ABSTRACT
Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease for over 20 years. Yet, over these two decades, the clinical approach to this condition has not much improved beyond the administration of glucose-lowering agents, renin-angiotensin-aldosterone system blockers for blood pressure control, and lipid-lowering agents. The proportion of diabetic patients who develop DKD and progress to end-stage renal disease has remained nearly the same. This unmet need for DKD treatment is caused by the complex pathophysiology of DKD, and the difficulty of translating treatment from bench to bed, which further adds to the growing argument that DKD is not a homogeneous disease. To better capture the full spectrum of DKD in our design of treatment regimens, we need improved diagnostic tools that can better distinguish the subgroups within the condition. For instance, DKD is typically placed in the broad category of a non-inflammatory kidney disease. However, genome-wide transcriptome analysis studies consistently indicate the inflammatory signaling pathway activation in DKD. This review will utilize human data in discussing the potential for redefining the role of inflammation in DKD. We also comment on the therapeutic potential of targeted anti-inflammatory therapy for DKD.
ABSTRACT
Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease for over 20 years. Yet, over these two decades, the clinical approach to this condition has not much improved beyond the administration of glucose-lowering agents, renin-angiotensin-aldosterone system blockers for blood pressure control, and lipid-lowering agents. The proportion of diabetic patients who develop DKD and progress to end-stage renal disease has remained nearly the same. This unmet need for DKD treatment is caused by the complex pathophysiology of DKD, and the difficulty of translating treatment from bench to bed, which further adds to the growing argument that DKD is not a homogeneous disease. To better capture the full spectrum of DKD in our design of treatment regimens, we need improved diagnostic tools that can better distinguish the subgroups within the condition. For instance, DKD is typically placed in the broad category of a non-inflammatory kidney disease. However, genome-wide transcriptome analysis studies consistently indicate the inflammatory signaling pathway activation in DKD. This review will utilize human data in discussing the potential for redefining the role of inflammation in DKD. We also comment on the therapeutic potential of targeted anti-inflammatory therapy for DKD.
ABSTRACT
Chronic kidney disease is developed commonly in type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care including optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for death and complications from cardiorenal causes. The recent studies using sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effect, but also a reduction in blood pressure, weight loss, and a lowering cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitor slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may be also associated with improved renal outcomes with long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in the patients with T2DM using meta-analysis. (Korean J Med 2020;95:236-243)
ABSTRACT
Diabetes is a leading cause of end-stage renal disease. Therefore, prevention of renal dysfunction is an important treatment goal in the management of diabetes. The data of landmark cardiovascular outcome trials of sodiumglucose cotransporter-2 (SGLT2) inhibitors showed profound reno-protective effects. The Korean Diabetes Association and the Korean Society of Nephrology reviewed clinical trials and performed a meta-analysis to assess the effects of SGLT2 inhibitors on the preservation of estimated glomerular filtration rate (eGFR). We limited the data of SGLT2 inhibitors which can be prescribed in Korea. Both eGFR value and its change from the baseline were significantly more preserved in the SGLT2-inhibitor treatment group compared to the control group after 156 weeks. However, some known adverse events were increased in SGLT2 inhibitor treatment, such as genital infection, diabetic ketoacidosis, and volume depletion. We recommend long-term use of SGLT2 inhibitors in patients with type 2 diabetes mellitus (T2DM) for attenuation of renal function decline. However, we cannot generalize our recommendations due to the lack of long-term clinical trials testing the reno-protective effects of every SGLT2 inhibitor in a broad range of patients with T2DM. This recommendation can be revised and updated after the publication of several large-scale renal outcome trials.
