Clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients / 고신대학교의과대학학술지

Background@#Copeptin is the carboxyl-terminal part of the vasopressin precursor protein, and its concentration is an independent predictor of the onset of chronic kidney disease and a rapid decline in the glomerular filtration rate. The glomerular filtration rate is regarded as the best indicator of kidney transplant function and is a predictor of graft and patient survival. We investigated the clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients. @*Methods@#We measured serum creatinine, cystatin C, and copeptin concentrations in renal transplant recipients on the day of their operation, as well as on postoperative days 3, 7, 30, and 365. Acute rejection was defined as a sudden decrease in renal function accompanied by histological changes. @*Results@#Eight renal transplant recipients were enrolled in the study from July 2018 to December 2019. Four patients experienced histologically confirmed transplant rejection. All four cases involved acute T-cell rejection. No significant correlation was found between the copeptin level and the presence or absence of rejection at any time point. In subgroup analyses, changes in creatinine, the estimated glomerular filtration rate, cystatin, and copeptin did not show statistical significance. @*Conclusions@#We anticipated that copeptin would be useful to identify individuals at high risk of transplant rejection; however, our study failed to show an association. Further research will be needed to overcome the limitations of this study.

Comparison of Different Types of Oral Adsorbent Therapy in Patients with Chronic Kidney Disease:A Multicenter, Randomized, Phase IV Clinical Trial

Purpose@#Oral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD. @*Materials and Methods@#A seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels. @*Results@#Significantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120. @*Conclusion@#DW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. NCT02681952).

Alterations in Structural and Functional Connectivities in Patients with End-Stage Renal Disease

Background@#and Purpose: The aim of this study was to evaluate the structural and functional connectivities of brain network using graph theoretical analysis in neurologically asymptomatic patients with end-stage renal disease (ESRD). We further investigated the prevalence of cognitive impairment (CI) in ESRD patients and analyzed the association between network measures of brain connectivity and cognitive function. @*Methods@#We prospectively enrolled 40 neurologically asymptomatic ESRD patients, 40 healthy controls, and 20 disease controls. All of the subjects underwent diffusion-tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI). We calculated measures of structural and functional connectivities based on DTI and rs-fMRI, respectively, and investigated differences therein between the ESRD patients and the healthy controls. We assessed cognitive function in the ESRD patients using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery. @*Results@#The ESRD patients exhibited decreased global structural and functional brain connectivities, as well as alterations of network hubs compared to the healthy controls and disease controls. About 70% of the ESRD patients had CI. Moreover, ESRD patients without CI exhibited decreased global connectivity and alterations of network hubs. Furthermore, there was a significant positive association between measures of brain connectivity and cognitive function. @*Conclusions@#We found that ESRD patients exhibited decreased structural and functional brain connectivities, and that there was a significant association between brain connectivity and cognitive function. These alterations in the brain network may contribute to the pathophysiological mechanism of CI in ESRD patients.

The Correlations among Depressive Symptoms, Cognitive Performance and Serum BDNF Levels in the Patients with Chronic Kidney Disease

OBJECTIVE: In the current study, we investigated whether there are relations among depressive symptoms, cognitive performance and serum BDNF levels in the patients with chronic kidney disease (CKD). METHODS: Sixty patients with CKD and 65 healthy controls participated. Depressive symptoms were evaluated with Beck depression inventory (BDI) and Hamilton Depression Rating Scale (HDRS). Mini-Mental State Examination included in the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (MMSE-KC) assessment packet was used for the evaluation of overall cognitive function. To assess memory function, the Korean version of the Hopkins Verbal Learning Test (K-HVLT) was used. BDNF levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The CKD patients showed more depressive symptoms when compared with controls. The depressive symptoms and cognitive function were not associated with serum BDNF levels in the CKD patients. CONCLUSION: In the current study, CKD patients had more depressive symptoms when compared controls. However, the serum BDNF levels of CKD patients were not associated with depressive symptoms and cognitive functions. These findings suggested that the serum BDNF levels may not be reflect the cognitive function and depressive mood state in the CKD patients.

Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone

BACKGROUND: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). METHODS: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. RESULTS: Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = −0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775–0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500–0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. CONCLUSION: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.

