IgA nephropathy (IgAN) is the most prevalent among primary glomerular diseases worldwide. Although our understanding of IgAN has advanced significantly, its underlying biology and potential drug ...targets are still unexplored. We investigated a combinatorial approach for the analysis of IgAN-relevant -omics data, aiming at identification of novel molecular signatures of the disease. Nine published urinary proteomics datasets were collected and the reported differentially expressed proteins in IgAN vs. healthy controls were integrated into known biological pathways. Proteins participating in these pathways were subjected to multi-step assessment, including investigation of IgAN transcriptomics datasets (Nephroseq database), their reported protein-protein interactions (STRING database), kidney tissue expression (Human Protein Atlas) and literature mining. Through this process, from an initial dataset of 232 proteins significantly associated with IgAN, 20 pathways were predicted, yielding 657 proteins for further analysis. Step-wise evaluation highlighted 20 proteins of possibly high relevance to IgAN and/or kidney disease. Experimental validation of 3 predicted relevant proteins, adenylyl cyclase-associated protein 1 (CAP1), SHC-transforming protein 1 (SHC1) and prolylcarboxypeptidase (PRCP) was performed by immunostaining of human kidney sections. Collectively, this study presents an integrative procedure for -omics data exploitation, giving rise to biologically relevant results.
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Progressive damage and decline in the number of podocytes often occur in the early stages of DN. Thus, nephrin as a ...podocyte-specific protein may be regarded as a potential biomarker of early detection of DN. The aim of this study is to determine whether urinary nephrin is an earlier marker in DN than microalbuminuria and to test the significance of urinary nephrin as a marker for early detection of DN.
Our cross-sectional study included 90 patients with type 2 diabetes mellitus (T2DM), 30 patients with diagnosed DN and 60 patients without diagnosed DN. As a control group, we used 30 healthy subjects. All patients with T2DM were classified into three subgroups according to urinary microalbumin/creatinine ratio (UMCR): normoalbuminuric, microalbuminuric and macroalbuminuric patients. Nephrin in urine was measured by immunoenzyme assay, microalbumin with turbidimetric and creatinine with the photometric method. In blood sera, we measured a few standard biochemical parameters.
Nephrinuria was found to be present in 100% of patients with T2DM and macroalbuminuria, in 88% with microalbuminuria, as well as 82% of patients with T2DM and normoalbuminuria. A concentration of urinary nephrin was significantly increased in all groups of subjects with T2DM compared to the control group (p<0.05). Nephrinuria correlated statistically negative with eGFR (r=-0.54). ROC analysis showed that nephrin has a total predicted probability of 96% in patients with DN.
Urinary nephrin is earlier, more specific and sensitive marker than microalbumin in early detection of DN.
Introduction. Podocyte injury has been reported as an early feature of DN therefore, the assessment of podocyte injury can be accomplished by estimation of podocalyxin in urine. This study aimed to ...estimate the urinary podocalyxin levels and to determine the sensitivity and specificity of this biomarker for early detection of DN.
An arteriovenous fistula (AVF) remains the best choice of vascular access (VA) for hemodialysis (HD). The aim of the study was to determine the factors associated with the achievement of adequate ...blood flow (BF) of AVFs at the 4th week after creation. Created AVFs in 63 patients with chronic kidney disease (CKD) stage 4/5 and CKD stage 5 on hemodialysis (CKD5D) were analyzed in a prospective study. Doppler ultrasound (DUS) was used for measuring the diameter of the radial artery, the brachial artery and the cephalic vein before AVF creation. The BF of AVF was calculated by DUS at the 4th week after creation and adequate BF was defined as ≥ 600 mL/min. The average age of patients was 61.31 ± 12.9 years. An adequate BF of AVF at the 4th week after creation was achieved in 43.54% of patients. The BF of AVF measured in male patients was significantly higher compared to the BF of AVF obtained in females (576.03 mL/min vs 375.12 mL/min, P = 0.004). The diameter of the blood vessels with achieved adequate BF was significantly larger compared to the diameter of the blood vessels without adequate BF (radial artery: 2.45 mm vs 2.03 mm, P = 0.000; brachial artery: 4.78 mm vs 4.06 mm, P = 0.001 and cephalic vein: 3.12 mm vs 2.83 mm P = 0.018). The gender and the diameter of the blood vessels before AVF creation were significantly associated with achievement of adequate BF of AVF at the 4th week of creation.
Chronic kidney disease (CKD) affects approximately 850 million people globally and is associated with an increased risk of cognitive impairment. The prevalence of cognitive impairment among CKD ...patients ranges from 30 to 60%, and the link between CKD and cognitive impairment is partially understood. Methodological challenges and biases in studying cognitive function in CKD patients need to be addressed to improve diagnosis, treatment, and management of cognitive impairment in this population. Here, we review the methodological challenges and study design issues, including observational studies’ limitations, internal validity, and different types of bias that can impact the validity of research findings. Understanding the unique challenges and biases associated with studying cognitive function in CKD patients can help to identify potential sources of error and improve the quality of future research, leading to more accurate diagnoses and better treatment plans for CKD patients.
Incidence of vascular anomalies in donor kidneys varies from 18% to 30% and presents a challenge for a transplant surgeon in kidney transplant. Here we present our personal experience for man - ...agement of the complicated and unexpected cases.
A total of 250 kidney transplants (226 living, 24 deceased) were performed in a period of 24 years; mean donor age was 55 years (range, 25-86 years), and mean recipient age was 38.6 years (range, 14-66 years). We analyzed the surgical techniques, complications and outcomes, rejection episodes, kidney function, and graft and patient survival rates.
