Early Stages Of Renal Disease Research Articles

Urinary Tamm-Horsfall protein excretion is a potential early biomarker of renal distal tubular damage in canine leishmaniosis.

This study evaluates distal tubular damage in early stages of renal disease in dogs with naturally acquired Leishmaniosis.Pherograms of urinary proteins separated in vertical electrophoresis system (SDS-PAGE) were evaluated. Peptide fingerprint and fragmentation (MALDI-TOF TOF) identified bands located at 100 and 60kDa as Tamm-Horsfall protein (THP) and albumin respectively.The variables examined were: urine protein to creatinine ratio (UPC), total number of bands, quantification of THP urinary excretion through the optical density of bands located at 100kDa, blood creatinine and urine specific gravity (USG).Positive correlation was found between UPC and the number of bands (ρ = 0.75849, P = <0.0001). Negative correlation was identified between UPC and OD % (optical density percentage) of 100kDa bands (ρ = -0.85332, P = <0.0001), and the number of bands and OD % of 100kDa bands (ρ = -0.74479, P = <0.0001).The area under the ROC curve was 0.991 (95% CI, 0.976 to 1). The optimal cut-off UPC that better discriminated between urines with high or low OD% of THP was 0.46 with 92.6% sensitivity and 96.2% specificity.Our findings indicate that non azotemic dogs with borderline proteinuria might excrete low concentrations of THP which could suggest tubular damage in early stages of chronic kidney disease.

Biomarkers and Predictors of Adverse Cardiovascular Events in Different Stages of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an important factor that contributes to the increase of all-cause morbidity and mortality in the group of non-communicable diseases, and it is also recognized as a strong and independent risk factor that contributes to cardiovascular disease (CVD). CVDs are a consequence of the action of a large number of risk factors among which are traditional and non-traditional. These risk factors have been the subject of a large number of studies which partially explained the unfavorable cardiovascular (CV) outcome of CKD patients. Therefore, valid studies about clinical and biohumoral predictors are of particular importance, especially in the early stages of renal disease, that is, in patients with creatinine clearance below 60 ml/min/1.73 m2 when preventive measures are most effective. Among potential predictors of adverse CV outcome are biomarkers of inflammation (Interleukin-18—IL-18), oxidative stress (ischemia-modified albumin—IMA; superoxide dismutase—SOD), acute kidney injury (kidney injury molecule-1—KIM-1; neutrophil gelatinase–associated lipocalin—NGAL), and microribonucleic acids (specific microRNA-133a). In this review, we tried to confirm the relationship between risk factors of CKD and CVD and newer, less frequently examined biomarkers with the occurrence of incidental CV events in renal patients.

Using nuclear magnetic resonance urine metabolomics to develop a prediction model of early stages of renal disease in subjects with type 2 diabetes

Type 2 diabetes mellitus (DM2) is a multimorbidity, long-term condition, and one of the worldwide leading causes of chronic kidney disease (CKD) –a silent disease, usually detected when non-reversible renal damage have already occurred. New strategies and more effective laboratory methods are needed for more opportune diagnosis of DM2-CKD. This study comprises clinical parameters and nuclear magnetic resonance (NMR)-based urine metabolomics data from 60 individuals (20–65 years old, 67.7% females), sorted in 5 experimental groups (healthy subjects; diabetic patients without any clinical sign of CKD; and patients with mild, moderate, and severe DM2-CKD), according to KDIGO. DM2-CKD produces a continuous variation of the urine metabolome, characterized by an increase/decrement of a group of metabolites that can be used to monitor CKD progression (trigonelline, hippurate, phenylalanine, glycolate, dimethylamine, alanine, 2-hydroxybutyrate, lactate, and citrate). NMR profiles were used to obtain a statistical model, based on partial least squares analysis (PLS-DA) to discriminate among groups. The PLS-DA model yielded good validation parameters (sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve (ROC) plot: 0.692, 0.778 and 0.912, respectively) and, thus, it can differentiate between subjects with DM2-CKD in early stages, from subjects with a mild or severe condition. This metabolic signature exhibits a molecular variation associated to DM2-CKD, and data suggests it can be used to predict risk of DM2-CKD in patients without clinical signs of renal disease, offering a new alternative to current diagnosis methods.

