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Background: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. Method: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. Results: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = −0.423, p = 0.018) and ANRIL levels (r = −0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = −0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = −0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). Conclusions: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis. [ABSTRACT FROM AUTHOR]

Background Peritoneal dialysis (PD) is a home-based renal replacement therapy. Since hospital staff are not often familiar with PD and its complications, PD patients may have an excess risk of developing PD-related peritonitis during hospital admission for unrelated reasons, and the outcome may be affected. Methods We reviewed 371 episodes of hospital-acquired PD peritonitis in our center from 2000 to 2019. Their clinical characteristics and outcomes were compared with 825 episodes that required hospital admission and 1964 episodes that were treated as outpatient. Results Hospitalized PD patients had a significantly higher risk of developing peritonitis than outpatients [incident rate ratio 4.41 (95% confidence interval 3.95–4.91]. Hospital-acquired peritonitis episodes were more commonly culture negative. Bacterial isolates from the hospital-acquired episodes were more likely resistant to ceftazidime (P < .0001) than the other groups. The primary response rate, complete cure rate and overall mortality of the hospital-acquired episodes were 66.6%, 62.0%, and 23.2%, respectively, all worse than episodes that developed outside the hospital (P < .0001 for all). Conclusion PD patients admitted to the hospital had a 4-fold increase in the risk of developing peritonitis. Hospital-acquired peritonitis episodes were more likely culture negative and resistant to antibiotics. They also had a lower primary response rate, a lower complete cure rate and higher mortality than episodes that developed outside the hospital. [ABSTRACT FROM AUTHOR]

• Previous studies showed that urinary levels of some miRNA targets are significantly altered in IgA nephropathy. • The persent study used healthy subjects and patients with biopsy-proved hypertensive nephrosclerosis as controls, so as to eliminate the confounding effect of kidney scarring. • The result showed that urinary miR-106a has good sensitivity but limited specificity in detecting IgA nephropathy. • Our result indicates that urinary miRNA level may be used for screening of IgA nephropathy. Urinary micro-RNA (miRNA) level may serve as non-invasive disease markers for immunoglobulin A nephropathy (IgAN), but urinary miRNA targets identified in previous studies may represent kidney scarring rather than being specific for IgAN. We aim to identify urinary miRNA targets for the diagnosis of IgAN by including hypertensive nephrosclerosis (HTN) as a control group. Methods In the development cohort, we performed complete miRNA profiling of urinary sediment in 33 patients with IgAN, 9 with HTN, and 9 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 72 IgAN, 34 HTN, and 20 healthy controls. Results In the development cohort, we identified 6 miRNA targets with urinary levels significantly increased in IgAN as compared to both HTN and CTL. In the validation study, all 6 miRNA targets remained increased than the other groups, although the result of miR-345 did not reach statistical significance. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-106a level for the diagnosis of IgAN was 0.742 (p < 0.0001), and the diagnostic performance was not further improved by having additional miRNA targets. At the cut-off ≥ 800 copy per 1000 copies of housekeeping gene, urinary miR-106a has 100% sensitivity and 14.8% specificity in detecting IgA nephropathy. Conclusions We identified 6 miRNA targets whose urinary levels are significantly elevated in IgAN, and urinary miR-106a level has an excellent sensitivity for the identification of IgAN. Further validation studies are needed to confirm its role in disease screening. [ABSTRACT FROM AUTHOR]

• Podocyte is the primary focus of many kidney diseases. • Podocytes and their microvesicles could be quantified in urine. • They may be used as biomarkers of various kidney disease. Podocytes play an important role in the maintenance of kidney function, and they are the primary focus of many kidney diseases. Podocyte injury results in the shedding of podocyte-derived cellular fragments and podocyte-specific molecular targets into the urine, which may serve as biomarkers of kidney diseases. Intact podocytes, either viable or dead, and podocyte-derived microvesicles could be quantified in the urine by various centrifugation, visualization and culture methods. Podocyte-specific protein targets from the nucleus, cytoplasm, slit-diaphragm, glomerular capillary basement membrane, and cytoskeleton, as well as their corresponding messenger RNA (mRNA), in the urine could be quantified by western blotting, ELISA, or quantitative polymerase chain reaction. Although some of these techniques may be expensive or labor-intensive at present, they may become widely available in the future because of the improvement in technology and automation. The application of urinary podocyte markers for the diagnosis and monitoring of various kidney diseases have been explored but the published data in this area are not sufficiently systematic and lack external validation. Further research should focus on standardizing, comparing, and automizing laboratory methods, as well as defining their added value to the routine clinical tests. [ABSTRACT FROM AUTHOR]

Background Relapsing and recurrent peritonitis episodes are major causes of technique failure in peritoneal dialysis (PD). We examined the efficacy of extended antibiotic therapy for the prevention of relapsing and recurrent peritonitis. Methods From February 2016 to November 2018 we recruited 254 PD patients who fulfilled the diagnostic criteria for PD peritonitis. They were randomized to a standard group, with the duration of intraperitoneal (IP) antibiotic treatment following the International Society for Peritoneal Dialysis (ISPD) guideline according to the causative microorganisms, and an extended group, with 1 extra week of IP antibiotics. The primary endpoint was relapsing, recurrent or repeat peritonitis episodes within 6 months. Results The primary endpoint developed in 36 and 29 patients of the extended and standard groups, respectively (28.3% versus 22.8%; P = 0.34). The rate of complete cure, without relapsing, recurrent or repeat peritonitis within 6 months, was 63.8 and 69.3% for the extended and standard groups, respectively (P = 0.35). Repeat peritonitis episodes were more common in the extended than the standard group (15.0% versus 5.5%; P = 0.013). Conclusions In patients with PD-related peritonitis, extending the antibiotic therapy for 1 extra week beyond the ISPD protocol should not be recommended. Extending the treatment does not reduce the risk of relapsing or recurrent peritonitis episodes but rather is associated with a higher risk of repeat peritonitis episodes. [ABSTRACT FROM AUTHOR]

Although diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease worldwide, the pathogenic mechanisms are poorly understood. There is increasing evidence that mitochondrial dysfunction contributes to the development and progression of DKD. Because the kidney is the organ with the second highest oxygen consumption in our body, it is distinctly sensitive to mitochondrial dysfunction. Mitochondrial dysfunction contributes to the progression of chronic kidney disease irrespective of underlying cause. More importantly, high plasma glucose directly damages renal tubular cells, resulting in a wide range of metabolic and cellular dysfunction. Overproduction of reactive oxygen species (ROS), activation of apoptotic pathway, and defective mitophagy are interlinked mechanisms that play pivotal roles in the progression of DKD. Although renal tubular cells have the highest mitochondrial content, podocytes, mesangial cells, and glomerular endothelial cells may all be affected by diabetes-induced mitochondrial injury. Urinary mitochondrial DNA (mtDNA) is readily detectable and may serve as a marker of mitochondrial damage in DKD. Unfortunately, pharmacologic modulation of mitochondrial dysfunction for the treatment of DKD is still in its infancy. Nonetheless, understanding the pathobiology of mitochondrial dysfunction in DKD would facilitate the development of novel therapeutic strategies. • Mitochondrial dysfunction is important for the development of diabetic kidney disease. • Reactive oxygen species, activation of apoptosis, and defective mitophagy contribute to the progression of DKD. • Urinary mitochondrial DNA may be a biomarker for DKD. [ABSTRACT FROM AUTHOR]

The article presents a clinical practice guideline for peritoneal dialysis (PD) in renal service in Hong Kong, China. It highlights the important role played by PD which requires doctors, nurses and paramedical staff to work together as a team to provide continuous ambulatory procedure and machine-assisted automated PD. It also outlines the structure requirements in PD and the recommendations that are based on expert opinion and limited observational data.