ABSTRACT
Background@#Online hemodiafiltration (OL-HDF) offers considerable advantages in clearance of molecules of various sizes. However, evidence of clinical effects of OL-HDF is scarce in Korea. In this study, we investigated changes in laboratory values over more than 12 months after switching to OL-HDF. @*Methods@#Adult patients with end-stage renal disease undergoing hemodialysis (HD) were prospectively enrolled in a K-cohort (CRIS no. KCT0003281) from 6 tertiary hospitals in South Korea. We recruited 435 patients, 339 of whom were on HD at enrollment. One hundred eighty-two patients were followed for more than 24 months. Among them, 44 were switched to OL-HDF for more than 12 months without conversion to HD. We used a paired t test to compare baseline and 24-month follow-up results. @*Results@#The mean age of the subjects was 61.2 ± 12.2 years, and 62.6% were male. The baseline hemoglobin level was not significantly different between HD and OL-HDF group (10.61 ± 1.15 vs. 10.46 ± 1.03 g/dL, P = 0.437). However, the baseline serum protein and albumin levels were significantly lower in the OL-HDF group (6.82 ± 0.49 vs. 6.59 ± 0.48 g/dL, P = 0.006; 3.93 ± 0.28 vs. 3.73 ± 0.29 g/dL, P < 0.001). In patients switched to OL-HDF, levels of hemoglobin and serum albumin significantly increased (10.46 ± 1.03 vs. 11.08 ± 0.82 g/dL, P = 0.001; 3.73 ± 0.29 vs.
ABSTRACT
Diabetes is a leading cause of end-stage renal disease. Therefore, prevention of renal dysfunction is an important treatment goal in the management of diabetes. The data of landmark cardiovascular outcome trials of sodium-glucose cotransporter-2 (SGLT2) inhibitor showed profound reno-protective effects. The Korean Diabetes Association and the Korean Society of Nephrology reviewed clinical trials and performed meta-analysis to assess the effects of SGLT2 inhibitors on the preservation of estimated glomerular filtration rate (eGFR). We limited the data of SGLT2 inhibitors which can be prescribed in Korea. Both eGFR value and its change from the baseline were significantly more preserved in the SGLT2 inhibitor treatment group compared to the control group after 156 weeks. However, some known adverse events were increased in SGLT2 inhibitor treatment, such as genital infection, diabetic ketoacidosis, and volume depletion. We recommend the long-term use SGLT2 inhibitor in patients with type 2 diabetes mellitus (T2DM) for attenuation of renal function decline. However, we cannot generalize our recommendation due to lack of long-term clinical trials testing reno-protective effects of every SGLT2 inhibitor in a broad range of patients with T2DM. This recommendation can be revised and updated after publication of several large-scale renal outcome trials.
ABSTRACT
Chronic kidney disease commonly develops in patients with type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care that includes optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for premature death and complications due to cardiorenal causes. Recent studies using sodiumglucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effects, but also a reduction in blood pressure, weight loss, and lower cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitors slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may also be associated with improved renal outcomes during long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in patients with T2DM using meta-analysis.
ABSTRACT
Chronic kidney disease commonly develops in patients with type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care that includes optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for premature death and complications due to cardiorenal causes. Recent studies using sodiumglucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effects, but also a reduction in blood pressure, weight loss, and lower cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitors slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may also be associated with improved renal outcomes during long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in patients with T2DM using meta-analysis.
ABSTRACT
Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⁺ T cells, CD8⁺ T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.
Subject(s)
Humans , B-Lymphocytes , Biomarkers , Flow Cytometry , Gene Expression , Immunosuppression Therapy , Kidney Transplantation , Kidney , Lymphocyte Subsets , Lymphocytes , Memory , Precursor Cells, B-Lymphoid , Real-Time Polymerase Chain Reaction , RNA, Messenger , T-Lymphocytes , Transplant Recipients , TransplantsABSTRACT
BACKGROUND: Several epidemiologic studies have suggested that the urine sodium excretion (USE) can be estimated in lieu of performing 24-hour urine collection. However, this method has not been verified in patients with chronic kidney disease (CKD) or in an interventional study. The purpose of this study was to evaluate the usefulness of estimating USE in a prospective low-salt diet education cohort (ESPECIAL). METHODS: A new formula was developed on the basis of morning fasting urine samples from 228 CKD patients in the ESPECIAL cohort. This formula was compared to the previous four formulas in the prediction of 24-hour USE after treatment with olmesartan and low-salt diet education. RESULTS: Most previously reported formulas had low predictability of the measured USE based on the ESPECIAL cohort. Only the Tanaka formula showed a small but significant bias (9.8 mEq/day, P < 0.05) with a low correlation (r = 0.34). In contrast, a new formula showed improved bias (−0.1 mEq/day) and correlation (r = 0.569) at baseline. This formula demonstrated no significant bias (−1.2 mEq/day) with the same correlation (r = 0.571) after 8 weeks of treatment with olmesartan. Intensive low-salt diet education elicited a significant decrease in the measured USE. However, none of the formulas predicted this change in the measured urine sodium after diet adjustment. CONCLUSION: We developed a more reliable formula for estimating the USE in CKD patients. Although estimating USE is applicable in an interventional study, it may be unsuitable for estimating the change of individual sodium intake in a low-salt intervention study.