Signatures of Gait Movement Variability in CKD Patients Scheduled for Hemodialysis Indicate Pathological Performance Before and After Hemodialysis: A Prospective, Observational Study.

Background: The frailty status of hemodialysis patients is well-known, but the role of the therapy in the frailty process is not yet clear. Nowadays gait analysis in nephrology is neglected, although gait performance is known to be related to frailty and kidney function. We hypothesized that gait quality and physical activity level is already affected before, and does not change because of the start of hemodialysis.Methods: Fourteen patients (72.3 ± 5.7 years old) in a pre-dialysis program underwent an instrumental gait analysis and their physical activity was monitored for a week. This protocol was repeated 3, 6, 12, and 24 months after the first hemodialysis session.Results: At baseline, our sample showed a conservative gait with pathologic gait variability, high dual-task cost, and a sedentary lifestyle. No statistically significant change was found in any parameter in the analyzed period, but there was a tendency toward an improvement of gait quality and physical activity in the first year of treatment, and a decline in the second year.Conclusion: Elderly patients in the pre-dialysis stage show a conservative gait, however variability was in a pathological range and did not change post-hemodialysis. This hints toward changes in the central nervous system due to the kidney disease. This finding suggests the importance of gait analysis in the early stages of renal disease in the diagnosis of changes in the nervous system due to kidney failure that affect gait. Early detection of these changes would potentially allow a prevention program tailored to this population to be developed.

Metabolic Syndrome a Cornerstone in Cardiorenal Syndrome

Objective: The purpose of the study was to evaluate the relationship of metabolic syndrome (MetS) and cardiorenal syndrome(CRS) type 4 in the early stage of chronic renal disease. Introduction: Metabolic syndrome is facing a continually increasing nowadays. That is why he is turning in to a worldwide problem. On the other hand, improving of life expectancy is associated with rising morbidity, which is also reflected in expanding number cardiorenal patients. Materials and Methods: We conducted an observational study.139 patients with chronic renal disease stage 3 and 4 were en-rolled Statistical analysis was performed by χ2 test, logistic regression, Fisher's exact test. Results: Cardiorenal syndrome was found in 85.6% of patients(pts). The mean age was 56.7 ± 12.5 years. Males were 60.4% patients. Metabolic syndrome was defined by NCEP -ATP III and was observed in 66.9% of patients, hypertension in 71.9% of pts, obesity in 68.3% of pts,diabetes mellitus in 78.4% of pts, dislipidemia in 71.9% of pts, and uricemia in 61.9% of pts. Study results showed that metabolic syndrome had a powerfull significant association with cardiorenal syndrome p≤0.002. Also, hypertension, obesity, dislipidemia, hyperuricemia ans diabetes had a strong relationship p≤0.05 with CRS. Conclusions: Cardiorenal syndrome is quite common even in the early stages of renal disease. Its linking with metabolic syndrome is very important. Our efforts should be focused in early recognition and timely identification of MetS compounds: obesity, hypertension, diabetes mellitus, so as to prevent and reduce morbidity and health costs these syndromes carried.

Pseudoxanthoma Elasticum and Cardiorenal Disease: A Case Report.

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by calcification of elastic fibres, skin lesions, fundus lesions and systemic vascular complications. PXE affects approximately 1 in 160,000 people, typically appearing as a formation of yellow papules containing abnormally calcified elastic fibres. The renal involvement of PXE has been reported. Several factors are known to promote soft tissue and accelerated arterial calcification in chronic kidney disease, including systemic inflammation, altered calcium and phosphate homeostasis, hypertension and a deficiency of endogenous calcification inhibitors. Given the impact of this disease, nephrologists may seek additional supportive features to improve and avoid the risk of complications. Moreover, PXE per se represents an interesting model to evaluate vascular disease in the early stages of renal disease.LEARNING POINTSPseudoxanthoma elasticum represents a rare disease that can involve renal problems.Vascular compromise in patients affected by pseudoxanthoma elasticum shares some components observed in patients with chronic kidney disease.Disorders of mineral and bone metabolism may coexist or be hidden in patients with pseudoxanthoma elasticum.