Background/Aims: Enterococcal peritonitis in peritoneal dialysis (PD) patients is associated with a high complication rate. The optimal treatment regimen of PD-related enterococcal peritonitis is controversial. The latest international guideline recommends intra-peritoneal (IP) vancomycin. Although ampicillin is often effective for systemic enterococcal infections, they have little in vitro activity when added to common PD solutions. Since oral amoxicillin achieves therapeutic drug level in the peritoneal cavity, we explore the efficacy of oral amoxicillin for enterococcal peritonitis. Methods: We studied 105 episodes of enterococcal peritonitis over 20 years in our unit; 43 (41.0%) were treated with oral amoxicillin, and 62 (59.0%) with IP vancomycin. Their clinical outcome was reviewed. Result: The overall primary response rate to oral amoxicillin and IP vancomycin was 76.4% and 85.5%, respectively (p = 0.3). The complete cure rate of oral amoxicillin and IP vancomycin was 55.8% and 54.8%, respectively (p = 0.8). When the 5 episodes of ampicillin-resistant Enterococcus episodes were excluded, the primary response rate and complete cure rate of oral amoxicillin were 86.8% and 63.2%, respectively. Conclusion: Oral amoxicillin has an excellent primary response rate and complete cure rate for PD-related peritonitis episodes caused by Enterococcus species, indicating that oral amoxicillin is a valid and convenient therapeutic option for enterococcal peritonitis episodes. [ABSTRACT FROM AUTHOR]

ABSTRACT In the past 20 years, extraction and quantification of mRNA from urinary sediment has emerged as a novel laboratory technique. The potential application of urinary mRNA quantification to the clinical care of patients with SLE has become an active field of research. However, published studies in this area are limited to small-scale ones. mRNA levels of several of cytokine and transcript factor genes have been found to have the potential for the diagnosis or monitoring of disease activity in patients with lupus nephritis. Our previous studies showed that a high urinary mRNA level of T-bet, the key transcription factor of type 1 T helper cells (Th1), was an independent predictor of lupus flare and probably reflects an intrinsic characteristic of patients with predisposition to Th1 activation. Other studies suggest that monitoring of monocyte chemoattractant protein-1(MCP-1), interleukin (IL)-17, GATA-3 (the key transcription factor of type 2 T helper cells) and forkhead box P3 (FOXP3, the key transcription factor of regulatory T cells) mRNA level in urinary sediment may provide an early clue for detecting disease flare in lupus patients. As a simple and non-invasive method, urinary mRNA level deserves further studies to validate its role in risk stratification and monitoring of patients with lupus nephritis. [ABSTRACT FROM AUTHOR]

Background The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain. Methods We studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients. Results Baseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated with dialysate-to-plasma creatinine concentration at 4 h (D/P4) at baseline (r = 0.377, p = 0.001 and r = 0.237, p = 0.037, respectively) and after one year of PD (r = 0.362, p = 0.014 and r = 0.402, p = 0.007). The change in PD effluent − 21 and miR-589 levels over one year correlated with the corresponding change in D/P4 (r = 0.470, p = 0.001 and r = 0.479, p = 0.002). The number of peritonitis episodes during follow up significantly correlated with the change in PD effluent miR-21 (r = 0.387, p = 0.009) and miR-589 (r = 0.336, p = 0.027) levels. There was no significant correlation between PD effluent miRNA level and ultrafiltration volume. Conclusion Amongst the 10 miRNA targets tested, miR-21 and miR-589 showed consistently significant relation with peritoneal transport. Further studies are needed to delineate their mechanisms of regulating peritoneal transport. [ABSTRACT FROM AUTHOR]

Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count. [ABSTRACT FROM AUTHOR]

Background/Aims: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that circulating mitochondrial DNA, which has a similar structure with bacterial DNA, correlates with systemic inflammatory state and predicts cardiovascular event in new PD patients. Methods: We measured plasma mitochondrial DNA level by quantitative polymerase chain reaction (PCR) in 197 new PD patients and 150 patients with chronic kidney disease. PD patients were followed for 24 months for the development of cardiovascular event, hospitalization, and patient survival. Results: There was a stepwise increase in plasma mitochondrial DNA level with worsening renal function. The average plasma mitochondrial DNA level was 18.0 ± 1.2 PCR cycles. Plasma mitochondrial DNA level correlated with serum CRP level (r = -0.538, p < 0.0001). At 24 months, the event-free survival was 67.4%, 66.4%, 63.4% and 44.2% for plasma mitochondrial DNA level quartiles I, II, III and IV, respectively (p = 0.049). After adjusting for confounders, plasma mitochondrial DNA level, malnutrition-inflammation score, and baseline arterial pulse wave velocity were independent predictors of composite cardiovascular end-point; each doubling in plasma mitochondrial DNA level confers 16.0% (95% confidence interval, 2.5 - 31.3%, p = 0.001) excess in risk. Plasma mitochondrial DNA also correlated with the number of hospital admission (r = -0.218, p = 0.002) and duration of hospitalization for cardiovascular reasons (r = -0.232, p = 0.001). Conclusion: Plasma mitochondrial DNA level significantly correlates with systemic inflammatory state, and is a strong predictor of cardiovascular event as well as the need of hospitalization in new PD patients. [ABSTRACT FROM AUTHOR]

The author reflects on the evolving concept of peritoneal dialysis (PD) which is commonly practiced as a mode of long-term renal replacement therapy (RRT). The author discusses the adequacy of PD dosage, the treatment effectiveness, and the use of PD as a critical component of dialysis for end stage renal disease (ESRD) patients.

