Association of ambulatory blood pressure monitoring with renal outcome in patients with chronic kidney disease

Background@#The significance of ambulatory blood pressure (ABP) in Korean patients with chronic kidney disease (CKD) in relation to renal outcome or death remains unclear. We investigated the role of ABP in predicting end-stage renal disease or death in patients with CKD. @*Methods@#We enrolled 387 patients with hypertension and CKD who underwent ABP monitoring and were followed for 1 year. Data on clinical parameters and outcomes from August 2014 to May 2018 were retrospectively collected. The composite endpoint was end-stage renal disease or death. Patients were grouped according to the mean ABP. @*Results@#There were 66 endpoint events, 52 end-stage renal disease cases, and 15 mortalities. Among all patients, one developed end-stage renal disease and died. Mean ABP in the systolic and diastolic phases were risk factors for the development of composite outcome with hazard ratios of 1.03 (95% confidence interval [CI], 1.01-1.04; P < 0.001) and 1.04 (95% CI, 1.02-1.07; P = 0.001) for every 1 mmHg increase in BP, respectively. Patients with mean ABP between 125/75 and 130/80 mmHg had a 2.56-fold higher risk for the development of composite outcome (95% CI, 0.72-9.12; P = 0.147) as compared to those with mean ABP ≤ 125/75 mmHg. Patients with mean ABP ≥ 130/80 mmHg had a 4.79-fold higher risk (95% CI, 1.68-13.70; P = 0.003) compared to those with mean ABP ≤ 125/75 mmHg. Office blood pressure (OBP) was not a risk factor for the composite outcome when adjusted for covariates. @*Conclusion@#In contrast to OBP, ABP was a significant risk factor for end-stage renal disease or death in CKD patients.

The Mildly Elevated Serum Bilirubin Level is Negatively Associated with the Incidence of End Stage Renal Disease in Patients with IgA Nephropathy

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: 0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.

The Prevalence of Chronic Kidney Disease and the Predictors of Decreased Kidney Function in Hypertensive Patients / 대한신장학회지

PURPOSE: Hypertension (HT) has been known to play an important role in progression of chronic kidney disease (CKD). However, limited data are available in Korean HT patients. We evaluated the prevalence of CKD and the predictors of decrease in kidney function (DKF) in HT patients. METHODS: We retrospectively analyzed the medical records of outpatients with HT in Bundang Seoul National University hospital. DKF was defined as annual loss of estimated glomerular filtration rate (eGFR) more than 7% of baseline eGFR. RESULTS: The prevalence of CKD was 51% in 981 total participants. In HT patients without CKD (NCKD-HT), the incidence of DKF was 46.2%. The incidence of DKF in HT patients with CKD (CKD- HT) was 40.8%. Age was only baseline risk factor of DKF in NCKD-HT group. In multifactorial analysis, history of diabetes mellitus (odds ratio [OR], 2.99; 95% Confidence Interval [CI], 1.88+/-4.78), hemoglobin levels (OR, 0.86; 95% CI, 0.76+/-0.98), proteinuria (OR, 1.86; 95% CI, 1.16+/-2.98), and hematuria (OR, 1.62; 95% CI, 1.02+/-2.58) were related to DKF in CKD-HT group. CONCLUSION: We suggest that the prevalence of CKD in HT patients is high and DKF is frequent in both NCKD-HT and CKD-HT groups. The pattern of the predictors of DKF shows the difference between the two groups. Especially diabetes, abnormal urinalysis, and anemia are strongly associated with DKF in CKD-HT group.

