The Effectiveness of the Serum IgA Level in Diagnosing IgA Nephropathy / 대한신장학회잡지

BACKGROUND: Immunoglogulin A(IgA) nephropathy is the most common primary glomerular disease throughout the world. 30-50% of patients with IgA nephropathy(IgAN) have high serum IgA concentrations. However, we do not know if the degree of elevation in IgA level increases the likelihood of having IgAN. Neither do we know if the IgA level has any association with pathological findings of IgAN. METHODS: We analyzed the relationships between IgAN and the levels of serum IgA which has been a routine part of the study in all patients with glomerulonephritis in our institution for the last 4 years. We reviewed 270 patients in whom the pathological diagnosis and the results of their IgA levels were both available. RESULTS: Of 80 patients who were IgA nephropathy, 26 patients(32.5%) had higher than normal cut- off value of serum IgA(385 mg/dL). In contrast, 8.9 % of patients with other types of glomerulonephropathies showed the values above normal(p<0.0001). The risk ratio for an increase of one unit of the IgA level was 1.0025(logistic regression, p=0.0043), which was increased to 1.0079 when patients with low complement levels were excluded from the analysis. The data were also analyzed according to the immunofluorescence microscopic findings of IgAN, which were found to have no significant correlation with IgA concentrations. CONCLUSION: The IgA level is a risk factor for IgAN throughout the whole range. However, it does not correlate with the IgA deposition in the renal tissue. We believe that this study will help understanding the interpretation of IgA levels in patients with IgAN.

Cyclophosphamide: Induced lung toxicity in a patient with Wegener's granulomatosis / 대한내과학회지

Lung toxicity associated with cyclophosphamide use is a rare but serious side effect, that may result in a fatal course. However no such cases have been reported in Korea, so clinicians would not be alert to this adverse effect. We recently experienced a woman with Wegener's granulomatosis and idiopathic pulmonary fibrosis. This patient had been administered 12 grams of cyclophosphamide for 4 months. At that time of admission, She felt aggravating dyspnea on exertion for 2 weeks. Her chest x-ray and high resolution CT revealed aggravated reticular opacities and ground glass appearances. Dyspnea was improved and ground glass appearances on HRCT was disappeared after discontinuation of cyclophosphamide. We diagnosed this case as cyclophosphamide-induced pneumonitis and report it with a brief review of the literature.

The Clinical Experience of Hemodialyzer Reuse / 대한신장학회잡지

The major clinical advantages of dialyzer reuse are improved biocompatibility and a decrease in the frequency of the first use syndrome. Dialyzer reuse has made it possible to use biocompatible high flux membranes of the high price. Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, it is not widely accepted in Korea. At Ajou University Hospital, we have reprocessed dialyzers since March 2000, and here we report our clinical experience for the 1st 8 weeks. We used high flux dialyzers with reprocessing practice in 24 chronic hemodialysis patients. Dialyzer reprocessing was performed by an automated machine(Renatron) using Renalin. We limited reuse upto 20 times, and we were able to reuse dialyzers upto this number in 17 patients. During the study period, no significant complication was observed as a result of the reuse program. Kt/Vurea and urea reduction ratio(URR) were not different between high and low flux dialyzers(1.41+/-0.29 vs 1.61+/-0.41 for Kt/Vurea and 66.70+/- 6.40% vs 65.69+/-5.63% for URR). In contrast, beta2-microglobulin(beta2M) reduction ratio and clearance were greater in high flux dialyzers than low flux dialyzers(p<0.001, -9.52+/-20.28% vs 42.00+/-8.61% for beta2M reduction ratio and 9.54+/-11.71mL/min vs 48.54+/-14.33mL/min for beta2M clearance). Kt/Vurea, URR, beta2M reduction ratio and beta2M clearance did not deteriorate with the increasing number of reuse. The predialysis values of beta2M decreased by 51% after 19 uses(p<0.001, 37.04+/-13.39 to 18.98+/-3.41mg/L). In summary, during the short pilot study period of 8 weeks, no significant clinical complication was encountered as a result of dialyzer reuse, and our results confirmed the effects of high flux dialyzers on removal of beta2M.

