Reduction in proteinuria after immunosuppressive therapy and long-term kidney outcomes in patients with immunoglobulin A nephropathy

Background/Aims@#Despite controversy regarding the benefits of immunosuppressive therapy in immunoglobulin A nephropathy (IgAN), clinical outcomes may vary depending on the patient’s responsiveness to this therapy. This study evaluated long-term kidney outcomes according to the extent of proteinuria reduction after immunosuppression in IgAN patients. @*Methods@#Among 927 patients with biopsy-proven IgAN, 127 patients underwent immunosuppression. Time-averaged urine protein-creatinine ratio before and within 1 year after start of immunosuppression were calculated, and responsiveness to immunosuppression was assessed as the reduction of proteinuria between the two periods. Patients were classified into tertiles according to the extent of proteinuria reduction. We compared the slopes of estimated glomerular filtration rate (eGFR) decline using a linear mixed model, and estimated hazard ratios (HRs) for disease progression (defined as development of a ≥ 30% decline in eGFR or end-stage renal disease) using a Cox proportional hazard model. @*Results@#Median extent of proteinuria reduction was –2.1, –0.9, and –0.2 g/gCr in the first, second, and third tertiles, respectively. There were concomitant changes in the slopes of annual eGFR decline: –2.03, –2.44, and –4.62 mL/min/1.73 m2 among the first, second, and third tertiles, respectively. In multivariable Cox analysis, the HRs (95% confidence intervals) for disease progression were 0.30 (0.12 to 0.74) in the first tertile and 0.70 (0.34 to 1.45) in the second tertile compared with the thirdtertile. @*Conclusions@#This study showed that greater proteinuria reduction after immunosuppression was associated with a lower risk of disease progression in patients with IgAN, suggesting that responsiveness to immunosuppression may be an important determinant of kidney outcomes.

Reduction in proteinuria after immunosuppressive therapy and long-term kidney outcomes in patients with immunoglobulin A nephropathy

Background/Aims@#Despite controversy regarding the benefits of immunosuppressive therapy in immunoglobulin A nephropathy (IgAN), clinical outcomes may vary depending on the patient’s responsiveness to this therapy. This study evaluated long-term kidney outcomes according to the extent of proteinuria reduction after immunosuppression in IgAN patients. @*Methods@#Among 927 patients with biopsy-proven IgAN, 127 patients underwent immunosuppression. Time-averaged urine protein-creatinine ratio before and within 1 year after start of immunosuppression were calculated, and responsiveness to immunosuppression was assessed as the reduction of proteinuria between the two periods. Patients were classified into tertiles according to the extent of proteinuria reduction. We compared the slopes of estimated glomerular filtration rate (eGFR) decline using a linear mixed model, and estimated hazard ratios (HRs) for disease progression (defined as development of a ≥ 30% decline in eGFR or end-stage renal disease) using a Cox proportional hazard model. @*Results@#Median extent of proteinuria reduction was –2.1, –0.9, and –0.2 g/gCr in the first, second, and third tertiles, respectively. There were concomitant changes in the slopes of annual eGFR decline: –2.03, –2.44, and –4.62 mL/min/1.73 m2 among the first, second, and third tertiles, respectively. In multivariable Cox analysis, the HRs (95% confidence intervals) for disease progression were 0.30 (0.12 to 0.74) in the first tertile and 0.70 (0.34 to 1.45) in the second tertile compared with the thirdtertile. @*Conclusions@#This study showed that greater proteinuria reduction after immunosuppression was associated with a lower risk of disease progression in patients with IgAN, suggesting that responsiveness to immunosuppression may be an important determinant of kidney outcomes.

Risk Factors Associated with Recurrent Urinary Tract Infection Caused by Escherichia coli / 대한임상미생물학회지

Background@#The purpose of this study was to analyze the clinical and microbiological characteristics of recurrent urinary tract infection (UTI) caused by Escherichia coli— the most common etiological agent. @*Methods@#Cases of recurrent and single episodes of UTI caused by E. coli were evaluated retrospectively for a period of 6 months (January-June 2019) to analyze the clinical and molecular characteristics of this disease. @*Results@#Healthcare-associated UTI, E. coli bacteremia, and poor microbial clearance 7 days post infection were associated more with the recurrent episodes of infection. E. coli isolates from subjects with recurrent UTIs showed higher rates of antimicrobial resistance and extended-spectrum β-lactamase (ESBL) production. The E. coli clone— sequence type 131 was detected in similar proportions in isolates, recovered from subjects in both groups— recurrent episodes and single episode of UTI. @*Conclusion@#The control of antimicrobial-resistant ESBL-producing E. coli strains may be difficult using antimicrobial therapy and subsequently delay the clearance of the etiologic agent. This could play a major role in the development of recurrent UTIs.