The Prevalence and the Associated Disorders of Chronic Kidney Disease in Subjects with Health Check-Up / 대한신장학회지

PURPOSE: The prevalence of chronic kidney disease (CKD) is increasing in Korea. Considerable resources have been consumed for patients with CKD. This study investigated the prevalence, the associated disorders, and the awareness of CKD and the current status of appropriate control for blood pressure and blood sugar in subjects with CKD. Methods: We included 14,856 subjects who underwent a health check-up in Seoul National University Bundang Hospital during the last 2 years. We selected K/DOQI guideline of CKD. We used the modified MDRD equation to estimate the glomerular filtration rate (eGFR). RESULTS: The mean eGFR was 83.3 mL/min/1.73m(2) and it decreased with aging at the rate of 5 (mL/ min/1.73m(2))/10 years. The prevalences of CKD stage 1, stage 2, and stage more than 3 were 3.2%, 9.4%, and 3.5%, respectively. The prevalence of CKD was higher in subjects with hypertension or diabetes mellitus than in subjects without it. The CKD was associated with disorders of hypertension, cardiovascular diseases, hyperuricemia, hyperphosphatenemia, hyperkalemia, and hypertriglyceridemia. The prevalence of reported kidney disease was only 6.5% in subjects with eGFR less than 60 mL/min/1.73m(2). The frequency of adequate control of blood pressure and blood sugar in subjects with CKD was lower than in subjects without CKD. Conclusion: The subjects were rarely aware of CKD whereas the frequencies of CKD and the associated diseases were considerably high. We have to pay more attention to diagnose and treat the CKD.

Removal of Amikacin in Patients Undergoing Continuous Venovenous Hemodiafiltration / 대한신장학회잡지

BACKGROUND: The purpose of this study was to investigate the pharmacokinetics of amikacin in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF). METHODS: Pharmacokinetic parameters in each of six renal failure patients were estimated by measurement of amikacin levels in serum and effluent samples. RESULTS: Average clearance of amikacin by CV VHDF was 28.5+/-4.6 mL/min (mean+/-standard deviation). The sieving coefficient was 0.62+/-0.2 in the hemodiafiltration system of Gambro AN69 membrane set. Volume of distribution of amikacin was estimated to be 0.47+/-0.08 L/kg lean body weight. The half-life of amikacin was significantly reduced by hemodiafiltration to 11.4+/-1.6 hr. 40% of the administered amikacin was removed by CVVHDF over the 24 hour study period. CONCLUSION: We recommend that 10 mg/kg of amikacin should be given i.v. every 48 hours to critically ill patients during CVVHDF. However, individualized approach based on therapeutic drug monitoring of plasma amikacin concentration is necessary for optimum amikacin therapy during CVVHDF due to the varying nature of critically ill patients.

Chronic Furosemide Administration Alters Abundance of Sodium Transporters in Rat Kidney / 대한신장학회잡지

BACKGROUND: Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7 days. RESULTS: Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2Cl- cotransporter after furosemide infusion was increased in cortex (151+/-10 vs. 100+/-10%, p< 0.05) and outer medulla (122+/-5 vs. 100+/-3%, p< 0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (alpha: 187+/-25 vs. 100+/-17%, p< 0.05; beta: 155+/-8 vs. 100+/-15%, p< 0.05; gamma: 168+/-16 vs. 100+/-9%, p< 0.05) and outer medulla (alpha: 171+/-27 vs. 100+/-17%, p< 0.05; beta: 986+/-91 vs. 100+/-33%, p< 0.01; gamma: 242+/-24 vs. 100+/-22%, p< 0.01). Consistent with these results, ENaC beta-subuint immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. CONCLUSION: These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.

V2 receptor-mediated regulation of aquaporin-2 by oxytocin in the kidney / 대한내과학회지

