Arkom Nongnuch

Mineral metabolism and outcomes in chronic kidney disease stage 2–4 patients

BackgroundMarked hyperphosphatemia, hyperparathyroidism and 25-hydroxyvitamin D deficiency are associated with mortality in dialysis patients. Such data in chronic kidney disease stage 2–4 population are limited. It has been suggested that high-normal serum phosphate predicts worse renal and patient outcomes. The data regarding parathyroid hormone and outcomes in this population is limited. The present study examined mineral metabolism and its association with the development of end-stage renal disease and mortality in stage 2–4 chronic kidney disease patients.MethodsThis is a prospective cohort study that included 466 non-dialysis chronic kidney disease stage 2–4 patients. Mineral parameters were obtained at the time of enrollment and the patients were followed prospectively for 25 (1–44) months or until they reached the endpoints of end-stage renal disease or mortality.ResultsHyperparathyroidism and 25-hydroxyvitamin D deficiency began to occur in the early stages of chronic kidney disease, whereas significant hyperphosphatemia only developed in the later stages. High-normal and mildly elevated serum phosphate (>4.2 mg/dL) predicted the composite outcome of end-stage renal disease or mortality after adjustments for cardiovascular risk factors, chronic kidney disease stage and other mineral parameters. Parathyroid hormone levels above the upper limit of normal (>65 pg/mL) predicted the future development of end-stage renal disease and the composite outcome of end-stage renal disease or mortality after adjustments. 25-hydroxyvitamin D deficiency (<15 ng/mL) was also associated with worse outcomes.ConclusionsIn chronic kidney disease, hyperparathyroidism developed prior to significant hyperphosphatemia confirming the presence phosphate retention early in the course of chronic kidney disease. High-normal serum phosphate and mildly elevated parathyroid hormone levels predicted worse renal and patient outcomes. This data emphasizes the need for early intervention in the care of chronic kidney disease stage 2–4 patients.

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis

Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

Predialysis NTproBNP predicts magnitude of extracellular volume overload in haemodialysis patients.

Introduction: Increased natriuretic peptides are associated with increased cardiovascular and all-cause mortality for haemodialysis (HD) patients. However, debate continues whether these biomarkers are increased by extracellular water (ECW) excess and can be used to aid clinical assessment of volume status and help determine target weight. Methods: We measured N terminal probrain natriuretic peptide (NT-proBNP) predialysis in 375 stable haemodialysis outpatients with corresponding pre and postdialysis multifrequency bioelectrical impedance assessments (MFBIA) of (ECW)/total body water (TBW). Results: Median age 64 (51-75), 63.9% male, 42.9% diabetic, 43.2% Caucasoid, 14.4% with a history of myocardial infarction, 8.4% coronary artery bypass surgery, dialysis vintage 28.2 (12.3-55.5) months. Median predialysis NT-proBNP 283 (123-989) pmol/l, and predialysis ECW/TBW ratio 0.397 ± 0.029. On multivariate analysis, predialysis log NT-proBNP was associated with predialysis systolic blood pressure (β 0.007, p = 0.000), weight (β −0.008, p = 0.001), valvular heart disease (β 0.342, p = 0.015, ECW/TBW (β 1.3, p = 0.019) and log CRP (β 0.145, p = 0.037). Dividing patients into NTproBNP quartiles, %ECW/TBW and relative ECW overhydration were significantly greater for the highest quartile vs. lowest (40.5 ± 4.1 vs. 39.0 ± 1.1, and 1.51 ± 1.24 vs. 0.61 ± 0.69 l, respectively, p < 0.001). Conclusion: In this study, predialysis NTproBNP values were associated with direct assessments of the extracellular volume excess measured by MFBIA and systolic arterial blood pressure. This suggests that predialysis NTproBNP values can potentially be used to aid clinical assessment of volume status in dialysis patients to determine target weight.

Chromosome 20p inverted duplication deletion identified in a Thai female adult with mental retardation, obesity, chronic kidney disease and characteristic facial features

We report on a 21-year-old Thai woman presenting with mental retardation, developmental delays, selective mutism, distinctive facial features, sensorineural hearing loss, single right kidney, uterine didelphys and obesity. A longitudinal clinical course beginning in childhood revealed excessive weight gain, poor language skills and poor school performance. Chronic kidney disease stage 4, with elevated blood pressure, was first noted in adulthood. Array comparative genomic hybridization detected a copy loss at 20p13 co-existing with a copy gain at 20p13-20p11.22. A conventional cytogenetic study revealed the complex structural rearrangement of chromosome 20 [der (20) dup (20) (p11.2p13) del (20) (p13.pter)]. A FISH analysis, using probes against duplication and deletion regions, confirmed that there was an inverted duplication of p11.2-p13 and a deletion in the subtelomere region. Previous reports have identified this cytogenetic characterization in a Caucasian boy. Therefore, this is the first reported case of chromosome 20p inverted duplication deletion syndrome in an adult from the Southeast Asian population group.