Acute kidney injury is a common condition in hospitalized patients and a strong predictor of short‐term morbidity and mortality. In this article, local epidemiological data on the prevalence and outcome of acute kidney injury amongst hospitalized patient in a tertiary referral center were discussed. The latest practice guidelines endorsed by the Hong Kong College of Physicians will be discussed, with emphasis on local practical issues and problems of guideline implementation. Summary at a Glance: We review the upcoming Hong Kong College of Physicians guideline on acute kidney injury. The global epidemiology of AKI is also discussed.. [ABSTRACT FROM AUTHOR]

Background: Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied. Methods: We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV. Result: After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001). Conclusion: Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Circulating bacterial DNA fragment is related to systemic inflammatory state in peritoneal dialysis (PD) patients. We hypothesize that plasma bacterial DNA level predicts cardiovascular events in new PD patients. Methods: We measured plasma bacterial DNA level in 191 new PD patients, who were then followed for at least a year for the development of cardiovascular event, hospitalization, and patient survival. Results: The average age was 59.3 ± 11.8 years; plasma bacterial DNA level 34.9 ± 1.5 cycles; average follow up 23.2 ± 9.7 months. At 24 months, the event-free survival was 86.1%, 69.8%, 55.4% and 30.8% for plasma bacterial DNA level quartiles I, II, III and IV, respectively (p < 0.0001). After adjusting for confounders, plasma bacterial DNA level, baseline residual renal function and malnutrition-inflammation score were independent predictors of composite cardiovascular end-point; each doubling in plasma bacterial DNA level confers a 26.9% (95% confidence interval, 13.0 – 42.5%) excess in risk. Plasma bacterial DNA also correlated with the number of hospital admission (r = -0.379, p < 0.0001) and duration of hospitalization for cardiovascular reasons (r = -0.386, p < 0.0001). Plasma bacterial DNA level did not correlate with baseline arterial pulse wave velocity (PWV), but with the change in carotid-radial PWV in one year (r = -0.238, p = 0.005). Conclusions: Circulating bacterial DNA fragment level is a strong predictor of cardiovascular event, need of hospitalization, as well as the progressive change in arterial stiffness in new PD patients. [ABSTRACT FROM AUTHOR]

Background: Heat shock proteins (HSPs) are expressed by cells in response to various environmental stresses. A single-nucleotide polymorphism A+1267G of the HSPA1B gene affects the expression of HSP70-2, with the A allele being protective against inflammatory conditions. We investigated the relation between the HSP A+1267G polymorphism and the clinical outcomes of Chinese peritoneal dialysis (PD) patients. Methods: We studied 347 new PD cases (181 males, age 56.6 ± 13.7 years). Genotyping was done by standard methods. Patients were followed for 40.5 ± 20.7 months for survival analysis. Results: For the entire cohort, there was no difference in the 5-year survival between genotype groups. However, there was a significant interaction between HSP polymorphism and diabetic status on the cardiovascular event-free survival. In patients without pre-existing diabetes, 5-year cardiovascular event-free survival of the GG/AG genotype group was significantly better than that of the AA genotype group (57.2 vs. 32.1%, p = 0.011). Conclusion: The G allele of the HSP70-2 A+1267G polymorphism confers survival advantages in non-diabetic PD patients. The role of HSP in the pathogenesis of cardiovascular disease in renal failure patients needs further investigation. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background The clinical benefits of using icodextrin during acute peritonitis in peritoneal dialysis are uncertain. On the premise that high glucose concentration might jeopardize the peritoneal defense during peritonitis, icodextrin administration during acute peritonitis could have the potential to improve the peritonitis outcome whilst improving ultrafiltration. Methods We conducted a single-center, open-label, randomized controlled trial in which 53 adult continuous ambulatory peritoneal dialysis patients underwent randomization to receive either icodextrin or original glucose-based dialysis solution. The primary outcome measure was the peritoneal dialyzate white cell count on Day 3. Secondary outcome measures comprised the need of additional hypertonic exchanges, fluid control as denoted by changes in body weight, and the clinical outcome of peritonitis including 30-day and 120-day all-cause mortality. Results Between icodextrin and control treatment groups, there were no statistically significant differences in the peritoneal dialyzate white cell count on day (1829 versus 987/mm3, P = 0.13). There was neither improvement in primary cure rate (31.8 versus 32.3%, P = 1.00), nor was there any change in 120-day mortality after icodextrin use (13.6 versus 12.9%, P = 1.00). However, requirement of hypertonic dialysis exchange was much more frequent in the control group than in those randomized to icodextrin (35.5 versus 0%, P = 0.001). Body weight did not change significantly in the icodextrin group, but body weight in the control group increased from 63.3 ± 14.5 kg at baseline to 64.2 ± 14.2 kg at Day 5 (P = 0.0002) and 65.2 ± 14.1 kg at Day 10 (P < 0.0001). Conclusions As compared with glucose-based peritoneal dialysis solution, use of icodextrin achieved better ultrafiltration and fluid control during acute peritonitis complicating continuous ambulatory peritoneal dialysis, although we found no evidence of a worthwhile clinical benefit on peritonitis resolution. (ClinicalTrial.gov number, NCT0104446 [ClinicalTrial.gov].). [ABSTRACT FROM AUTHOR]

Aim Although calcimimetics cinacalcet can reduce parathyroid hormone level and control secondary hyperparathyroidism in end-stage renal disease patients, risk of vascular calcification remains high. Whether cinacalcet can further reduce vascular damage or arterial stiffness is unknown. Methods We studied the effect of cinacalcet in 33 peritoneal dialysis patients with inadequately controlled secondary hyperparathyroidism despite standard treatment. The primary outcome was the aortic pulse wave velocity at 26 and 52 months after cinacalcet treatment. The pulse wave velocity was compared with that of a matched control cohort of 37 peritoneal dialysis patients with secondary hyperparathyroidism. Results Thirty-three patients completed the cinacalcet treatment, after median dialysis duration of 1.0 year. Significant improvement of parathyroid hormone level was achieved after 52 weeks, from 87.5 ± 28.7 pmol/L to 34.5 ± 45.5 pmol/L ( P < 0.0001). Serial carotid-femoral pulse wave velocity did not differ between cinacalcet treatment group and control group (general linear model with repeated measures, P = 0.19). Among patients receiving cinacalcet, the average carotid-femoral pulse wave velocity increased from 10.46 ± 2.12 m/s at baseline to 11.41 ± 2.79 m/s at 52 weeks ( P = 0.001). The change in carotid-femoral pulse wave velocity over 1 year had no significant correlation with the final parathyroid hormone level or change in parathyroid hormone level. Conclusions Among prevalent patients receiving peritoneal dialysis and with hyperparathyroidism, a reduction of 60.6% parathyroid hormone level after cinacalcet treatment for one year did not reduce the carotid-femoral pulse wave velocity. [ABSTRACT FROM AUTHOR]