BACKGROUND: Oxytocin is a nonapeptide hormone secreted from posterior pituitary gland and has a very similar structure to vasopressin. The aquaporin-2 (AQP2) water channel is predominantly expressed in the kidney and plays a key role in regulation of water permeability of mammalian collecting duct, exerted by both short-term and long-term vasopressin action. We speculated that oxytocin may be involved in some part of vasopressin-independent urinary concentrating mechanism by regulating AQP2 trafficking in the kidney. METHODS: This study was undertaken to investigate whether and how the acute stimulation of oxytocin induces changes in AQP2 localization in the kidney. Immunohistochemistry and semiquantitative immunoblotting of AQP2 were carried out from Sprague-Dawley rat kidneys after a single intraperitoneal injection of oxytocin with or without pretreatment of a vasopressin-2 receptor (V2R) antagonist. RESULTS: Urinary cAMP excretion was increased by oxytocin administration. Immuno- histochemistry of inner medullary collecting duct (IMCD) revealed that AQP2 was shifted from diffuse cytoplasmic localization in controls to the apical and basolateral membrane domains in oxytocin-treated rats. This pattern of AQP2 redistribution was noted in connecting tubule, cortical collecting duct and outer medullary collecting duct as in IMCD, although the tendency to basolateral localization was somewhat less. Semiquantitative immunoblotting of membrane fractions of whole kidney homogenates was also used to assess redistribution of AQP2. The band density ratio of the plasma membrane-rich fraction over cytoplasmic vesicle-rich fraction was higher in oxytocin-treated rats than in controls (3.64+/-0.60 vs. 1.09+/-0.14, P<0.05). Regarding the receptor pathway of oxytocin action in the kidney, we found that pretreatment with a V2R antagonist (OPC-31260) blocked redistribution of AQP2 which was induced by oxytocin. CONCLUSION: In conclusion, oxytocin induces a V2R-mediated redistribution of AQP2-containing cytoplasmic vesicles to both apical and basolateral plasma membrane domains in rat kidney. Oxytocin may be one of the factors that accounts for vasopressin-independent AQP2 targeting in the kidney.

Acute Renal Failure after Hematopoietic Cell Transplantation : Cause and Prognosis / 대한신장학회잡지

BACKGROUND: Common complications after hematopoietic stem cell transplantation(HCT) include sepsis, graft versus host disease(GVHD), veno-occlusive disease(VOD), drug-induced nephrotoxicity, and acute renal failure(ARF). Prior studies report that the presence of ARF affects prognosis. However, we are unaware of such reports on the incidence of ARF after HCT in Koreans, and whether or not the development of ARF is related to prognosis. The purpose of our study was to investigate the cause of ARF after HCT and its relation to prognosis. METHODS: 163 patients received HCT at Seoul National University Hospital since 1985, of which, 107 were available for review. RESULTS: ARF after HCT developed in 52 patients (48.6%). In the three clinical causes, VOD, sepsis, and GVHD, risk factor related to the development of ARF was preexisting VOD. Logistic regression confirmed this association(odds ratio 4.4). The causes of ARF were different according to the periods it developed, and cyclosporin nephrotoxicity was the main cause through the whole period after HCT. The overall survival was worse in the ARF group(60 vs 73 %; p < 0.05). ARF group was split into two groups : patients whose peak serum creatinine levels were below 3.0 mg/dL(mild ARF group) and those who were above 3.0 mg/dL(severe ARF group). Severe ARF group had worse survival than mild ARF group and patients without ARF(p < 0.01). CONCLUSION: VOD, sepsis, GVHD after HCT increase the risk of the deveolopment of ARF, but cyclosprin nephrotoxicity is the main cause of ARF. Severe ARF is a factor influencing the prognosis of patients who received HCT.

No Association of TGF-beta Gene Polymorphism with the Progression of Autosomal Dominant Polycystic Kidney Disease(ADPKD) in Korean Patients / 대한신장학회잡지

