Drug-induced nephrotoxicity

Drugs are a common cause of acute and chronic kidney disease and contribute to patient morbidity and increased healthcare utilization. Drug-induced nephrotoxicity is approximately 14% to 26% in adults and tends to increase among certain patients and/or with complex clinical conditions. Unfortunately, apart from conservative management, including drug withdrawal, no effective treatment is known for this condition. Therefore, in order to reduce the frequency of drug-induced nephrotoxicity, early recognition of renal toxicity and appropriate prevention strategies, such as understanding the exact mechanisms of renal injury, patient and drug-related risk factors, and preemptive measures are needed. In this review, we will present the mechanisms of drug-induced nephrotoxicity and general preventive strategies for clinical physicians.

Drug-induced nephrotoxicity

Drugs are a common cause of acute and chronic kidney disease and contribute to patient morbidity and increased healthcare utilization. Drug-induced nephrotoxicity is approximately 14% to 26% in adults and tends to increase among certain patients and/or with complex clinical conditions. Unfortunately, apart from conservative management, including drug withdrawal, no effective treatment is known for this condition. Therefore, in order to reduce the frequency of drug-induced nephrotoxicity, early recognition of renal toxicity and appropriate prevention strategies, such as understanding the exact mechanisms of renal injury, patient and drug-related risk factors, and preemptive measures are needed. In this review, we will present the mechanisms of drug-induced nephrotoxicity and general preventive strategies for clinical physicians.

The effect of the type of anesthesia on the quality of postoperative recovery after orthopedic forearm surgery / 대한마취과학회지

Background@#Although the quality of postoperative recovery may be affected by factors, there are few investigations whether the type of anesthesia also affects it. In this single-blinded, prospective, observational study, we compared the quality of postoperative recovery in patients undergoing orthopedic forearm surgery under general or regional anesthesia (brachial plexus block). @*Methods@# Ninety-seven subjects, aged 18–65 years and American Society of Anesthesiologists physical status I or II, undergoing orthopedic forearm surgery, were allocated to general or regional anesthesia group. The quality of postoperative recovery was assessed using a validated Korean version of Quality of Recovery-40 (QoR-40K) questionnaire. Patients were surveyed three times, the day before surgery (baseline) and 1st and 7th day after the surgery, and the scores of both groups were compared. @*Results@# We analyzed 47 and 50 patients in general and regional anesthesia, respectively. The global QoR-40K score and those of each of its five dimensions were not significantly different between the two groups at baseline, 1st and 7th day postoperatively. In two-way RM ANOVA, the global QoR-40K score at postoperative 1st day was significantly lower than that of baseline (P < 0.001) and postoperative 7th day (P < 0.001), respectively, in both general and regional anesthesia groups. However, there was no significant difference at each timepoint between the two groups. @*Conclusions@# The present study suggests that brachial plexus block with intravenous dexmedetomidine infusion does not improve the quality of postoperative recovery compared to sevoflurane inhalation anesthesia with remifentanil infusion in patients undergoing orthopedic forearm surgery.

Drug-induced nephrotoxicity

Drugs are a common cause of acute and chronic kidney disease and contribute to patient morbidity and increased healthcare utilization. Drug-induced nephrotoxicity is approximately 14% to 26% in adults and tends to increase among certain patients and/or with complex clinical conditions. Unfortunately, apart from conservative management, including drug withdrawal, no effective treatment is known for this condition. Therefore, in order to reduce the frequency of drug-induced nephrotoxicity, early recognition of renal toxicity and appropriate prevention strategies, such as understanding the exact mechanisms of renal injury, patient and drug-related risk factors, and preemptive measures are needed. In this review, we will present the mechanisms of drug-induced nephrotoxicity and general preventive strategies for clinical physicians.