SAT-177 THE ASSESSMENT OF THE UTILITY OF SELECTED EARLY MARKERS OF CHRONIC KIDNEY DISEASE IN CHILDREN WITH URINARY TRACT DISORDERS SUBJECTED TO RENOSCINTIGRAPHY

Chronic kidney disease usually has no characteristic symptoms. The processes started in childhood often lead to end-stage renal failure in the future. Commonly used markers of renal function (creatinine, cystatin c, albuminuria, eGFR) do not have high sensitivity. Therefore, searching for candidates for an early, sensitive and specific biomarker became very popular. The tested new biomarkers may be more useful in the pediatric population than in adult patients, as children are usually not affected by other non-renal pathologies that may influence the results. There are several concepts of risk factors for chronic kidney disease: e.g. post-inflammatory scarring in renoscintigraphy and glomerular hyperfiltration. The aim of the study is the apraisal of the usefulness of new markers: KIM-1, FGF-23, NAG, NGAL, uromodulin in monitoring early stage of renal damage in children. 59 children (15 boys, 44 girls from 6 months to 17 years old) with kidney disorders, which had clinical indications for renoscintigraphy, were included in the study. The exclusion criteria were: elevated creatinine level, albuminuria, proteinuria, hypertension. Firstly, all patients were divided depending on the result of renoscintigraphy: the study group consisted of children with renal scarring, the control group consisted of children with normal kidney picture. Secondly, all patients were divided depending on the level of glomerular filtration calculated during isotopic scanning: the study group included children with glomerular hyperfiltration (>200ml/min), the control group included children with normal glomerular filtration rate. Concentration of KIM-1, FGF-23, NAG, NGAL in serum as well as concentration of NGAL and uromoduline in urine was measured in all patients. The results were compared in the above-mentioned groups. In children with renal glomerular hyperfiltration statistically significantly higher serum values of FGF-23 and NGAL were found in comparison to children with normal glomerular filtration rate (p<0,05). There were no statistically significant differences in serum concentrations of the tested markers in children with confirmed scars in the renal parenchyma in the renoscintigraphy compared to children with normal renal image. There were no statistically significant differences in concentration of tested markers in urine. The results of the study indicate the usefulness of FGF-23 and NGAL in monitoring the early stage of renal disease with glomerular hyperfiltration in children.

Renoprotective Effects of Metformin are Independent of Organic Cation Transporters 1 &2 and AMP-activated Protein Kinase in the Kidney.

The type-2 diabetes drug metformin has proven to have protective effects in several renal disease models. Here, we investigated the protective effects in a 3-day unilateral ureteral obstruction (3dUUO) mouse model. Compared with controls, ureteral obstructed animals displayed increased tubular damage and inflammation. Metformin treatment attenuated inflammation, increased the anti-oxidative response and decreased tubular damage. Hepatic metformin uptake depends on the expression of organic cation transporters (OCTs). To test whether the effects of metformin in the kidney are dependent on these transporters, we tested metformin treatment in OCT1/2−/− mice. Even though exposure of metformin in the kidney was severely decreased in OCT1/2−/− mice when evaluated with [11C]-Metformin and PET/MRI, we found that the protective effects of metformin were OCT1/2 independent when tested in this model. AMP-activated protein kinase (AMPK) has been suggested as a key mediator of the effects of metformin. When using an AMPK-β1 KO mouse model, the protective effects of metformin still occurred in the 3dUUO model. In conclusion, these results show that metformin has a beneficial effect in early stages of renal disease induced by 3dUUO. Furthermore, these effects appear to be independent of the expression of OCT1/2 and AMPK-β1, the most abundant AMPK-β isoform in the kidney.

