•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.
Peritoneal Dialysis-Associated Peritonitis Szeto, Cheuk-Chun; Li, Philip Kam-Tao
Clinical journal of the American Society of Nephrology,
07/2019, Letnik:
14, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Peritonitis is a common and severe complication in peritoneal dialysis (PD). Detailed recommendations on the prevention and treatment of PD-associated peritonitis have been published by the ...International Society for Peritoneal Dialysis (ISPD), but there is a substantial variation in clinical practice among dialysis units. Prophylactic antibiotics administered before PD catheter insertion, colonoscopy, or invasive gynecologic procedures, daily topical application of antibiotic cream or ointment to the catheter exit site, and prompt treatment of exit site or catheter infection are key measures to prevent PD-associated peritonitis. When a patient on PD presents with clinical features compatible with PD-associated peritonitis, empirical antibiotic therapy, with coverage of both Gram-positive and Gram-negative organisms (including
species), should be started once the appropriate microbiologic specimens have been obtained. Intraperitoneal is the preferred route of administration. Antifungal prophylaxis, preferably oral nystatin, should be added to prevent secondary fungal peritonitis. Once the PD effluent Gram stain or culture and sensitivity results are available, antibiotic therapy can be adjusted accordingly. A detailed description on the dosage of individual antibiotic can be found in the latest recommendations by the ISPD. The duration of antibiotics is usually 2-3 weeks, depending on the specific organisms identified. Catheter removal and temporary hemodialysis support is recommended for refractory, relapsing, or fungal peritonitis. In some patients, a new PD catheter could be inserted after complete resolution of the peritonitis. PD catheter removal should also be considered for refractory exit site or tunnel infections. After the improvement in clinical practice, there is a worldwide trend of reduction in PD-associated peritonitis rate, supporting the use of PD as a first-line dialysis modality.
Summary
Background
In clinical trials involving patients with preserved renal function, tenofovir disoproxil fumarate (TDF) use was associated with mild renal impairment in 1% of patients.
Aim
To ...compare serial renal function of entecavir (ETV)‐treated, TDF‐treated, and untreated patients with chronic hepatitis B.
Methods
We studied the risk of chronic kidney disease (CKD) progression in a territory‐wide cohort of patients with chronic hepatitis B without treatment and of those on ETV or TDF treatment. Estimated glomerular filtration rate (eGFR) was determined by the CKD Epidemiology Collaboration equation and was classified into five CKD stages. CKD progression, defined as an increase of at least one CKD stage, was compared among treated and untreated patients.
Results
After propensity score matching, 2254 ETV‐treated, 2254 TDF‐treated, and 2254 untreated patients were included in the analysis. Their mean baseline eGFR was 90.3 ± 19.6, 91.3 ± 20.6, and 92.2 ± 20.0 mL/min/1.73 m2, respectively. During a mean follow‐up of 2.4 ± 1.5 years, 639 ETV‐treated, 706 TDF‐treated, and 564 untreated patients exhibited CKD progression ≥1 stage. The 5‐year cumulative incidence (95% confidence interval) of CKD progression was 43% (40%‐46%) in ETV‐treated, 48% (45%‐51%) in TDF‐treated, and 43% (39%‐47%) in untreated patients (reference group), respectively (P = 0.267 and <0.001, respectively). The number of patients who exhibited CKD progression ≥2 stages was 92 (4.1%) in the untreated cohort, 95 (4.2%) in the ETV‐treated cohort, and 51 (2.3%) in the TDF‐treated cohort.
Conclusions
The use of TDF was associated with mild renal impairment in a minority of patients; those treated with ETV had a similar risk compared to untreated patients.
Nephrotic syndrome is a common problem in clinical nephrology. In general, nephrotic syndrome is pathognomonic of glomerular disease, but the underlying pathological etiology is highly variable. ...Although kidney biopsy is the standard method to classify the histology and determine the extent of renal scarring, it is an invasive procedure with potential complications, and is generally not suitable for serial monitoring. MicroRNAs (miRNAs) are short noncoding RNA molecules that regulate gene expression. Recent studies show that the urinary levels of several miRNAs are significantly changed in nephrotic syndrome; some appear to be disease specific, others being damage related. Specifically, urinary miR-192 level is lower in patients with diabetic nephropathy than other causes of nephrotic syndrome, while patients with minimal change nephropathy or focal glomerulosclerosis had higher urinary miR-200c level than those with other diagnosis. Elevated urinary miR-21, miR-216a, and miR-494 levels may predict a high risk of disease progression and renal function loss, irrespective of the histological diagnosis. Furthermore, a number of small scale studies suggest that the urinary levels of certain miRNA targets may assist in the diagnosis and assessment of disease activity in patients with lupus nephritis. Since miRNA in urinary sediment is relatively stable and easily quantified, it has the potential to be developed as biomarkers for disease diagnosis and monitoring. However, available published evidence is limited to small scale studies. Further research is urgently needed in many areas.
•Urinary miRNA may serve as biomarkers for the diagnosis and disease monitoring.•Some urinary miRNAs appear to be disease specific, others being damage related.•Clinical application of urinary miRNA needs further development.
Epigenetic markers are potential biomarkers for diabetes and related complications. Using a prospective cohort from the Hong Kong Diabetes Register, we perform two independent epigenome-wide ...association studies to identify methylation markers associated with baseline estimated glomerular filtration rate (eGFR) and subsequent decline in kidney function (eGFR slope), respectively, in 1,271 type 2 diabetes subjects. Here we show 40 (30 previously unidentified) and eight (all previously unidentified) CpG sites individually reach epigenome-wide significance for baseline eGFR and eGFR slope, respectively. We also develop a multisite analysis method, which selects 64 and 37 CpG sites for baseline eGFR and eGFR slope, respectively. These models are validated in an independent cohort of Native Americans with type 2 diabetes. Our identified CpG sites are near genes enriched for functional roles in kidney diseases, and some show association with renal damage. This study highlights the potential of methylation markers in risk stratification of kidney disease among type 2 diabetes individuals.
Evidence implicated the diagnostic significance of microRNAs in whole urine/urine sediments in urothelial carcinoma of the bladder (UCB). However, the contaminated blood cells in patients with ...haematouria significantly altered the expression profiles of urinary microRNA, influencing the test accuracy.
MicroRNA profiles of the urine supernatants of UCB patients and controls without any malignancy and profiles of malignant and corresponding normal mucosa tissues from the patients were determined by microRNA microarray and compared to identify differentially expressed microRNAs. The differential expression was verified in the tissues of an independent patient cohort by RT-qPCR. The diagnostic significance of selected microRNAs as biomarkers in the urine supernatant was investigated in the expanded cohorts.
MicroRNA-99a and microRNA-125b were down-regulated in the urine supernatants of UCB patients. The degree of down-regulation was associated with the tumor grade. A diagnostic model was developed using a combined index of the levels of microRNA-99a and microRNA-125b in the urine supernatant with a sensitivity of 86.7%, a specificity of 81.1% and a positive predicted value (PPV) of 91.8%. Discriminating between high- and low-grade UCB, the model using the level of microRNA-125b alone exhibited a sensitivity of 81.4%, a specificity of 87.0% and a PPV of 93.4%.
The results revealed a unique microRNA expression signature in the urine supernatants of UCB patients for the development of molecular diagnostic tests. An effective cell-free urinary microRNA-based model was developed using a combined index of the levels of microRNA-99a and microRNA-125b to detect UCB with good discriminating power, high sensitivity and high specificity.
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.
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