Conversion from acetate dialysate to citrate dialysate in a central delivery system for maintenance hemodialysis patients

BACKGROUND: The objective of this study was to compare the impact of citrate dialysate (CD) and standard acetate dialysate (AD) in hemodialysis by central delivery system (CDS) on heparin demand, and clinical parameters. METHODS: We retrospectively evaluated 75 patients on maintenance hemodialysis with CDS. Patients underwent hemodialysis with AD over a six-month period (AD period), followed by another six-month period using CD (CD period). Various parameters including mean heparin dosage, high sensitivity C-reactive protein (hsCRP), calcium-phosphate product (CaxP), intact parathyroid hormone (iPTH), and urea reduction ratio (URR) were collated at the end of each period. RESULTS: Patients were 60.5 ± 14.7 years old, of whom 62.7% were male. Patients required less heparin when receiving CD (AD period: 1,129 ± 1,033 IU/session vs. CD period: 787 ± 755 IU/session, P < 0.001). After the CD period (Δ(CD)), pre-dialysis total CO₂ increased to 1.21 ± 2.80 mmol/L, compared to −2.44 ± 2.96 mmol/L (P < 0.001) after the AD period (Δ(AD)). After the CD period, concentrations of iPTH (Δ(AD): 73.04 ± 216.34 pg/mL vs. Δ(CD): −106.66 ± 251.79 pg/mL, P < 0.001) and CaxP (Δ(AD): 4.32 ± 16.63 mg²/dL² vs. Δ(CD): −4.67 ± 15.27 mg²/dL², P = 0.015) decreased. While hsCRP levels decreased after the CD period (Δ(AD): 0.07 ± 4.09 mg/L vs. Δ(CD): −0.75 ± 4.56 mg/L, P = 0.705), the change was statistically insignificant. URR remained above clinical guideline of 65% after both periods (Δ(AD): 72.33 ± 6.92% vs. Δ(CD) period: 69.20 ± 4.49%, P = 0.046). CONCLUSION: Our study confirmed that the use of CD in CDS required lower heparin doses compared to the use of AD. The use of CD also provided a more stable acid-base status.

Body Mass Index as a Predictor of Acute Kidney Injury in Critically Ill Patients: A Retrospective Single-Center Study / 결핵및호흡기질환

BACKGROUND: The aim of this study was to examine the influence of body mass index (BMI) on the development of acute kidney injury (AKI) in critically ill patients in intensive care unit (ICU). METHODS: Data of patients admitted to medical ICU from December 2011 to May 2014 were retrospectively analyzed. Patients were classified into three groups according to their BMI: underweight ( < 18.5 kg/m2), normal (18.5–24.9 kg/m2), and overweight (≥25 kg/m2). The incidence of AKI was compared among these groups and factors associated with the development of AKI were analyzed. AKI was defined according to the Risk, Injury, Failure, Loss of kidney function, and End-stage (RIFLE) kidney disease criteria. RESULTS: A total of 468 patients were analyzed. Their mean BMI was 21.5±3.9 kg/m2, including 102 (21.8%) underweight, 286 (61.1%) normal-weight, and 80 (17.1%) overweight patients. Overall, AKI occurred in 82 (17.5%) patients. The overweight group had significantly (p < 0.001) higher incidence of AKI (36.3%) than the underweight (9.8%) or normal group (15.0%). In addition, BMI was significantly higher in patients with AKI than that in those without AKI (23.4±4.2 vs. 21.1±3.7, p < 0.001). Multivariate analysis showed that BMI was significantly associated with the development of AKI (odds ratio, 1.893; 95% confidence interval, 1.224–2.927). CONCLUSION: BMI may be associated with the development of AKI in critically ill patients.

Syndrome of inappropriate antidiuretic hormone secretion associated with seronegative neuromyelitis optica spectrum disorder

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a potential cause of hyponatremia of the central nervous system (CNS). Although SIADH has been reported to be associated with many other central nervous disorders, its association with neuromyelitis optica (NMO) or NMO spectrum disorders are rare. NMO is a demyelinating disorder characterized by optic neuritis and transverse myelitis. Aquaporin-4 (AQP4), which is the target antigen for a NMO autoantibody, is the predominant CNS water channel. However, some NMO patients show seronegative AQP4 antibody results. The spectrum of NMO has been changed, and new findings about the disease have been reported. Here, we report a case of seronegative NMO spectrum disorder associated with SIADH.

