Background: Imbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN. Methods: Thirty-one patients with biopsy-proven IgAN (age, 34.48 ± 12.10 years) and 25 healthy controls (age, 44.84 ± 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment. Results: The levels of serum interferon-gamma (IFNγ) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFNγ, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFNγ among representative Th1/Th2 cytokines. Conclusion IFNγ was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.

Background: Imbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN. Methods: Thirty-one patients with biopsy-proven IgAN (age, 34.48 ± 12.10 years) and 25 healthy controls (age, 44.84 ± 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment. Results: The levels of serum interferon-gamma (IFNγ) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFNγ, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFNγ among representative Th1/Th2 cytokines. Conclusion IFNγ was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.

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.
Acetates ; C-Reactive Protein ; Citric Acid ; Heparin ; Humans ; Male ; Parathyroid Hormone ; Renal Dialysis ; Retrospective Studies ; Urea

BACKGROUND: Several factors had been suggested to contribute to the development of hypertension in chronic glomerulonephritis (GN). This study was conducted to find the association of baseline blood pressure (BP) with pathophysiologic findings and later renal progression in chronic GN. METHODS: Clinico-pathological findings including serum creatinine (Cr), proteinuria, pathological findings, and urinary Na excretion were analyzed in a total of 233 patients with IgA nephropathy from The Kyung-Hee Cohort of GN. Glomerular surface area (GSA) was measured by imaging analysis and urine angiotensinogen (AGT) concentrations by human ELISA kits. RESULTS: Systolic BP was ≥130mmHg in 124 patients (53%). Systolic BP was negatively correlated with follow-up eGFR (r=−0.32, p<0.0001) and positively serum uric acid concentrations, while it had no significant relationships with initial serum Cr and eGFR. As compared with patients with systolic BP<130 mmHg, those with ≥130 mmHg were older and showed higher serum Cr, proteinuria, 24 hr urinary Na excretion, mean GSA, and T-I fibrosis, lower follow-up eGFR, and steeper decline in slope of eGFR. The results in patients with normal serum Cr concentrations were comparable to those in whole group. Systolic BP was positively correlated with age, baseline and follow-up proteinuria, serum uric acid concentrations and IgM deposit and negatively with follow-up eGFR. In subgroup analysis, systolic BP was also positively correlated with mean GSA and urinary AGT concentrations. CONCLUSION This study showed that baseline systolic BP is related to urinary Na excretion, glomerulomegaly, T-I fibrosis and later renal progression in patients with IgA nephropathy.

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.
Acid-Base Equilibrium ; Acidosis ; Acidosis, Renal Tubular* ; Autoantibodies ; Diagnosis ; Exocrine Glands ; Fanconi Syndrome ; Female ; Femoral Fractures ; Glomerulonephritis ; Humans ; Hypokalemia ; Kidney ; Muscle Weakness ; Nephritis, Interstitial ; Osteomalacia ; Paralysis ; Saliva ; Tears

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.
Central Nervous System ; Demyelinating Diseases ; Humans ; Hyponatremia ; Inappropriate ADH Syndrome ; Myelitis, Transverse ; Neuromyelitis Optica* ; Optic Neuritis ; Water

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.
Genetic Variation* ; Hypertension* ; Polymorphism, Single Nucleotide ; Sympathetic Nervous System ; Tyrosine 3-Monooxygenase* ; Tyrosine*

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.
C-Reactive Protein ; Endothelial Cells ; Glomerulonephritis, IGA* ; Humans ; Immunoglobulin A* ; Immunoglobulins* ; Multivariate Analysis ; Phosphorus ; Plasma* ; Prognosis* ; Proportional Hazards Models ; Proteoglycans ; Renal Insufficiency, Chronic ; Risk Factors

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.
Anaphylaxis ; Creatinine ; Disease Progression ; Follow-Up Studies ; Glomerular Filtration Rate ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Hematuria ; Humans ; Immunoglobulin A* ; Immunoglobulin E* ; Immunoglobulins* ; Male ; Nephrotic Syndrome ; Proteinuria

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.
Alleles ; Asthma ; Fibrosis ; Humans ; 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 beta2