The Clinical Experience of Hemodialyzer Reuse / 대한신장학회잡지

The major clinical advantages of dialyzer reuse are improved biocompatibility and a decrease in the frequency of the first use syndrome. Dialyzer reuse has made it possible to use biocompatible high flux membranes of the high price. Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, it is not widely accepted in Korea. At Ajou University Hospital, we have reprocessed dialyzers since March 2000, and here we report our clinical experience for the 1st 8 weeks. We used high flux dialyzers with reprocessing practice in 24 chronic hemodialysis patients. Dialyzer reprocessing was performed by an automated machine(Renatron) using Renalin. We limited reuse upto 20 times, and we were able to reuse dialyzers upto this number in 17 patients. During the study period, no significant complication was observed as a result of the reuse program. Kt/Vurea and urea reduction ratio(URR) were not different between high and low flux dialyzers(1.41+/-0.29 vs 1.61+/-0.41 for Kt/Vurea and 66.70+/- 6.40% vs 65.69+/-5.63% for URR). In contrast, beta2-microglobulin(beta2M) reduction ratio and clearance were greater in high flux dialyzers than low flux dialyzers(p<0.001, -9.52+/-20.28% vs 42.00+/-8.61% for beta2M reduction ratio and 9.54+/-11.71mL/min vs 48.54+/-14.33mL/min for beta2M clearance). Kt/Vurea, URR, beta2M reduction ratio and beta2M clearance did not deteriorate with the increasing number of reuse. The predialysis values of beta2M decreased by 51% after 19 uses(p<0.001, 37.04+/-13.39 to 18.98+/-3.41mg/L). In summary, during the short pilot study period of 8 weeks, no significant clinical complication was encountered as a result of dialyzer reuse, and our results confirmed the effects of high flux dialyzers on removal of beta2M.

The Effect of ACE Inhibitors on The Gene Expression of TGF-beta and TNF-alpha in Renal Tissues from Patients with IgA Nephropathy / 대한신장학회잡지

Progressive nephropathies are characterized by the enhanced accmulation of extracellular matrix in the kidney. Overproduction of transforming growth factor-beta(TGF-beta) was shown to result in pathological fibrosis of tissue via the accumulation of extracellular matrix proteins. It has been proposed that angiotensin II stimulates the production of TGF-beta. Despite accumulating volume of data supporting the effects of angiotensin converting enzyme(ACE) inhibitors in the attenuation of TGF-beta in vitro and in rats, studies in humans are absolutely lacking. There is evidence that TNF-alpha expression is increased in various glomerulonephritis. The present study sought to determine the effects of ACE inhibitors on TGF-beta1 and TNF-alpha in patients with IgA nephropathy. Using competitive polymerase chain reaction, TGF-beta1 and TNF-alpha mRNA abundance were measured. Patients taking ACE inhibitors showed significantly lower renal TGF-beta1 gene expression compared with patients not on these medications(ratios of TGF-beta1/beta-actin, 4.27+/-0.62 versus 14.81+/-3.87, p<0.05), whereas no difference was noted between patients on ACE inhibitors and normal controls(4.27+/-0.62 versus 2.78+/-0.71). ACE inhibitor therapy did not affect the TNF-alpha mRNA expres- sion in renal tissue. In conclusion, we observed a significant reduction of the TGF-beta1 expression in the kidney by ACE inhibitors, and this suggests that the effects of ACE inhibitors observed in animals can be extrapolated to patients with chronic renal disease.

Blood Volume Change and Side Effects during Various Sodium Ramping in Hemodialysis / 대한신장학회잡지

Chronic hemodialysis patients frequently experience hemodialysis(HD)-related side effects caused by excessive ultrafiltration and abrupt change of osmolality. Sodium ramping in HD is known to reduce ultrafiltration-related side effects, but it frequently induces symptoms related to sodium overload. We wanted to know the relationship between blood volume changes and the side effects related to ultrafiltration during hemodialysis and whether we can individualize various sodium ramping methods according to the effect of change in blood volume( BV) and side effects of sodium ramping. We studied 9 hypotension-prone patients during HD. The duration of the study lasted for 5 weeks, each week using different sodium ramping protocols: protocol 1; dialysate [Na+] of 140mEq/L, protocol 2; dialysate [Na+] same as the predialysis serum [Na+], protocol 3; dialysate [Na+] was 20mEq/L greater than that of the patient's serum for 1hr, 10mEq/L greater than patient's serum [Na+] for 2hr and then the same as patient's serum [Na+] for the last 1hr, protocol 4; at the beginning of dialysis, dialysate sodium was ramped to 20mEq/L above the patient's serum sodium and then on a straight linear fashion lowered to the predialysis serum [Na+] at the end of dialysis, protocol 5; sodium was constantly ramped to 10 mEq/L above serum [Na+]. We measured the BV with Crit-Line IIR(In-Line Diagnostics, Corp., Riverdale, USA), the blood pressure during each HD and interdialytic weight gain. We documented subjective symptoms which occurred during the 5 treatment protocols by patient's questionnaire after each HD. The results were as follows. 1) The mean age of the patients(M:F=3:6) was 54.1years and 6 patients were diabetics. 2) There was no significant difference in the BV among the 5 protocols in both whole study population and individual. Neither was there a statistically significant difference in the BV with respect to hypotension during HD. 3) There were no episodes of hypotension(P value <0.001) with protocols 3, 4, 5 compared to protocols 1 and 2. 4) Three patients during protocols 4 and 5 experienced more thirst after HD than during protocol 1 and one patient during protocol 4, 5 had more interdialytic weight gain than the protocol 1. As a whole, patients while on protocol 4 & 5 experienced more thirst than protocol 1 but patients during protocol 3 experienced the same degree of thirst as protocol 1. In summary, sodium ramping reduced HD-related side effects but this benefit could not be explained on the basis of blood volume change measured by the Crit-Line IIR. Protocol 3 may be more appropiate sodium ramping method in 4 of the 9 patients. These data suggest that protocol 3 may be used before protocol 4, 5 when we apply sodium ramping to the patients who frequently have hypotension during HD.