Outcomes of very elderly (≥ 80 years) critical-ill patients in a medical intensive care unit of a tertiary hospital in Korea

BACKGROUND/AIMS: This study evaluated clinical characteristics and outcomes in very elderly (≥ 80 years of age) critical-ill patients admitted to a medical intensive care unit (MICU) in a regional single tertiary hospital. METHODS: We retrospectively evaluated prospectively collected data in the MICU for the period of December 2011 to May 2014. Patients were divided into ≥ 80 and < 80 years of age and clinical characteristics and outcomes were compared among these patients. RESULTS: A total of 468 patients were evaluated and 102 patients (21.7%) were ≥ 80 years of age. Overall mortality was 38.5% in the intensive care unit (ICU) and 44.7% in the hospital. There was no significant difference in ICU and in-hospital mortalities between those ≥ 80 years and those < 80 years (34.9% vs. 39.5% for ICU mortality; 40.6% vs. 45.9% for in-hospital mortality). Lengths of ICU and hospital stays were significantly longer in patients < 80 years compared to patients ≥ 80 years (10.57 ± 19.96 days vs. 8.19 ± 8.78 days for ICU stay; 27.95 ± 39.62 days vs. 18.17 ± 15.44 days for hospital stay). The rate of withholding intensive care in hospital stay over 48 hours was significantly higher in patients ≥ 80 years compared to patients < 80 years (22.9% vs. 11.8%). In multivariate analysis, weaning failure and withdrawal or withholding of intensive care in ICU was significantly related to death in patients with age ≥ 80. CONCLUSIONS: Clinical outcomes were not significantly different for very elderly critical-ill patients compared to those of their younger counterparts in the MICU in this study.

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.

C-ANCA-positive glomerulonephritis associated with subacute infective endocarditis caused by Bartonella infection / 영남의대학술지

Glomerulonephritis (GN) is sometimes associated with infective endocarditis (IE). Bartonella endocarditis is difficult to diagnose because it is rare and cannot be detected by blood culture. This is the first report of cytoplasmic anti-neutrophil cytoplasmic antibody-positive subacute endocarditis-associated GN caused by Bartonella infection in South Korea. A 67-year-old man was hospitalized due to azotemia. He complained of weight loss and anorexia for 6 months. A diagnosis of IE was made based upon echocardiographic detection of vegetations on the mitral and aortic valves and a Bartonella antibody titer of 1:2,048. Renal histology identified focal crescentic GN. Azotemia and proteinuria improved after doxycycline and rifampin treatment combining with steroid therapy.

C-ANCA-positive glomerulonephritis associated with subacute infective endocarditis caused by Bartonella infection / 영남의대학술지

Glomerulonephritis (GN) is sometimes associated with infective endocarditis (IE). Bartonella endocarditis is difficult to diagnose because it is rare and cannot be detected by blood culture. This is the first report of cytoplasmic anti-neutrophil cytoplasmic antibody-positive subacute endocarditis-associated GN caused by Bartonella infection in South Korea. A 67-year-old man was hospitalized due to azotemia. He complained of weight loss and anorexia for 6 months. A diagnosis of IE was made based upon echocardiographic detection of vegetations on the mitral and aortic valves and a Bartonella antibody titer of 1:2,048. Renal histology identified focal crescentic GN. Azotemia and proteinuria improved after doxycycline and rifampin treatment combining with steroid therapy.

Genetic Variations of Tyrosine Hydroxylase in the Pathogenesis of Hypertension

One of the major pathophysiological features of primary hypertension is an inappropriate activation of the sympathetic nervous system, which is mediated by excessive synthesis and secretion of catecholamine into the blood. Tyrosine hydroxylase (TH), a rate-limiting enzyme in the synthesis of catecholamine, has been highlighted because genetic variations of TH could alter the activity of the sympathetic nervous system activity and subsequently contribute to the pathogenesis of hypertension. Here, we discuss the role of TH as a regulator of sympathetic activity and review several studies that investigated the relationship between genetic variations of TH and hypertension.