Basiliximab-Induced Non-Cardiogenic Pulmonary Edema in a Kidney Transplant Patient / 대한이식학회지

Induction therapy with basiliximab is widely administered after kidney transplantation to prevent acute rejection. Herein, we report a case of non-cardiogenic pulmonary edema induced by basiliximab. To the best of our knowledge, such case has not been reported to date in Korea. A 54-year-old man with polycystic kidney disease received kidney transplantation. As induction therapy, he was prescribed basiliximab. On day 4, the second dose of basiliximab was administered. The patient complained of acute hypoxia 23 hours later, which led to circulatory collapse. He was discharged 3 weeks later with stable renal function. Pulmonary edema was presumed to have been caused by increased pulmonary capillary permeability. A possible hypothesis for this event occurring after the second basiliximab injection is steroid-related effects. Non-cardiogenic pulmonary edema is a complication that might occur after basiliximab induction therapy. Physicians should be aware of this potentially life-threatening complication.

The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial

BACKGROUND: Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (www.ClinicalTrials.gov NCT01282073). METHODS: A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared. RESULTS: The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, −0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks. CONCLUSION: In combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms. Trial registry at ClinicalTrials.gov (www.ClinicalTrials.gov NCT01282073).

Confronting Practical Problems for Initiation of On-line Hemodiafiltration Therapy

Conventional hemodialysis, which is based on the diffusive transport of solutes, is the most widely used renal replacement therapy. It effectively removes small solutes such as urea and corrects fluid, electrolyte and acid-base imbalance. However, solute diffusion coefficients decreased rapidly as molecular size increased. Because of this, middle and large molecules are not removed effectively and clinical problem such as dialysis amyloidosis might occur. Online hemodiafiltration which is combined by diffusive and convective therapies can overcome such problems by removing effectively middle and large solutes. Online hemodiafiltration is safe, very effective, economically affordable, improving session tolerance and may improve the mortality superior to high flux hemodialysis. However, there might be some potential limitations for setting up online hemodiafiltaration. In this article, we review the uremic toxins associated with dialysis, definition of hemodiafiltration, indication and prescription of hemodiafiltration and the limitations of setting up hemodiafiltration.

Urosepsis with Aerococcus urinae in a Patient with Complicated Urinary Tract Infection / 대한내과학회지

Aerococcus urinae is a gram-positive coccus that produces alpha-hemolysis on blood agar and is negative for catalase. A. urinae can often be misidentified as a streptococcus, staphylococcus, or enterococcus by most commercial identification systems. Although A. urinae is a rarely reported human pathogen, it can be fatal in some cases. Here we report on a case of urosepsis caused by A. urinae, identified by 16S rRNA gene sequencing in a patient with ureter stones and hydronephrosis, for the first time in Korea. It is important for physicians to consider A. urinae as a potential pathogen and to prescribe the most suitable antibiotics to ensure the best outcome.

Symptomatic Hypermagnesemia in Normal Kidney Function with a Colonic Cleansing Agent / 대한내과학회지

Most reported cases of hypermagnesemia are related to laxative abuse and impaired renal function, while hypermagnesemia is uncommon without iatrogenic magnesium administration and decreased renal function. Magnesium-containing bowel-cleansing agents are widely used before colonoscopy, usually without complications. However, we experienced a case of symptomatic hypermagnesemia with normal renal function after using a bowel-cleansing agent. A 74-year-old man with normal renal function complained of lethargy and motor weakness after taking a bowel-cleansing agent containing 14 grams of magnesium before a colonoscopy for hematochezia. His magnesium level was 12 mg/dL. Fluid stasis in the gut due to colonic obstruction might have caused the hypermagnesemia. He was treated successfully with a bowel enema and intravenous calcium. We should be cautious when prescribing drugs for colonoscopy if colonic obstruction is suspected.

Successfully treated isolated renal artery pseudoaneurysm in a patient with Behçet's disease

Renal artery aneurysms and pseudoaneurysms are an uncommon clinical problem with a low incidence rate. They are abnormal dilatations of the vessel lumen with some different natures. However, the rupture of an aneurysm and pseudoaneurysm is the most dreaded complication because it causes death of the patient. There are many causes of renal artery aneurysm and pseudoaneurysm, including Behçet's disease; however, renal involvement in Behçet's disease is less frequent. We report a case of renal artery pseudoaneurysm induced by Behçet's disease and treated successfully with coil embolization. A 56-year-old woman with Behçet's disease presented with an incidental left renal artery pseudoaneurysm measuring 18 mm. We successfully performed endovascular treatment with coil embolization instead of surgical treatment.