Early Changes in Monocyte Adhesion Molecule Expression and Tumor Necrosis Factor-α Levels in Chronic Kidney Disease - A 5-Year Prospective Study

Background: Despite the absence of clinical symptoms, patients with chronic kidney disease (CKD) exhibit elevated levels of pro-inflammatory markers. To investigate whether it is possible to detect inflammatory activity and altered monocyte function at an early stage of renal disease, we studied patients with CKD stages 2-3 over 5 years. Methods: The expression of adhesion molecules on monocytes at resting state and after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP), as well as oxidative metabolism capacity was measured with flow cytometry in 108 CKD patients and healthy controls. Soluble markers of inflammation, such as cytokines, were analyzed using the Milliplex technique. Results: Patients showed significantly lower CD11b expression after stimulation during the 3rd (p = 0.002) and the 5th year (p < 0.001), together with a lower oxidative burst in response to fMLP over time (p = 0.02). The expression of CD62L on resting monocytes was lower during the 3rd (p = 0.001) and the 5th (p = 0.001) year in patients. Levels of tumor necrosis factor-α and RANTES were significantly increased (p = 0.001, p = 0.006) and interleukin-12 levels were also higher in CKD patients during the 5th year (p = 0.007). Conclusion: Monocytes in CKD stages 2-3 show emerging functional abrasions, with altered adhesion molecule expression and impaired fMLP response. These findings suggest that a transformation of monocyte function occurs at an early phase of renal impairment and may together with increased plasma levels of pro-inflammatory cytokines contribute to the higher vulnerability of CKD patients to comorbidities, such as infections and cardiovascular disease.

Dynamics of salivary cortisol in chronic kidney disease patients at stages 1 through 4.

End-stage renal disease has been associated with derangement of the HPA function. The dynamics of this axis in early stages of renal disease (CKD) has not been assessed. To evaluate in patients with CKD at stages 1-4 (KDOQI): the diurnal variation of salivary cortisol; the suppressibility of cortisol in saliva and serum after an overnight oral 1 mg dexamethasone suppression test (1 mg DST) with simultaneous measurement of circulating dexamethasone. 80 CKD outpatients and 40 healthy subjects were included. All CKD collected whole saliva at 08·00 and 23·00 h (SAF23 ) on two nonconsecutive days. Thereafter at 08·00 h, following 1 mg DST, saliva and blood were obtained. Salivary and serum cortisol as well as CBG were assessed by RIA, dexamethasone by ELISA and serum free cortisol was calculated. SAF23 correlated negatively with glomerular filtration rate (GFR). The fraction of free cortisol in serum and saliva after 1 mg DST, correlated positively and significantly in both patients with CKD and healthy subjects (r: 0·86 and r: 0·85, respectively; P < 0·0001 for both). Ten percent of CKD with GFR < 90 ml/min/1·73 m(2) had false positive results unrelated to dexamethasone and CBG concentrations. False positive responses to 1 mg DST were associated with GFR < 90 ml/min/1·73 m(2) . This could not be ascribed to either defects in dexamethasone absorption or CBG concentrations. Higher dexamethasone doses were necessary to achieve adequate HPA suppression. Salivary cortisol was useful to assess circadian cortisol levels and feed-back regulation in CKD.

Evaluation of Human Urinary N-acetyl beta – D- glucosaminidase index in children with urinary tract anomalies

Background: The kidneys perform glomerular filtration, tubular reabsorption, and tubular secretion and the study of urinary excretion of some enzymes considered as a sensitive test for the detection of early stages of renal disease, particularly N-acetyl-β-D-glucosaminidase (NAG) which is a hydrolytic lysosomal enzyme present in the epithelial cells of the proximal convoluted tubule. Increased urinary NAG due to tubular damage could be used as a marker by a simple non invasive test for prediction of urinary tract problems like pelviureteric junction(PUJ) obstruction ,vesicouretric reflux(VUR) and pyelonephritis.Objectives: to assess urinary NAG/ urinary creatinine (NAG/ Cr) ratio in children with different urinary tract anomalies and compare it with normal healthy children.Patients and Methods: A prospective study was conducted from November, 2012 to April, 2013. Urine samples were collected from 51 patients with Urinary tract problems, and 40 healthy children as a control group, their age range (1month-13years). Children were admitted to Pediatric nephrology department, Children Welfare Teaching Hospital / Medical City Complex, Baghdad, Iraq. The Glomerular filtration rate was in normal range in all of them. Urine samples were tested for NAG by (ELISA,Cusabio ,China) while, both Serum creatinine (S-Cr) and urine creatinine (U-Cr) were estimated by Jaffe’s kinetic method.Results: The current results revealed that NAG/creatinine index was significantly higher in patients with vesicoureteral reflux, Pelviureteric junction obstruction and pyelonephritis in comparison with cystitis.Conclusions: The assessment of urinary NAG could be considered as a useful marker in prediction of the vesicoureteral reflux, hydronephrosis secondary to Pelviureteric junction obstruction .Urinary NAG is elevated in children with pyelonephritis and it can be considered as a further criterion in the diagnosis of upper urinary tract infection.