The Effect of ACE Inhibitors on the Gene Expression of Various Cytokines in Peripheral Blood Mononuclear Cells from Patients with Glomerular Diseases: TGF-beta, IL-6, IL-10 and TNF-alpha / 대한신장학회잡지

Angiotensin II(ANG II) has been known to induce systemic and glomerular hypertension, which leads to renal tissue injury and progressive fibrosis of kidney. Some effects of ANG II may be mediated by its effect on the cytokine synthesis. In the present study, we investigated the effect of ANG II inhibition on the expression of various cytokines implicated in the pathogenesis and progression of the kidney disease. Blood samples of 11 patients with glomerulonephritis were obtained before the ACE inhibitor therapy and then while they were taking ACE inhibitors. Using peripheral blood mononuclear cells(PBMC) harvested from the samples, RT-PCR was performed to evaluate the changes in mRNA expression of TGF-beta1, IL-6, TNF-alpha and IL-10. The ratios of target cytokines and beta-actin were calculated. TGF-beta1 mRNA expression was decreased in five pat ients after ANG II inhibition with ACE inhibitors, while it was increased in the remaining six patients. ACE inhibitors consistently decreased IL-6 mRNA expression in all 11 patients. IL-10 expression was decreased in 4 patients, and increased in 3 patients after ANG II inhibition. It was not expressed in 4 patients. TNF-alpha expression was increased in 8 patients, and decreased in only 1 patient. In two patients, it was not changed while on ACE inhibitors. Conclusion: ACE inhibitors attenuate IL-6 expression consistently in all 11 patients. This is the first-time demonstration of the in vivo inhibitory effect of ACE inhibitors on IL-6 mRNA expression in humans. The lack of significant suppression of TGF-beta1 in PBMC suggests that the in vivo attenuating effect of ACE inhibitors on TGF-beta1 may be derived from renal hemodynamic changes. The tendency of heightened expression of TNF-alpha confirms the previous investigations in which IL-6 was shown to down regulate TNF-alpha expression

Cystoscopy in the Evaluation of Hematuria / 대한신장학회잡지

Hematuria is a common presentation of bladder cancer. As medical examinations for health screening are becoming more popular, increasing number of patients are found to have hematuria. When to refer these patients to urologists for cystoscopy is a common problem to nephrologists and a matter of debate as well. In fact, many authors differ in their opinions on this issue, especially in cases of microscopic hematuria. Given the fact that the incidence of bladder cancer varies between countries, it will be reasonable that the investigation strategy for Koreans should be determined according to the studies on Korean people. In the present study, we retrospectively analyzed 349 patients who underwent cystoscopic examinations in our institution to investigate causes of microscopic or gross hematuria. Bladder cancer was detected on cystoscopy in 35(15.9%) of 220 patients with gross hematuria, in contrast to patients with microscopic hematuria in whom 2(1.6%) of 129 patients were found to have bladder cancer. Eighty nine percents of cancer patients were male. Bladder cancer was detected even in relatively young patients with gross hematuria, while no bladder cancer was found in patients with microscopic hematuria below 60 years of age. Urine cytology was revealing in 59.5% of cancer patients. Bladder cancer was detected in 71.4% and 76.2% of cancer cases by sonography and IVP, respectively. Urine protein by dipstick was unreliable in predicting the presence of cancer. In conclusion, decision on cystoscopy in patients with asymptomatic microscopic hematuria younger than 50-60 years of age should be made conservatively, while more aggressive diagnostic work up is necessary in patients with gross hematuria regardless of their age.

