Effects of Losartan on the Urinary Angiotensinogen Excretion in Chronic Non-diabetic Proteinuric Renal Disease / 대한신장학회지

PURPOSE: There were experimental evidences supporting that intrarenal activation of the renin-angiotensin system contributes to increase BP, proteinuria and urinary angiotensinogen (UAGT) excretion. The purpose of this prospective, open label, controlled study was to investigate the effect of losartan on proteinuria and UAGT excretion in chronic non-diabetic proteinuric (0.4 to 2.0 g/day) renal disease with normal renal function (glomerular filtration rate, GFR>60 mL/min/1.73m2). METHODS: Thirty two patients were randomly allocated to the losartan group (100 mg/day; n=17) or the control group (n=15). Systolic BP, diastolic BP, estimated GFR, urinary protein to creatinine ratio (UP/Cr), UAGT and plasma angiotensinogen (PAGT) level were compared between two groups at baseline, 6 months and 12 months. RESULTS: UP/Cr (1.13+/-0.36 g/g vs. 1.07+/-0.34 g/g) was similar in two groups at baseline. Target BP (<140/90 mmHg) was maintained in both groups. After 6 months, UP/Cr (0.63+/-0.35 g/g vs. 0.97+/-0.41 g/g, p<0.01) was significantly decreased in the losartan group compared to the control group. In addition, UAGT (baseline 1.0) was noticeably suppressed in the losartan group (0.72+/-0.42 vs. 1.07+/-0.81, p=0.13). However, PAGT was not changed in both groups. Moreover, our study at 12 months period has demonstrated continuous suppression of UP/Cr (0.79+/-0.53 g/g vs. 1.00+/-0.50 g/g, p=0.06) and UAGT (0.60+/-0.51 vs. 1.51+/-1.36, p<0.05) in the losartan group. UP/Cr was highly correlated with UAGT (Correlation Coefficient=0.74, p<0.01), but not with PAGT. CONCLUSION: Losartan not only induced a remarkable decrease in proteinuria but also contributed a reduction in UAGT in patients with chronic non-diabetic proteinuric renal disease.

Association of Metabolic Syndrome in Non-diabetic and Non-hypertensive Adults with Increased Risk for Chronic Kidney Disease / 대한신장학회지

PURPOSE: The significance of metabolic syndrome (MS) was recently raised as a risk factor in chronic kidney disease (CKD). Diabetes and hypertension are not only well known diagnostic criteria for MS, but also risk factors for CKD. However, the association between MS and CKD in patients without diabetes and hypertension is unknown. METHODS: A total of 9586 subjects who registered in the health check service at Samsung Medical Center between January 2004 and December 2005 were included. MS was defined according to the criteria of the revised ATP III, and CKD was defined by the reduction of the glomerular filtration rate or the appearance of albuminuria. RESULTS: The prevalence of MS was 9.0% of study subjects. CKD was noticed in 6.2% of the subjects without MS, and 13.1% with MS. MS was a significant determinant of CKD {Odd ratio (OR) 1.80 and 95% confidence interval (CI) 1.42-2.28, p<0.001}. Compared with subjects lacking components of MS, subjects with one, two, three, four or five components of MS had a higher risk of acquiring CKD (OR, 1.04, 1.43, 1.89, 2.48, 3.29, Respectably). The relationship between each component of MS and CKD was different according to sex and age groups. Abdominal obesity was a significant determinant for CKD in female subjects, while high fasting glucose levels were a significant determinant in younger subjects (<60 years) (p<0.05). CONCLUSION: Even in non-diabetic and non-hypertensive adults, MS is independently associated as a risk factor for CKD.

Mycophenolate Mofetil or Intravenous Cyclophosphamide for the Initial Induction Therapy of Lupus Nephritis; Clinical Observations / 대한신장학회지

PURPOSE: The combination of intravenous cyclophosphamide (CYC) and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects. Mycophenolate mofetil (MMF) Is a new immunosuppressive agent that selectively inhibits activated lymphocytes. This study reports on the clinical experiences at our clinic with MMF and intravenous CYC for the initial induction treatment in patients with lupus nephritis. METHODS: 50 patients with lupus nephritis received induction therapy consisting of MMF and prednisolone (n=22) or intravenous CYC and prednisolone (n=28), and followed up for six months. Complete remission was defined as a value for urinary protein: urinary creatinine ratio (U(p/Cr)) that was less than 0.3, with normal urinary sediment, a normal serum albumin concentration and values for serum creatinine that were no more than 15 percent above the base-line values. Partial remission was defined as a value for U(p/Cr) that was between 0.3 and 2.9, with a serum albumin concentration of at least 3.0 g/dL. RESULTS: 22 patients treated with MMF and 28 patients with intravenous CYC resulted in complete remission (31.8% vs 39.3%), partial remission (45.5% vs 39.3%) and treatment failure (22.7% vs 21.4 %). Fewer severe infections occurred among patients treated with MMF and prednisolone. CONCLUSION: As for the induction therapy of lupus nephritis, the combination of MMF and prednisolone may be an effective regimen. However, further randomized, prospective studies are needed to prove the effectiveness of MMF therapy in lupus nephritis.