BACKGROUND: Two genetic loci, PKD1 and PKD2, have been identified as being responsible for ADPKD, and PKD1 is known to be associated with poor prognosis. However, the presence of intrafamilial clinical diversity suggests the presence of disease-modifying loci. Because the mechanism of renal failure in ADPKD includes cystic growth and tubulointerstitial atrophy and fibrosis, we studied the associations between two cytokine gene polymorphisms in the TGF-beta gene, which are known to be related with chronic tubulointerstitial inflammation, and ADPKD progression in Korean patients. METHODS: 47 normal controls and 114 individuals with ADPKD were genotyped by PCR-RFLP, and the TGF-beta gene leader sequence of T869C(Leu10Pro) variant was compared with MspA1I and G915C (Arg25Pro) with BglI. Statistic significances were determined using the Chi-square test. RESULTS: The distribution of alleles for the TGF-beta Leu10Pro polymorphism in ADPKD was : T 52%, C 48%, which was similar to the Korean(56 : 44, p= 0.670) and Western controls(65 : 35), and in addition, no differences were found between the CRF and the non-CRF groups(p=0.571) or the early hypertension and the normotension groups(p=0.252). The distribution of alleles for the TGF-beta Arg25Pro polymorphism was all GG type, which was different from Western controls(90 : 10, p=0.000). CONCLUSION: Our results suggest that the polymorphism at Arg25Pro of TGF-beta in Korean population has different allele distribution from Western, and the polymorphism at Leu10Pro of TGF-beta has no association with the renal progression of Korean ADPKD patients.

The Effects of Polymorphism in the MCP-1 Gene Regulatory Region on MCP-1 Expression and the Manifestation of Lupus Nephritis / 대한신장학회잡지

BACKGROUND: Monocyte chemoattractant protein- 1(MCP-1) plays an important role in progression of lupus nephritis.(LN) The genetic polymorphism in the regulatory region would influence clinical manifestations by controlling serum levels of MCP-1. METHODS: We determined the genotypes of the MCP-1 gene, the secretion of MCP-1 by pheripheral blood monocytes(PBMCs) and transcription activity according to polymorphism on ELISA and luciferase assay. We also correlated serum MCP-1 level with proteinuria according to the genotypes to evaluate the clinical implication of genetic polymorphism in LN. RESULTS: 10 patients with SLE(20%) were AA homozygous, 21(42%) GA heterozygous, and 18(38%) GG homozygous, which was similar with normal controls[AA 9(20%), GA 27(58%), GG 46(22%)](n= 46). By in-vitro stimulation of PBMCs using Phytohemagglutinin, differential expression of MCP-1 appeared according to the genotypes at -2518 position; PBMCs from AA homozygotes 22.37+/-.07 ng/mL, GA 6.98+/-.72 ng/mL, GG 5.48+/-.22 ng/mL. In the luciferase assay, the gene construct with G at -2518 site showed decreased activity to 39% of that showed by A gene construct. In addition, After cells were treated with TNF-alpha 10 ng/mL), the transcription activity of A gene construct was approximately 3 fold greater than that of G gene construct. Levels of serum MCP-1 were significantly higher in patients with SLE(n=89) than normal controls(n=21)(418.17+/-35.30 pg/mL vs. 127.78+/-14.53 pg/mL, respectively; p0.05). But, in patients with LN, levels of serum MCP-1 were significant higher in patients with AA genotype than those of GA genotyes and GG genotypes(p<0.01). CONCLUSION: MCP-1 gene polymorphism at regulatory region may be a considerable marker for LN and may modulate the level of protein expression. Our study could make it possible to screen high risk individuals, thus help us to develop a practical application of the molecular findings in clinical practice.

Clinical Features and Effects on Prognosis of ARF that Occurred after Liver Transplantation / 대한신장학회잡지

