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Background/Aims@#The neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in cardiovascular disease, infection, inflammatory disease, and several malignancies. Therefore, the NLR has a possible predictive value in patients with chronic kidney disease (CKD), but this predictive value has not been validated. Here, we aimed to investigate the possibility of NLR as a predictor of CKD progression. @*Methods@#This retrospective observational study included 141 patients with non-dialysis CKD. The participants were divided into terciles (T1, T2, and T3) according to NLR. The primary outcome was defined as a composite kidney event, which included a decline in the estimated glomerular filtration rate (eGFR) of at least 50% or initiation of renal replacement therapy during the follow-up period. @*Results@#The mean follow-up duration was 5.45 ± 2.11 years. The mean NLRs were 1.35 ± 0.05 in T1 (n = 47), 2.16 ± 0.04 in T2 (n = 47), and 4.29 ± 0.73 in T3 (n = 47). The group with the highest NLR (T3) had higher baseline CKD and serum creatinine and lower eGFR levels than the group with the lowest NLR (T1). The cumulative incidence rate of composite kidney events was significantly higher in T3 compared with T1 (p < 0.001, log-rank test). Cox regression analysis revealed that high NLR was associated with the risk of composite kidney events (adjusted hazard ratio, 3.33; 95% confidence interval, 1.43–7.76). @*Conclusions@#A higher NLR reflects the more advanced stage of CKD and suggests a role for NLR as a biomarker for predicting CKD progression.
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Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC). Methods: A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period. Results: Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190–0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios. Conclusion: High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.
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Although multiple factors influence the risk of major adverse cardiovascular events (MACE), the effects of socioeconomic status on MACE in the presence and absence of renal dysfunction (RD) have not been comprehensively explored in Korea. Methods: We examined the effects of socioeconomic status on MACE in individuals with and without RD. The data of 44,473 Koreans from 2008 to 2017 were obtained from the Health Care Big Data Platform of the Ministry of Health and Welfare in Korea. Their socioeconomic status was assessed using a socioeconomic score (SES) based on marital status, education, household income, and occupation. The incidence of myocardial infarction (MI), stroke, and death was compared according to SES level (0–4). Multiple linear regression analysis was used to evaluate the hazard ratios and 95% confidence intervals for outcomes based on participant SES. Results: MI risk was only affected by education level. The participants’ income, education, and SES affected their stroke risk, whereas death was associated with all four socioeconomic factors. The incidence of stroke and death increased as SES worsened (from 0 to 4). SES was positively related to risk of stroke and death in participants without RD. SES did not affect MI, stroke, or death in participants with RD. Conclusion: A low socioeconomic status is associated with risk of stroke and death, especially in individuals without RD.
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Several studies have reported that depression is prevalent in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD). Methods: From the Korean National Health Insurance Service database, we selected 67,866 patients with DKD and body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. Weight change over 2 years was categorized into five groups: ≥–10%, <–10% to ≥–5%, <–5% to <5%, ≥5% to <10%, and ≥10%. The occurrence of depression was monitored via the codes of International Statistical Classification of Diseases, 10th revision through the end of 2018. Results: During the 5.24-year follow-up, 17,023 patients with DKD developed depression. Weight change and the risk of depression had a U-shaped relationship: patients with ≥–10% weight change (hazard ratio [HR], 1.12) and those with ≥10% weight change (HR, 1.11) showed higher HRs for depression than those with <–5% to <5% weight change, even after adjusting for several confounding factors. In the subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups. Conclusion: Both weight loss and weight gain increased the risk of depression in patients with DKD.