High prevalence of early chronic kidney disease in high risk outpatients.

Introduction:Chronic kidney disease (CKD) is a significant public health problem. The aim of this study was to determine the presence of early stages of renal disease in hypertensive and diabetic outpatients without previously diagnosed renal damages.Methods:In this cross-sectional study we studied a random sample of outpatients with essential hypertension and/or diabetes mellitus type 2 in the general practice ambulance of city Sarajevo. Renal function was evaluated by using MDRD (Modification of Diet in Renal Disease) equation and with measurement of renal biomarkers. K/DOQI classification was used to define the stages of CKD.Results:The study included 200 patients, of whom 75 (37.5%) were females, mean age of 54.81 ± 6.1 years, and 125 (62.5%) male, mean age 52.46 ± 8.2 years. More than half of respondents (54.0%) were hypertensive during the follow up period. Early CKD was detected in 52% respondents. Higher prevalence of early CKD was verified in the group of patients who had hypertension associated with diabetes mellitus type 2 (59.6% vs. 47.2% in hypertension group vs. 54,0% in diabetic group, p<0.05). Significant negative correlation was found between estimated glomerular filtration rate and presence of albuminuria (p<0.001), duration of hypertension (p=0.003), duration of type 2 diabetes mellitus (p=0.021), stages of hypertension (p=0.012), female gender (p<0.001) and older age of subjects (p=0.040).Conclusion:Our results confirmed high prevalence of CKD and the importance of early detection of CKD in high risk groups of patients in order to prevent the progression of the same. Prevention of chronic kidney disease in our country is still not carried out satisfactorily. Required is a much greater collaboration between primary care health givers and nephrologists.

Correlation between renal function and common risk factors for chronic kidney disease in a healthy middle-aged population: a prospective observational 2-year study.

Background/AimsAge, proteinuria, metabolic syndrome, and hyperuricemia are the reported risk factors for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the best predictor of changes in renal function in the early stages of renal disease in a healthy middle-aged population is still unknown. Our study evaluated the correlation between changes in renal function and common risk factors to determine such a predictor.MethodsIn total, 2,853 healthy persons aged ≤50 years participated in the study. They had no proteinuria and were not on medications for hypertension, diabetes mellitus, hyperlipidemia, or hyperuricemia. Over 2 years, participants underwent annual health screening. The relationship between changes in estimated glomerular filtration rate (eGFR) and changes in risk factors for CKD was evaluated using univariate and multivariate linear regression analyses.ResultsOver 2 years, eGFR showed a significant decrease. Univariate regression analysis revealed that changes in fasting plasma glucose (FPG), total cholesterol, LDL-cholesterol, serum uric acid levels, and hemoglobin showed a significant negative correlation with changes in eGFR. Multiple regression analysis confirmed that changes in FPG, serum uric acid levels, in particular, and hemoglobin had a significant negative correlation with changes in eGFR.ConclusionThe changes in eGFR and other variables over 2 years were small and could be within expected biologic variation. A longer observational study is needed to elucidate whether FPG, serum uric acid and hemoglobin represent the earliest markers of eGFR decline.