Subject(s)
Humans , Bias , Cohort Studies , Diet , Diet, Sodium-Restricted , Education , Epidemiologic Studies , Fasting , Methods , Prospective Studies , Renal Insufficiency, Chronic , Sodium , Urine Specimen CollectionABSTRACT
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.
Subject(s)
Female , Humans , Acid-Base Equilibrium , Acidosis , Acidosis, Renal Tubular , Autoantibodies , Diagnosis , Exocrine Glands , Fanconi Syndrome , Femoral Fractures , Glomerulonephritis , Hypokalemia , Kidney , Muscle Weakness , Nephritis, Interstitial , Osteomalacia , Paralysis , Saliva , TearsABSTRACT
Early detection and proper management of kidney rejection are crucial for the long-term health of a transplant recipient. Recipients are normally monitored by serum creatinine measurement and sometimes with graft biopsies. Donor-derived cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as a system for monitoring graft status using single nucleotide polymorphism (SNP)-based detection of donor DNA in plasma or urine. We compared the detection abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was the most accurate and sensitive. Plasma and/or urine samples were isolated from 34 kidney recipients at multiple time points after transplantation, and analyzed by dPCR using the QX200. We found that donor DNA was almost undetectable in plasma DNA samples, whereas a high percentage of donor DNA was measured in urine DNA samples, indicating that urine is a good source of cfDNA for patient monitoring. We found that at least 24% of the highly polymorphic SNPs used to identify individuals could also identify donor cfDNA in transplant patient samples. Our results further showed that autosomal, sex-specific, and mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we found that donor-derived cfDNA measurement by dPCR was not sufficient to predict a patient's clinical condition. Our results indicate that donor-derived cfDNA is not an accurate predictor of kidney status in kidney transplant patients.
Subject(s)
Humans , Biopsy , Creatinine , DNA , Kidney Transplantation , Kidney , Monitoring, Physiologic , Plasma , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Tissue Donors , Transplant Recipients , TransplantsABSTRACT
A high degree of sensitization to human leukocyte antigen requires more intensive induction therapy; however, this increases vulnerability to opportunistic infections following kidney transplantation. Although recent studies have suggested that combined induction therapy with antithymocyte globulin and rituximab would be more effective in highly sensitized kidney recipients, we experienced a case of near-fatal invasive pulmonary aspergillosis 2 months after combined induction and early rejection therapy for graft dysfunction. Fortunately, the patient recovered with intensive antifungal treatment and lung lobectomy for a necrotic cavity. Antifungal prophylaxis should be considered in cases undergoing intensive induction therapy.
Subject(s)
Humans , Antilymphocyte Serum , Immunoglobulins , Invasive Pulmonary Aspergillosis , Kidney Transplantation , Kidney , Leukocytes , Lung , Opportunistic Infections , Plasmapheresis , Rituximab , TransplantsABSTRACT
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.
Subject(s)
Genetic Variation , Hypertension , Polymorphism, Single Nucleotide , Sympathetic Nervous System , Tyrosine 3-Monooxygenase , TyrosineABSTRACT
BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% +/- 26.1% (p < 0.001) in the regular-dose group and -21.1% +/- 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Biomarkers/urine , Blood Pressure , Creatinine/urine , Glomerulonephritis, IGA/diagnosis , Prospective Studies , Proteinuria/diagnosis , Republic of Korea , Time Factors , Treatment Outcome , Valsartan/administration & dosageABSTRACT
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.
Subject(s)
Humans , Male , Anaphylaxis , Creatinine , Disease Progression , Follow-Up Studies , Glomerular Filtration Rate , Glomerulonephritis , Glomerulonephritis, IGA , Hematuria , Immunoglobulin A , Immunoglobulin E , Immunoglobulins , Nephrotic Syndrome , ProteinuriaABSTRACT
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.
