Moon-Jae Kim

Plasma brain natriuretic peptide concentration on assessment of hydration status in hemodialysis patient

BACKGROUND Brain natriuretic peptide (BNP) is released into circulation in response to ventricular dilatation and pressure overload. Plasma BNP concentration correlates with left ventricular mass and dysfunction, which is prevalent in hemodialysis (HD) patients. METHODS To evaluate the potential of BNP level for determination of hydration status, we measured inferior vena caval diameter (IVCD) and BNP levels and performed bioimpedance analysis in 49 HD patients. RESULTS Pre-HD BNP levels remained unchanged after HD. Agreement between IVCD and pre-HD BNP level in overhydration was significant (kappa = 0.304). The area under the receiver operating characteristic (ROC) curve for overhydration was 0.819 for pre-HD BNP level. When extracellular fluid/total-body water (ECF/TBW) ratios of HD patients were compared with those of 723 controls, pre- and post-HD BNP levels were significantly greater in overhydrated patients. The area under the ROC curve for overhydration by ECF/TBW ratio was 0.781 for pre-HD BNP level. However, there was no significance for pre- or post-HD BNP levels on assessment of normohydration or underhydration. Pre-HD BNP level correlated significantly with post-HD BNP level, post-HD diastolic blood pressure, pulse pressure, and ECF/TBW ratio. IVCD correlated significantly with post-HD BNP level. CONCLUSION BNP level seems to have a limited potential for assessment of overhydration in HD patients.

The effects of dual blockade of the renin-angiotensin system on urinary protein and transforming growth factor-beta excretion in 2 groups of patients with IgA and diabetic nephropathy.

AIMS The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1 level were measured as surrogate markers of renal injury. METHODS We conducted a prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5 mg/day for 16 weeks. RESULTS All baseline data except for the age factor were statistically the same between the 2 disease groups. Twenty-four-hour mean arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial pressure did not change by the addition of candesartan or placebo in both groups. The addition of candesartan (combination) reduced 24-hour urinary protein excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%, which is significantly greater compared to a mean change of -0.1 +/- 3.3% after the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 - 23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3; p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/- 6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/- 9.5% decrease, but it did not reach statistical significance compared to placebo of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour urinary protein excretion rate and urinary TGF-beta1 level were neither correlated with each other, nor with the change in mean arterial pressure. Significant changes in the renal function were not detected during the study period. CONCLUSION Definite beneficial effects of dual blockade of RAS on proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which was independent of blood pressure-reducing effect. With our 16-week trial, such benefits were not observed in type 2 diabetic nephropathy. The reduction in urinary TGF-beta1 level suggests that the combination therapy may provide additional renoprotection through the antisclerosing effects. Based on our results, for a proper interpretation the therapeutic effects of the combination therapy should be evaluated separately according to the underlying renal disease.

Effect of High Glucose on Basal Intracellular Calcium Regulation in Rat Mesangial Cell

Background: A number of cellular mechanisms are critically dependent on intracellular Ca²⁺ homeostasis. A sustained increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) is capable of activating a number of potentially harmful processes including phenotype change to secretory type, dysregulated cell proliferation, and cell injury and death. Mesangial cells (MCs) play an important role in the pathophysiology of diabetic nephropathy. Methods: We evaluated the effect of high glucose on basal [Ca²⁺]_i in the unstimulated state and identified its contributing pathways. MCs were isolated and cultured from Sprague-Dawley rats. [Ca²⁺]_i was measured by fluorometric technique with fura-2AM. Results: In a dose-dependent manner, superfusion of MCs with Tyrode’s solution containing high glucose (30 and 50 mM) induced a delayed spontaneous increase in [Ca²⁺]_i, which was not found in those with normal (5.5 mM) glucose or mannitol. The high glucose-induced increase in [Ca²⁺]_ioccurred through transmembrane influx of extracellular Ca²⁺ and was blocked by SKF96365, an inhibitor of store-operated Ca²⁺ influx. Na⁺-Ca²⁺ exchanger (NCX) activity, a major channel regulating basal [Ca²⁺]_i, and the clearing ability of intracellular Ca²⁺ were depressed after MCs were cultured in high-glucose medium. Western blot analysis revealed the decreased expression of a 70-kD NCX protein in MCs cultured in high-glucose medium. Conclusions: A high-glucose concentration induced a spontaneous increase in basal [Ca²⁺]_i of MCs without stimulation. There was a decrease in the activity of NCX in the high-glucose condition, which seems to occur at the level of protein expression. The present results provide a novel insight into the mechanisms of diabetic nephropathy in that intracellular Ca²⁺ homeostasis is an important secondary messenger and a mediator in hormonal signaling.

