pleurodesis / 대한신장학회잡지

Continuous ambulatory peritoneal dialysis (CAPD) is an effective renal replacement therapy for end- stage renal disease. Hydrothorax secondary to leakage of dialysate via pleuroperitoneal communication is a rare complication of CAPD. Earlier treatments of CAPD-induced hydrothorax have included pleurodesis with tetracycline, talc, fibrin, or autologous blood and surgical treatment. These procedure have made many patients switch to hemodialysis, because of the high relapse rate of the former and the invasiveness and morbidity of the latter. The talc pleurodesis with video-assisted thoracic surgery (VATS) allows not only direct visualization of potential diaphragmatic defect but also direct application of the talc to the visceral or parietal pleura. This procedure is less invasive than thoracotomy and can perform more accurate poudrage of talc than conventional methods. We have recently managed a patient CAPD-induced massive hydrothorax using thoracoscopic talc pleurodesis. This patient was successfully returned to CAPD.

Peritoneopleural Leakage in Continuous Ambulatory Peritoneal Dialysis : Successful Treatment with Video-Assisted Thoracoscopic Talc Pleurodesis / 대한신장학회잡지

Continuous ambulatory peritoneal dialysis (CAPD) is an effective renal replacement therapy for end- stage renal disease. Hydrothorax secondary to leakage of dialysate via pleuroperitoneal communication is a rare complication of CAPD. Earlier treatments of CAPD-induced hydrothorax have included pleurodesis with tetracycline, talc, fibrin, or autologous blood and surgical treatment. These procedure have made many patients switch to hemodialysis, because of the high relapse rate of the former and the invasiveness and morbidity of the latter. The talc pleurodesis with video-assisted thoracic surgery (VATS) allows not only direct visualization of potential diaphragmatic defect but also direct application of the talc to the visceral or parietal pleura. This procedure is less invasive than thoracotomy and can perform more accurate poudrage of talc than conventional methods. We have recently managed a patient CAPD-induced massive hydrothorax using thoracoscopic talc pleurodesis. This patient was successfully returned to CAPD.