Subject(s)
Humans , C-Reactive Protein , Endothelial Cells , Glomerulonephritis, IGA , Immunoglobulin A , Immunoglobulins , Multivariate Analysis , Phosphorus , Plasma , Prognosis , Proportional Hazards Models , Proteoglycans , Renal Insufficiency, Chronic , Risk FactorsABSTRACT
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.
Subject(s)
Humans , Arteriovenous Fistula , Dialysis , Fistula , Hyperphosphatemia , Incidence , Renal DialysisABSTRACT
BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine involved in immune disorders, cancer, asthma, lung fibrosis, and chronic kidney disease, and its signal pathways are considered crucial mediators of a variety of cellular processes. In addition, several recent studies have reported that TGF-beta receptor (TGF-betaR) gene polymorphism is associated with chronic kidney disease. However, the association between end-stage renal disease (ESRD) and the TGF-beta gene polymorphism has not been sufficiently investigated. In this study, we hypothesized that polymorphisms of the TGF-beta ligands or their receptors may be related to ESRD. METHODS: We assessed the relationship between four single-nucleotide polymorphisms (SNPs) in the TGF-betaR2 and TGF-beta2 genes and ESRD, in 312 patients with ESRD and 258 controls. RESULTS: Compared with the control participants, the frequencies of the TGF-betaR2 (rs764522*C) and TGF-betaR2 (rs3087465*G) alleles were significantly higher in the patients with ESRD. Genotyping analysis demonstrated that two SNPs in TGF-betaR2 of the four SNPs included in the study were significantly associated with ESRD in the codominant 1 [rs764522, odds ratio (OR)=1.65; rs3087465, OR=1.63], dominant (rs764522, OR=1.63; rs3087465, OR=1.57), and log-additive (rs764522, OR=1.54; rs3087465, OR=1.39) models after adjusting for age and sex. CONCLUSION: We suggest that TGF-betaR2 polymorphisms (rs764522 and rs3087465) increase the risk of development of ESRD.
Subject(s)
Humans , Alleles , Asthma , Fibrosis , Immune System Diseases , Kidney Failure, Chronic , Ligands , Lung , Odds Ratio , Polymorphism, Single Nucleotide , Receptors, Transforming Growth Factor beta , Renal Insufficiency, Chronic , Signal Transduction , Transforming Growth Factor beta , Transforming Growth Factor beta2ABSTRACT
BACKGROUND: The plasma levels of cell-free DNA (cfDNA) are known to be elevated under inflammatory or apoptotic conditions. Increased cfDNA levels have been reported in hemodialysis (HD) patients. The aim of this study was to investigate the clinical significance of cfDNA in HD patients. METHODS: A total of 95 patients on HD were enrolled. We measured their predialysis cfDNA levels using real-time EIF2C1 gene sequence amplification and analyzed its association with certain clinical parameters. RESULTS: The mean plasma cfDNA level in the HD patients was 3,884 +/- 407 GE/mL, and the mean plasma cfDNA level in the control group was 1,420 +/- 121 GE/mL (P < 0.05). Diabetic patients showed higher plasma cfDNA levels compared with nondiabetic patients (P < 0.01). Patients with cardiovascular complications also showed higher plasma cfDNA levels compared with those without cardiovascular complication (P < 0.05). In univariable analysis, the cfDNA level was associated with 3-month mean systolic blood pressure (SBP), white blood cell, serum albumin, creatinine (Cr), normalized protein catabolic rate in HD patients. In diabetic patients, it was significantly correlated with SBP, hemoglobin A1c, and serum albumin. In multivariate analysis, SBP was the independent determinant for the cfDNA level. In diabetic patients, cfDNA level was independently associated with hemoglobin A1c and SBP. CONCLUSIONS: In patients with HD, cfDNA is elevated in diabetic patients and patients with cardiovascular diseases. Uncontrolled hypertension and poor glycemic control are independent determinants for the elevated cfDNA. Our data suggest that cfDNA might be a marker of vascular injury rather than proinflammatory condition in HD patients.