Association between Blood Pressure and Renal Progression in Korean Adults with Normal Renal Function

Background@#Although hypertension (HTN) is a well-established major risk factor for renal progression in patients with chronic kidney disease (CKD), few studies investigating its role in renal deterioration in the general population with normal renal function (NRF) have been published. Here, we analyzed the correlation between blood pressure (BP) and impaired renal function (IRF) in Korean adults with NRF. @*Methods@#Data for the study were collected from the national health screening database of the Korean National Health Insurance Service. Patients whose baseline estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m 2 or whose baseline urinalysis showed evidence of proteinuria were excluded. IRF was defined as an eGFR below 60 mL/min/1.73 m 2 . We performed follow up for eGFR for 6 years from 2009 to 2015 and investigated IRF incidence according to baseline BP status. We categorized our study population into two groups of IRF and NRF according to eGFR level in 2015. @*Results@#During 6 years of follow-up examinations, IRF developed in 161,044 (2.86%) of 5,638,320 subjects. The IRF group was largely older, and the incidence was higher in females and patients with low income, HTN, diabetes mellitus, dyslipidemia, and obesity compared with the NRF group. Subjects whose systolic BP was more than 120 mmHg or whose diastolic BP was more than 70 mmHg had an increased risk of developing IRF compared with subjects with lower BP (odds ratio [OR], 1.037; 95% confidence interval [CI], 1.014–1.061 vs. OR, 1.021; 95% CI, 1.004–1.038). @*Conclusion@#BP played a major role in renal progression in the general population with NRF.Strict BP control may help prevent CKD in the general population.

Circulating renalase predicts all-cause mortality and renal outcomes in patients with advanced chronic kidney disease

BACKGROUND/AIMS@#Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse cardiovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in patients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT 00860431).@*METHODS@#A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes.@*RESULTS@#The mean level of serum renalase was 75.8 ± 34.8 μg/mL. In the multivariable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10-μg/mL increase in serum renalase was associated with significantly greater hazards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD.@*CONCLUSIONS@#Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.

Erratum: Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea Volume 36, Issue 1, March 2017, Pages 68–

The values of y axis in Fig. 3 should be corrected. The authors would like to apologize for any inconvenience this has caused.

Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea

BACKGROUND: We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD). METHODS: We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment. RESULTS: The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046). CONCLUSION: Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.

Hypercalcemia in a Patient with Systemic Lupus Erythematosus / 대한내과학회지

Hypercalcemia is a common clinical problem. The most frequent causes of hypercalcemia include primary hyperparathyroidism and malignancy; systemic lupus erythematosus (SLE) is a very rare cause of hypercalcemia. Here we describe a case of symptomatic severe hypercalcemia, which developed during a lupus flare. After treatment with intravenous fluids, diuretics, pamidronate, and hemodialysis, calcium levels normalized and were maintained on low-dose prednisolone treatment. To the best of our knowledge, this is the first case of hypercalcemia in a patient with SLE in Korea. Clinicians should consider lupus as a differential diagnosis for patients with severe hypercalcemia.

Angiotensin III increases monocyte chemoattractant protein-1 expression in cultured human proximal tubular epithelial cells

BACKGROUND/AIMS: We investigated whether angiotensin III (Ang III) is involved in monocyte recruitment through regulation of the chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal tubular epithelial cells (HK-2 cells). METHODS: We measured MCP-1 levels in HK-2 cells that had been treated with various concentrations of Ang III and Ang II type-1 (AT1) receptor antagonists at various time points. The phosphorylation states of p38, c-Jun N-terminal kinases (JNK), and extracellular-signal-regulated kinases were measured in Ang III-treated cells to explore the mitogen-activated protein kinase (MAPK) pathway. MCP-1 levels in HK-2 cell-conditioned media were measured after pre-treatment with the transcription factor inhibitors curcumin or pyrrolidine dithiocarbamate. RESULTS: Ang III increased MCP-1 protein production in dose- and time-dependent manners in HK-2 cells, which was inhibited by the AT1 receptor blocker losartan. p38 MAPK activity increased significantly in HK-2 cells exposed to Ang III for 30 minutes, and was sustained at higher levels after 60 minutes (p < 0.05). Total phosphorylated JNK protein levels tended to increase 20 minutes after stimulation with Ang III. Pre-treatment with a p38 inhibitor, a JNK inhibitor, or curcumin significantly inhibited Ang III-induced MCP-1 production. CONCLUSIONS: Ang III increases MCP-1 synthesis via stimulation of intracellular p38 and JNK MAPK signaling activity and subsequent activated protein-1 transcriptional activity in HK-2 cells.