Lactic Acidosis Associated with Acute Lymphoblastic Leukemia / 대한신장학회잡지

Occurence of lactic acidosis with adequate tissue oxygenation(type B lactic acidosis) has been described in association with leukemia, lymphoma, small cell carcinoma and breast cancer. However, no such case has been reported in Korea. Therefore, we report a case of type B lactic acidosis in a man with rapidly progressing acute lymphoblastic leukemia which had been transformed from lymphoma.

A Case of Distal Renal Tubular Acidosis Detected after Glue Sniffing / 대한신장학회잡지

We describe a case of distal renal tubular acidosis in a 20-year-old woman with a history of glue sniffing. On admission she complained of nausea and somnolence. Severe hypokalemia and hyperchloremic metabolic acidosis with normal anion gap were noted. Her urinary osmolar gap and anion gap results were consistent with presence of renal tubular acidosis. Bicarbonate loading test along with urine PCO2 confirmed that she had type 1 renal tubular acidosis due to hydrogen ion secretion defect. Immunohistochemical staining of renal biopsy specimen with anti H+-ATPase antibody showed absence of proton pump in the collecting duct. Thus a case of distal renal tubular acidosis in association with glue sniffing is reported with a review of literatures.

Factors Affecting Serum Albumin Level in Continuous Ambulatory Peritoneal Dialysis Patients / 대한내과학회지

OBJECTIVES: Protein-calorie malnutrition is a common problem in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Serum albumin(SA) concentration has been used as a marker for assessing nutritional status. Hypoalbuminemia has been linked to an increased risk of morbidity and mortality and more numerous, prolonged hospitalization for peritoneal dialysis patients. The aim of this study was to determine factors affecting SA value in CAPD patients. METHODS: We performed a cross-sectional study which included patients' demographics, anthropometric data, biochemical parameters, urea kinetic data and comorbidity in 106 stable CAPD patients. RESULTS: 1) There were 50 men and 56 women with a mean CAPD duration of 43 months and mean age of 49 years. The mean concentration of SA was 3.9+/-0.5 (range 2.5-5.3) g/dl and weekly Kt/Vurea 2.0+/-0.4 (range 1.32-3.79) 2) Twenty-one patients(20%) were classified as group I(SA<3.5g/dl)and the remaining patients(80%) as group II(SA 3.5g/dl) 3) Group I patients were significantly older(55+/-11 vs 47+/-11 years, p<0.05) and had significantly higher comorbidity score(1.5+/-0.8 vs 0.7+/-0.9, p<0.05), C-reactive protein (4.5+/-0.9 vs 0.5+/-0.1 mg/dl, p<0.05), 24-hr dialysate-toplasma creatinine(D/PCr) ratio(0.84+/-0.1 vs 0.76+/-0.1, p<0.05), 24-hr dialysate protein (7167+/-2031 vs 5471+/-1515 mg, p<0.05) and had significantly lower residual renal function(RRF)(0.2+/-0.3 vs 0.7+/-1.2 ml/min, p<0.05), BUN(48+/-14.8 vs 55.6+/-14.9 mg/dl, p<0.05), serum creatinine(10.4+/-2.8 vs 12.6+/-3.5 mg/dl, p<0.05), IGF-1(186+/-99 vs 260+/-131 ng/ml, p<0.05), serum phosphorus(4.1+/-1.2 vs 5.0+/-1.3 mg /dl, p<0.05) than group II.4) SA showed positive correlation with anion gap (r=0.43, p value=0.001), transferrin(r=0.41, p value= 0.001) phosphorus(r=0.31, p value=0.001) and negative correlation with 24-hr dialysate protein loss(r=-0.51, p value=0.001), 24-hr D/PCr ratio(r=-0.49, p value=0.001), comorbidity score(r=-0.36, p vluue=0.001). NPCR(r=0.22, p value=0.023), IGF-1(r=0.30, p value=0.002), BUN(r=0.23, p value=0.016) weakly correlated with SA.5) By stepwise multiple logistic regression analysis, age, CRP, 24-hr D/PCr ratio and RRF independently influenced SA level. CONCLUSION: SA level seems to be affected by non-nutritional factors such as age, peritoneal membrane transport characteristics, residual renal function and presence of acute phase protein response manifested by CRP elevation, in addition to nutritional factors.