BACKGROUND: One of the major complications of liver transplantation is acute renal failure(ARF). The outcome in patients who develop postoperative renal failure has been dismal. But there are few reports on ARF after liver transplantation in Korea. The aim of this study was to determine the incidence, clinical characteristics, and prognosis of ARF in patients undergoing liver transplantation. METHODS: The records of 35 adult patients who received liver transplantation at the Seoul National University Hospital between october 1992 and June 2001 were reviewed retrospectively. RESULTS: 22 patients were male and 13 were female, with an age range of 15 years to 65 years(median, 49 years). The 35 recipients included 18 with liver cirrhosis, 10 with liver cirrhosis and hepatoma, 3 with hepatoma, 3 with fulminant hepatitis, and 1 with biliary atresia. Death occurred in 10 patients (29%) overall. ARF was developed in 25 cases(71%), and 8 cases(32%) expired. Among the 9 patients with peak serum creatinine level > or = 2.0 mg/dL, 7 patients expired. 2 patients required hemodialysis following liver transplantation and all of them expired. ARF was developed within 1day(0-39 days). Of 25 ARF cases, 21 cases of hypotension, 6 acute rejection, 10 spontaneous bacterial peritonitis(SBP), and 8 massive packed RBC transfusion were associated. Renal function at latest follow-up was improved in patients who were suffered with ARF. CONCLUSION: ARF is a frequent complication of liver transplantation, and the strategy of management and prevention of ARF needs to be developed.

Changes of Urinary Acidification and Collecting Duct H(+)-ATPase Abundance in Response to Chronic Diuretic Administration / 대한신장학회잡지

PURPOSE: Commonly used diuretics such as furosemide and hydrochlorothiazide may cause metabolic alkalosis by increasing proton secretion from distal nephron. We evaluated changes in urinary acidification and abundance of proton-secreting transporters in response to chronic subcutaneous infusion of diuretics. METHODS: Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day furoemide or hydrochlorothiazide 7.5 mg/day for 7 days. All animals were offered tap water and a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. RESULTS: Compared with vehicle-infused controls, diuretic and natriuretic responses were evident from furosemide or hydrochlorothiazide infusion. However, there were no changes in body weight, serum aldosterone and creatinine clearance between diuretic- infused(n=6) and control(n=6) rats. In both furosemide-infused and hydrochlorothiazide-infused rats, urine pH was significantly lowered compared with controls. Furosemide-infused rats showed significantly larger excretion of urinary ammonium. Semiquantitative immunoblotting was carried out from rat kidneys to investigate abundance of proximal tubule or medullary thick ascending limb Na(+)/H(+) exchanger type 3(NHE3) and collecting duct H(+)- ATPase using specific polyclonal antibodies to NHE3 and H(+)-ATPase B1 subunit, respectively. The abundance of NHE3 from cortical homogenates was not changed by either furosemide or hydrochlorothiazide infusion. However, the abundance of NHE3 from outer medullary homogenates was increased by furosemide infusion. The H(+)-ATPase B1 subunit abundance was increased by furosemide or hydrochlorothiazide infusion in both cortical and outer medullary homogenates. CONCLUSION: These increases in the abundance of proton-secreting transporters may account for the enhanced distal urinary acidification in response to chronic diuretic administration.

Antidiuretic Action of Oxytocin in Normal Men / 대한신장학회잡지

BACKGROUND: The antidiuretic action of oxytocin in human has been controversial. To investigate whether oxytocin directly acts on water balance in human, we evaluated the parameters of urinary concentration in response to administration of oxytocin in ten healthy male volunteers. METHODS: Oxytocin was infused intravenously at a rate of 20 mU/hour for 2.5 hours and urine was collected during the last 2 hours of oxytocin infusion. Changes in urine volume, urine osmolality, excretions of urine electrolytes and free water clearance after the administrartion of oxytocin were compared with the baseline data. RESULTS: The changes in the levels of serum electrolytes and osmolality after the administration of oxytocin were not significant compared with the baseline data. The volume of 2 hours' urine were 446+/-75 mL and 289+/-53 mL in the basal state and after the administration of oxytocin, respectively. The urine osmolality was increased significantly by the infusion of oxytocin(427+/-63 mOsm/kg) compared with that in the basal state(223+/-25 mOsm/kg)(p < 0.05). The free water clearance was 110+/-51 mL/2 hours in the basal state and decreased significantly to -57+/-51 mL/2 hours(p < 0.05). CONCLUSION: We conclude that administration of oxytocin to normal men enhances urinary concentration, evidenced by increased urinary osmolality and decreased free water clearance. In human, oxytocin may play an important role in the regulation of renal water excretion as an antidiuretic hormone.