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Background/Aims@#Hypertension is considered a risk factor in immunoglobulin A nephropathy (IgAN). However, after IgAN diagnosis, the relationship between early blood pressure control and renal prognosis remains unclear. This study aimed to analyze the association between the prognosis of IgAN patients and a controlled status of hypertension within the first year of IgAN diagnosis. @*Methods@#We retrospectively analyzed 2,945 patients diagnosed with IgAN by renal biopsy. The patients were divided into ‘normal,’ ‘new-onset,’ ‘well-controlled,’ and ‘poorly-controlled’ groups using blood pressure data from two consecutive measurements performed within a year. The Kaplan-Meier survival analysis and Cox proportional-hazards regression model were used to survey the independent association between recovery from hypertension and the risk of IgAN progression. The primary endpoint was IgAN progression defined as the initiation of dialysis or kidney transplantation. @*Results@#Before IgAN diagnosis, 1,239 patients (42.1%) had been diagnosed with hypertension. In the fully adjusted Cox proportional-hazards models, the risk of IgAN progression increased by approximately 1.7-fold for the prevalence of hypertension. In the subgroup analyses, the ‘well-controlled’ group showed a statistically significant risk of IgAN progression (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.103 to 9.245; p = 0.032). Moreover, the ‘new-onset’ and ‘poorly-controlled’ groups had an increased risk of IgAN progression compared to the ‘normal’ group (HR, 2.58; 95% CI, 1.016 to 6.545; p = 0.046 and HR, 3.85;95% CI, 1.541 to 9.603; p = 0.004, respectively). @*Conclusions@#Although hypertension was well-controlled in the first year after IgAN diagnosis, it remained a risk factor for IgAN progression.
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Osteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients. Methods: We analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression. Results: The median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041–1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results. Conclusion: Serum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression.
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Background/Aims@#The obesity paradox has been known in end-stage renal disease (ESRD). However, the effect of body mass index (BMI) or waist circumference (WC) prior to percutaneous coronary intervention (PCI) on the development of ESRD is not clear. @*Methods@#Using nationally representative data from the Korean National Health Insurance System, we enrolled 140,164 subjects without ESRD at enrolment who underwent PCI between 2010 and 2015, and were followed-up until 2017. Patients were stratified into five levels based on their baseline BMI and six levels based on their WC with 5-cm increments. BMI and WC were measured at least 2 years prior to PCI. The primary outcome was the development of ESRD. @*Results@#During a median follow-up of 5.4 years, 2,082 (1.49%) participants developed ESRD. The underweight group (hazard ratio [HR], 1.331; 95% confidence interval [CI], 0.955 to 1.856) and low WC (< 80/< 75) (HR, 1.589; 95% CI, 1.379 to 1.831) showed the highest ESRD risk and the BMI 25 to 30 group showed the lowest ESRD risk (HR, 0.604; 95% CI, 0542 to 0.673) in all participants after adjusting for all covariates. In the subgroup analysis for diabetes mellitus (DM) duration, WC < 85/80 cm (men/women) increased ESRD risk in only the DM group (DM < 5 years and DM ≥ 5 years) compared to the reference group (85–90/80–85 of WC), but not the normal or impaired fasting glucose group. @*Conclusions@#Low WC prior to PCI showed an increased ESRD risk in patients with DM undergoing PCI as compared to those without DM.
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Background/Aims@#This study aimed to investigate whether urinary angiotensinogen (UAGT) excretion was associated with elevated blood pressure in patients with chronic kidney disease (CKD) and to evaluate the relationship among blood pressure, intra-renal renin-angiotensin system (RAS) activity, and dietary sodium in patients with CKD. @*Methods@#Participants from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD) were included. Of the total cohort of 2,238 individuals with CKD, we included 1,955 participants who underwent complete 24-hour urinary sodium (24-hour UNa) analysis. They were categorized into three groups according to three tertiles of their 24-hour UNa, reflecting daily salt intake. To measure intra-renal RAS activity, the UAGT excretion was assayed with an enzyme-linked immunosorbent assay. @*Results@#Elevated 24-hour UNa levels, logarithm of UAGT-to-creatinine ratio (UAGT/Cr), increased waist-to-hip ratio, and decreased estimated glomerular filtration rate were the risk factors for increased systolic blood pressure. Systolic blood pressure showed a positive correlation with 24-hour UNa levels and logarithm of UAGT/Cr. @*Conclusions@#UAGT and urinary sodium excretion are independent determinants of systolic blood pressure in patients with CKD. These findings suggest that increased systolic blood pressure in CKD patients is associated with both increased dietary sodium levels and intra-renal RAS activity. The risk of elevated systolic blood pressure in the 3rd tertile of both the UAGT/Cr and 24-hour UNa groups was about 2.3 times higher than that in the reference group.