Mixed- versus predilution hemodiafiltration effects on convection volume and small and middle moleculeclearance in hemodialysis patients: a prospective randomized controlled trial

Background@#The use of newly developed mixed-dilution hemodiafiltration (HDF) can supplement the weaknesses of pre- and postdilution HDF. However, it is unclear whether mixed-HDF performs well compared to predilution HDF. @*Methods@#We conducted a prospective, open-labeled, randomized controlled trial from two hemodialysis centers in Korea. Between January 2017 and September 2019, 60 patients who underwent chronic hemodialysis were randomly assigned at a 1:1 ratio to receive either predilution HDF (n = 30) or mixed-HDF (n = 30) for 6 months. We compared convection volume, changes in small- and medium-sized molecule clearance, high-sensitive C-reactive protein (hs-CRP) level, and dialysis-related parameters between the two dialysis modalities. @*Results@#A mean effective convection volume of 41.0 ± 10.3 L/session in the predilution HDF group and 51.5 ± 9.0 L/session in the mixed-HDF group was obtained by averaging values of three time-points. The difference in effective convection volume between the groups was 10.5 ± 1.3 L/session. This met the preset noninferiority criteria, suggesting that mixed-HDF was noninferior to predilution HDF. Moreover, the β2-microglobulin reduction rate was greater in the mixed-HDF group than in the predilution HDF group, while mixed-HDF provided greater transmembrane pressure. There were no significant between-group differences in Kt/V urea levels, changes in predialysis hs-CRP levels, proportions of overhydration, or blood pressure values. Symptomatic intradialytic hypotension episodes and other adverse events occurred similarly in the two groups. @*Conclusion@#Use of mixed-HDF was comparable to predilution HDF in terms of delivered convection volume and clinical parameters. Moreover, mixed-HDF provided better β2-microglobulin clearance than predilution HDF.

Application of 16S rRNA Gene-Targeted Next-Generation Sequencing for Bacterial Pathogen Detection in Continuous Ambulatory Peritoneal Dialysis Peritonitis / 대한임상미생물학회지

BACKGROUND: 16S rRNA gene-targeted next-generation sequencing (NGS) can detect microorganisms in a comprehensive reference database. To date, NGS has been successfully applied to samples such as urine, blood, and synovial fluid. However, there is no data for continuous ambulatory peritoneal dialysis (CAPD) fluid. The purpose of this study was to evaluate the clinical usefulness of microbiome analysis of CAPD fluids for the diagnosis of CAPD peritonitis.METHODS: We included 21 patients with high suspicion of CAPD peritonitis. Routine CAPD fluid culture was performed using a pellet of 50 mL CAPD fluid onto the chocolate and blood agar for two days, and thioglycollate broth for one week. 16S rRNA gene-targeted NGS of pellets, stored at −70℃ was performed with MiSeq (Illumina, USA).RESULTS: Many colonized or pathogenic bacteria were detected from CAPD fluids using NGS and the microbiomes were composed of 1 to 29 genera with a cut-off 1.0. Compared to the culture results, NGS detected the same pathogens in 6 of 18 valid results (three samples failed with low read count). Additionally, using NGS, anaerobes such as Bacteroides spp. and Prevotella spp. were detected in six patients. In two of five samples in which no bacterial growth was detected, possible pathogens were detected by NGS.CONCLUSION: To our knowledge, this is the first report about the application of 16S rRNA gene-targeted NGS for diagnosis of CAPD peritonitis. Etiology of culture-negative CAPD peritonitis can be better defined in NGS. Furthermore, it also helped the detection of anaerobic bacteria.

