Altered Regulation of Water Channels and Sodium Transporters in Fasting-induced Polyuria in Rat Kidney / 대한신장학회잡지

PURPOSE: Starvation causes impairment in the urinary concentration ability. However, the molecular basis for the impaired urinary concentration and polyuria remains undefined. We examined the effects of food deprivation on the water handling by the kidney and it's regulatory mechanism. METHODS: Sprague-Dawley rats were used. They were placed in metabolic cages and deprived of food but had free access to water for 24 hours. Control rats had free access to both water and food. Protein expression of aquaporin-2 (AQP2) and Na+-K+-2Cl- cotransporter (NKCC2) was determined in the kidney by Western blot analysis. Protein expression of type VI adenylyl cyclase and prostaglandin E2 synthase (PGES) was determined. Urinary PGE2 excretion was also determined by radioimmunoassay. RESULTS: Food deprivation (FD) resulted in impaired urinary concentration associated with decreased tubular water reabsorption and increased urine output. The expression of AQP2 proteins was significantly decreased in the inner stripe of the outer medulla (ISOM). The expression of NKCC2 was not affected in ISOM. The adenylyl cyclase VI expression was increased in ISOM in FD rats. The protein expression of PGES was decreased in the cortex/OSOM and ISOM. The 24 hr urinary excretion of PGE2 was significantly decreased in FD rats compared with controls. CONCLUSION: These findings indicate that FD-induced urinary concentration defect may related to a reduced abundance of AQP2 in the kidney. It is also suggested that the primary impairment in the pathway to the activation of AQP2 in food deprivation is independent of vasopressin/cAMP or prostaglandin activity.

Erectile dysfunction in diabetic nephropathy / 대한내과학회지

BACKGROUND: Erectile dysfunction (ED) is prevalent among patients with diabetes mellitus and impaired renal function. To estimate the prevalence of ED in diabetic nephropathy and to identify its risk factors, we carried out a survey of patients with diabetic nephropathy attending Chonnam University Hospital. METHODS: The presence of ED was assessed among 106 type 2 diabetic patients with microalbuminuria or overt diabetic nephropathy or renal replacement therapy using its self- administered International Index of Erectile Function (IIEF). ED was also classified into five validated severity levels, ranging from none (22-25), mild (17-21), mild/moderate (12-16), moderate (8-11), through severe (5-7). Logistic regression was used to examine associations between ED and other medical conditions. RESULTS: The mean age was 45.30+/-8.57 years in patients without ED and 58.53+/-8.46 years in patients with ED. The prevalence of any level of ED was 72% using IIEF. An independent t-test and chi-square demonstrated age, smoking, smoking duration, degree of nephropathy, coronary heart disease, neuropathy, diabetic foot, and retinopathy to be associated with the presence of any level of ED. Patients with ED had lower serum levels of hemoglobin, albumin, triglyceride, HDL-cholesterol and higher serum levels of BUN in unadjusted analyses compared with patients without ED. A multivariable logistic regression demonstrated age, serum creatinine concentration, and renal replacement therapy to be independently associated with the presence of any level of ED. CONCLUSION: ED is extremely prevalent among type 2 diabetic patients with microalbuminuria or overt diabetic nephropathy or renal replacement therapy. Increased age and serum creatinine concentration, and renal replacement therapy were associated with higher prevalence of ED.

Unilateral Autosomal Dominant Polycystic Kidney Disease with Contralateral Renal Agenesis: A Case Report

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. There are some reports in the literature concerning unilateral ADPKD. However, in adults, only a few cases of unilateral ADPKD with agenesis of contralateral kidney have been reported. We present a case of unilateral ADPKD with agenesis of contralateral kidney in a 66-yr-old man. Radiographic images showed the enlarged right kidney with multiple variable-sized cysts and the absence of the left kidney. The diagnosis of ADPKD was confirmed by the family screening. The patient received maintenance hemodialysis for endstage renal disease. We report a case of unilateral ADPKD associated with contralateral renal agenesis in a 66-yr-old male patient with a literature review.