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Background/Aims@#This study aimed to investigate whether urinary angiotensinogen (UAGT) excretion was associated with elevated blood pressure in patients with chronic kidney disease (CKD) and to evaluate the relationship among blood pressure, intra-renal renin-angiotensin system (RAS) activity, and dietary sodium in patients with CKD. @*Methods@#Participants from the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD) were included. Of the total cohort of 2,238 individuals with CKD, we included 1,955 participants who underwent complete 24-hour urinary sodium (24-hour UNa) analysis. They were categorized into three groups according to three tertiles of their 24-hour UNa, reflecting daily salt intake. To measure intra-renal RAS activity, the UAGT excretion was assayed with an enzyme-linked immunosorbent assay. @*Results@#Elevated 24-hour UNa levels, logarithm of UAGT-to-creatinine ratio (UAGT/Cr), increased waist-to-hip ratio, and decreased estimated glomerular filtration rate were the risk factors for increased systolic blood pressure. Systolic blood pressure showed a positive correlation with 24-hour UNa levels and logarithm of UAGT/Cr. @*Conclusions@#UAGT and urinary sodium excretion are independent determinants of systolic blood pressure in patients with CKD. These findings suggest that increased systolic blood pressure in CKD patients is associated with both increased dietary sodium levels and intra-renal RAS activity. The risk of elevated systolic blood pressure in the 3rd tertile of both the UAGT/Cr and 24-hour UNa groups was about 2.3 times higher than that in the reference group.
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In the decades since the discovery of angiotensin-converting enzyme 2 (ACE2), its protective role in terms of antagonizing activation of the classical renin-angiotensin system (RAS) axis has been recognized in clinical and experimental studies on kidney and cardiovascular diseases. The effects of ACE inhibitor/angiotensin type 1 receptor blockers (ACEi/ARBs) on ACE2-angiotensin-(1-7) (Ang- (1-7))-Mas receptor (MasR) axis activation has encouraged the use of such blockers in patients with kidney and cardiovascular diseases, until the emergence of coronavirus disease 2019 (COVID-19). The previously unchallenged functions of the ACE2-Ang-(1-7)-MasR axis and ACEi/ARBs are being re-evaluated in the era of COVID-19; the hypothesis is that ACEi/ARBs may increase the risk of severe acute respiratory syndrome coronavirus 2 infection by upregulating the human ACE2 receptor expression level. In this review, we examine ACE2 molecular structure, function (as an enzyme of the RAS), and distribution. We explore the roles played by ACE2 in kidney, cardiovascular, and pulmonary diseases, highlighting studies that defined the benefits imparted when ACEi/ARBs activated the local ACE2- Ang-(1-7)-MasR axis. Finally, the question of whether ACEi/ARBs therapies should be stopped in COVID-19-infected patients will be reviewed by reference to the available evidence.
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Background/Aims@#Despite recent improvements in the quality of life of patients with systemic lupus erythematosus (SLE), osteoporosis, and osteoporotic fractures are one of the major complications of SLE. Furthermore, limited data are available on the incidence and predictor of osteoporotic fractures in Korean patients with SLE. Herein, we aimed to assess the incidence and risk factors for osteoporotic fractures in Korean SLE patients compared to those without SLE. @*Methods@#SLE patients aged ≥ 40 years (n = 10,434; mean age, 51.3 ± 9.1 years;women, 89.7%) were selected from the Korean National Health Insurance Service database, spanning a period from 2008 to 2014. Age- and sex-matched controls (n = 52,170) were randomly sampled in a 5:1 ratio from non-SLE individuals. The primary outcome was the first occurrence of osteoporotic fracture. @*Results@#The incidence of osteoporotic fractures was significantly higher in the SLE patients (19.085 per 1,000 person-years) than in matched controls (6.530 per 1,000 person-years). According to the multivariable Cox proportional analysis, patients with SLE exhibited a higher osteoporotic fracture rate than the control group (hazards ratio, 2.964; 95% confidence interval, 2.754 to 3.188), even after adjustment for confounding variables. In the subgroup analysis, male SLE patients or SLE patients aged 40 to 65 years were associated with a higher osteoporotic fracture rate than women SLE patients or SLE patients aged ≥ 65 years, respectively. @*Conclusions@#We found a 2.964-fold increased risk of osteoporotic fracture in SLE patients compared to age- and sex-matched non-SLE controls. Male or middle-aged SLE patients had a relatively higher fracture risk among patients with SLE.