Effects of 12 months of continuous positive airway pressure therapy on cognitive function, sleep, mood, and health-related quality of life in a peritoneal dialysis patient with obstructive sleep apnea

This report describes the case of a hypertensive 51-year-old male with a 3-year history of peritoneal dialysis. We followed the patient through his diagnosis of severe obstructive sleep apnea (OSA) and treatment with continuous positive airway pressure (CPAP). Therapeutic use of CPAP led to the improvement of not only sleep-related problems, but also cognitive function and quality of life. To our knowledge, this is the first paper describing the benefits of long-term CPAP treatment in an OSA patient undergoing dialysis. This case report emphasizes the need for the proactive diagnosis and treatment of OSA in end-stage renal disease patients to improve patient-centered healthcare.

A Case of Polymyositis Associated with Immunoglobulin A Nephropathy

Polymyositis (PM) is a chronic inflammatory disease that predominantly affects muscles. Systemic organ involvement, including the respiratory and gastrointestinal tracts, is frequently observed in PM, but renal involvement is rare. Herein, we report the case of a 56-year-old woman presenting with weight gain, edema, and generalized myalgia. Laboratory tests revealed elevated creatinine kinase level, hypoalbuminemia, and proteinuria. Histopathological examination of muscle biopsy revealed inflammatory myositis, and a renal biopsy confirmed immunoglobulin A (IgA) nephropathy. Based on the clinico-pathological results, the patient was diagnosed with PM with IgA nephropathy. This is a report of a rare occurrence of IgA nephropathy in a patient with PM presenting with chronic glomerulonephritis.

A Case of Peritonitis caused by Chryseobacterium meningosepticum in a Patient Treated with Peritoneal Dialysis / 대한신장학회지

Chryseobacterium meningosepticum is rarely encountered as a pathogen causing peritonitis in peritoneal dialysis (PD) patients. We report a case of peritonitis due to Chryseobacterium meningosepticum, which was treated successfully with intraperitoneal (IP) vancomycin and ciprofloxacin, and without PD catheter removal. Peritonitis was developed in a 53-year-old PD patient on the third hospital day. Although empirical IP treatment with cefazolin and tobramycin was initiated and maintained for 3 days, the fever and signs of peritonitis persisted. Antibiotics were changed to cefoperazone/sulbactam, amikacin, and vancomycin due to clinical deterioration. After 3 days of vancomycin use, leukocyte count in PD fluid was less than 100/mm3 and the patient became asymptomatic. On seventh day after the onset of peritonitis, Chryseobacterium meningosepticum was isolated from initial dialysate sample, and this strain was susceptible to ciprofloxacin, piperacillin, and piperacillin/tazobactam. Accordingly, we changed the antibiotics to ciprofloxacin and vancomycin, which were given for the total of 14 days. Even though Chryseobacterium meningosepticum is an uncommon causative organism of peritonitis in PD patients, this report suggests that vancomycin and ciprofloxacin are effective as empiric therapy, and early suspicion and appropriate antimicrobial therapy are crucial to the successful treatment of peritonitis due to Chryseobacterium meningosepticum without catheter removal.

Spontaneous Remission of Nephrotic Syndrome in IgA Nephropathy / 대한신장학회지

Although a moderate degree of proteinuria is common in patients with IgA nephropathy (IgAN), nephrotic syndrome combined with IgAN is rare. It has been reported that approximately 5% of all patients with IgAN are complicated by minimal change disease and these patients respond well to corticosteroid therapy. However, spontaneous remission is uncommon in heavy proteinuric patients with IgAN. Recently, we experienced two cases of spontaneous remission of nephrotic syndrome combined with IgAN without use of corticosteroid. In these patients, heavy proteinuria disappeared in 1 month after the onset and no recurrence occurred during follow-up. With such limited number of cases, factors associated with spontaneous remission in these patients could not be explored. Further study with a larger number of patients is required and careful attention should be paid to these complicated cases.