Plasma endocan level and prognosis of immunoglobulin A nephropathy

BACKGROUND: Endocan, previously called endothelial cell–specific molecule-1, is a soluble proteoglycan that is secreted from vascular endothelial cells. Elevated plasma endocan levels were shown to be associated with poor cardiovascular outcomes in patients with chronic kidney disease (CKD). We investigated the clinical relevance of plasma and urine endocan levels in patients with immunoglobulin A nephropathy (IgAN). METHODS: Sixty-four patients with IgAN and 20 healthy controls were enrolled in this study. Plasma and urine endocan levels were measured. Clinical parameters, pathologic grades, and renal outcomes were compared among subgroups with different plasma and urine endocan levels. RESULTS: Both plasma and urine endocan levels were significantly higher in patients with IgAN than in controls. Elevated serum phosphorus and C-reactive protein were independent determinants for plasma endocan, and elevated C-reactive protein was also an independent determinant for urine endocan levels in multivariate analysis. Plasma endocan level was not significantly different across CKD stages, but patients with higher plasma endocan levels showed adverse renal outcome. Urine endocan levels were also elevated in patients with poor renal function. Cox proportional hazard models showed that high plasma endocan was an independent risk factor for CKD progression after adjusting for the well-known predictors of outcome in patients with IgAN. CONCLUSION: This study suggested that plasma endocan might be useful as a prognostic factor in patients with IgAN.

Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy

BACKGROUND: Immunoglobulin E (IgE) has traditionally been associated with anaphylaxis and atopic disease. Previous studies reported that serum IgE levels are elevated in nephrotic syndrome and suggested IgE levels as a prognostic indicator in glomerular diseases. The aim of this study was to explore the association between serum IgE levels and renal outcome in patients with immunoglobulin A nephropathy (IgAN). METHODS: We included 117 patients with biopsy-proven IgAN. Renal progression was defined if a patient meets one of these criteria: (1) a negative value of delta estimated glomerular filtration rate (mL/min/1.73 m²/mo) or (2) a rise in serum creatinine to an absolute level of ≥ 1.3 mg/dL (male) or 1.2 mg/dL (female). We defined delta changes in serum creatinine, estimated glomerular filtration rate, and proteinuria as a difference of values during the follow-up period. RESULTS: A total of 117 patients with IgAN were included. The serum IgE level was significantly high in the renal progressive group compared with the nonprogressive group. Sex and history of gross hematuria were significantly different between the high-IgE group and the low-IgE group. Regression analysis showed that a male sex, initial proteinuria, and change of proteinuria were significantly associated with serum IgE levels. CONCLUSION: The serum IgE level is potentially associated with disease progression and pathogenesis of IgAN.

Epstein-Barr Virus Associated Hemophagocytic Syndrome after Scrub Typhus Infection / 감염과화학요법

There have been a small number of cases of scrub typhus-associated hemophagocytic syndrome (HPS), most of which were treated successfully using adequate antibiotics. Here, we report a case of Epstein-Barr virus (EBV)-associated HPS after scrub typhus infection that was not improved using antirickettsial treatment. A 73-year-old male who had been diagnosed with scrub typhus according to an eschar and a positive serology was transferred to our institution because of a persistent fever despite 7-day doxycycline therapy. Physical and laboratory data showed hepatosplenomegaly, bicytopenia, hyperferritinemia, and hypofibrinogenemia. A bone marrow examination (BM) revealed hypercellular marrow with hemophagocytosis and histiocyte infiltration. EBV was detected in BM aspirates using polymerase chain reaction. After a diagnosis of HPS was made, the patient was treated successfully using high-dose steroids.