Background: Laboratory research and previous study suggest that aliskiren, a direct renin inhibitor, has anti-proteinuric effects. We conducted a randomized crossover study to evaluate the anti-proteinuric effect of aliskiren in patients with immunoglobulin A (IgA) nephropathy. Methods: We studied 22 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to either oral aliskiren 300 mg/day or placebo for 16 weeks and then crossed over to the other treatment arm after a washout period. Proteinuria, estimated glomerular filtration rate (eGFR), blood pressure, and serum potassium were monitored. Results: After aliskiren treatment, there was a significant reduction in proteinuria in 4 weeks (1.76±0.95 to 1.03±0.69 g:g-Cr, p<0.0001), which remained at a low level throughout the treatment period. There was a significant difference in proteinuria between the aliskiren and placebo groups from 4 to 16 weeks after treatment (p<0.01 for all comparisons). After aliskiren treatment, there were modest but statistically significant reductions in eGFR (57.2±29.1 to 54.8±29.3 ml/min/1.73 m2, p = 0.013) and diastolic blood pressure (72.6±12.3 to 66.2±11.2 mmHg, p<0.0001). None of the patient developed severe hyperkalemia (serum potassium ≥6.0 mmol/l) during the study period. Conclusions: Aliskiren has anti-proteinuric effect in patients with IgA nephropathy and persistent proteinuria despite ACE inhibitor or ARB. Further studies are needed to confirm the renal protecting effect of direct renin inhibition in chronic proteinuric kidney diseases. Trial Registration: ClinicalTrials.gov NCT00870493 [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Two decades ago, the common co‐existence of malnutrition and systemic inflammation PD patients with atherosclerosis and CVD led to the proposed terminology of 'malnutrition‐inflammation‐atherosclerosis (MIA) syndrome'. Although the importance of malnutrition is well accepted, frailty represents a more comprehensive assessment of the physical and functional capability of the patient and encompasses the contributions of sarcopenia (a key component of malnutrition), obesity, cardiopulmonary as well as neuropsychiatric impairment. In recent years, it is also increasingly recognized that fluid overload is not only the consequence but also play an important role in the pathogenesis of CVD. Moreover, fluid overload is closely linked with the systemic inflammatory status, presumably by gut oedema, gastrointestinal epithelial barrier dysfunction and leakage of bacterial fragments to the systemic circulation. There are now a wealth of published evidence to show intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on PD, a phenomenon that we propose the term 'FIFA complex'. In this system, frailty and atherosclerotic disease may be regarded as two patient‐oriented outcomes, while inflammation and fluid overload are two inter‐connected pathogenic processes. However, there remain limited data on how the treatment of one component affect the others. It is also important to define how treatment of fluid overload affect the systemic inflammatory status and to develop effective anti‐inflammatory strategies that could alleviate atherosclerotic disease and frailty. Summary at a Glance: There are intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on peritoneal dialysis (PD).We propose the term 'FIFA complex', with frailty and atherosclerotic disease as two patient‐oriented outcomes, while inflammation and fluid overload as two inter‐connected pathogenic processes. [ABSTRACT FROM AUTHOR]

Background: Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). We explored the possibility of using urinary miRNA as non-invasive biomarkers for CKD. Methods: We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. Patients were followed for 16.2 ± 15.5 months. Results: Patients with diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with IgA nephropathy had higher urinary miR-17 expression, than other diagnosis groups. Baseline proteinuria had significant inverse correlation with urinary expression of miR-15, miR-192, and miR-216a; baseline renal function correlated with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of renal function decline correlated with urinary expression of miR-21 (r=0.301, p=0.026) and miR-216a (r=0.515, p < 0.0001). Patients with a high urinary expression of miR-21 and miR-216a had better dialysis-free survival than those with low expression (log rank test, p=0.005 and p=0.003, respectively). Conclusions: Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure. Our results suggest that urinary miRNA profiling has the potential of further development as biomarkers of CKD. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular and renal diseases. In chronic kidney disease (CKD), blockade of RAS by angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) has been shown to reduce proteinuria and retard the progression of renal function deterioration. However, aldosterone, another key hormone of the RAS, is not directly targeted by ACEI or ARB. Hyperaldosteronism, apart from promoting sodium and fluid retention, causes inflammation and fibrosis in the heart and kidney. Studies have shown that although plasma aldosterone level shows an initial decrease following ACEI or ARB treatment, it returns to pretreatment level or even increases paradoxically after prolonged treatment. This 'aldosterone breakthrough' forms the basis of adding mineralocorticoid receptor (MR) antagonist on top of ACEI or ARB for renal protection. New insights into the pathophysiological role of aldosterone in CKD further expands its potential indications, and there was a growing body of evidence in the past 10 years, which showed a substantial antiproteinuric effect and possibly a considerable renoprotective effect of MR antagonist. Since aldosterone does not act on the efferent glomerular arteriole and has no effect on intraglomerular hemodynamics, the very fact that MR antagonist ameliorates proteinuria sheds light on the physiology of glomerular permeability barrier. This review summarizes the data regarding the theoretical benefit as well as clinical use of MR antagonist in renal diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can counteract inflammation and atherosclerosis, both common causes of morbidity in peritoneal dialysis (PD) patients. We examined the relation between serum soluble TRAIL (sTRAIL) levels and the outcome of Chinese PD patients. Methods: We studied 116 new PD patients (67 males, age 56.7 ± 13.4 years). Baseline serum sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest). All patients were followed for 20.9 ± 7.0 months. Results: Patient survival was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months ( P = 0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was an independent predictor of patient survival after adjusting for confounding factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935-0.991, P = 0.010). Conclusion: A higher baseline serum sTRAIL level was associated with a better survival of PD patients. The detailed mechanism deserves further investigation. [ABSTRACT FROM AUTHOR]

Background: Myeloid-related protein 8/14 (MRP8/14) is released by cells of myeloid lineage upon inflammatory challenges. Experimental data suggested that MRP8/14 is important in the initiation and progression of inflammation and cardiovascular diseases. We examined the relation between serum MRP8/14 level and cardiovascular disease in Chinese peritoneal dialysis (PD) patients. Methods: We studied 102 new PD patients (58 males, mean age 57.3 ± 11.9 years). Baseline serum MRP8/14 was determined and grouped to quartiles for analysis. All patients were then followed for an average of 23.9 ± 6.9 months. Results: There was a trend of lower 3-year cardiovascular event-free survival for patient quartiles with high serum MRP8/14 levels (log-rank test, p = 0.064). The 3-year actuarial survival was significantly lower for quartile groups with higher MRP8/14 levels (96.0, 94.7, 72.9, and 62.5% for quartiles 1–4, respectively, p = 0.003). Cox regression analysis showed that serum MRP8/14 level and Kt/V were independent predictors of actuarial survival; in this model, every 1 µg/ml increase in serum MRP8/14 level confers a 25.1% increase in risk of death (95% confidence interval, 1.3–54.4%, p = 0.037). There was no significant difference in technique survival between the MRP8/14 quartile groups. Conclusion: A high baseline serum MRP8/14 level was associated with a lower actuarial survival in Chinese PD patients. The pathogenic role of MRP8/14 in the cardiovascular disease of PD patients needs further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Systemic lupus erythematosus (SLE) is characterized by disease flares and remission. We hypothesize that in clinically quiescent SLE patients, the mRNA level of target genes in the urinary sediment is an early indicator of disease flare. Methods: From a cohort of 134 adult SLE patients prospectively followed for 56weeks, we identified 19 patients with a single disease flare. The mRNA level of eight pre-defined target genes in their urinary sediment before disease flare was compared to 19 matched controls with no disease flare during the same period. Results: Urinary mRNA level remained static in the control group during the study period. Before disease flare, there was a significant increase in the mRNA level of monocyte chemotactic protein (MCP)-1and forkhead box P3 (FOXP3), and decrease in interleukin (IL)-17 and GATA-3, in the urinary sediment. The mRNA level of FOXP3 in urinary sediment increases 8weeks prior to a flare, which precedes the corresponding change in serum complement and anti-DNA antibody titer, while that of MCP-1, IL-17, and GATA3 began to change 4weeks prior to a flare. The same pattern of change in urinary mRNA level was observed in patients with mild-to-moderate or severe flare, and those with renal or non-renal flare. The SLE Disease Activity Index (SLEDAI) score at the time of flare significantly correlated with the change in urinary level of IL-17 (r=−0.462, p=0.046) and GATA-3 (r=−0.455, p=0.05), but not MCP-1 or FOXP3, prior to the flare. Conclusion: Monitoring of MCP-1, IL-17, GATA-3 and FOXP3 mRNA level in urinary sediment may provide an early clue for detecting disease flare in SLE patients. [Copyright &y& Elsevier]