A Case of IgA Nephropathy associated with Acute Hepatitis A / 대한신장학회지

IgA nephropathy is the most common type of glomerulonephritis worldwide. Although primary IgA nephropathy receives the most attention, many other diseases are also associated with IgA nephropathy. Among these, chronic liver diseases such as alcoholic liver disease or hepatitis B or C have been reported as secondary causes of glomerular IgA deposits. Recently, as the prevalence of hepatitis A virus (HAV) infection is increasing in Korea, HAV-associated renal diseases occur frequently. Acute kidney injury (AKI) is one of the most common complications of HAV infection, mainly due to acute tubular necrosis or interstitial nephritis. However, unlike hepatitis B and C, glomerular involvement is extremely rare in acute HAV infection. Here, we report a case of biopsy-proven IgA nephropathy with serologically documented HAV infection. The patient presented moderate degree of proteinuria without evidence of AKI. Renal biopsy revealed mesangial IgA deposits but tubular or interstitial inflammation was not observed. This report suggests that HAV infection may be a secondary cause of IgA nephropathy. However, further studies are required to elucidate a causal link between hepatitis A and mesangial IgA deposits.

A Case of AA Amyloidosis Treated with Infliximab / 대한신장학회지

AA amyloidosis is one of the most significant complications of rheumatoid arthritis characterized by the deposition of amyloid A (AA) in multiple organs and tissues in the body. This disorder displays variable clinical symptoms depending upon the involved organ and a diagnosis is rendered through a biopsy of the affected organ, followed by staining using Congo-red which reveals an apple-green birefringence. Fundamental disease control is critical in the treatment of AA amyloidosis. Anti-tumor necrosis factor alpha (anti TNF-alpha) agents are promising in inducing clinical remission by suppressing systemic inflammation in AA amyloidosis. We report a case of AA amyloidosis in a 71 year old woman with rheumatoid arthritis that responded well to infliximab therapy.

A Case of Systemic Lupus Erythematosus Presenting with Acute Pancreatitis / 대한류마티스학회지

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disorder mediated by autoantibodies and immune complexes that exhibit a range of symptoms. Although thirty-five to forty percent of patients with SLE show signs or symptoms of gastrointestinal involvement, acute pancreatitis is an uncommon complication of SLE, and SLE presenting with acute pancreatitis is extremely rare. We report a case of a 28-year-old female SLE patient who initially presented with acute abdominal pain and elevated pancreatic enzyme levels. The patient was diagnosed clinically with acute pancreatitis and then with SLE after further investigations. Her condition improved after high dose steroid therapy.

Bilateral Anterior Ischemic Optic Neuropathy with Sudden Sensorineural Hearing Loss in a Long term Hemodialysis Patient / 대한신장학회지

Anterior ischemic optic neuropathy (AION) is rarely reported in end stage renal disease. In particular, AION combined with sudden sensorineural hearing loss (SNHL) has not been reported in domestic and international journals. Here we report the first case of this combined condition. A 58-year-old male patient in end-stage renal disease presented on painless bilateral visual and hearing deterioration. Clinical findings and imaging studies were compatible with a diagnosis of AION and SNHL. Despite of high-dose steroid therapy, vision and hearing were not significantly recovered. Uremic patients often have coexisting pathology such as hypotension during dialysis, atherosclerosis and anemia, predisposing to AION and SNHL. We describe a patient of dialysis for 10 years who presented with bilateral visual and hearing loss due to complications of long-term dialysis. Our case suggests that nephrologists have to know and treat more carefully this rare but emergent complications of dialysis.

Nephron Numbers in Patients with Minimal Change Nephrotic Syndrome (MCNS) and Focal Segmental Glomerulosclerosis (FSGS) / 대한신장학회지

PURPOSE: It has been proposed that a decreased nephron number may be associated with the increased risk of glomerulosclerosis. In order to test the hypothesis that a reduced number and an increased volume of glomeruli may contribute to the pathogenesis of focal segmental glomerulosclerosis (FSGS), we compared the number and volume of glomeruli between 9 patients with FSGS and 8 with minimal change nephrotic syndrome (MCNS). METHODS: Mean glomerular volume was measured using the method of Weibel and Gomez. An estimate of glomerular number (index) was obtained by multiplying the cortical volume of a kidney by the fraction of renal cortex made up of glomeruli and dividing this by the mean glomerular volume for that kidney x 10(6). We determined kidney volume from ultrasonographic measurement. RESULTS: Patients with FSGS had significantly greater glomerular volume than patients with MCNS [2.02+/-0.36 (x10(6) micrometer3) vs. 1.57+/-0.27 (x10(6) micrometer3)] (p<0.025). However, there was no significant difference in the index of glomerular number (estimated glomerular number) between FSGS & MCNS patients (2.8+/-1.4 vs. 3.0+/-0.8). CONCLUSION: The glomerular volume was greater in FSGS patients than MCNS patients. But there was no significant difference in the index of glomerular number between patients with FSGS and MCNS.

