Effects of online hemodiafiltration on anemia and nutritional status in chronic hemodialysis patients

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.

Korean clinical practice guidelines for preventing transmission of coronavirus disease 2019 (COVID-19) in hemodialysis facilities

Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease that is caused by the novel virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). COVID-19 has become pandemic since December 2019, when the first case developed in Wuhan, China. Patients receiving hemodialysis are more vulnerable to viral transmission because their immune functions are impaired and they receive treatment within a narrow space. Calling on previous experience with Middle East Respiratory Syndrome during the 2015 outbreak, the joint committee of the Korean Society of Nephrology and the Korean Society of Dialysis Therapy quickly formed a COVID-19 task force team to develop a manual before the first index case was diagnosed in the hemodialysis unit. This special article introduces clinical practice guidelines to prevent secondary transmission of COVID-19 within hemodialysis facilities, which were developed to protect patients, healthcare workers, and caregivers from this highly transmissible virus. The areas of infection control covered by these guidelines include standard precautions, performing dialysis therapy for confirmed or suspected cases, performing cohort isolation for contact patients, and disease monitoring and contact surveillance. We hope these guidelines help healthcare workers and hemodialysis patients around the world cope with the COVID-19 pandemic.

Estimating the urinary sodium excretion in patients with chronic kidney disease is not useful in monitoring the effects of a low-salt diet

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.

Validation Study of an Operational Tolerance Signature in Korean Kidney Transplant Recipients

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.

Korean clinical practice guidelines for preventing the transmission of infections in hemodialysis facilities

Patients receiving hemodialysis are vulnerable to infectious diseases due to their impaired immunity and high risk of exposure to pathogens. To protect patients, staff, and visitors from potential infections, each hemodialysis unit should establish and follow standard infection control and prevention measures. Therefore, clinical practice guidelines were developed by a working group of nephrologists and infection control specialists to provide evidence-based guidance for dialysis physicians and nurses, with the aim of preventing infection transmission and controlling infection sources in hemodialysis facilities. The areas of infection control covered by these guidelines include standard precautions, isolation strategies, vascular access, water treatment, cleaning/disinfecting/sterilizing, and vaccination. This special report summarizes the key recommendations from the Korean clinical practice guidelines for preventing the transmission of infections in hemodialysis facilities.

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.

Evaluation of Digital PCR as a Technique for Monitoring Acute Rejection in Kidney Transplantation

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.

Fatal Invasive Pulmonary Aspergillosis after Combined Induction with Rituximab and Antithymocyte Globulin for Kidney Transplantation in a Sensitized Recipient, and Early Rejection Therapy with Plasmapheresis and Low-dose Immunoglobulin / 대한이식학회지

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.

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.

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.

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.

Transforming growth factor-beta receptor 2 gene polymorphisms are associated with end-stage renal disease

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.

Effect of blood pressure and glycemic control on the plasma cell-free DNA in hemodialysis patients

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.

A case of Ramsay Hunt syndrome diagnosed after kidney transplantation

We report the first case of Ramsay Hunt syndrome (RHS) diagnosed after kidney transplantation in Korea. RHS is a disease caused by latent varicella-zoster characterized to involve geniculate ganglion of the seventh cranial nerve. Patients who have undergone kidney transplantation can be easily affected by viral infections because of their immune-compromised status. A 35-year-old man with hypertensive end-stage renal disease underwent kidney transplantation. Two months after surgery, the recipient was diagnosed with RHS and treated with antivirals and steroids. However, after using the antiviral agents for the recommended duration, facial paralysis occurred as a new presentation and he required further treatment. Otalgia and periauricular vesicles improved, but the facial palsy remained.

Clinicopathological role of kidney injury molecule-1 in immunoglobulin A nephropathy

BACKGROUND: Urinary kidney injury molecule-1 (KIM-1) is an early and sensitive biomarker of acute kidney injury, but it is unclear if it is a biomarker of chronic glomerulonephritis. We evaluated whether urinary KIM-1 levels in patients with immunoglobulin A (IgA) nephropathy can be a marker to reflect clinicopathological severity and predict the prognosis. METHODS: We measured urinary KIM-1 levels in 40 patients (15 males; mean age 36.67+/-12.9 years) with IgA nephropathy and 10 healthy people (5 males; mean age 37.37+/-9.6 years) as controls. The correlation of urinary KIM-1 levels with patients' clinical parameters, histological grades, and follow-up data were analyzed using the modified H. S. Lee grading system and tubulointerstitial change scores. RESULTS: Urinary KIM-1 levels were higher in patients with IgA nephropathy than healthy controls (P=0.001). Univariate and multivariate regression analyses showed that urinary KIM-1 levels had a direct correlation with H. S. Lee grade and tubulointerstitial inflammation (P=0.004 and P=0.011, respectively). CONCLUSION: In patients with IgA nephropathy, urinary KIM-1 has a significant correlation with histopathologic severity.