ABSTRACT: Aim: Long term dialysis is life-saving for patients with end stage renal disease (ESRD). However, in ESRD patients with multiple comorbid conditions, dialysis may actually be futile, and conservative management is advisable. We studied the life expectancy of Chinese ESRD patients treated conservatively. Methods: We reviewed 63 consecutive ESRD patients who were treated conservatively in our centre. Duration of survival was calculated from the date of initial assessment for dialysis, as well as the expected date of needing dialysis based on previous trend of renal function decline. Results: At the end of the observation period, 55 patients died. Twelve patients died before the expected date of needing dialysis because of unrelated reasons, while 36 deaths were directly attributed to uraemia. The median overall survival after initial assessment for dialysis was 41.3 months (95% confidence interval (CI), 33.2 to 49.4 months). The median overall survival was 6.58 months (inter-quartile range, 0.92 to 9.33 months) from the theoretical date of needing dialysis. The survival from the theoretical date of needing dialysis did not correlate with patient age, sex, diabetic status, or baseline renal function. Conclusions: In Chinese ESRD patients treated conservatively, the median survival is around 6 months after the theoretical date of needing dialysis. Our result provides an important piece of information for the decision of dialysis and patient counselling. [ABSTRACT FROM AUTHOR]

Background. Although originally described in dialysis patients treated with recombinant human erythropoietin (rHuEPO), haemoglobin variability has recently also been noted to be increased in patients who have chronic kidney disease (CKD) without dialysis. In our country, pre-dialysis CKD patients generally would not receive rHuEPO treatment. We studied the degree of haemoglobin variability and its prognostic implication in this group of patients.Methods. We reviewed 332 patients with Stages 3 through 5 CKD; patients with overt iron deficiency or requiring blood transfusion were excluded. Patients were followed for up to 5 years. End points include all-cause mortality, progression to dialysis-dependent renal failure and hospitalization.Results. The average haemoglobin level was 11.4 ± 2.8 g/dL; intra-individual SD of haemoglobin was 0.76 ± 0.61 g/dL. Haemoglobin variability, as represented by intra-individual SD of haemoglobin, was significantly associated with the average haemoglobin level (r = −0.130, P = 0.017), Charlson's comorbidity score (r = 0.113, P = 0.040) and proteinuria (r = 0.151, P = 0.044). Univariate analysis showed that patients with high haemoglobin variability had a significantly higher all-cause mortality (log-rank test, P = 0.030) and risk of progression to end-stage renal disease (log-rank test, P = 0.021) and was associated with the adjusted duration of hospitalization (r = 0.134, P = 0.015). However, all associations become statistically insignificant after multivariate analysis to control for confounding factors.Conclusions. Fluctuation of haemoglobin level is common and substantial in Chinese pre-dialysis CKD patients. Our results suggests that the observed clinical effect of haemoglobin variability in this patient population is an epiphenomenon secondary to the association between haemoglobin variability and other clinical factors. [ABSTRACT FROM PUBLISHER]

Aim: Interleukin-18 (IL-18) is a pro-inflammatory cytokine and possibly plays an important role in the pathogenesis of cardiovascular disease. The relationship between two IL-18 gene polymorphisms, namely C-607A and G-137C, and cardiovascular disease in patients with diabetic nephropathy was examined. Methods: Two hundred and twenty patients (91 male) with diabetic nephropathy were studied. The IL-18 promoter genotypes were determined. All patients were then prospectively followed for the cardiovascular events. Cardiovascular mortality and all-cause mortality were also compared. Results: Mean age was 64.3 ± 10.6 years; average follow up was 73.9 ± 33.6 months. The frequencies of CC, CA and AA genotypes of the C-607A polymorphism were 25.5%, 48.2% and 26.8%, respectively; GG, GC and CC genotypes of the G-137C polymorphism were 71.8%, 25.0% and 3.2%, respectively. Neither of the polymorphisms were associated with the development of primary cardiovascular end-point. Cardiovascular survival was 84.8% and 70.6% at 60 months for GG and GC/CC genotypes of the G-137C polymorphism, respectively ( P = 0.027); the corresponding actuarial survival was 69.0% and 54.8%, respectively ( P = 0.053). However, the G-137C genotype was not an independent predictor of cardiovascular or actuarial survival after adjusting for confounders by multivariate analysis with the Cox model. The C-607A polymorphism had no significant effect on cardiovascular or actuarial survival. Conclusion: The G-137C polymorphism of the IL-18 promoter is associated with the cardiovascular mortality, and a trend of association with all-cause mortality, in patients with diabetic nephropathy. The association, however, becomes insignificant after adjusting for confounding factors. Further studies are needed to test other genetic determinants of the association between systemic inflammation and cardiovascular disease in renal failure patients. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is the most common cause of chronic renal failure worldwide. Only a few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with renal failure. Among them is thiazolidinedione, which is the agonist of peroxisome proliferator-activated receptor (PPAR)-γ. PPAR-γ receptors are expressed in many tissues including the kidney. Recently, beneficial effects of PPAR-γ agonists on several aspects related to renal function have been reported. These drugs have been shown to have favourable haemodynamic and anti-inflammatory effects on the kidneys. On the other hand, there is a rising concern on the association between thiazolidinedione treatment and the risk of cardiovascular disease. In the present paper, we review the recent studies that evaluated these potential effects of thiazolidinedione in patients with kidney diseases. [ABSTRACT FROM AUTHOR]

Background: Percutaneous transluminal angioplasty has now been increasingly accepted as a primary treatment option for transplant renal artery stenosis. Methods: This single-centre study evaluated the treatment effect of percutaneous transluminal angioplasty as primary intervention among 18 consecutive patients with angiographically demonstrated transplant renal artery stenosis. Results: Patients (14 men and 4 women, mean age 49 ± 9 years) were followed up for a mean duration of 21.6 months after procedure. Highly significant improvement was noted in the mean arterial pressure (from baseline 105.9 ± 10.4 mmHg to 98.6 ± 10.0 mmHg, P < 0.001), systolic blood pressure (148.5 mmHg to 137.1 mmHg, P = 0.002) and diastolic blood pressure (85.3 mmHg to 79.4 mmHg, P = 0.002). Estimated glomerular filtration rate before and 6 months after intervention was 41.4 ± 16.8 mL/min per 1.73 m2 and 42.0 ± 16.2 mL/min per 1.73 m2, respectively ( P = 0.82). Conclusion: These findings show that percutaneous transluminal angioplasty in transplant renal artery stenosis appears to have a significant beneficial effect on hypertension but less impact on the improvement in renal function. [ABSTRACT FROM AUTHOR]