Successful Treatment of BK Virus-Associated Hemorrhagic Cystitis in a Kidney Transplant Patient: a Case Report / 대한내과학회지

Hemorrhagic cystitis is defined as diffuse mucosal inflammation of the urinary bladder that presents with gross hematuria. A variety of factors, including chemotherapeutic agents, radiation therapy and infection, can cause hemorrhagic cystitis. Among them, BK virus-associated hemorrhagic cystitis is common in patients who have undergone stem cell transplantation but relatively rare in kidney transplantation patients. Here, we present the case of a kidney-transplant patient with BK virus-associated hemorrhagic cystitis and interstitial nephritis who was successfully treated with leflunomide and ciprofloxacin.

Cavitary Lung Lesion in a Patient with Systemic Lupus Erythematosus: An Unusual Manifestation of Cytomegalovirus Pneumonia

Cytomegalovirus (CMV), a member of the human herpesvirus group, causes severe disease in immunocompromised patients. In particular, CMV pneumonia can be a life-threatening disease to patients taking immunosuppressive drugs. The radiographic manifestations of CMV are variable and may consist of reticular or reticulonodular patterns, ground-glass opacities, air-space consolidations, or mixed patterns. A cavitary lesion in pneumonia associated with CMV infection is extremely rare. Herein we report on a case of CMV pneumonia which presented with a cavitary lesion and was treated successfully in a systemic lupus erythematosus patient who was taking immunosuppressive drugs.

Nephrotic syndrome complicated with portal, splenic, and superior mesenteric vein thrombosis

Thromboembolism is a major complication of nephrotic syndrome. Renal vein thrombosis and deep vein thrombosis are relatively common, especially in membranous nephropathy. However, the incidence of portal vein and superior mesenteric vein (SMV) thrombosis in patients with nephrotic syndrome is very rare. To date, several cases of portal vein thrombosis treated by anticoagulation therapy, not by thrombolytic therapy, have been reported as a complication of nephrotic syndrome. Here, we report a case of portal, splenic, and SMV thrombosis in a patient with a relapsed steroid dependent minimal change disease who was treated successfully with anticoagulation and thrombolytic therapy using urokinase. Radiologic findings and his clinical conditions gradually improved. Six months later, a complete remission of the nephrotic syndrome was observed and the follow-up computed tomography scan showed the disappearance of all portal vein, splenic vein, and SMV thrombi.

Concurrence of Membranous Glomerulonephritis and Pulmonary Alveolar Proteinosis / 대한내과학회지

Membranous glomerulonephritis is one of the most common causes of nephrotic syndrome in adults. Pulmonary alveolar proteinosis (PAP) is a rare lung disease in which abnormal accumulation of surfactant occurs within the alveoli. We describe a 61-year-old man with concurrent membranous glomerulonephritis and PAP, which is very rare; both are pathophysiologically related to an abnormal immune response. A patient came to hospital with leg edema but no respiratory symptoms. Chest X-ray and CT showed classical PAP findings, which are ground-glass opacities with interlobular septal thickening, in both lung fields. A bubbly whitish secretion retrieved via broncho-alveolar lavage showed neutrophils and lymphocytes as well as Periodic acid-Schiff-positive proteinaceous materials. A kidney biopsy revealed findings of membranous glomerulonephritis with irregular subepithelial deposits by electron microscopy. At 1 year after diagnosis, the membranous glomerulonephritis was well under control with steroids and mycophenolate mofetil but PAP became aggravated gradually and whole-lung lavage was needed.

Endocarditis Caused by Community-Acquired Klebsiella pneumoniae Infection - A Case Report - / 대한구급학회지

In community-acquired Klebsiella pneumoniae infection, pyogenic liver abscess is common as a primary site of infection, particularly in Asia, that can progress to bacteremia. Diabetes mellitus is a usual predisposing factor. Pneumonia as primary site of infection by community-acquired Klebsiella pneumoniae infection is not common but carries a poor outcome. Early administration of appropriate antibiotics is extremely important to avoid the development of bacteremia and septicemia. An infective endocarditis caused by community-acquired Klebsiella pneumoniae infection is very rare; particularly, such a case of endocarditis in which pneumonia was the primary site of infection has never been reported previously. In this report we described a case of community-acquired Klebsiella pneumoniae infection that started with pneumonia and progressed to bacteremia, leading to endocarditis, liver abscess, and other systemic septic complications. Delayed administration of appropriate antibiotics may have played a role in this case.