A case of emphysematous empyema and pneumomediastinum associated with emphysematous pyelonephritis / 대한내과학회지

Emphysematous pyelonephritis (EPN) is a necrotizing infection characterized by the accumulation of gas in the renal parenchyma and surrounding tissues. Although there have been a few cases of EPN accompanied by either pneumoperitoneum or pneumomediastinum, this case should be considered important due to the marked extent of the emphysematous empyema. The patient did not know of her diabetes until admission. Her HbA1c was 15.3% on admission. Her symptoms included dyspnea, fever, and left-side flank pain. Hypotension and tachycardia were strongly suggestive of sepsis. The simple x-ray and abdominal and chest computed tomography (CT) findings confirmed the diagnosis of EPN extending to the thoracic cavity. A combination of antibiotics and percutaneous drainage was performed. After several weeks, the patient underwent a nephrectomy. Despite these attempts, the patient died due to postoperative infection combined with hospital-acquired pneumonia.

Carotid Artery Intima-Media Thickness According to the Stage of Chronic Kidney Disease / 대한신장학회지

PURPOSE: Carotid artery intima-media thickness (cIMT) has been reported as the predictive factor of mortality of cardiovascular disease in dialysis patients but only a few reports are available on the patients with earlier stages. We compared cIMT according to the stage of chronic kidney disease, and analyzed the data in association with cardiovascular risk factors. METHODS: Study subjects were 88 patients with chronic kidney disease less than 60 ml/min/1.73m2 of glomerular filtration rate. cIMT was measured by means of high- resolution B-mode ultrasonography. Cardiovascular risk factors and cIMT were analyzed and compared with 30 subjects with normal renal function. RESULTS: cIMT was significantly increased with the stage of chronic kidney disease. When the stage was increased from 3 to 5, cIMT was increased (p=002). cIMT was further increased in all stages of chronic kidney disease than in patients with normal kidney function. But association of diabetic chronic kidney disease with non-diabetic chronic kidney disease was not significant (p=0.127). Multiple regression analysis showed that cIMT in patients with chronic kidney disease was significantly correlated to age, glomerular filtration rate, and the stage of chronic kidney disease. CONCLUSION: We suggest that carotid atherosclerosis could increase in no dialysis patients with early stage of chronic kidney disease. Carotid artery intima-media thickness was correlated with age, glomerular filtration rate, and the stage of chronic kidney disease.

Effect of Visible Light Therapy in Patients with Somatic Pain

OBJECTIVE: The purpose of this study is to evaluate the effect of visible light therapy for the management of somatic pain. METHOD: Subjects consisted of 42 patients with pain and were divided into two groups; control (n=22) and experimental (n=20) groups. Control group received conventional physical therapy only, while experimental group received additional light therapy with blue light (light intensity 4080 lux, wave length 581 nm, distance from lamp 5 cm). Intensity of pain was assessed by visual analogue scale (VAS) and McGill pain questionnaire. Sympathetic skin response was measured to assess the status of autonomic nervous system. VAS and McGill pain questionnaire were administered before treatment and at 1 day, 2 days, 3 days, 1 week, and 2 weeks after treatment. Sympathetic skin response were performed before and 2 weeks aftertreatment. RESULTS: 1) In both experimental and control groups, VAS became significantly lower at two weeks after treatment compared to pretreatment scale (p<0.05). 2) McGill pain questionnaire showed significantly lower scores two weeks after treatment compared to pretreatment score, only in experimental group (p<0.05). 3) Experimental group showed significantly lower McGill pain questionnaire score than control group at two weeks after treatment (p<0.05). 4) Latency and amplitude of sympathetic skin response showed no significant difference between experimental and control groups. CONCLUSION: Visible light therapy can be used as an effective therapeutic modality for the management of symptomatic pain in combination with conventional physical therapy.