Hydronephrosis by an Aberrant Renal Artery: A Case Report

Ureteropelvic junction obstruction is usually intrinsic and is most common in children. Aberrant renal arteries are present in about 30% of individuals. Aberrant renal arteries to the inferior pole cross anteriorly to the ureter and may cause hydronephrosis. To the best of our knowledge, although there are some papers about aberrant renal arteries producing ureteropelvic junction obstruction, there is no report of a case which is diagnosed by the new modalities, such as computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA). We describe a 36-year-old woman with right hydronephrosis. Kidney ultrasonogram and excretory urogram revealed right hydronephrosis. CTA and MRA clearly displayed an aberrant renal artery and hydronephrosis. The patient underwent surgical exploration. For the evaluation of hydronephrosis by an aberrant renal artery, use of CTA and MRA is advocated.

Serum CRP level is positively correlated with the cardiovascular disease in dialysis patients / 대한내과학회지

BACKGROUND: Atherosclerosis, a major problem in patients undergoing chronic dialysis treatment, has been characterized as an inflammatory disease. Cardiovascular disease is the major cause of mortality, accouting for approximately half of all deaths in this population. The present study was aimed whether CRP, an important inflammatory marker, might be associated with cardiovascular risk in dialysis patients. METHODS: We performed retrospective study in 77 dialysis patients. Patients were divided into the elevated CRP group (>8 mg/L, n=11) and the normal CRP group (8 mg/L) showed significant higher cardiovascular events (by chi-squre test, p=0.032). BMI, smoking, alcohol, dialysis modality, lipid parameters, BUN, serum creatinine, serum protein, serum albumin and seurm TIBC did not show significant difference between two groups. Correlation between CRP and other biochemical parameters was analysed. Only ESR was positively correlated with CRP. In a subsequent analysis, elevated CRP group had significantly higher cardiovascular risk (by stepwise logistic regression method, odd ratio = 6.59;95% CI, 1.13 to 38.28). CONCLUSION: These results suggest that CRP level is correlated with cardiovascular risk in dialysis patients.

Serum homocysteine concentration in kidney transplant recipients / 대한내과학회지

BACKGROUND: Cardiovascular disease (CVD) after kidney transplantation is a major cause of both graft loss and patient death in kidney transplant recipeints. There are several well known risk factors of CVD, such as hyperlipidemia, hypertension, diabetes melitus, old age and smoking. Non-classic risk factors are acute rejection episode, LVH, C-reactive protein and hyperhomocysteinemia. Homocysteine is an amino acid filtered through the glomerulus and hyperhomocysteinemia is considered as a risk factor of CVD in end-stage renal disease (ESRD) and kidney transplant patients. So homocysteine lowering trials, such as folic acid and vitamine supplement therapy, are being made. We evaluated the prevelance and determinants of hyperhomocysteinemia in kidney transplant recipients. METHODS: We measured serum total homocysteine concentration (tHcy) and its determinants in 21 normal persons, 37 chronic renal failure (CRF) patients with conservative treatment (predialysis) and 48 kidney transplant patients. RESULTS: The prevalence of hyperhomocysteinemia was 4.8%, 83.8% and 45.8% among normal persons, predialysis and kidney tranplant patients, respectively. Among the kidney transplant recipients the prevelence of hyperhomocysteinemia was 18.8% in normal renal function (serum creatitine concentration male: below 1.2 mg/dL, female: below 1.1 mg/dL) group and 59.4% in abnormal renal function group. The tHcy values in kidney transplant patients are significantly lower than those in predialysis patients (16.38+/-6.48 nmol/L vs. 24.68+/-9.01 nmol/L, p < 0.01), but higher than those in normal persons (16.38+/-6.48 nmol/L vs. 8.80+/-2.07 nmol/L, p < 0.01). Among the kidney transplant recipients the tHcy values in normal creatinine group are significantly lower than those in abnormal creatinine group (12.02+/-3.68 nmol/L vs. 18.57+/-6.51 nmol/L, p < 0.01). Using muliple regression analysis, this study showed increased serum creatinine concentration is a major determinant of tHcy concentrations in kidney transplant recipients and hyperhomocysteinemia is not correlated with whole blood trough level of cyclosporin (mean 126.26+/-62.19 ng/mL, range: 26~322 ng/mL) or vitamines supplement therapy. CONCLUSION: In this study the serum homocysteine values in kidney transplant recipients were higher than in normal control group but significantly lower than in CRF patients with conservative treatment. The major determinant for serum homocysteine concentration is a serum creatinine concentration.