Time points for obtaining representative values of 24-hour blood pressure in chronic kidney disease

BACKGROUND/AIMS: Ambulatory blood pressure (BP) monitoring has been widely recommended for evaluating the status of BP, but is lacking in practicality. Determination of the specific time points for BP measurement that are representative of 24-hour mean BP could be useful and convenient in hypertensive patients with chronic kidney disease (CKD). METHODS: A total of 1,317 patients for whom 24-hour ambulatory BP monitoring was performed were enrolled in a multicenter study on hypertensive CKD. We analyzed the time points at which systolic blood pressure (SBP) values exhibited the smallest differences from 24-hour mean SBP (mSBP). We included office mSBP and analyzed the relationships between SBPs at the office and the time points with the smallest differences from 24-hour mSBP using several methods. RESULTS: The time points with the smallest differences from 24-hour mSBP were 7:00 AM, 2:00 PM, and 9:30 PM. In regression analysis, SBPs at 7:00 AM and 9:30 PM were better correlated with 24-hour mSBP than SBPs at 2:00 PM and the office. The proportions of patients with SBPs within 30% of 24-hour mSBP were higher at 7:00 AM and 9:30 PM. The best consistency between the uncontrolled hypertensive groups, defined as > or = 135 mmHg of 24-hour mSBP and higher values of SBPs corresponding to 135 mmHg of 24-hour mSBP, were observed at the 7:00 AM and 9:30 PM time points. CONCLUSIONS: The specific time points for SBPs that correlated well with 24-hour mSBP in hypertensive CKD patients were 7:00 AM and 9:30 PM.

The Clinical Association of the Blood Pressure Variability with the Target Organ Damage in Hypertensive Patients with Chronic Kidney Disease

It is known that blood pressure variability (BPV) can independently affect target organ damage (TOD), even with normal blood pressure. There have been few studieson chronic kidney disease (CKD) patients. We evaluated the relationship between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure monitoring. BPV was defined as the average real variability, with a mean value of the absolute differences between consecutive readings of systolic blood pressure. TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score > or =4 in electrocardiography) and kidney injury (as determined from an estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m2 and proteinuria).The mean BPV of the subjects was 15.9+/-4.63 mmHg. BPV displayed a positive relationship with LVH in a univariate analysis and after adjustment for multi-variables (odds ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no relationship with kidney injury. These data suggest that BPV may be positively associated with LVH in hypertensive CKD patients.

Benefits of a Continuous Ambulatory Peritoneal Dialysis (CAPD) Technique with One Icodextrin-Containing and Two Biocompatible Glucose-Containing Dialysates for Preservation of Residual Renal Function and Biocompatibility in Incident CAPD Patients

In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Delta1.2+/-2.9 mL/min/1.73 m2, P=0.027) and urine volume (-Delta363.6+/-543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Delta0.5+/-2.7 mL/min/1.73 m2, P=0.266; -Delta108.6+/-543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, beta2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549]

Benefits of a Continuous Ambulatory Peritoneal Dialysis (CAPD) Technique with One Icodextrin-Containing and Two Biocompatible Glucose-Containing Dialysates for Preservation of Residual Renal Function and Biocompatibility in Incident CAPD Patients

In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Delta1.2+/-2.9 mL/min/1.73 m2, P=0.027) and urine volume (-Delta363.6+/-543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Delta0.5+/-2.7 mL/min/1.73 m2, P=0.266; -Delta108.6+/-543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, beta2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549]

An Unusual Cause of Left Brachiocephalic Vein Occlusion: Extrinsic Compression by the Aortic Arch in a Hemodialysis Patient / 대한내과학회지

The most common cause of central venous obstruction including left braciocephalic vein is intrinsic stenosis associated with a previous central venous catheter or other devices. Occasionally, patients with no history of central venous catheterization present with left brachiocephalic vein occlusion. This occurs as a result of extrinsic compression of the brachiocephalic vein by adjacent vascular structures, especially the aortic arch and its branches. Here, we report a case of left brachiocephalic vein compression caused by a tortuous, ectatic aortic arch in a patient with no history of central vein catheterization. To our knowledge, this is the first report of extrinsic compression of the brachiocephalic vein by the aortic arch in Korea.

A Case of Chylothorax in an Adult Patient with Down Syndrome Developed after Mechanical Ventilation / 대한내과학회지

Chylothorax is the accumulation of chyle-containing lymphatic fluid within the pleural space. It is mainly caused by injury or obstruction of the thoracic duct due to neoplasm or trauma. There have been several reports of chylothorax associated with chromosomal anomaly such as Down syndrome. Most cases are congenital, and development of chylothorax in an adult with Down syndrome is rare. Here, we report a case of chylothorax in an adult with Down syndrome who had been treated with mechanical ventilation. A 31-year-old woman with Down syndrome was admitted with urosepsis. She was treated with mechanical ventilation due to severe respiratory acidosis. Four days after mechanical ventilation, she developed unilateral pleural effusion, and analysis indicated chylothorax. After conservative treatment, including fasting and total parenteral nutritional support, the chylous formation completely disappeared.