Successful Treatment of Vancomycin-Resistant Enterococcal Peritonitis with linezolid in a Patient on CAPD / 대한신장학회지

Peritonitis is one of the major complications of CAPD (continuous ambulatory peritoneal dialysis). Among its causative organisms, vancomycin-resistant enterococcus (VRE) is rare, but serious causative organism, because it is refractory to antibiotics commonly used for CAPD peritonitis. Some drugs such as linezolid and dalfopristin have been introduced for VRE infections nowadays, but reports about usefulness of those drugs in VRE peritonitis are rare. We experienced a case of CAPD peritonitis caused by VRE, which was treated successfully with removal of CAPD catheter and use of linezolid. We report our experience with review of the literature.

Scalp Edema and Insufficient Maturation of Arteriovenous Fistula Due to Cephalic Vein Variation in Patient with End Stage Renal Disease / 대한신장학회잡지

Vascular access is the prerequisite and mainstay of extra-corporeal renal replacement therapy and its management is central to maintain the health and quality of life of end-stage renal disease (ESRD) patients. Success of maturation of AVF depends on the quality and size of the vessels and anatomic structure. There have been several reports on non-maturation by vascular stenosis or small vascular size after AVF procedure, but reports demonstrating that AVF non-maturation is due to by latent vessel variation are uncommon. We report a rare case of scalp edema and insufficient maturation of AVF due to cephalic vein variation in a 27 year-old female patient with ESRD on hemodialysis. Conclusively, meticulous observation on not only vessels used for AVF but also its proximal connection to other vessels should be considered.

Affecting Factors on Endothelial Dysfunction in Diabetic End Stage Renal Disease Patients on Hemodialysis / 대한신장학회잡지

BACKGROUND: Non-traditional risk factors of cardiovascular disease such as endothelial dysfunction, inflammation and malnutrition may be significant contributors to the excessive cardiovascular mortality in end stage renal disease (ESRD) patients. This study was undertaken to evaluate endothelial function in diabetic ESRD patients on hemodialysis and correlation between endothelial dysfunction and clinical, biochemical parameters. METHODS: Twenty eight stable diabetic ESRD patients (M: F=1.3: 1, average age: 60.1+/-1.0 yr) on hemodialysis were included. flow-mediated dilation (FMD) of brachial artery was measured using Doppler ultrasonography with 10 MHz transducer. Subjective global assessment (SGA) was used to assess the nutritional status of patients. RESULTS: The FMD (%) (% change of brachial artery diameter between before and after cuff inflation) was 5.1+/-1.0%. Serum albumin and C-reactive protein (CRP) were independent factors influencing SGA. When the patients were divided into groups according to history of ischemic heart disease (IHD), systolic pressure was significantly higher and FMD (%) was significantly lower in the group of patients with IHD compared with the group of patients without IHD. The FMD (%) showed significant positive correlation with SGA, serum albumin, and significant negative correlation with CRP. On multiple regression analysis, however, only CRP was an independent factor affecting FMD (%). CONCLUSION: These findings suggest that CRP influenced the nutritional status of diabetic ESRD patients on hemodialysis, and endothelial dysfunction, estimated by FMD, was significantly correlated with CRP. Therefore, CRP can be a modifiable risk factor for endothelial dysfunction in diabetic ESRD patients on hemodialysis.