The Efficacy and Safety of Intravenous Iron Sucrose in Hemodialysis Patients / 대한신장학회잡지

BACKGROUND: The objective of the present study was to assess the efficacy and safety of iron sucrose by determining the subsequent change in hemoglobin (Hgb), hematocrit (Hct), transferrin saturation (TAST), serum ferritin values and blood pressures in hemodialysis patients receiving Epoetin. METHODS: A total of 19 adult patients who had been receiving hemodialysis three times a week at Chonnam Natinal University Hospital were assigned. Their Hgb level was less than 10 g/dL and their serum ferritin level was less than 100 ng/mL, and/or TSAT was less than 20%. Iron sucrose was administered as 1,000 mg in 10 divided doses diluted in 100 mL normal saline over the last 60 minutes during hemodialysis with a one-time prior test dose of 20 mg on 10 consecutive dialysis sessions. Iron sucrose dosage was adjusted to 25-100 mg/week depending on serum ferritin level, and TSAT in the following 3 months. Epoetin administration was stopped due to insurance regulation when Hgb level was more than 10 g/dL and Hct level was more than 30 %. To evaluate efficacy of iron sucrose, assessment of serum iron parameters and anemia indices was determined just before the first dose (baseline), at 1 month after the first dose (loading) and then, monthly for 3 months (maintenance). To evaluate safety of iron sucrose, we recorded blood pressure 1 hour before and at the time of completion of iron sucrose injection, and also recorded blood pressure during observation sessions before dialysis and at intervals of 2 hours and 4 hours after starting dialysis. We determined routine serum chemistry and hematologic results at 1 month after the first dose and compared results with those obtained at baseline. RESULTS: 1,000 mg iron surcose injection in 10 divided dose (loading) produced a significant rise in Hgb, Hct, serum iron, serum ferritin, TSAT, MCV and MCH at 1 month after first dose (respectively p<0.001, p<0.001, p<0.01, p<0.001, p<0.01, p<0.01, p< 0.01). During the following maintenance period of 3 months, Hgb, Hct, serrum ferritin, and TSAT level remained more elevated than at baseline respectively. In 19 enrolled patients, we experienced no serious adverse drug reactions and no significant changes in intradialytic blood pressure associated with iron sucrose administration. Serum albumin concentrations was higher at 1 month than at base line and however, changes in other serum chemistry and hematologic results were not statistically significant. CONCLUSION: Intravenous iron sucrose administration is an efficient and safe method to supply iron in end-stage renal disease patients receiving Epoetin with iron deficiency, who are undergoing hemodialysis.

The Predictive Parameters of Erythropoietin Hyporesponsiveness in Patients on Continuous Ambulatory Peritoneal Dialysis

