Encapsulating peritoneal sclerosis (EPS) is a potentially devastating complication of peritoneal dialysis (PD). Diagnosis is often delayed due to the lack of effective and accurate diagnostic tools. ...We therefore examined peritoneal effluent for potential biomarkers that could predict or confirm the diagnosis of EPS and would be valuable in stratifying at-risk patients and driving appropriate interventions. Using prospectively collected samples from the Global Fluid Study and a cohort of Greek PD patients, we utilized 2D SDSPAGE/ MS and iTRAQ to identify changes in the peritoneal effluent proteome from patients diagnosed with EPS and controls matched for treatment exposure. We employed a combinatorial peptide ligand library to compress the dynamic range of protein concentrations to aid identification of low-abundance proteins. In patients with stable membrane function, fibrinogen γ-chain and heparan sulphate proteoglycan core protein progressively increased over time on PD. In patients who developed EPS, collagen-α1(I), γ-actin and Complement factors B and I were elevated up to five years prior to diagnosis. Orosomucoid-1 and a2-HS-glycoprotein chain-B were elevated about one year before diagnosis, while apolipoprotein A-IV and α1-antitrypsin were decreased compared to controls. Dynamic range compression resulted in an increased number of proteins detected with improved resolution of protein spots, compared to the full fluid proteome. Intelectin-1, dermatopontin, gelsolin, and retinol binding protein-4 were elevated in proteome-mined samples from patients with EPS compared to patients that had just commenced peritoneal dialysis. Thus, prospective analysis of peritoneal effluent uncovered proteins indicative of inflammatory and pro-fibrotic injury worthy of further evaluation as diagnostic/prognostic markers.
Immune dysregulation in patients with acute COVID-19 under chronic hemodialysis (CHD) is fully not elucidated. The changes of mononuclear counts and mediators before and after HD and associations ...with final outcome were studied. In this prospective study, hospitalized patients with moderate-to-severe COVID-19 under CHD and matched comparators under HD were analyzed for their absolute counts of lymphoid cells and circulating inflammatory mediators. Blood samples were collected before start and at the end of the first HD session; dialysate samples were also collected. Fifty-nine patients with acute COVID-19 under CHD and 20 uninfected comparators under CHD were enrolled. Circulating concentrations of tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-10, interferon-gamma and platelet-derived growth factor-A were increased in patients. Concentrations of mediators did not differ before and after HD. Significant decreases of CD4-lymphocytes and CD19-lymphocytes were found in patients. The decrease of the expression of HLA-DR on CD14-monocytes was associated with unfavorable outcome (defined as WHO-CPS 6 or more by day 28); increased counts of CD19-lymphocytes were associated with better outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flowchart showing the patient groups studied and the cytokine levels that were significantly higher (in red) or similar (in black) to healthy controls. Display omitted
•Higher levels of urinary ...excretion of Th-cytokines and MCP-1 in GN patients.•Most urinary Th-cytokines increased even in patients in clinical remission.•Strong positive correlation between MCP-1 and TGF-β1 urinary levels.•Higher TGF-β1 and MCP-1 levels in MN patients with a progressive clinical course.
Glomerulonephritides (GNs) represent common causes of chronic kidney disease associated with a wide spectrum of clinical and histological features. Various factors that activate the inflammatory cascade are involved in the development of kidney injury. The aim of this study was to estimate the urinary excretion of pro-inflammatory (IL-2, INF-γ, TNF-α, IL-6, IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as the chemokine MCP-1 in patients with various types of GN treated by immunosuppressive drugs and to identify any prognostic value of excreted cytokines for future renal function.
Ninety-seven patients (62M/35F, age 53.1±15.6years) with primary glomerulonephritis and 32 healthy controls were studied. The original diagnoses were membranous nephropathy (MN, n=36), IgA nephropathy (IgAN, n=31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n=30). All patients had been treated with immunosuppressive drugs and, at the time of measurement of urinary cytokine excretion, were either in clinical remission or still had active disease with persistent proteinuria.
GN patients had significantly higher levels of all cytokines and MCP-1 compared to healthy controls. A strong positive correlation between TGF-β1 and MCP-1 concentrations was observed in all GN patients. Increased urinary excretion of all tested cytokines apart from TNF-α and TGF-β1 was observed even in patients with clinical remission. The main difference between patients with proteinuria and those in clinical remission was the level of MCP-1 urinary excretion. The urinary excretion of MCP-1 and TGF-β1 was significantly higher in patients with MN who showed deterioration of renal function over a follow-up period of five years.