Clinical Characteristics of Fungal Peritonitis from Peritoneal Dialysis Patients / 대한신장학회잡지

PURPOSE: Fungal peritonitis is a fatal disease with a high mortality and morbidity to the peritoneal dialysis(PD) patients. This study was implemented to provide a guideline for the prevention and treatment of fungal peritonitis in PD patients by analyzing the clinical and microbiologic features of fungal peritonitis cases. METHODS: We analyzed retrospectively into the 15 cases(14 patients) of fungal peritonitis among 376 end stage renal disease(ESRD) patients who newly started PD in the Seoul National University Hospital from Jan. 1991 to Dec. 1999. RESULTS: The patients' age was 53.6+/-11.6 years (mean+/-standard deviation) and their male to female ratio was 12:3. They have been on PD for 29.2+/-27.7 months before the fungal peritonitis developed. Candida species was the most common etiologic agent, accounting for 10(62.5%) out of the 16 fungal organisms isolated from our patients. Among others were two Aspergillus, one Cryptococcus, one Penicillium, one Torulopsis, and one Trichosporon beigelii cases. Bacterial agents were isolated simultaneously in five fungal peritonitis cases. Peritoneal catheters were all removed no later than 72 hours after the diagnosis was made. Patients were given a single or combined therapy with amphotericin B, fluconazole, or flucytosine on the physician's choice. The outcomes of fungal peritonitis were as follows; 20% continued PD, 60% converted to HD and 20% died of fungal peritonitis. We made a comparative analysis between the fungal and bacterial peritonitis cases which developed in the same 5-year period, which showed significantly higher catheter removal and technique failure rates in the fungal cases. CONCLUSION: Fungal peritonitis is a rare but a fatal disease with a high mortality and a technique failure rate. Candida species was the most prevalent microorganism in our study.

A Case of Emphysematous Pyelonephritis in a Autosomal Dominant Polycystic Kidney Disease Patient Successfully Treated by Medical Treatment / 대한신장학회잡지

Emphysematous pyelonephritis is an uncommon and potentially life-threatening infectious disease. Although there is still controversy about optimal treatment of emphysematous pyelonephritis, published results indicate that the mortality rate in the patients treated with radical nephrectomy is equivalent to that in patients given more conservative treatment. Emphysematous pyelonephritis with autosomal dominant polycystic kidney disease is extremely rare and its clinical course is not revealed clearly. Hearin, we report an emphysematous pyelonephritis in a 64- year-old female patient with autosomal dominant polycystic kidney disease, successfully treated by antibiotics and percutaneous cyst drainage.

A Case of Emphysematous Pyelonephritis in a Autosomal Dominant Polycystic Kidney Disease Patient Successfully Treated by Medical Treatment / 대한신장학회잡지

Emphysematous pyelonephritis is an uncommon and potentially life-threatening infectious disease. Although there is still controversy about optimal treatment of emphysematous pyelonephritis, published results indicate that the mortality rate in the patients treated with radical nephrectomy is equivalent to that in patients given more conservative treatment. Emphysematous pyelonephritis with autosomal dominant polycystic kidney disease is extremely rare and its clinical course is not revealed clearly. Hearin, we report an emphysematous pyelonephritis in a 64- year-old female patient with autosomal dominant polycystic kidney disease, successfully treated by antibiotics and percutaneous cyst drainage.