BACKGROUND: The present study was aimed at investigating the predictive parameters of erythropoietin (epoetin) hyporesponsiveness in patients on continous ambulatory peritoneal dialysis (CAPD). METHODS: We studied 40 patients with end-stage renal disease who had been receiving CAPD for at least 6 months and epoetin therapy for at least more than 2 months. Pearson's simple correlation and multiple stepwise linear regression analysis was used to discover what parameter can predict epoetin resistance. We expressed epoetin resistance index (ERI) as 'weekly epoetin dose/hematocrit/ body weight'. The dose of epoetin is titrated by about 25% every 2 to 4 weeks to maintain a target hematocrit level between 33% and 36%. RESULTS: We analyzed the relationship between ERI and other predictive parameters by Pearson's correlation. These results showed ERI has a statistically significant correlation with transferrin saturation (TS) (r=-0.327, p=0.042), total weekly Kt/Vurea (r=-0.423, p=0.018), serum albumin level (r=-0.458, p= 0.003), normalized protein catabolic rate (nPCR) (r=-0.479, p=0.006), normalized protein equivalent of total nitrogen appearance (nPNA) (r=-0.488, p=0.005) and serum C-reactive protein (CRP) (r=0.332, p=0.036). Regression analysis was performed using stepwise linear regression for multiple variables to discover the most independent variable which is correlated with ERI. ERI was entered as a dependent variable, whereas the other parameters (age, duration of peritoneal dialysis, serum albumin level, CRP, serum ferritin, total weekly Kt/Vurea, nPCR, nPNA, serum iPTH, serum aluminium, TS) were entered as independent variables. This analysis showed CRP is the most significant variable and, if CRP is excluded, nPNA is the significant variable. CRP has a statistically significant correlation with serum albumin level (r=-0.418, p=0.007) and total weekly Kt/Vurea (r=-0.366, p=0.043). High CRP group has more increased level of ERI (p<0.05), age (p<0.05) and serum creatinine level (p<0.05) than normal control, but more decreased level of serum albumin (p<0.01) and serum iron levels (p<0.05). CONCLUSION: These results indicate that CRP is the most important predictor of epoetin hyporesponsiveness.

Dialysis Adequacy and Nutritional Status in Patients with Continuous Ambulatory Peritoneal Dialysis(CAPD) / 대한신장학회잡지

PURPOSE: Malnutrition is common in CAPD patients and depends on many factors such as dialysis-related and nondialysis-related factors. The present study aimed to assess nutritional status, dialysis adequacy and their relationships with overall mortality and morbidity. METHODS: We studied 102 patients who had been receiving CAPD for at least 6 months. Dialysis adequacy was assessed by parameters derived from urea kinetic modeling(UKM) and nutritional status was assessed by serum biochemical measurement, normalized protein catabolic rate(nPCR), normalized protein equvalent of total nitrogen appearance(nPNA) and urea kinetic studies. Spearman's simple correlation and multiple linear stepwise regression analysis were used to assess correlation between dialysis adequacy and nutritional status in CAPD patients. We compared the differences between patients who suf fered morbid events, defined as either an infectious complication or hospitalization, and patients who remained well. RESULTS: The results showed that the total dialysis dose(total weekly Kt/Vurea) has statistically significant correlation with nPCR(r=0.234, p=0.028), nPNA (r=0.246, p=0.021), total weekly creatinine clearance (WCC)(r=0.479, p=0.0001), serum albumin levels(r= 0.233, p=0.029), serum cholesterol(r=0.266, p=0.013), serum BUN(r=-0.290, p=0.006) and serum creatinine levels(r=-0.408, p=0.0001). nPNA was positively correlated with serum cholesterol(r=0.217, p=0.045), serum transferrin(r=0.218, p=0.042) and serum ferritin levels(r=0.220, p=0.043). Patients who suffered morbid events had an old age(p=0.001), long duration of CAPD(p=0.0001), higher CRP(p=0.021), lower serum albumin level(p=0.020), lower hematocrit(p=0.049) and lower WCC(p=0.017). Conclusions : These results indicate that adequate dialysis is very important for the maintenance of adequant nutrition because nutritional status positively correlated with dialysis dose, which is best assessed by UKM. In addition, assessment of nutritional status and dialysis adequacy are important in predicting clinical outcomes in CAPD patients.