Increased levels of cytokines are observed in the urine of patients with different types of glomerulonephritis, even after the achievement of clinical remission with the administration of immunosuppressive drugs. Urinary excretion of MCP-1 and TGF-β1 indicates the ongoing inflammatory and fibrotic processes in the kidney and is probably related to unfavourable outcomes.
High aldosterone levels contribute to kidney disease progression, while spironolactone in combination with ACEi or ARBs can potentially reduce proteinuria and ameliorate kidney function ...deterioration. However, evidence on the impact of eplerenone in patients with glomerulonephritis is scarce.
In this prospective observational study, we assessed the effects of eplerenone in patients with biopsy-proven glomerulonephritis who were already treated with ACEi or ARBs. Patients received either eplerenone (25 mg daily) on top of ACEi or ARBs or standard treatment alone. Proteinuria (24 h total protein excretion), kidney function, blood pressure and serum K
levels were assessed at 3, 6 and 12 months after the initiation of treatment.
Sixty-six patients were included in the study. Eplerenone was administered in 30 patients, while 36 received only ACEi or ARB. Proteinuria decreased from 1768 to 1152 mg/24 h after 1 year of eplerenone treatment, while it remained stable in controls. Eplerenone showed significant impact on proteinuria in those with baseline proteinuria of >1000 mg/24 h. Patients who received eplerenone showed a reduction in systolic blood pressure, while eGFR and serum K
levels remained stable.
Addition of eplerenone has a beneficial effect on proteinuria in patients with glomerulonephritis and significant baseline proteinuria.
The appearance of new onset diabetes is common after kidney transplant. Treatment options are limited because of renal function-related contraindications, interactions with immunosuppressive drugs, ...and side effects. We investigated the long-term safety and efficacy of dipeptidyl peptidase IV inhibitors in renal transplant recipients with new onset diabetes.
We treated 12 patients with dipeptidyl peptidase IV inhibitors, and 5 patients received insulin monotherapy as initial treatment of new onset diabetes after kidney transplant. All patients were followed for 12 months after diagnosis. Glycosylated hemoglobin A1c, estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight were measured during outpatient visits. Effects of dipeptidyl peptidase IV inhibitors and insulin on the aforementioned parameters were measured to compare values at time of diagnosis versus mean values of the last 6 months of follow-up.
Patients were treated with linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients), and alogliptin (2 patients). Patients had a mean age of 59.4 ± 12 years and a mean glycosylated hemoglobin A1c of 6.6% at diagnosis, which was decreased to 6.1% (P = .03) at 1 year of follow-up. Renal function remained stable, and plasma tacrolimus levels did not appear to be affected. No significant differences were shown in serum total, low-density lipoprotein, and high-density lipoprotein cholesterol levels aftertreatment. Nevertheless,triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dL; P = .0039). A decrease in body weight was also observed. Finally, patients treated with dipeptidyl peptidase V inhibitors achieved better glycosylated hemoglobin A1c levels than those treated with insulin.
Dipeptidyl peptidase IV inhibitors appear to be a safe, effective, and hypoglycemia-free option fortreatment of new onset diabetes in renaltransplant recipients and possibly provide better diabetes control than insulin therapy.
Maintenance peritoneal dialysis (PD) is commonly associated with cardiovascular diseases (CVDs), whose risk is assessed via LDL-C. Nonetheless, oxidized LDL (oxLDL), as being a key component of ...atherosclerotic lesions, could be also associated with atherosclerosis and related CVDs. However, its predictive value for CVDs risk assessment is subject of research studies due to the lack of specific methods to measure oxLDL status from its individual lipid/protein components. In the present study, six novel oxLDL markers, representative of certain oxidative modifications on the LDL protein and lipid components, are measured in atherosclerosis-prone PD patients (39) versus those in chronic kidney disease patients (61) under hemodialysis (HD) and healthy controls (40). LDL from serum of PD, HD and control subjects were isolated and fractionated into cholesteryl esters, triglycerides, free cholesterol, phospholipids and apolipoprotein B100 (apoB100). Subsequently the oxLDL markers cholesteryl ester hydroperoxides (-OOH), triglyceride-OOH, free cholesterol-OOH, phospholipid-OOH, apoB100 malondialdehyde and apoB100 dityrosines were measured. LDL carotenoid levels and LDL particle serum concentration were also measured. The levels of all oxLDL lipid-OOH markers were significantly elevated in PD patients versus control, while the levels of cholesteryl ester-/triglyceride-/free cholesterol-OOH were significantly elevated in PD versus HD patients, regardless of patients’ underlying medical conditions, sex, age, PD type, clinical biochemical markers and medication. It should be noted that all fractionated lipid-OOH levels were inversely correlated with LDL-P concentration, while LDL-P concentration was not correlated with LDL-C in PD patients. Moreover, LDL carotenoids were significantly lower in PD patients versus control. The increased levels of oxLDL status specific markers in both PD and HD patients (compared to control), support a potential prognostic value of oxLDL regarding CVD risk assessment in both patient groups. Lastly, the study introduces the oxLDL peroxidation markers free cholesterol-OOH and cholesteryl ester-OOH as complementary to LDL-P number, and as possible alternatives to LDL-C.