Evidence for Rat Organic Anion Transporter 3 Association with Caveolin‐1 in Rat Kidney

The rat organic anion transporter 3 (rOAT3) has recently been identified as the third isoform of the OAT family. The mechanisms that regulate rOAT3s functions remain to be elucidated. rOAT3 contributes for moving a number of negatively charged organic compounds between cells and their extracellular milieu. Caveolin (Cav) also plays a role as a membrane transporter. To address the relationship of these two proteins, we investigated the protein‐protein interaction between rOAT3 and Cav‐1. The rOAT3 mRNA and protein expression were observed in the rat kidney, and the expressions of Cav‐1 mRNA and protein were also detected in the kidney. Confocal microscopy of the immuno‐cytochemistry experiments using primary cultured renal proximal tubular cells showed that rOAT3 and Cav‐1 were co‐localized at the plasma membrane. This finding was confirmed by Western blot analysis using isolated caveolae‐enriched membrane fractions from the rat kidney and immuno‐precipitation experimentation. When rOAT3s synthesized cRNA of rOAT3 along with the antisense oligo deoxynucleotide of Xenopus Cav‐1 were co‐injected into Xenopus oocytes, the [3H] estrone sulfate uptake was significantly decreased. These findings suggest that rOAT3 and caveolin‐1 share a cellular expression in the plasma membrane and Cav‐1 up‐regulates the organic anionic compound uptake via rOAT3 under normal physiological conditions. IUBMB Life, 57: 109‐117, 2005

Optimization of dialysate sodium in sodium profiling haemodialysis

SUMMARY:  Sodium profiling haemodialysis is a modified method of sodium gradient dialysis during which dialysate sodium follows a time‐dependent profile. Sodium profiling haemodialysis has claimed to reduce intradialytic discomforts such as hypotension, muscle cramps, and disequilibrium syndrome. Having the low sodium period is an essential part of the sodium profiling haemodialysis to compensate for the sodium gain during the high sodium period. In spite of this, however, the incidence of interdialytic complications that results from the excessive sodium gain has been reported in previous literature. Making the prediction of optimal dialysate sodium concentration for isonatric dialysis is practically very difficult since too many variables influence the sodium gradient, including the initial plasma sodium and tonicity and/or dialysis dynamics that differ from patient to patient and from treatment to treatment. As for sodium profiling haemodialysis, complexities are added further since details of profile, such as type and form of profile, or initial, terminal, or time‐distribution of dialysate sodium are varied considerably. We have recently reported that the intradialytic sodium balance and interdialytic weight gain are directly related to the time‐averaged concentration of dialysate sodium (TACNa). The dialysate sodium can be optimized using this concept of TACNa for sodium profiling dialysis. TACNa should be approximately 0.5–0.8 mmol/L lower than patients predialysis serum sodium concentrations to achieve a sodium balance neutral dialysis. In that study the optimal TACNa, seems to be between 137.8 and 143.5 mmol/L. Such an optimal value should be defined for the individual centres based on their profile protocols for clinical use. In the future, dialysate sodium should be optimized based on the exact prediction of the postdialysis plasma sodium levels.

Agreements between Indirect Calorimetry and Prediction Equations of Resting Energy Expenditure in End-Stage Renal Disease Patients on Continuous Ambulatory Peritoneal Dialysis

Purpose Equations are frequently used to estimate resting energy expenditure (REE) in a clinical setting. However, few studies have examined their accuracy in end-stage renal disease (ESRD) patients. Materials and Methods To investigate agreement between indirect calorimetry and several REE estimating equations in 38 ESRD patients on peritoneal dialysis, we performed indirect calorimetry and compared the results with REEs estimated using 5 equations [Harris-Benedict (HBE), Mifflin, WHO, Schofield, and Cunningham]. Results Measured REE was 1393.2 ± 238.7 kcal/day. There were no significant differences between measured and estimated REEs except Mifflin (1264.9 ± 224.8 kcal/day). Root mean square errors were smallest for HBE, followed by Schofield, Cunningham, and WHO, and largest for Mifflin (171.3, 171.9, 174.6, 175.3, and 224.6, respectively). In Bland-Altman plot, correlation coefficients between mean values and differences were significant for HBE (r = 0.412, p = 0.012) and tended to be significant for Cunningham (r = 0.283, p = 0.086). In DM patients and patients with overhydration, HBE showed significant underestimation when REE increased. Conclusion In ESRD patients on continuous ambulatory peritoneal dialysis (CAPD), REE-estimating equations have no significant differences from indirect calorimetry, except Mifflin. However, HBE showed greater bias than others when REE was high.