Hyperhomocysteinemia in Patients with Chronic Renal Failure / 대한신장학회잡지

OBJEVTIVE: It has been reported that hyperhomocysteinemia is an independent risk factor for atherosclerotic complications, although the mechanisms remain unclear. The major determinents of total fasting plasma homocysteine(tHcy) concentrations have been recently reported but there are still conflicting data on the influence of those in peritoneal and hemodialysis patients. Therefore, we evaluated the prevalence and association of vascular complications and the determinents of hyperhomocysteinemia in chronic renal failure patients receiving conservative treatment(predialysis), peritoneal dialysis(PD) and hemodia- lysis (HD) patients. METHODS: We measured the factors, including fasting plasma vitamine levels(folate, vitamin B6 and vitamin B12), serum creatinine concentration, dialysis adequacy-related varibles as well as associated risk factors for vascular diseases that might affect tHcy concentrations in 37 predilysis, 30 PD, 34 HD patients and 21 normal persons. Continuous variables were compared using independent sample t-test. Spearman's correlation was used to determine the strength of association between tHcy and other predictive variables. Percentages were compared using Pearson's chi-square test or Fisher's exact test, depending on the frequencies. Independent determinents of tHcy concentration and atherosclerotic vascular complications were identified using multiple regression analysis. RESULTS: The prevalence of hyperhomocysteinemia was 83.8, 72, 88% among predialysis, PD and HD patients,respectively(Odds ratio was 103.33, 81.43, 150.0 vs. controls, respectively). tHcy values in predialysis, PD and HD patients are significantly higher than those in controls(24.68+/-9.01, 21.04+/-8.82, 23.62+/-9.46 vs. 8.80+/-2.07 mumoL/L, repectively, p<0.01). Predialysis, PD and HD patients with atherosclerotic vascular complications had higher tHcy concentrations than did predialysis, PD and HD patients without vascular complications(21.93+/-8.71 vs. 32.09+/-4.71 mumoL/L, p<0.01, 17.57+/-5.85 vs. 28.74+/-9.70 mumoL/L, p<0.01, 19.00+/-4.29 vs. 33.28+/-10.13, p<0.01 respectively). We also observed increasing odds ratios of vascular events with increasing tHcy concentrations. For predialysis, PD and HD patients, fasting plasma folate level had negative correlation with tHcy concentrations by spearman's simple correlaltion. And using muliple regression analysis, we recognized hyperhomocysteinemia is an independent risk factor for atherosclerosis and fasting plasma folate is a major determinent of tHcy concentrations in predialysis, PD and HD patients. CONCLUSIONS: Hyperhomocysteinemia in predialysis, PD and HD patients was more prevalent than that in normal controls. Risk of atherosclerotic vascular complications increased with increasing tHcy concentrations. Hyperhomocysteinemia is an independent risk factor for atherosclerosis and fasting plasma folate is a major determinent of tHcy concentrations in predialysis, PD and HD patients.

Relationship Between Serum Magnesium and Parathyroid Hormone Levels in Hemodialysis Patients / 대한신장학회잡지

The important factors involved in the regulation of PTH are calcium, vitamin D, and phosphorus. However, recent studies have suggested that magnesium may also play a significant role in the modulation of PTH. The aims of this study was to analyze the relationship between serum magnesium and PTH levels in the hemodialysis patients. We studied 66 stable patients under maintenance hemodialysis for more than 6 months. Calcium carbonate was used as a phosphate binder in all patients. No patient had been previously treated with vitamin D and aluminum hydroxide. Biochemical parameters were evaluated 3 times during 7 months, and the mean values were computed. The mean serum magnesium level was 2.7+/-0.4 mEq/L. Hypermagnesemia(defined as serum Mg>2.2 mEq/L) was found in 60 patients(90.1%). Serum magnesium levels were inversely correlated with serum iPTH levels(r=-0.579; p<0.001). Serum total and ionized calcium levels were inversely correlated with serum iPTH levels(r=-0.743; p<0.001, r=-0.699; p<0.001, respectively). Serum alkaline phosphatase levels positively correlated with serum iPTH levels (r=0.364; p=0.003). In lower iPTH group(serum iPTH