Brain Natriuretic Peptide (BNP), N-terminal pro-BNP (NT-proBNP) and Cardiac Troponin T (cTnT) as Markers of Cardiac Diseases in Stable Hemodialysis Patients / 대한신장학회지

PURPOSE: The prevalence of coronary artery disease and left ventricular hypertrophy (LVH) is higher in patients with chronic kidney disease (CKD) than in the general population. In the general population, BNP, NT-proBNP, and cTnT are useful markers of cardiac disease. Recently, studies on biomarkers in patients with CKD have been reported. However, the effect of renal disease on these markers is still uncertain particularly in hemodialysis patients. We investigated the potential of BNP, NT-proBNP, and cTnT as biomarkers of cardiac disease in hemodialysis patients. Methods: We prospectively studied 27 hemodialysis patients without cardiovascular event within the last 6 months. We performed an echocardiography and blood samples for plasma BNP, NT-proBNP and cTnT. RESULTS: Median BNP, NT-proBNP, and cTnT level (pg/mL) were 433, 10,598, and 0.021, respectively. NT-proBNP was correlated with BNP (r=0.940, p=0.000) and cTnT (r=0.504, p=0.009). There was a negative correlation between BNP and left ventricular ejection fraction (LVEF) (r=-0.502, p=0.008), between NT-proBNP and LVEF (r=-0.556, p=0.003), and between cTnT and LVEF (r=-0.513, p=0.007). There was a positive correlation between BNP and LV mass index (LVMI) (g/m2) (r=0.619, p=0.001). Also, a positive correlation between NT-proBNP and LVMI was shown (r=0.718, p=0.000). There was an insignificant positive correlation between cTnT and LVMI (r=0.369, p=0.063). Albumin, cholesterol, LDL-cholesterol, and NT-proBNP had an independent effect on LVEF (R2=0.80). Age, body mass index, LDL-cholesterol, NT-proBNP, and cTnT had an independent effect on LVMI (R2=0.78). Conclusion: BNP, NT-proBNP, and cTnT may be as a noninvasive diagnostic or prognostic marker of cardiac disease in stable hemodialysis patients.

Two cases of adenovirus pneumonia treated with cidofovir / 대한내과학회지

Adenovirus is one of the major viral cause of upper respiratory tract infection. Life-threatening adenovirus pneumonia is often reported in neonates, young children and immunocompromised hosts. It can rarely occur in previously healthy adults. Because there is no report on adenovirus pneumonia in adult patients in Korea, we report two cases of adenovirus pneumonia which developed in adult women. Despite of intravenous antibiotics therapy, the respiratory distress worsened and mechanical ventilation was applied. Microbiological tests for bacteria or fungi were negative. A high-resolution chest computed tomography showed bilateral patch ground-glass opacification. Subsequently, open lung biopsy specimen revealed diffuse alveolar damage and adenovirus was documented with immunohistochemical stain. Treatment with cidofovir led to prompt clinical improvement in our cases.

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.

Plasma Levels of N-terminal pro-brain Natriuretic Peptide (NT-proBNP) and Left Ventricular Function in Patients with Chronic Renal Failure / 대한신장학회잡지

BACKGROUND: Circulating levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) have been used to identify and monitor myocardial dysfunction in patients with various cardiac diseases. However, its clinical significance in patients with chronic renal failure (CRF) is uncertain because NT-proBNP clearance may be affected by renal function. METHODS: We studied 331 patients with CRF (eGFR 0.01) was strong independent correlate of NT-proBNP, eGFR (beta=-0.358, p0.01) and diastolic dysfunction 2 or higher (beta=0.171, p< 0.05) were also independent correlates of NT-proBNP. Receiver-operating characteristic (ROC) analyses demonstrated NT-proBNP to be 75% sensitive and 76% specific for the detection of left ventricular systolic dysfunction, as indicated by area under the ROC curve of 0.78 (p<0.05), with NT-proBNP cutoff concentration of 25,000 pg/mL. CONCLUSION: Circulating NT-proBNP levels increased with declining renal function. However, its level were significantly correlated with LVH, systolic and diastolic dysfunction in patients with CRF. The measurement of NT-proBNP levels might be useful to predict left ventricular dysfunction in patients with CRF.

A Case of Sarcoidosis Presented with Myofasciitis / 대한류마티스학회지

Sarcoidosis is a systemic granulomatous disorder of unknown cause. The isolated noduar type muscular sarcoidosis without other systemic involvement is very rare in Korea. We report a case of sarcoidosis presented with myofasciitis. A 46-year-old man visited hospital with painful nodular swelling on the right arm for 1 month. We performed a humerus MRI and it revealed irregular shaped subcutaneous mass infiltrating along the fascial plane. The biopsy of triceps mass showed non-caseating granuloma of muscle and fascia. To find out the cause of granuloma, we checked chest CT scan and found out some enlargement of mediastinal lymph nodes. The biopsy also demonstrated non-caseating granulomas. It had no cancerous component and culture for microorganisms were all negative. He was diagnosed as sarcoidosis and given NSAID. On follow up evaluation, the size of mass was decreased.

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.