Clinical Characteristics and Risk Factors of Acute Kidney Injury in Patients with Acute Alcohol Intoxication / 대한신장학회지

PURPOSE: Acute alcohol intoxication (AAI) causes various complications such as electrolyte imbalance, alcoholic ketoacidosis (AKA), rhabdomyolysis, and acute kidney injury (AKI). Although there have been some reports about AKA and rhabdomyolysis, AKI due to acute alcohol intoxication is rarely reported. METHODS: We retrospectively evaluated the medical records of 371 patients with AAI between January 2004 and May 2010 in Uijeongbu St. Mary's Hospital. We compared the clinical findings, morbidity and mortality rate between AKI and normal kidney function (NKF) groups. RESULTS: Of the total 371 patients with AAI, AKI occurred in 107 patients (28.8%). The peak serum creatinine level in AKI patients was 2.9+/-1.9 mg/dL. Thirteen of the 107 patients (12.1%) received renal replacement therapy. AKI group had higher incidence of decreased mentality (29.0% vs 16.3%, p=0.006), dyspnea (11.2% vs 4.9%, p=0.029) and hypotension (66.0% vs 41.7%, p<0.001), and lower incidence of gastrointestinal bleeding (22.4% vs 34.8%, p=0.019), compared to NKF group. The AKI group also had higher incidence of ketoacidosis (78.5% vs 28.8%, p<0.001), rhabdomyolysis (19.6% vs 4.2%, p<0.001), and pneumonia (22.4% vs 8.0%, p<0.001), compared to NKF group. The length of ICU stay was longer (7.4+/-10.8 vs 4.1+/-6.1 days, p=0.003) and the mortality rate was higher (17.8% vs 2.3%, p<0.001) in AKI group. CONCLUSION: This study demonstrated that incidence of AKI in patients with AAI was 28.8% and AKI was associated with high morbidity and mortality. And multivariate analysis demonstrated that independent risk factors of AKI were ketoacidosis and increased serum osmolality.

Anatomical Variation of Internal Jugular Vein in Korean Hemodialysis Patients / 대한신장학회지

PURPOSE: The internal jugular vein (IJV) is a preferred site for central cannulation for hemodialysis (HD) because of its low incidence of central vein stenosis. Although anatomically IJV is commonly located on the anterior-lateral side of the carotid artery, some patients have anatomical variation of IJV, which can lead to difficulty and complication of cannulation. This study was performed to evaMETHODS: We enrolled 358 patients receiving IJV catheter cannulation for HD using doppler ultrasonography between January 2007 and February 2009. We examined the anatomical positions of IJV in relation to the position of carotid artery (CA) and incidence of anatomical variation on both sides. We also investigated incidence of inadequate IJV for cannulation, RESULTS: The mean age of 358 enrolled patients was 57+/-15 years (14-88 years) (M:F=203:155). Anatomical variations of the left (Lt) and right (Rt) IJV position relative to the CA were found in 36.3% and 27.1%, respectively. Various anatomical variations of IJV position were discovered in the anterior side (Lt 23.7%, Rt 21.2%), anterior-medial side (Lt 7%, Rt 2.5%), and the lateral side (Lt 1.1%, Rt 1.7%) relative to CA. Inadequate Lt and Rt IJVs for cannulation, which can be too small sized or obstructed, were 6.4% and 2.8%, respectively. CONCLUSION: About one third of Korean HD patients had anatomical variations of IJV position relative to the CA. This study supports the use of doppler ultrasound guided technique for IJV cannulation in HD patients.

A Case of Digital Gangrene Complicated by Atypical Hemolytic Uremic Syndrome in a Patient with Systemic Lupus Erythematosus / 대한신장학회지

Atypical hemolytic uremic syndrome (HUS) in adults is a life-threatening disorder characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia, which is not related to E. coli. Digital gangrene is one of the grave signs in emergency medicine because it requires prompt evaluation and treatment. We describe a 37 year-old Thailand woman, initially treated for suspected Neisseria septicemia, who went on to develop renal complications, thrombocytopenia and hemolytic anemia, which made the diagnosis of atypical hemolytic uremic syndrome. The patient was complaining of dysesthesia on all extremities and severe pain in both legs. Serologically, she was diagnosed as systemic lupus erythematosus (SLE). She was treated with plasma exchanges using fresh frozen plasma, parenteral steroid, anticoagulant and antibiotics, successfully. This is the first report of digital gangrene complicated by atypical HUS in a patient with SLE in Korea.