Effects of Walking Exercise Program for Health Status in Patients on Continuous Ambulatory Peritoneal Dialysis / 대한신장학회잡지

BACKGROUND: It is necessary to exercise in Continuous Ambulatory Peritoneal Dialysis (CAPD) patients but it's difficult because of their physical condition and little motivation. The purpose of this study was to evaluate the effects of the walking exercise program on health status in CAPD patients. METHODS: A nonequivalent control group with pre- and post-test was designed to examine the effects of the program. Data collection was done from December, 2002 to June, 2003. The study participants were selected according to the criteria among the patients who were receiving CAPD at the department of Kidney Center, NIHC Ilsan hospital. The walking exercise program was consisted of an exercise education protocol, an exercise prescription, and a counselling protocol based on a framework of self-efficacy promotion. The exerciser group which was composed of 19 participants was educated based on an exercise education protocol and carried out walking exercise for two to four times a week upon taking verbal persuasion biweekly through telephone or face-to-face interview for 12 weeks, while 17 participants in control group were received no intervention. RESULTS: There was significant differences between two groups; the exerciser group showed better physical function (p=0.03), higher VO2 max (p=0.01) and higher serum albumin level (p=0.02) than the results of control group. However, there were no differences in lipid metabolism. CONCLUSION: The walking exercise program was found to have an effect to increase health status of CAPD patients. The results provided evidences for the importance of continuous physical activity in CAPD patients.

The Effects of On-line Hemodiafiltration on Oxidative Stress and beta2-Microglobulin in Comparison with High-Flux Hemodialysis / 대한신장학회잡지

OBJECTIVE: On-line hemodiafiltration (OL-HDF) is a method that combines diffusive and convective solute transport component. OL-HDF provides improved solute clearance for both low-and large molecular-weight uremic toxins by enhancing convective clearance through highly permeable membranes. The aim of this study is to evaluate the effect of OL-HDF on oxidative stress and beta2-microglobulin (beta2-MG) in comparison with high-flux hemodialysis (HF-HD). METHODS: Twenty-one patients on thrice-weekly low-flux hemodialysis (LF-HD) for at least 6 months were studied. Every patient underwent OL-HDF and HF-HD for four weeks, respectively. There were 2 weeks of wash-out period in which patients were treated with LF-HD, between different treatment periods. Predialysis and postdialysis solute (creatinine, BUN, phosphate, beta2-MG) concentrations were measured in the serum. In addition, predialysis solute (MDA, TAC, hsCRP) concentrations were measured. RESULTS: The urea reduction ratio (64.2+/-14.5 vs. 60.1+/-11.2%), Kt/V (1.4+/-0.2 vs. 1.3+/-0.3), beta2-MG reduction ratio (53.8+/-9.7 vs. 44.3+/-8.7%) and beta2- MG clearance (120.7+/-33.4 vs. 92.7+/-17.6 mL/min) were significantly higher in patients treated with on- line HDF compared with those treated with HF-HD. After 4 weeks of treatment, predialysis serum MDA levels were significantly lower in patients treated with OL-HDF compared with those treated with HF-HD (1.04+/-0.26 vs. 1.19+/-0.25 umol/L). After 4 weeks of treatment with 2 different dialysis modes, predialysis serum beta2-MG (3.7+/-1.0 vs. 2.2+/-0.4 mg/ dL), MDA (1.19+/-0.21 vs. 1.04+/-0.26 umol/L), TAC (265.9+/-21.1 vs. 290.2+/-23.9 umol/L) and log hsCRP (0.07+/-0.51 vs. -0.23+/-0.62) levels were significantly improved compared to the baseline in OL-HDF patients. However, for HF-HD patients, only predialysis serum beta2-MG level at 4 weeks was significantly lower than baseline (3.8+/-1.0 vs. 2.5+/-0.4 mg/dL). CONCLUSION: This study shows that OL-HDF has been significant increase in oxidative stress and inflammatory marker removal compared to HF-HD.

A case of renal arterial embolization using 99% ethanol and lipiodol mixture for autosomal dominant polycystic kidney disease in a hemodialysis patient / 대한내과학회지

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by innumerable bilateral renal cysts. It has an prevalence rate of one in 200~1,000 individuals and is a relatively common cause of renal failure. As renal function deteriorates, overall renal size usually diminish in patients with chronic renal failure. However, renal size of patients with ADPKD usually continues to increase, even after the initiation of dialysis therapy, because numerous cysts replace renal mass. Attempted methods to reduce the size of enlarged kidneys have included needle aspiration and sclerotherapy, cyst decompression surgery, laparoscopic and surgical nephrectomy. The outcome of these therapy frequently has been suboptimal, and there is a need to develop a more effective therapy. We report a case of renal arterial embolization using 99% ethanol and lipiodol mixture for ADPKD in a hemodialysis pathient, which has not been previously reported.