The predictive parameters of erythropoietin hyporesponsiveness in patients with continuous ambulatory peritoneal dialysis(CAPD) / 대한내과학회지

BACKGROUND: The present study was aimed at investigating the predictive parameters of erythropoietin (EPO) hyporesponsiveness in patients with continuous ambulatory peritoneal dialysis (CAPD). METHODS: We studied 40 patients with end stage renal failure who were receiving peritoneal dialyis for at least 6 months and EPO therapy for at least more than 2 months. Pearson's simple correlation and multiple stepwise linear regression analysis was used to discover what parameter can predict EPO resistance. We expressed EPO resistance index (ERI) as 'weekly EPO dose/hematocrit/body weight'. The dose of EPO is titrated by about 25% every 2 or 4 weeks to maintain a target hematocrit between 33% and 36%. RESULTS: We analyzed the relationship between ERI and other predictive parameters by Pearson's correlation. These results showed ERI has a statistically significant correlation with transferrin saturation (TS) (r=-0.327, p=0.042), total Kt/V (r=-0.423, p=0.018), serum albumin (r=-0.458, p=0.003), normalized protein catabolic rate (nPCR) (r=-0.479, p=0.006), normalized protein equivalent of total nitrogen appearance (nPNA) (r=-0.488, p=0.005) and serum C-reactive protein (CRP) (r=0.332, p=0.036). Regression analysis was performed using stepwise linear regression for multiple variables to discover the most independent variable which is correlated with ERI. ERI was entered as a dependent variable, whereas the other parameters (age, duration of peritoneal dialysis, serum albumin, CRP, serum ferritin, total Kt/V, nPCR, nPNA, serum iPTH, serum aluminium, TS) were entered as independent variables. This analysis showed CRP was the most significant variable, and if CRP is excluded, nPNA was the significant variable. CRP had a statistically significant correlation with serum albumin (r=-0.418, p=0.007) and total Kt/V (r=-0.366, p=0.043). High CRP group had more increased level of ERI(p<0.05), age(p<0.05) and serum creatinine(p<0.05) than normal control, but more decreased level of serum albumin(p<0.01) and serum iron level(p<0.05). CONCLUSION: These results indicate that CRP is the most important predictor of EPO hyporesponsiveness.

Prevalence and Determinants of Hyperhomocysteinemia in Patients with Chronic Renal Failure / 대한신장학회잡지

BACKGROUND: Hyperhomocysteinemia plays an important role in atherosclerosis resulting from endothelial dysfunction and injury followed by platelet activation and thrombus formation. We evaluated the prevalence and determinants of hyperhomocysteinemia in patients with chronic renal failure(CRF) and relationship between hyperhomocysteinemia and cardiovascular diseases. METHODS: We evaluated the prevalence of hyperhomocysteinemia in CRF patients and hemodialysis patients. Fasting plasma homocysteine, vitamin B12, vitamin B6, creatinine, fibrinogen, lipoprotein(a), glucose, total cholesterol, HDL cholesterol, and TG levels were assessed in 69 patients. RESULTS: Hyperhomocysteinemia was detected 5% in controls, 86% in CRF groups, and 85% in hemodialysis group. Serum folate value in hemodialysis group was significantly higher than normal controls (10.7+/-4.8 vs. 15.3+/- 5.4nmoL/L; p<0.05). Plasma homocysteine concentration negatively correlated with serum folate level in hemodialysis patients(r=-0.42, p<0.05). Cardiovascular diseases were deteceted 14% in CRF patients and 25% in hemodialysis patients. Matched odds ratios(with 95% confidence intervals) were respectively 118.75, 107.7 for homocysteine in CRF and hemodialysis patients compaired with control group. CONCLUSION: Plasma homocysteine level correlated negatively with serum folate level in hemodialysis patients. In univariate analysis, determinant of plasma homocysteine concentration in hemodialysis patients is plasma folate concentration. We considered that hyperhomocysteinemia is also an independent risk factor of cardiovascular diseases.