Epidural Leakage of Polymethylmethacrylate Following Percutaneous Vertebroplasty in the Patients with Osteoporotic Vertebral Compression Fractures

OBJECTIVES: The percutaneous vertebroplasty provides a good result in the treatment of osteoporotic vertebral compression fractures. But, the epidural leakage of polymethylmetacrylate(PMMA) after vertebroplasty may decrease the therapeutic effects because of the compression of thecal sac and/or nerve roots. The authors carried out a prospective study to evaluate the causative factors of epidural leakage of PMMA and to assess the influence on the outcome. METHODS: This study involved 347 vertebral levels of compression fractures in 159 patients. Among these, the epidural leakages were identified in 92 vertebral levels(26.5%) in 64 patients(40.3%) on post-operative CT scan. RESULTS: The incidence of epidural leakage of PMMA was significantly higher in the level above T7(p=0.001). The large amount of the injected PMMA and the use of an injector also increased the incidence(p=0.03 and p=0.045, respectively). The position of the needle tip in the vertebral body and the pattern of venous drainage did not influence. The immediate post-operative visual analogue scale(VAS) scores and facial scales(FS) were higher in the patients with epidural leakage(p=0.009). But there were no significant differences between the two groups after three months of operation(p=0.541). Conclusions: The incidence of epidural leakage of PMMA after percutaneous vertebroplasty appears to have relationship with the amount of PMMA and the levels injected. The epidural leakage of PMMA reduced the immediate therapeutic effects of vertebroplasty, but did not influence the late outcome. However, the epidural leakage should be avoided because of its potential neurological complications.

Mechanisms of Diuretic Resistance and Tolerance / 대한신장학회잡지

Diuretics are natriuretic agents which inhibit sodium reabsorption at their major site of action on the renal tubules and increase the excretion of sodium and combined anions. Increment of urine volume is the secondary to the natriuretic effects. Diuretic resistance occurs that threshold dose of diuretics is higher than that of other patients. It is frequently manifested among the edematous patients such as those with the nephrotic syndrome. Prolonged use of diuretics decreases the natriuretic effect of diuretics, which is called diuretic tolerance. This is important adaptations of distal nephron segment. To elucidate the mechanism of diuretic resistance, 1 mg of bumetanide was given to the nephrotic syndrome(NS) patients group and control group, respectively. The peak plasma concentration was delayed in NS patients. The proportion of urine free bumetanide for 24 hours was 73% in NS patients but 100% in control group. The ratio of urine volume and amount of Na+ and Cl - for 24 hours to the total and free urine bumetanide was decreased in NS patients. The study suggests that pharmacokinetic and pharmacodynamic changes of the diuretics induce the diuretic resistance. To determine the additive diuretic effect of albumin to the action of the furosemide, 160 mg of furosemide was administered intravenously with albumin in NS patients. Simultaneous infusion of albumin and furosemide did not enhance the diuretic effect of furosemide pharmacodynamically and pharmacokinetically. Albumin preinfusion 30 minutes before furosemide administration potentiates the diuresis, but natiuresis and pharmacokinetics were not changed. Semiquantitative immunoblotting of rat kidneys was carried out to investigate whether chronic diuretics adminstration induces changes in the abundance of Na+ transporters in distal nephron. Furosemide infusion increased cortical and outer medullary abundances of Na+-Cl- cotransporter(TSC) and all 3 subunits of the epithelial sodium channel(ENaC). Hydrochlorothiazide infusion increased abundances of some kinds of subunits of ENaC. These increases in the abundances of Na+ transporters may account for the generation of diuretic tolerance.These data suggest that to overcome the diuretic resistance or tolerance, diuretic dose increment over the threshold level and more frequent administration of the diuretics are recommended. Diuretic combinations are also proposed. Addition of albumin to augment the diuretics effect ought to be considered cautiously.