Does the presence of an arteriovenous fistula alter changes in body water following hemodialysis as determined by multifrequency bioelectrical impedance assessment

Multifrequency bioelectrical impedance assessments (MFBIAs) aid clinical assessment of hydration status for hemodialysis (HD) patients. Many MFBIA devices are restricted to whole body measurements and as many patients dialyze using arteriovenous fistulas (AVFs), we wished to determine whether AVFs affected body water measurements. We reviewed pre‐ and post‐HD segmental MFBIA measurements in 229 patients attending for midweek HD sessions. Up to 144 were dialyzed with a left arm AVF (L‐AVF), 42 with a right arm AVF (R‐AVF), and 43 by central venous access catheter (CVC). Water content and lean tissue were greater in the left compared to right arm in those patients with L‐AVFs both pre and post dialysis (pre 2.1 ± 0.7 vs. 2.0 ± 0.7 L, and post 1.9 ± 0.6 vs. 1.8 ± 0.6 L and pre 2.65 ± 0.9 vs. 2.56 ± 0.8 kg, and post 2.34 ± 0.8 vs. 2.48 ± 0.8 vs. 2.34 ± 0.8 kg, respectively) and were also greater in the right compared to left arm for those patients dialyzing with R‐AVFs (pre‐HD 1.92 ± 0.5 vs. 1.86 ± 0.6 L and post‐HD 1.79 ± 0.5 vs. 1.7 ± 0.5 L, and pre‐HD 2.47 ± 0.6 vs. 2.38 ± 0.7 kg and post‐HD 2.3 ± 0.74 vs. 1.28 ± 0.7 kg, respectively), all Ps < 0.05. There were no significant differences in arm volumes or composition pre or post dialysis in those dialyzing with CVCs. Segmental MFBIA detects differences in arm water and lean mass in patients with AVFs. The presence on an AVF increases the water content in the ipsilateral arm both pre and post HD. This increased water content of the fistula arm will not be detected by whole body bioimpedance devices.

Screening of Fabry disease in patients with end-stage renal disease of unknown etiology: the first Thailand study

Abstract We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease (ESRD) of an unknown origin. Venous blood samples were collected from ESRD patients for biochemical and molecular studies. Alpha-galactosidase A (α-GAL A) screening was performed from dried-blood spots using fluorometry. Molecular confirmation was performed using DNA sequencing of the GLA gene. A total of 142 male and female patients were included in this study. Ten patients (7.04%) exhibited a significant decrease in α-GAL A activity. There were no definitive pathogenic mutations observed in the molecular study. However, four patients revealed a novel nucleotide variant at c.1 -10 C>T, which was identified as a benign variant following screening in the normal population. In conclusion, the α-GAL A assay utilizing dried-blood spots revealed a significant false positive rate. There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.

Early posttransplant nephrotic range proteinuria as a presenting feature of minimal change disease and acute T cell-mediated rejection.

Early-onset nephrotic range proteinuria is an extremely rare presentation of an acute rejection episode. Herein, we have reported a patient who developed nephrotic range proteinuria 7 days after receiving a renal allograft from his sister despite minor changes in serum creatinine levels. A kidney biopsy spcimen revealed a T cell-mediated acute rejection process concomitant with minimal change disease (MCD). Proteinuria and renal dysfunction improved dramatically in response to corticosteroids. The possibility of acute cellular rejection and coexisting MCD should be considered in patients with early posttransplantation nephrosis and normal serum creatinine levels. The coexistence of these entities provides support for the role of T cells in the pathogenesis of MCD.

Urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors of complete remission in primary glomerulonephritis

Background: The balance of several cytokines likely influences the resolution of glomerulonephritis. Monocyte chemoattractant protein‐1(MCP‐1) is a chemokine that promotes renal inflammation whereas epidermal growth factor (EGF) stimulates protective responses. Previously, high urine MCP‐1(MCP‐1) and low urine EGF (EGF) levels were found to be associated with tubulointerstitial fibrosis, but there is limited information on the value of these mediators as predictors of therapeutic responses or long term outcome in primary glomerulonephritis. Objectives: To determine the performance of urine EGF, MCP‐1 or their ratio at baseline as biomarkers to predict complete remission, and the relationship of these mediators with subsequent renal function 24months later in primary glomerulonephritis. Methods: This is a prospective study of patients with biopsy‐proven primary glomerulonephritis. Baseline urine samples were collected at biopsy before therapy. MCP‐1 and EGF were analyzed by enzyme‐linked immunosorbent assays and expressed as a ratio to urine creatinine (ng/mgCr) or as EGF/MCP‐1 ratio (ng/ng). Proteinuria and estimated glomerular filtration rate (eGRF) were monitored after therapy. Complete remission (CR) was defined as proteinuria≤0.3g/gCr. Results: Median follow‐up was 20months. Of all patients (n=74), 38 patients (51.4%) subsequently achieved CR. Baseline urine EGF and EGF/MCP‐1 levels were significantly higher in CR compared to Not CR. By contrast, MCP‐1 was not different. High EGF (EGF>75ng/mgCr) was a significant predictor (OR 2.28) for CR by multivariate analysis after adjusting for proteinuria, blood pressure, baseline eGFR. In patients who completed 24months follow‐up (n=43), baseline EGF correlated inversely with proteinuria and positively with eGFR at 24months. Conclusion: High urine EGF level is a promising biomarker of CR. Baseline EGF levels correlated with kidney function at 2years. EGF/MCP‐1 was not superior to EGF alone. Further studies are necessary to determine the role of urine EGF as a guide to therapy in primary GN. HIGHLIGHTSUrine cytokines were assessed for ability to predict outcome in glomerulonephritis.High epidermal growth factor was a significant predictor of complete remission.Baseline epidermal growth factor correlated with kidney function at 24months.Levels of monocyte chemoattractant protein‐1 levels did not add useful information.