A Case of Central Vein Stenosis Complicated by Calcified Lesions of Pulmonary Tuberculosis / 대한신장학회지

Central venous stenosis or occlusion is commonly associated with placement of central venous catheters or devices. Although rare, central venous stenosis or occlusion may also develop without a history of previous central venous catheter placement. Here we report a case of central venous stenosis without a previous central catheter placement. A 76-year-old woman with hypertensive nephropathy was admitted due to deterioration of renal function. Tunneled cuffed catheter for hemodialysis was inserted in the right external jugular vein, and we intended to insert central venous catheter because of poorly functioning peripheral vein. But, left internal jugular vein was not cannulated. The patients had a history of pulmonary tuberculosis and chest x-ray revealed extensive calcified lesions mainly in left upper lung. Venography and CT angiogram showed complete occlusion at the confluent point of the left subclavian vein and left internal jugular vein, and left brachiocephalic vein by calcified lesion. The anterior cervical vein and jugular venous arch forming an anastomosis between the neck vein were marked dilated. The patient did not show any clinical symptoms and signs associated with central venous stenosis, and the central venous catheter functioned well, correction of central vein stenosis was not necessary. After the supportive care including temporary hemodialysis, the patient improved from renal dysfunction.

Glyphosate Induced Severe Tubulointerstitial Nephritis Requiring Hemodialysis / 대한신장학회지

This is the first case of glyphosate induced severe tubulointerstitial nephritis requiring hemodialysis without cardiovascular collapse. A 67-year-old man presented to the hospital 30 minutes after ingesting 90 mL of glyphosate herbicide. On arrival, his serum creatinine was 0.8 mg/dL and other laboratory findings including liver, cardiac, and muscle enzymes were all normal. Two days after admission, although his vital signs were stable, his creatinine abruptly increased to 8.2 mg/dL and oliguria developed. As a result, we started hemodialysis treatment and two weeks after initiation of hemodialysis, his renal function started to improve slowly. After discontinuation of hemodialysis, his renal function gradually recovered and serum creatinine level decreased to 1.6 mg/dL three weeks after admission.

A case of syndrome of inappropriate secretion of antidiuretic hormone associated with paroxetine / 대한내과학회지

Paroxetine is a well-known selective serotonin reuptake inhibitor, and has been reported to be advantageous for chronic pain control. Paroxetine is increasingly used for various types of chronic pain because of its safety; however, hyponatremia, or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with paroxetine, has been reported. This complication is relatively rare, but some patients have presented with severe neurological symptoms. Here, we report the first case of SIADH associated with paroxetine in Korea.

Successful Angioplasty of Arteriovenous Graft Obstruction Using Gadolinium chelate in a Patient with Iodine Hypersensitivity / 대한신장학회지

Percutaneous transluminal angioplasty (PTA) using iodine contrast dye has been used as the definitive method of choice for treating hemodialysis vascular access dysfunction. Occasionally, iodine material can not be used in the hemodialysis patients with a history of severe hypersensitivity reactions or the predialysis patients with premature access awaiting hemodialysis treatment. Gadolinium chelates have been reported as an alternative contrast agent for angiography or angioplasty in such patients. Here we report a case of successful angioplasty of arteriovenous graft obstruction using gadolinium chelate (gadopentetate dimeglumine) in a patient with repetitive iodine hypersensitivity reactions.

The Treatment of Post Transplant Tuberculosis: Rifampin Sparing Regimen / 대한이식학회지

BACKGROUND: Rifampin reduces the blood levels of cyclosporin (CsA) and steroids by increasing the activity of hepatic cytochrome P450 system and the inclusion of rifampin in the anti-tuberculosis treatment protocol increases the risk of acute allograft rejection and mortality due to its interaction with cyclosporine. We report the successful treatment outcome of post-renal transplant tuberculosis patients who were treated with quinolone substituted for rifampin in anti-tuberculosis regimen. METHODS: This was a retrospective study of 14 patients with tuberculosis diagnosed among 218 transplant recipients from Feb. 1988 through Dec. 2003 at Daejeon St. Mary's hospital of catholic university of Korea and 6 patients with tuberculosis who underwent transplantation in other hospital and followed up in our hospital. RESULTS: The incidence of post-renal transplant tuberculosis was 6.4%. The mean time to diagnosis of tuberculosis after transplantation was 58.6 months (3.3~180.7). 9 were pulmonary and 11 were extrapulmonary tuberculosis. The graft failure was not occurred in quinolone group (0/15) and 2 of 3 in rifampin group. The serum creatinine levels before tuberculosis were not different to that of post-treatment in quinolone group. (P=0.58) The CsA levels before tuberculosis were not also different to that of posttreatment in quinolone group (P=0.68). CONCLUSIONS: The treatment of post-renal transplant tuberculosis with rifampin sparing anti-tuberculosis regimen was successful. Rifampin, although a mainstay drug in the treatment of tuberculosis, can be avoided in patients receiving cyclosporine, thus avoiding the risk of precipitating allograft rejection.