Background: There is substantial evidence that renal transplant recipients with obesity or body mass index >30 kg/m2 have increased risk of graft loss. However, few data exist for Asian population; clinicians have to rely upon indirect evidence by extrapolating the results from Caucasians to Asian recipients. Study: Using data from a study population of 150 consecutive cadaveric or living related Chinese renal transplant recipients at our center between 1985 and 2002, we examined the effect of baseline body mass index cut-off 25 kg/m2 on the transplant outcomes using Kaplan–Meier analysis and Cox proportional hazards analysis. Primary study end point was overall graft survival. Results: The mean body mass index was 22.9 ± 4.0 kg/m2. Thirty-seven (25%) patients were classified as overweight and 113 patients as non-overweight, using the cut-off of 25 kg/m2. After median follow up period of nine yr, 15 graft losses (41%) occurred in the overweight group, as compared with 14 graft losses (12%) in the non-overweight group. Kaplan–Meier estimates of cumulative graft survival at five yr were significantly worse for the overweight group than non-overweight group (83.6% versus 92.7%, p = 0.0041). By multivariate Cox proportional hazards analysis, baseline body mass index ≥25 kg/m2 conferred a significantly higher risk of graft loss (with relative risk of 4.78, 95% CI = 1.52–15.2) and doubling of serum creatinine (relative risk 3.19, 95% CI = 1.22–8.40). Death with a functioning graft occurred in 11% of overweight recipients, compared with 3% among the non-overweight group (p = 0.041). Conclusion: Our results draw attention to a recipient body mass index cut-off value ≥25 kg/m2, which might confer an increased risk of graft loss in Asian kidney transplant populations. [ABSTRACT FROM AUTHOR]

Background . Vascular endothelial growth factor (VEGF) plays a pivotal role in the capillary endothelial cell growth and proliferation and has known effects on glomerular microvascular permeability. Because certain VEGF polymorphisms are correlated with alterations in VEGF expression, we hypothesized that VEGF genetic polymorphisms may affect the renal survival and progression of primary IgA nephropathy. Methods . The study population consisted of 195 biopsy-proven IgA nephropathy patients at our center between 1984 and 2004. VEGF genotype polymorphism at -2578 positions was determined from peripheral blood leukocytes DNA using polymerase chain reaction methodologies. The primary end point was kidney survival as measured by the time interval from renal biopsy to end-stage renal disease or the requirement of renal replacement therapy. Results . In total, we studied 119 women (61%) and 76 men (39%), with a mean age of 35 ± 10 yr at the time of renal biopsy. Observed genotype frequency was 55.6%, 38.8%, and 5.1% for CC, CA, and AA genotypes respectively. Baseline characteristics did not differ significantly between three genotype groups for patient age, sex, prevalence of hypertension, degree of proteinuria, initial serum creatinine concentration, and the histological grading. After a median follow-up period of 11 yr, doubling of the baseline serum creatinine occurred in 107 of them; 99 patients reached end-stage renal disease requiring renal replacement therapy with a median renal survival of 88 months. The kidney survival in the CC genotype subgroup was similar to that of the CA/AA genotype subgroup during the first 2 yr but became worse than the latter thereafter (log-rank test P = 0.023). The kidney survival rates at the end of 6 yr were 76.8% in the CA genotype, 67.0% in the CC, and 50.0% in the AA genotype groups. Unadjusted hazard ratio of developing end-stage renal disease was 2.65 (95% CI, 1.16 to 6.06) for the CC group as compared to the CA/AA group. The influence of VEGF genotype upon renal survival, however, was not significant after multivariate Cox regression analysis. Conclusion . Our preliminary results raise the concern that the CC genotype of the VEGF promoter at -2578 position might be associated with increased risk of renal progression in patients with IgA nephropathy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Podocyte slit diaphragm plays an important role in the control of glomerular permeability. We hypothesize that studying the gene expression profile of podocyte in urinary sediment may provide diagnostic and prognostic information on acquired proteinuric diseases. Methods: We studied 28 patients who required kidney biopsy for acquired proteinuric diseases (diabetic glomerulosclerosis, 9 cases; IgA nephropathy, 10 cases; minimal change disease, 5 cases; membranous nephropathy, 5 cases). We also studied 10 cases of diabetic microalbuminuria and 9 healthy controls. The mRNA expressions of nephrin (NephRNA), podocin (PodRNA) and synaptopodin (SynRNA) in urinary sediment were measured by real time quantitative PCR. After recruitment, all patients were followed for at least 12 months. Results: There were significant differences in the NephRNA and PodRNA in the urinary sediment between diagnosis groups (p <0.005). On the other hand, SynRNA was only marginally significant between diagnosis groups (p <0.05). Although statistically significant, the degree of proteinuria had only modest correlations with the urinary expression of nephrin. After a median follow up for 23 months, there was a significant correlation between the rate of decline in renal function and NephRNA (r =0.559, p =0.001) and PodRNA (r =0.530, p =0.002), but not SynRNA (r =0.054, p =NS). The correlation remained statistically significant after multivariate analysis to adjust for the degree of proteinuria and initial renal function. Conclusions: Urinary mRNA expression of podocyte markers, such as nephrin and podocin, are significantly different between proteinuric disease categories. Further, NephRNA and PodRNA correlated with the rate of decline in renal function. Our results suggest that urinary podocyte gene expression may be a useful non-invasive tool which provides additional information for the management of proteinuric diseases. [Copyright &y& Elsevier]

Toxic nephropathy is an important cause of reversible renal injury. This article focuses on the nephrotoxicity of several new therapeutic compounds. Selective cyclooxygenase-2 inhibitor is associated with sodium retention, hypertension, ankle edema, and acute renal failure. The incidence of renal complication is similar to conventional nonsteroidal anti-inflammatory drugs. Bisphosphonates, especially when used in high dose for prolonged duration, can cause toxic acute tubular necrosis and renal failure. Pamidronate is also associated with a specific form of collapsing focal segmental glomerulosclerosis similar to one found in patients with human immunodeficiency virus (HIV) infection. Acyclic nucleoside phosphonate, a new group of antiviral agents, can cause Fanconi-like syndrome and progressive renal impairment. On the other hand, indinavir, a potent protease inhibitor for the treatment of HIV infection, can cause crystalluria, renal stone, acute tubular obstruction and chronic interstitial nephritis. Intravenous immune globulin and hydroxyethyl starch, a new plasma expander, are associated with acute renal failure with characteristic renal histology known as osmotic nephrosis. In short, physicians should be cautious about possible renal toxicity during the use of any new therapeutic agents. [ABSTRACT FROM AUTHOR]