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Background@#Hypertension is the most important modifiable risk factor for mortality and morbidity in chronic kidney disease and coronary artery syndrome. The effect of hypertension prior to percutaneous coronary intervention (PCI) on the development of end-stage renal disease (ESRD) is unknown. @*Methods@#We used nationally representative data from the Korean National Health Insurance System—140,164 subjects were enrolled during 2010–2015; they were free of ESRD at enrolment, underwent PCI, and were followed up until 2017. Blood pressure (BP) was measured within at least 2 years prior to PCI. The primary outcome was the development of ESRD. @*Results@#During a median follow-up of 5.4 years, 2,082 participants (1.5%) developed ESRD. The highest systolic BP group (>160 mmHg) showed a higher hazard ratio (3.69; 95% confidence interval, 2.61–5.23) than the reference group (110–119 mmHg). Similar results were observed in the highest diastolic BP group (>120 mmHg), which showed a higher hazard ratio than the reference group (70–79 mmHg). However, ESRD risk showed a J-shaped relationship with baseline systolic and diastolic BP at 113 and 74 mmHg in diabetes mellitus subgroup, respectively, after adjustment for potential confounders. @*Conclusion@#Our study showed that a high systolic or diastolic BP prior to PCI was independently associated with an increased incidence of ESRD.
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Background@#Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD. @*Methods@#A total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation. @*Results@#A total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09–1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59–7.31; p < 0.001). @*Conclusion@#Our study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.
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A 44-year-old man with chronic alcoholism presented with seizure and loss of consciousness. He was diagnosed with alcoholic hepatic encephalopathy, and his neurologic symptoms recovered after lactulose enema treatment. His initial serum sodium level was 141 mEq/L. However, his mental state became confused after treatment with lactulose enema for five days, and his serum sodium level increased to 178 mEq/L. After five days of gradual correction of serum sodium level from 178 mEq/L to 140 mEq/L, the patient’s mental state recovered, but motor weakness in both limbs remained. Therefore, magnetic resonance imaging of the brain was performed. T2-weighted brain images showed bilateral symmetrical hyperintensities in the central pons, basal ganglia, thalami, hippocampi and unci, which were consistent with central pontine and extrapontine myelinolysis. We report a rare case of osmotic demyelination syndrome that occurred as a result of a rapid increase from a normal sodium level to hypernatremia caused by lactulose enema administered to treat alcoholic hepatic encephalopathy.
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We report a case of severe hyperphosphatemia in advanced CKD with poor compliance. A 55-year-old male patient with underlying type 2 diabetes mellitus, hypertension, and chronic kidney disease presented emergently with general weakness and altered mental status. The creatinine level was 14 mg/dL (normal range: 0.5-1.3 mg/dL) 2 months prior to consultation, and he was advised initiation of hemodialysis, which he refused. Subsequently, the patient stopped taking all prescribed medications and self-medicated with honey and persimmon vinegar with the false belief it was detoxifying. At the time of admission, he was delirious, and his laboratory results showed blood urea nitrogen level of 183.4 mg/dL (8-23 mg/dL), serum creatinine level of 26.61 mg/dL (0.5-1.3 mg/dL), serum phosphate level of 19.3 mg/dL (2.5-5.5 mg/dL), total calcium level of 4.3 mg/dL (8.4-10.2 mg/dL), vitamin D (25(OH)D) level of 5.71 ng/mL (30-100 ng/mL) and parathyroid hormone level of 401 pg/ml (9-55 pg/mL). Brain computed tomography revealed non-traumatic spontaneous subdural hemorrhage, presumably due to uremic bleeding.Emergent hemodialysis was initiated, and hyperphosphatemia and hypocalcemia were rectified; calcium acetate and cholecalciferol were administered. The patient’s general condition and laboratory results improved following dialysis. Strict dietary restrictions with patient education were implemented. Multifaceted interventions, including dietary counseling, administration of phosphate-lowering drugs, and lifestyle modifications, should be implemented when encountering patients with CKD, considering the extent of the patient’s adherence.