Additional antihypertensive effect of magnesium supplementation with an angiotensin II receptor blocker in hypomagnesemic rats

BACKGROUND/AIMS: Magnesium (Mg) is an essential element for vascular function and blood pressure regulation. Several studies have demonstrated that Mg concentration is inversely associated with blood pressure, and that Mg supplementation attenuates hypertension. The purpose of this study was to evaluate the effect of dietary Mg supplementation on the blood pressure effects of an angiotensin II receptor blocker (ARB) in hypomagnesemic rats. METHODS: Fifty male Sprague-Dawley rats were randomly divided into Mg-deficient (n = 30), normal diet plus Mg (n = 10), and control groups (n = 10). Mg-free, high-Mg, and normal-Mg diets were respectively fed to the rats. After 14 weeks, 10 of the 30 Mg-deficient rats were treated with Mg, 10 Mg-deficient rats received an ARB, and 10 Mg-deficient rats received an ARB plus Mg for 4 weeks. RESULTS: Systolic blood pressure was significantly higher in the Mg-deficient rats than in the control rats at week 14. Hypomagnesemic rats exhibited decreased systolic blood pressure after treatment with Mg, and systolic blood pressure showed a greater decrease after ARB treatment. Treatment with the ARB/Mg combination resulted in the greatest decrease in systolic blood pressure. Mg deficiency did not affect the serum angiotensin II level, but did increase the serum aldosterone concentration. Concomitant Mg/ARB supplementation significantly decreased the elevated serum aldosterone level in hypomagnesemic rats. Kidney tissues of the hypomagnesemic rats revealed mild to moderate inflammatory infiltrates. Mg and/or ARB treatment did not reverse the inflammatory reaction in the kidneys of hypomagnesemic rats. CONCLUSIONS: Concurrent dietary Mg supplementation can enhance ARB-induced blood pressure reduction in rats with hypomagnesemic hypertension.

A Carcinoid Tumor Arising from a Normal Kidney in a Young Man / 대한내과학회지

Carcinoid tumors are low-grade malignant tumors arising from neuroendocrine cells. Primary renal carcinoid tumor is very rare due to the absence of neuroendocrine cells in the kidney and ureter. Therefore, little is known about the management and prognosis of renal carcinoid. Here, we report a case of a primary renal carcinoid tumor arising from a normal kidney in a 21-year-old man. He presented with a left renal mass, which was found accidentally. Abdominal computed tomography (CT) showed a 5.5 x 5.0-cm cystic mass with calcification. We suspected a cystic renal cell carcinoma and performed a laparoscopic radical nephrectomy. However, the histology revealed a well-differentiated neuroendocrine tumor. We concluded that it was a primary renal carcinoid tumor with no distant metastasis and did not administer chemotherapy or radiation therapy. He is recurrence-free after 8 months.

Hemolytic Uremic Syndrome with Clopidogrel after Coronary Angioplasty / 대한내과학회지

Thienopyridines are antiplatelet agents used in post-percutaneous coronary angioplasty patients and patients with acute coronary syndrome, stroke, and peripheral arterial disease. Ticlopidine has been shown to reduce the incidence of stent thrombosis, but it may also cause serious hematological side effects. Among the thienopyridines, clopidogrel is considered to be a safe alternative to ticlopidine because of its decreased incidence of hematological adverse effects. However, some hematological side effects can occur and may be fatal. In this case, a 47-year-old man complained of dyspnea and generalized edema. He had been taking clopidogrel after coronary angioplasty. His laboratory findings showed acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia, which were consistent with hemolytic uremic syndrome (HUS). After discontinuing clopidogrel and undergoing plasma exchange, he recovered fully. To our knowledge, this is the first reported case of clopidogrel-induced HUS in Korea.

Nephrotic syndrome associated with early neurosyphilis / 대한내과학회지

Nephrotic syndrome, hepatitis, and CNS involvement resulting from secondary syphilis are well-documented complications of neurosyphilis. However, the simultaneous occurrence of these complications is rare. The present report describes a 49-year-old male with early neurosyphilis who presented with features of nephritic syndrome and hepatitis. A diagnosis of neurosyphilis was made by CSF study and serologic tests. After the diagnosis of neurosyphilis, nephrotic syndrome and hepatitis were suspected to be factors of the neurosyphilis. A kidney biopsy revealed membranous nephropathy characterized by subepithelial electron dense deposits and diffuse effacement of foot processes. Abdominal ultrasonography showed hepatitis. The patient was treated with intravenous potassium penicillin G, 4 million units for 2 weeks, and the symptoms and signs resolved after the penicillin therapy. In conclusion, complications experienced by patients with a history of syphilis or syphilis lesions need to be minimized through careful observations and multi-organ treatments.