Neurological complications of antibiotics are relatively common in renal failure. Central nervous system neurotoxicity due to penicillin and β-lactam antibiotics is best documented with fewer accounts of ototoxicity, peripheral nerve toxicity and neuromuscular blockade. In the context of risk stratification, the goal of this review is to explore the mosaic of factors in renal impairment that may contribute to susceptibility to antibiotic neurotoxicity. Improved knowledge of the pathogenesis of these formidable adverse events among the renal failure subjects should help prevent antibiotic neurotoxicity in the future. [Copyright &y& Elsevier]

Urinalysis has been used extensively in clinical practice to aid in the diagnosis of various renal and urologic diseases. The innovation of urinalysis is marching on right along with the rapid developments in biotechnology and astride from the solo urine cytology to sophisticated studies of individual component in the urinary sediment. In this review article, we focus on the use of flow cytometry and other technical advances in the examination of urinary sediment, the detection of urologic malignancies by the presence of microsatellite alteration in the urinary sediment, as well as the quantification of cytokine messenger RNA (mRNA) expression in urinary sediment by reverse transcription and real-time quantitative polymerase chain reaction (RT-QPCR). Notably, the study of cytokine mRNA expression in urinary sediment by RT-QPCR has recently been reported to provide important diagnostic information in kidney allograft recipients and patients with lupus nephritis. This simple and non-invasive method requires further study to determine its role in risk stratification and monitoring of therapeutic response in patients with other kidney diseases. [Copyright &y& Elsevier]

Hydrothorax as a result of pleuroperitoneal communication occurs in approximately 2% of continuous ambulatory peritoneal dialysis (CAPD) patients. Although our understanding of its mechanisms is incomplete, it is apparent that the key to successful therapy is obliteration of a transdiaphragmatic route of dialysate leakage (pleuroperitoneal communication), possibly coupled with reduction of intra-abdominal pressure. This review corroborated the findings from 10 major population-based case series in which 60 of the 104 cases (58%) were able to resume long-term peritoneal dialysis (PD). Temporary interruption of PD alone was successful in half of them. As compared to this conservative approach, as well as chemical pleurodesis via intercostal chest drain, video-assisted thoracoscopic intervention (including direct pleurodesis and diaphragmatic repair) has shown a promising role. Efficacy of thoracoscopic treatment has been confirmed by several case series from various centers and the demonstration of a success rate in excess of 90%. With accumulating experience using the thoracoscopic technique, it remains to be seen whether this mode of treatment will obviate the traditional closed pleurodesis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We compared the Bergstrom's and Randerson's formula for PNA determination, and compared the normalization of PNA by ideal body weight (IBW) and standard body weight (SBW) as estimated by the Watson's formula. METHODS: We studied 208 Chinese PD patients. Two 24-h dialysate and urine collections were performed six months apart. Protein nitrogen appearance was determined by the Randerson's formula (PNA-Rand) and Bergstrom's formula (PNA-Berg), the latter used as the gold standard. PNA-Berg was normalized with IBW and SBW, denoted as NPNA-IBW and NPNA-Watson respectively. The change of PNA over six months, denoted as ΔPNA-Rand and ΔPNA-Berg, were calculated. The results were compared by the Bland and Altman's method. RESULTS: At zero month, the average PNA-Berg was 61.8 ± 14.8 g/day, and the average PNA-Rand was 58.1 ± 14.5 g/day. The value of PNA-Rand was consistently lower than the corresponding PNA-Berg. The bias of PNA-Rand was -3.7 g/day. The limits of agreement were -9.2 to +1.8 g/day. When NPNA-Watson was compared to NPNA-IBW, the bias of NPNA-Watson, using NPNA-IBW as gold standard, was 0.01 g/kg/day; the limits of agreement were -0.22 to +0.23 g/kg/day. The difference between NPNA-Watson and NPNA-IBW correlated with the body mass index (r = -0.820, p<0.001) and body weight (r = -0.834, r<0.001). After six month, there was a significant reduction in urine protein loss. However, total protein loss was only slightly reduced (7.3 ± 3.0 to 6.9 ± 2.8 g/day, p = 0.029). The correlation between ΔPNA-Berg and ΔPNA-Rand remained excellent (r = 0.983, p<0.001). The bias of ▵PNA-Rand was +0.3 g/day; the limits of agreement were -4.7 to +5.2 g/day. CONCLUSION: Ideal body weight that is validated for specific ethnic group, rather than the Watson's formula, should be used for normalization of PNA. Although the Randerson's formula under-estimates PNA when compared to the Bergstrom's formula, it is a reliable method... [ABSTRACT FROM AUTHOR]

: PurposeBecause polymicrobial peritonitis is believed to be caused by bowel perforation in peritoneal dialysis patients, surgical exploration is often recommended. However, there is recent evidence that antibiotic therapy may be a safe alternative.: MethodsWe studied 140 consecutive episodes of dialysis-related polymicrobial peritonitis from January 1995 to June 2001. All episodes were treated primarily with intraperitoneal antibiotics. When there was no response, the Tenckhoff catheter was removed, usually after about 10 days of treatment. Laparotomy was performed only when there was clinical suspicion of surgical pathology.: ResultsNinety patient-episodes (64%) responded to antibiotics alone by day 10; 56 patients (40%) had complete cure with no relapse in 4 months. Nine patients (6%) died within 2 days. Laparotomy was performed in 8 patients who did not respond by day 10, but only 3 had underlying surgical disease (strangulated hernia, ischemic colitis, and colonic cancer). In a multivariate logistic regression analysis, age and the presence of fungus, anaerobes, or Pseudomonas species in the dialysis fluid were independent predictors of poor primary response; and presence of fungus was the only independent predictor of failure to cure in 4 months.: ConclusionMost patients with dialysis-related polymicrobial peritonitis responded to antibiotic therapy, and surgical exploration was needed only in a few patients. A careful examination of isolated organisms may help in identifying patients who need Tenckhoff catheter removal or surgical intervention. [Copyright &y& Elsevier]

Metabolic complications are common with tacrolimus therapy. Recent evidence suggests that there is ethnical variability in the side-effect profile of tacrolimus. We performed an open-label study to examine the metabolic profile of tacrolimus-based immunosuppressive therapy in 10 consecutive adult Chinese patients after cadaveric renal transplantation. One case withdrew because of parvovirus infection. The mean age of the remaining nine cases was 33 ± 2.9 yr. Mean tacrolimus whole blood trough level at 0 and 12 months were 11.4 ± 1.8 and 7.0 ± 0.7 ng/mL, respectively. The dosage at corresponding time points were 0.31 ± 0.001 and 0.10 ± 0.003 mg/kg, respectively. We found no difference in lipid profile, blood pressure control, and most importantly, fasting glucose level, before and 1 yr after tacrolimus therapy. Standard 75-g oral glucose tolerance test and whole blood HbA1c level were normal in all patients. Our preliminary data suggest good short-term safety among Chinese renal transplantation recipients after tacrolimus-based immunosuppressants, with a very low incidence of hyperglycemia, hypertension and dyslipidemia. The long-term implications and the underlying explanation for this ethnical difference require further investigations. [ABSTRACT FROM AUTHOR]