Angiotensin I Converting Enzyme Polymorphism and the Progression of IgA Nephropathy / 대한신장학회잡지

IgA nephropathy(IgAN) is the most common glomerulonephritis(GN) in worldwide, and accounts for 20% to 40% of all patients with primary GN in Korea. IgAN has diverse clinical courses, but the risk factors affecting the deterioration of renal function are not established. Recently, there were some suggestions that systemic or local expression of peptides of angiotensin system exerts several effects on the progression of renal disease, and the genetic polymorphisms may associated with peptide expression. To evaluate the role of genetic polymorphism of angiotensin I converting enzyme(ACE) polymorphism in the progression of IgAN, the genotypic distributions in 278 biopsy-proven cases of IgAN were studied, which had undergone a renal biopsy at Seoul National University Hospital, between 1979 and 2000. We also compared the genotypes with clinical manifestations to evaluate the clinical implications of genetic polymorphism. The study shows that there was no difference in the ACE genotype frequencies between the patients (II : 26.6%, ID : 55.0%, DD : 18.4%) and normal controls(II : 31.4%, ID : 57.4%, and DD : 11.2%). Seventy- two percent and 48% of patients maintained renal function for 10 years and 20 years after the initial diagnosis in 278 patients, respectively. However, in 153 patients who were followed more than 5 years, the DD genotype was more prevalent in patients with deteriorating renal function than in those with stable renal function(31.8% vs. 13.8%; p=0.0146). Presence of systemic hypertension increased the risk of renal disease progression(OR=3.3), and it was showed 7.4 fold risk whenever the creatinine was increased by 1 mg/dL. Renal disease progression is not associated with DD genotype among normotensive patients at the biopsy. But, in patients with hypertension, II and DD/ID genotypes have an increased risk for disease progression when compared with II genotype of normotensive patients(OR=1.4, OR=7.8; respectively). ACE polymorphisms did not have any interaction with the levels of serum creatinine at the time of biopsy in our patients. Our results suggested that ACE genotypes(D allele) affected the progression of IgAN, especially in hypertensive patients. One of the prospects of the present study is the potential for screening high risk individuals, thus helping to develop a practical application of the molecular findings in clinical practice.

The Effect of Uteroglobin Exon 1, 5' Untranslated Region Polymorphism on the Progression of IgA Nephropathy / 대한신장학회잡지

Uteroglobin(UG) is an anti-inflammatory/immunomodulatory protein secreted by the epithelial cells of vertebrates. Targeted disruption of UG rendered mouse glomerulonephritis resembling IgA nephropathy(IgAN). Sequence analysis on exon 1 of UG showed several putative binding sites for transcription factors, and genetic polymorphisms in this site might influence the expression level of UG as a competitive protein. We speculated that the single nucleotide polymorphism at the 38th nucleotide from the transcription initiation site of UG exon 1 would impact the progression of IgAN. PCR-RFLP was instituted to determine the genetic polymorphism in 60 patients with IgAN. Other measures like SSCP and direct sequencing were also adopted for the verification of polymorphic sites. Seventeen patients with IgAN(28%) were homozygous for adenine at position 38(38AA), 26 patients(43%) were heterozygous(38AG), and 17 patients(28%) were homozygous for the polymorphism(38GG), which was similar to the pattern obtained from the 60 normal controls. The amount of daily proteinuria, presence of hypertension, the level of IgA, and the amount of IgA-fibronectin(FN) complexes was similar between the genotypes. Serum IgA-FN level did not influence the progression of disease. However, 8 out of 17 patients (47%) with the AA genotype had progressive disease(PD), 10 of 26 patients(38%) with the AG genotype had PD, and only 1 of 17 patients(6%) with GG homozygocity had PD after 94+/-30.1 months of follow-up(mean+/-S.D.). The odds ratio for the progression of renal disease in patients with the AA genotype was 14.93(p=0.0355) and in patients with AG genotype was 12.94(p=0.0496) compared with patients have the GG genotype. Moreover, serum creatinine at the time of kidney biopsy was higher in patients with AA and AG genotypes than in patients with the GG genotype(1.5+/-0.69 : 1.3+/-0.53 : 1.0+/-0.31mg/dL; AA : AG : GG; p=0.0137 AA vs. GG; p=0.0269 AG vs. GG). Our results suggest that polymorphism at the 5' UTR region of UG exon 1 is an important marker for the progression of IgAN.