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A 56-year old female patient who was undergoing follow-up for cervical cancer in our oncology center was presented to the emergency center with anxiety and excessive thirst. The initial serum sodium level of the patient exceeded 200mEq/L, rising up to 238mEq/L during hospitalization. The extremely severe hypernatremia was caused by patient’s wrong belief that bay salt would cure the cancer. The patient was treated with hypotonic solution and finally with appropriate hydration, she was fully recovered without any neurological complications.
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Background/Aims@#The aim of this study was to evaluate the trend of incidence and prevalence of systemic lupus erythematosus (SLE) in South Korea from 2005 to 2015. @*Methods@#From 2005 to 2015, individuals with SLE were identified from the National Health Insurance database, which records information on almost all Koreans. SLE was defined according to the International Classification of Diseases, 10th revision (ICD-10), code M32. The incidence was calculated per 100,000 person-years. The prevalence was calculated per 100,000 people and stratified by year, age group, sex, region, and income. @*Results@#The annual prevalence of SLE increased slightly from 21.25/100,000 people in 2005 to 35.45/100,000 people in 2015. In contrast, the annual incidence of SLE decreased slightly from 5.42/100,000 person-years in 2005 to 3.6/100,000 person-years in 2015. The prevalence and incidence of SLE were 10- and 6-fold higher in women than in men, respectively. The peak age of prevalence and incidence was 30 to 39 years in 2005; in 2015, the peak age of prevalence was 30 to 49 years and of incidence was 20 to 49 years. Regional variation was observed in both incidence and prevalence of SLE. Jeju province showed the highest prevalence of SLE (44.54/100,000 person-years), and Gwangju province showed the highest incidence of SLE (6.98/100,000 person-years) in 2015. The income status did not affect the prevalence or incidence of SLE except in patients without income who received medical aid. @*Conclusions@#The incidence of SLE has declined, but the prevalence has increased in Korea in recent years. Peak age of SLE trend to right shift in Korea.
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A 56-year old female patient who was undergoing follow-up for cervical cancer in our oncology center was presented to the emergency center with anxiety and excessive thirst. The initial serum sodium level of the patient exceeded 200mEq/L, rising up to 238mEq/L during hospitalization. The extremely severe hypernatremia was caused by patient’s wrong belief that bay salt would cure the cancer. The patient was treated with hypotonic solution and finally with appropriate hydration, she was fully recovered without any neurological complications.
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BACKGROUND/AIMS: Indoxyl sulfate (IS) is a uremic toxin and an important causative factor in the progression of chronic kidney disease. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was shown to exhibit protective effects in kidney injury. Here, we investigated the effects of paricalcitol treatment on IS-induced renal tubular injury. METHODS: The fluorescent dye 2ʹ,7ʹ-dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS) following IS administration in human renal proximal tubular epithelial (HK-2) cells. The effects of IS on cell viability were determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and levels of apoptosis-related proteins (Bcl-2-associated protein X [Bax] and B-cell lymphoma 2 [Bcl-2]), nuclear factor-κB (NF-κB) p65, and phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) were determined by semiquantitative immunoblotting. The promoter activity of NF-κB was measured by luciferase assays and apoptosis was determined by f low cytometry of cells stained with f luorescein isothiocyanate-conjugated Annexin V protein. RESULTS: IS treatment increased ROS production, decreased cell viability and induced apoptosis in HK-2 cells. IS treatment increased the expression of apoptosis-related protein Bax, decreased Bcl-2 expression, and activated phosphorylation of MAPK, NF-κB p65, and Akt. In contrast, paricalcitol treatment decreased Bax expression, increased Bcl-2 expression, and inhibited phosphorylation of MAPK, NF-κB p65, and Akt in HK-2 cells. NF-κB promoter activity was increased following IS, administration and was counteracted by pretreatment with paricalcitol. Additionally, flow cytometry analysis revealed that IS-induced apoptosis was attenuated by paricalcitol treatment, which resulted in decreased numbers of fluorescein isothiocyanate-conjugated Annexin V positive cells. CONCLUSIONS: Treatment with paricalcitol inhibited IS-induced apoptosis by regulating MAPK, NF-κB, and Akt signaling pathway in HK-2 cells.