Usefulness of neutrophil to lymphocyte ratio in patients with chronic obstructive pulmonary disease: a prospective observational study

BACKGROUND/AIMS: Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker. However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the usefulness of NLR in patients with COPD. METHODS: NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28). NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period. The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression. RESULTS: NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001). NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs. 11.5 ± 8.8, p < 0.001). NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale. NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079). Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization. CONCLUSIONS: NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD.

Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Hyperphosphatemia is associated with patency loss of arteriovenous fistula after 1 year of hemodialysis

BACKGROUND: The patency of arteriovenous access is important for stable and effective hemodialysis, and long-term technical survival is best achieved with a native arteriovenous fistula (AVF). However, maintaining AVF patency remains a challenge. This study was designed to determine the independent prognostic factors for AVF patency according to hemodialysis duration. METHODS: The primary study end point was unassisted patency of the AVF, which was defined as the time from the first fistula surgery to the first AVF failure. AVF failure was defined as an event that required percutaneous intervention or surgery to revise or replace the fistula, which occurred at least 2 months after fistula formation. RESULTS: We enrolled 478 patients with a mean age of 55.5+/-14.0 years, and mean duration of dialysis was 2.5+/-2.1 years. There were 109 cases (22.8%) of AVF failure. The factors related to AVF patency differed according to hemodialysis duration. Using a Cox-adjusted model, we observed a significant correlation between the incidence of AVF failure and diabetes within the initial 12 months of hemodialysis. Uncontrolled hyperphosphatemia (mean serum phosphorus>5.5 mg/dL during hemodialysis) was associated with patency loss of AVF after 1 year of hemodialysis. CONCLUSION: Various factors were associated with the development of patency loss of AVF as hemodialysis duration differed, and a preventive role of hyperphosphatemia control in AVF survival needs further clinical study.

A Case Report of Familial Renal Hypouricemia Confirmed by Genotyping of SLC22A12, and a Literature Review

A 24-year-old male visited our hospital because of pain in both flanks. His biochemistry profile showed an elevated serum creatinine level and low serum uric acid level. History taking revealed that he had undertaken exercise prior to the acute kidney injury (AKI) event, and he stated that family members had a history of urolithiasis. His renal profile improved after hydration and supportive care during hospitalization. Although the patient was subsequently admitted again due to AKI, his status recovered with similar treatment. Since the diagnosis of the patient was familial renal hypouricemia with exercise-induced AKI, we performed genotyping of SLC22A12, which encodes human urate transporter 1. The diagnosis was confirmed by the detection of a homozygous mutation of W258X. We herein, report a case of familial renal hypouricemia confirmed by genotyping of SLC22A12, and review the relevant literature.

Unplanned Extubation in Patients with Mechanical Ventilation: Experience in the Medical Intensive Care Unit of a Single Tertiary Hospital / 결핵및호흡기질환

BACKGROUND: Potentially harmful unplanned extubation (UE) may occur in patients on mechanical ventilation (MV) in an intensive care unit (ICU) setting. This study aimed to evaluate the clinical characteristics of UE and its impact on clinical outcomes in patients with MV in a medical ICU (MICU). METHODS: We retrospectively evaluated MICU data prospectively collected between December 2011 and May 2014. RESULTS: A total of 468 patients were admitted to the MICU, of whom 450 were on MV. Of the patients on MV, 30 (6.7%) experienced UE; 13 (43.3%) required reintubation after UE, whereas 17 (56.7%) did not require reintubation. Patients who required reintubation had a significantly longer MV duration and ICU stay than did those not requiring reintubation (19.4+/-15.1 days vs. 5.9+/-5.9 days days and 18.1+/-14.2 days vs. 7.1+/-6.5 days, respectively; p<0.05). In addition, mortality rate was significantly higher among patients requiring reintubation than among those not requiring reintubation (54.5% vs. 5.9%; p=0.007). These two groups of patients exhibited no significant differences, within 2 hours after UE, in the fraction of inspired oxygen, blood pressure, heart rate, respiratory rate, and pH. CONCLUSION: Although reintubation may not always be required in patients with UE, it is associated with a poor outcome after UE.