A Case of Acute Pancreatitis as a Complication of Systemic Lupus Erythematosus / 대한신장학회잡지

Systemic lupus erythematosus(SLE) is a multisystem disease. Gastrointestinal manifestations are common in SLE, occurring in 35% to 40% of patients at some stage of their illness. Acute pancreatitis is a rare complication of SLE. To date, seventy cases of acute pancreatitis related to SLE have been reported and fourteen cases were unrelated to drugs such as steroids, diuretics or other immunosuppressive agents. Furthermore, only seven out of fourteen cases manifested acute pancreatitis in their initial course of SLE as was seen in our case. Additionally, there have been no such cases reported in Korea. Corticosteroids have been considered as both a cause and as a therapy for acute pancreatitis. We report a case of acute pancreatitis in a 40 year old Korean man presenting with multi-organ manifestations and diagnosed to have SLE. Renal biopsy showed membranous glomerulonephritis(WHO Class V). His serum amylase and lipase returned to normal on high dose prednisolone treatment.

A Prospective Comparative Study Between Manual and Automated Renal Biopsy by Randomized Sampling / 대한신장학회잡지

OBJECTIVES: Percutaneous renal biopsy may be carried out in several ways. Recently, the use of a spring-loaded biopsy gun has become popularized. There have been much controversies on the tissue adequacy and the incidence of complications when compared to the manual biopsy. The present study was performed to compare tissue adequacy and the incidence of complications between manual biopsy and automated biopsy. METHODS: We have studied 108 patients in whom the method of renal biopsy was assigned to one of the two methods[14G Tru-cut needle manual bx (group I) and 18G automated gun biopsy(group II)] according to their national resident's identification number in a randomized and prospective manner. RESULTS: There were 50 patients in group I and 58 patients in group II. There was no difference in gender, age, hemoglobin, prothrombin time, partial thromboplastin time, diastolic and systolic blood pressure pre-biopsy in group I and II. Indications for biopsies were proteinuria accompained by hematuria (37%), proteinuria(34.3%), acute renal failure (9.3%), SLE (8.3%), chronic renal failure (5.6%), hematuria only (5.6%). In Group I the number of passes was 2.4+/-0.8, the glomeruli obtained were 25.3+/-13.2 and the number of glomeruli per pass were 11.6+/-6.5, and in Group II 3.4+/-1.1, 19.4+/-10.8, and 6.8+/-4.0, respectively. These showed a significant difference (p<0.05). In all cases pathological diagnosis were possible. The histology showed IgA nephropathy in 27.8%, MCNS in 14.8%, lupus nephritis in 11.1, MGN in 11.1%, MPGN in 7.4%, and others. The incidence and area of perinephric hematoma demonstrated on ultrasound 24 hours post-biopsy was increased in group I (24%, 937.7+/-640.0mm2 compared to 10.3%, 372.4+/-327.4mm2 in group II) although no statistically significant difference existed. There was no significant difference in gender, age, prothrombin time, partial thromboplastin time, systolic and diastolic blood pressure between the group with and without hematomas. Hematocrit levels before and after biopsy showed a significant difference (34.5+/-8.2, 33.5+/-8.1, p<0.05) in group I, but no significant difference was observed in group II (34.7+/-6.4, 34.8+/-6.4). CONCLUSION: Both techniques rendered adequate tissue sampling, but the extent of bleeding seems to be more severe with manual 14G Tru-cut needle biopsy.

Emergency Debridement with Empirical Antibiotics Treatment for Clinically Diagnosed Vibrio Sepsis / 감염

BACKGROUND: To evaluate the role of emergency debridement performed in conjunction with an empirical antibiotic therapy in clinically diagnosed, full-blown Vibrio vulnificus sepsis. METHODS: Immediate surgical debridement was performed on 13 out of 15 patients who were clinically diagnosed as having Vibrio vulnificus sepsis. RESULTS: Among 15 patients Vibrio vulnificus was isolated in 8 patients. Underlying diseases were liver cirrhosis (2), chronic alcohol ingestion or chronic liver disease (10), diabetes mellitus (3), gastrectomy (1) and in 4 cases no underlying condition was identified. All patients had skin lesions such as erythema, bulla, vesicle and gangrene. All but one initially showed variable degree of hypotension, thrombocytopenia, hepatic dysfunction, renal failure and mental confusion. Their mean APACHE III score was 84. Immediate survival (within 48hrs) in clinically diagnosed Vibrio sepsis was 80% (12/15) and long term survival rate among them was 66.6%. Forty-eight hour survival rate in bacteriologically confirmed cases of Vibrio vulnificus sepsis was 75%, where their long-term survival was 62.5%. CONCLUSION: In treating full-blown Vibrio vulnificus sepsis, immediate emergency surgical debridement performed in conjunction with the empirical antibiotics gives a possibility to improve both immediate and long term prognosis of the disease.