Display omitted
•Association of oxidized LDL (oxLDL) with peritoneal dialysis (PD) patients.•Six novel oxLDL markers based on oxLDL lipid/protein components.•OxLDL markers are higher in PD versus hemodialysis patients.•OxLDL markers do not correlate with LDL-C and LDL-C/HDL-C in PD patients.•Most oxLDL marker levels correlate inversely with LDL particle number.
Persistent secondary hyperparathyroidism is common after successful kidney transplant, with concomitant hypercalcemia and hypophosphatemia potentially leading to reduced graft survival and increased ...cardiovascular risk. Cinacalcet, a calcimimetic agent that activates the calcium-sensing receptors in parathyroid glands, is a therapeutic option. In this study, we assessed the long-term treatment effects of cinacalcet for a period of up to 5 years in a cohort of kidney transplant recipients.
Forty-seven patients with secondary hyperparathyroidism (intact parathyroid hormone level > 70 pg/mL or 7.43 pmol/L) and hypercalcemia (corrected calcium > 10.4 mg/dL or 2.6 mmol/L) were considered eligible for treatment with cinacalcet and were included in the analysis. Data were recorded at initiation of treatment and every 6 months up to a maximum follow-up of 60 months. A control group of patients treated with placebo, conventional treatment, or surgical treatment was not available for this study.
Mean follow-up time was 45 ± 16 months. Treatment with cinacalcet was initiated at a median of 25 months after renal transplant. Serum calcium decreased by 0.21 mmol/L (2.69 vs 2.48 mmol/L; 95% confidence interval, 0.08-0.345; P < .001) during the first 6 months, and this reduction was sustained during follow-up. Intact parathyroid hormone level decreased by 7.68 pmol/L (32.96 ± 36.4 vs 25.28 ± 19.5 pmol/L; 95% confidence interval, -6.42 to 21.75; P = not significant) at 6 months, whereas at the end of follow-up intact parathyroid hormone level decreased further by 20.07 pmol/L (32.96 ± 36.4 vs 12.89 ± 5.73 pmol/L; 95% confidence interval, 2.02-38.1; P < .01). Mean starting dose of cinacalcet was 33.5 ± 10 mg/day. According to the therapeutic response, cinacalcet dose increased steadily and reached 51.1 ± 33 mg/day at the end of the observation period. Mean serum phosphorus increased significantly, whereas estimated glomerular filtration rate remained virtually stable throughout follow-up. Adverse reactions were observed in 4 patients, comprising mild gastro-intestinal complaints.
Long-term treatment with cinacalcet in kidney transplant recipients with secondary hyperparathyroidism is effective in controlling hypercalcemia and correcting hypophosphatemia, without affecting graft function while being well-tolerated.
Chronic Kidney Disease (CKD) is considered as a major public health problem as it can lead to end-stage kidney failure, which requires replacement therapy. A prompt and accurate diagnosis, along with ...the appropriate treatment, can delay CKD’s progression, significantly. Herein, we sought to determine whether CKD etiology can be reflected in urine metabolomics during its early stage. This is achieved through the analysis of the urine metabolic fingerprint from 108 CKD patients by means of Nuclear Magnetic Resonance (NMR) spectroscopy metabolomic analysis. We report the first NMR—metabolomics data regarding the three most common etiologies of CKD: Chronic Glomerulonephritis (IgA and Membranous Nephropathy), Diabetic Nephropathy (DN) and Hypertensive Nephrosclerosis (HN). Analysis aided a moderate glomerulonephritis clustering, providing characterization of the metabolic fluctuations between the CKD subtypes and control disease. The urine metabolome of IgA Nephropathy reveals a specific metabolism, reflecting its different etiology or origin and is useful for determining the origin of the disease. In contrast, urine metabolomes from DN and HN patients did not reveal any indicative metabolic pattern, which is consistent with their fused clinical phenotype. These findings may contribute to improving diagnostics and prognostic approaches for CKD, as well as improving our understanding of its pathology.
PDF