We report a HBsAg-positive patient who developed hepatocellular carcinoma (HCC) 7 years after cadaveric kidney transplantation. The tumor was unresectable because of coexisting cirrhosis. Selective internal radiation (SIR) therapy, a novel therapy with the technique recently perfected, was used. Yttrium-90 microspheres were given via an angiographic catheter under fluoroscopy guidance. Serum alpha-fetal protein (AFP) was normalized within 2 wk. A follow-up abdominal CT scan revealed significant necrosis of the tumor and compensatory hypertrophy of non-diseased liver. The treatment was well tolerated except for transient liver function deterioration. The patient enjoyed 15 months of symptom-free survival before she died of liver failure. Practical aspects and potential applications of SIR therapy in this group of patients are discussed. [ABSTRACT FROM AUTHOR]

Clinical course of peritonitis due to Pseudomonas species complicating peritoneal dialysis: A review of 104 cases. Background. Peritonitis due to Pseudomonas species is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) patients. The clinical course of peritonitis due to Pseudomonas complicating CAPD remains unclear. Methods. All of the Pseudomonas species episodes of peritonitis in our dialysis unit were studied from 1995 to 1999. During this period, there were 859 episodes of peritonitis recorded, 113 of which were caused by the Pseudomonas species. Nine episodes were excluded because they were mixed growth. The remaining 104 episodes in 68 patients were reviewed. Results. The underlying renal diagnosis and prevalence of comorbid conditions of the 68 patients were similar to those found in our entire dialysis population. There was a history of antibiotic therapy within 30 days of the onset of peritonitis due to the Pseudomonas species in 69 episodes (66.3%). In 47 episodes (45.2%) there was a concomitant exit site infection. The overall primary response rate was 60.6% and the complete cure rate was 22.1%. The presence of exit site infection was associated with a lower primary response rate (22 in 47 vs. 41 in 57 episodes, P < 0.01) and a lower complete cure rate (5 in 47 vs. 18 in 57 episodes, P < 0.02). The episodes that had received recent antibiotic therapy had a significantly lower complete cure rate than the de novo cases (8 in 69 vs. 15 in 35 episodes, P < 0.001). Episodes receiving third-generation cephalosporin as part of the initial antibiotic regimen had a significantly higher primary response rate than the ones that initially received aminoglycoside (54 in 81 episodes vs. 8 in 22 episodes, P < 0.05), but their complete cure rates were similar. Twenty-four cases failed to respond to antibiotics and the Tenckhoff catheter was removed. The chance of returning to CAPD was higher when the Tenckhoff catheter was removed on day 10 than on day 15 (9 in 14 cases vs. 5 in 10 cases), although the result was not statistically significant. The Tenckhoff catheter was removed and replaced at another site simultaneously in another 14 cases after the effluent cleared up. None of these patients had a relapse of peritonitis within three months. Conclusions. Recent antibiotic therapy is the major risk factor for peritonitis due to the Pseudomonas species. Exit site infection and recent antibiotic therapy are associated with poor therapeutic response to antibiotics. When the therapeutic response is suboptimal, early Tenckhoff catheter removal may help preserve the peritoneum for further peritoneal dialysis. Elective Tenckhoff catheter exchange after clearing up the peritoneal dialysis effluent may also reduce the likelihood of relapse. It is desirable to use third-generation cephalosporin in the initial antibiotic regimen for peritonitis treatment in localities with a high incidence of peritonitis due to the Pseudomonas species. [ABSTRACT FROM AUTHOR]

Importance of dialysis adequacy in mortality and morbidity of Chinese CAPD patients. Background. In continuous ambulatory peritoneal dialysis (CAPD), the impact of dialysis adequacy on patient outcome is well established in Caucasian patients but is less clear in Asian patients. Recent evidence suggests that Asian dialysis patients enjoy better overall survival. We hypothesize that dialysis adequacy may be less important in determining outcome for this ethnic group. Methods. We performed a single-center prospective observational study. From September 1995, we enrolled 150 existing and 120 new CAPD patients. They were followed for up to three years. We monitored dialysis adequacy and nutritional indices, including Kt/V, weekly creatinine clearance (CCr ), residual glomerular filtration rate (GFR), normalized protein catabolic rate (NPCR), percentage of lean body mass (%LBM), and plasma albumin level. Clinical outcomes included mortality, technique failure, and duration of hospitalization. Results. The duration of study follow-up was 22.1 ± 12.3 months. In our study population, 136 were male. Seventy were diabetic (25.9%), and 212 were treated with 6 L exchanges per day (78.5%). The body weight was 59.3 ± 9.4 kg. Baseline total Kt/V was 1.78 ± 0.41, peritoneal Kt/V 1.48 ± 0.36, and median residual GFR 0.98 mL/min (range 0 to 7.45). Two-year patient survival was 83.0%, and technique survival was 72.8%. Multivariate analysis showed that the duration of dialysis, diabetes, %LBM, index of dialysis adequacy (Kt/V or CCr ), residual GFR, and requirement of a helper for CAPD exchanges were independent factors of patient survival; serum albumin, adequacy index (Kt/V or CCr ), and requirement of a helper were independent factors of technique survival. Duration of dialysis, body weight, requirement of helper, cardiovascular disease, HBsAg carrier, serum albumin, and CCr had independent effects on... [ABSTRACT FROM AUTHOR]

The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on calcium phosphate homeostasis in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remain uncertain. A retrospective observational cohort study of patients with T2DM at CKD stage G3b-5ND who received SGLT2i as compared to control from 1 January 2015 through 31 December 2021 was recruited. Propensity score assignment at 1:3 ratio by logistic regression was done. All patients were followed for 12 months. Outcomes were changes in phosphate level. We analyzed 1,450 SGLT2i users and 4,350 control subjects. At the 12th month, SGLT2i users had a slower increase in phosphate levels (absolute change: −0.01 ± 0.28 vs + 0.14 ± 0.34 mmol/L; percentage change: −0.74 % ± 25.56 vs + 10.88 ± 28.15 %, P for both < 0.001). The proportion of patients with high phosphate was lower with SGLT2i (8.2 % vs 24.6 % increase). In the generalized estimating equation, SGLT2i was linked to a longitudinal reduction in phosphate (B −0.039, P <0.001). SGLT2i can effectively slow down the progression of phosphate retention in advanced CKD with T2DM. [ABSTRACT FROM AUTHOR]

The article discusses hypokalemia and cardiac event as risk factors in patients receiving peritoneal dialysis, based on a study by Torlén et al., published in the 2012 issue of the "Clinical Journal of the American Society of Nephrology." Patients on peritoneal dialysis were more likely to have hypokalemia than were patients on hemodialysis. Further studies on the relationship of hypokalemia with mortality and the effect of the changes in serum potassium concentration are suggested.

The article evaluates the chronic phenytoin therapy in a patient with a history of refractory epilepsy and mental insufficiency with encephalitis. Clinical implications of skull thickening and cerebral atrophy are offered. The result of the CT scan after a head injury is presented. Effects of phenytoin on skull thickening are discussed.