Successful antibiotic treatment of Pseudomonas stutzeri-induced peritonitis without peritoneal dialysis catheter removal in continuous ambulatory peritoneal dialysis

Pseudomonas stutzeri is a Gram-negative, rod-shaped, motile, single polar-flagellated, soil bacterium that was first isolated from human spinal fluid and is widely distributed in the environment. It was isolated as an uncommon opportunistic pathogen from humans, and a few cases of P. stutzeri-induced peritonitis have been reported in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Catheter removal with antibiotic treatment is generally recommended because peritonitis by Pseudomonas species is commonly associated with catheter-related infection. Here, we describe the first case of P. stutzeri-induced peritonitis in an 82-year-old woman in Korea. She had received two antipseudomonal antibiotics, an aminoglycoside (isepamicin, Yuhan corporation, Seoul, Korea) and a fluoroquinolone (ciprofloxacin), and was successfully treated without removal of the CAPD catheter.

The association between mortality and abdominal aortic calcification and relation between its progression and serum calcium concentration in chronic hemodialysis patients

Background The composite summary score (range, 0–24) of abdominal aortic calcification (AAC) devised by Kauppila et al is a simple method of assessing AAC severity. However, few studies have been conducted to determine an optimal AAC cutoff score for the prediction of mortality or to investigate the relation between mineral metabolism and AAC progression using the scoring system. Methods The medical records of 112 patients on hemodialysis who had undergone simple lateral lumbar radiography every 6 months from August 2009 were reviewed. Patients were followed until November 2012, and the relationship between the degree of AAC at baseline and mortality was evaluated. In addition, the relationship between the progression of AAC and serum concentrations of calcium and phosphate was evaluated in the 75 patients who were successfully followed until November 2012. Results The mean AAC score at baseline was 5.5±4.8, and the cutoff calcification score for the prediction of mortality was 7.75 (sensitivity=61%, specificity=81%). Patients were allocated to Group A (baseline total calcification score ≤8.0, n=85) or Group B (baseline total calcification score>8.0, n=27), and multivariate analysis showed that Group B was an independent risk factor of all-cause mortality and cardiovascular events. Of the 75 patients successfully followed, 51 showed AAC progression (Group 1) and 24 showed no change or improvement (Group 2). Group 1 was found to have significantly higher mean serum corrected calcium levels during the 2nd year and 3rd year of follow-up than Group 2. Furthermore, repeated-measures analysis of variance showed higher monthly corrected calcium concentrations (P=0.099) and mean corrected calcium levels during the 1st year, 2nd year, and 3rd year of follow-up (P=0.062) in Group 1, but without statistical significance. The cutoff values of mean corrected calcium of the 2nd year and 3rd year for the prediction of AAC progression during follow-up years were 8.96 mg/dL and 9.45 mg/dL, respectively. Serum phosphate levels and corrected calcium×phosphate values were similar in Groups 1 and 2. Conclusion Patients with an AAC score of>8 at baseline seem to be at higher risk of mortality during follow-up. Of the serum variables examined, such as corrected calcium, phosphate, and corrected calcium×phosphate, corrected calcium was found to be marginally associated with AAC progression. However, a larger-scale prospective study is required to confirm our findings.

A Case of Post-radiotherapy Urethral Stricture with Spontaneous Bladder Rupture, Mimicking Obstructive Uropathy due to Cancer Metastasis

Non-traumatic, spontaneous urinary bladder rupture is a rare complication of urethral stricture. Furthermore, its symptoms are often nonspecific, and misdiagnosis is common. The authors experienced a case of urethral stricture with spontaneous bladder rupture and bilateral hydronephrosis, mimicking obstructive uropathy attributed to cancer metastasis. A 55-year-old woman was admitted with abdominal pain and distension, oliguria, and an elevated serum creatinine level. She had undergone radical hysterectomy for uterine cervical cancer and received post-operative concurrent chemoradiation therapy 13 years previously. Non-contrast enhanced computed tomography showed massive ascites and bilateral hydronephrosis. The initial diagnosis was acute kidney injury due to obstructive uropathy caused by malignant disease. After improvement of her renal function by bilateral percutaneous nephrostomy catheterization, contrast-enhanced computed tomography and a cytologic examination of ascites showed no evidence of malignancy. However, during retrograde pyelography, a severe urethral stricture was found, and subsequent cystography showed leakage of contrast into the peritoneal cavity and cystoscopy revealed a defect of the posterior bladder wall. After urethral dilatation and primary closure of the bladder wall, acute kidney injury and ascites were resolved.

Different pattern of fluid loss from the lower extremities in normohydrated and overhydrated stage 5 chronic-kidney-disease patients after haemodialysis.

Aim:  It is unclear whether fluid is lost from each body segment in a similar manner during haemodialysis (HD) in normohydrated (NH) and overhydrated (OH) patients.