Of 250 nephrectomies, 209 had a single artery (83.6%), 34 had 2 arteries (13.6%), and 7 had 3 arteries (2.8%). Of 34 double arteries, 14 had 2 main arteries, 15 had a main and a polar artery, and 5 had an aortic Carrel patch after deceased donation. According to the size, type, and position, the anastomoses were performed with branches of hypogastric, epigastric inferior, iliac external, and main renal artery, intracorporeally or in bench surgery. Regarding veins, 1 double inferior vena cava, 1 left-side inferior vena cava, 4 retroaortic, 2 circumaortic, 10 large lumbar veins draining into the left renal veins, and 8 cases with 2 or more different size renal veins were managed. In 9 cases with short right renal vein, an extension with vena cava (a "Barry cavoplasty") was performed in deceased donor organs. No serious surgical complications related to vascular anomalies were observed. There were no statistical differences in 1-, 6-, and 12-month graft survival rates between the groups with or without vascular anomalies.
Vascular anomalies should no longer be considered a contraindication for transplant, if careful anastomosis is performed in every case to avoid ischemia and further complications. Therefore, management of vascular anomalies could be a graftsaving procedure.
The hemolytic uremic syndrome (HUS) is a heterogeneous group of similar entities characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure (ARF) and is an ...important cause of ARF in childhood. Mutations have been reported in the complement regulatory protein factor H in both sporadic and familial HUS and have been identified in 10-20% of cases. Inherited HUS is unusual. We report the occurrence of HUS in two siblings after delivery, complicated with ARF and with a good outcome.
It is known that in the presence of even subtle kidney dysfunction an intensive prevention of cardiovascular risk is required. Apart from the conventional factors which contribute to cardiovascular ...disease (CVD), there are also some specific conditions of the chronic kidney disease (CKD) population such as oxidative stress of uremia and dialysis (D). However, hyperphosphatemia, hypercalcemia, and elevated calcium-phosphorus product remain as major contributors to the development of vascular calcification (VC) in this population, as part of the systemic complication known as mineral and bone disorders (MBD) in CKD patients. Importantly, the retention of phosphate remains as main culprit in the pathogenesis of CKD–-MBD. Over the years, various treatment options for phosphate removal and controlling mineral metabolism, bone health, VC and CVD have failed, mainly through an over-suppression of PTH, development of ABD and promotion of VC and mortality.
Although KDOQI and KDIGO published CKD–-MBD guidelines has clearly stated where calcium-based phosphate binders should not be used in D patients (hypercalcemia and low PTH) and where non calcium-containing phosphate binders are preferred (patients with severe vascular and/or other soft tissue calcifications), the greatest controversy and disagreements within the nephrological community still exists upon the cost-effectiveness of non calcium binder (sevelamer) use. Indeed, despite the evidence and recognised trend towards both a decrease in VC and CVD associated with sevelamer use, it is still an ongoing matter of debate. The magnitude of this controversy is increased when the issue of advanced medical and/or budgetary evaluation related to the implementation of clinical guidelines for CKD–-MBD treatment is considered. Despite advocated use of sevelamer across a range of common clinical scenarios in CKD, its widespread utilization is challenged as exceeding what would usually be considered good value for money. If so, it is questionable whether the recommendations and suggestions from the guidelines should be followed, and further, do we need guidelines and innovative drugs for treatment of hyperphosphatemia? While awaiting the answer, as clinicians we should proceed with a treatment to “do no harm”, trying to at least limit the calcium exposure of our dialysis patients.
Abnormal bone in chronic kidney disease (CKD) may adversely affect vascular calcification via disordered calcium and phosphate metabolism. In this context, bone health should be viewed as a ...prerequisite for the successful prevention/treatment of vascular calcification (VC) along with controlled parathyroid hormone (PTH) secretion, the use of calcium-based phosphate binders and vitamin D therapy. In CKD patients, VC occurs more frequently and progresses more rapidly than in the general population, and is associated with increased cardiovascular disease (CVD) morbidity and mortality. A number of therapies aimed at reducing PTH concentration are associated with an increase of calcaemia and Ca x P product, e.g. calcium-containing phosphate binders or active vitamin D. The introduction of calcium-free phosphate binders has reduced calcium load, attenuating VC and improving trabecular bone content. In addition, a major breakthrough has been achieved through the use of calcimimetics, as first agents which lower PTH without increasing the concentrations of serum calcium and phosphate. Nowadays, it is becoming evident that even early stage CKD is recognised as an independent CVD risk factor. Moreover, the excess of CVD among dialysis patients cannot be explained entirely on the basis of abnormal mineral and bone metabolism. Hence, much controversy has surrounded the cost-effectiveness of treatment with the new phosphate-binding drugs as well as new vitamin D analogs and calcimimetics. Thus, it seems prudent and reasonable that maintaining bone health and mineral homeostasis should rely on some modifications of standard phosphate binding and calcitriol therapy. Hypophosphataemia and hypercalcaemia in adynamic bone disease (ABD) might be treated by reducing the number of calcium carbonate/acetate tablets in order to increase serum phosphate and decrease serum calcium, which, in turn, might positively stimulate PTH secretion. The same rationale is assumed for the use of a low calcium dialysate. On the other hand, secondary hyperparathyroidism with hyperphosphataemia and hypocalcaemia should be treated with a substantial number of calcium carbonate/acetate tablets in combination with calcitriol and low calcium dialysate in order to decrease serum phosphate and maintain the Ca x P product within K/DOQI guidelines (<4.4 mmol l(-1)). Finally, it becomes apparent that prevention, with judicious use of calcium-based binders, vitamin D and a low calcium dialysate without adverse effects on Ca x P or oversuppression of PTH, provides the best management of VC and mineral and bone disorder in CKD patients.
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