Therapeutic Use of Calcitriol

The synthesis of 1α,25-dihydroxyvitamin D3 (Calcitriol) takes place mostly in the kidneys through the action of 1α-hydroxylase (CYP27B1) which converts 25(OH)D into 1,25(OH)2D3. Renal production of calcitriol is stimulated by PTH, low calcium and low phosphate and it is reduced by high phosphate and FGF23. Binding of 1α,25-dihydroxyvitamin D3 to its receptor (VDR) causes gut absorption of calcium and phosphate, decrease in PTH synthesis, stimulation of FGF23. At the bone level calcitriol suppresses pre-osteoblasts and activates mature osteoblasts. VDR is present in a large variety of cells that do not have any direct role in the regulation of mineral metabolism. Calcitriol regulates immune and inflammatory response, cell turnover, cell differentiation, Renin production, reduces proteinuria and others. In patients with Chronic Kidney Disease (CKD) there is a decrease in calcitriol that is apparent at early stages of renal disease; this is probably due to the elevation of FGF23 which is present since very early stage of CKD. In CKD stage, 3-4 moderate doses of calcitriol are effective to control secondary hyperparathyroidism and observational studies suggest that calcitriol therapy increases survival and slows the progression of renal disease as long as phosphate and calcium levels are controlled. Calcitriol (0.5 µg calcitriol twice per week) has been effective in decreasing proteinuria in patients with IgA nephropathy. In dialysis patients, the administration of calcitriol reduces serum PTH levels but it is also known that high doses of calcitriol are associated with hypercalcemia and worse control of hyperphosphatemia. In kidney transplant patients, the administration of calcitriol, 0.5 µg/48h prevents bone mass loss during the first few months after transplantation.

Proteinuria in Cynomolgus macaques (Macaca fascicularis) with Spontaneously Developed Metabolic Disorder and Diabetes: Transcriptome Analysis of Biopsy Kidney

Although Type 2 Diabetes Mellitus (T2DM) is well characterized Non-Human Primate (NHP), the phenotypes of diabetic nephropathy, and its molecular mechanisms are not well studied in NHPs. Diabetic nephropathy in cynomolgus macaques with spontaneous dysmetabolism (Pre-DM, n=19) and diabetes (DM, n=20) were compared with normal controls (N, n=11). There were 9 NHPs with albuminuria (>42 mg/day) in the DM (45%), only 1 in Pre-DM and none in N group. The renal function measured by estimated glomerular filtration rate (eGFR) was not significantly different among the 3 groups, indicating that these NHPs were in an early stage of renal disease. From these NHPs, 3 N, 3 Pre-DM without albuminuria and 6 DM with albuminuria were selected for transcriptome analysis of kidney biopsies. There were 95 differentially expressed genes (DEGs) detected amongst the 3 groups, of which, 75DEGs between the N and DM related to diabetic nephropathy; 66 DEGs between the N and Pre-DM related to dysmetabolism without nephropathy; 68 DEGs between N and both Pre-DM & DM related to dsymetabolism; but only 1 nephropathy specific gene (LCT lactase) between the DM with albuminuria (DM) and Pre-DM without albuminuria; only 4 DEGs between the DM with albuminuria and both N & Pre-DM without albuminuria specific to nephropathy. Signaling pathway analysis of the relevant DEGs and encoded proteins highlighted the role of a kidney failure, renal and urological diseases, and inflammatory diseases related network, in which the most pivotal gene in this network is Tumor Necrosis Factor (TNF), indicating that nephropathy is a disease closely related to inflammation and cell death. Thus, the present study was the first detailed characterization of the diabetic nephropathy phenotypes and the kidney histopathological changes in NHPs and provided molecular insights into novel mechanisms of disease progression, potential new drug targets as well as specific diagnostic biomarkers.

Adenosine A2B receptor-mediated VEGF induction promotes diabetic glomerulopathy

Diabetic nephropathy ranks as the most devastating kidney disease worldwide. It characterizes in the early onset by glomerular hypertrophy, hyperfiltration and mesangial expansion. Experimental models show that overproduction of vascular endothelial growth factor (VEGF) is a pathogenic condition for podocytopathy; however the mechanisms that regulate this growth factor induction are not clearly identified. We determined that the adenosine A2B receptor (A2BAR) mediates VEGF overproduction in ex vivo glomeruli exposed to high glucose concentration, requiring PKCα and Erk1/2 activation. The glomerular content of A2BAR was concomitantly increased with VEGF at early stages of renal disease in streptozotocin-induced diabetic rats. Further, in vivo administration of an antagonist of A2BAR in diabetic rats blocked the glomerular overexpression of VEGF, mesangial cells activation and proteinuria. In addition, we also determined that the accumulation of extracellular adenosine occurs in glomeruli of diabetic rats. Correspondingly, raised urinary adenosine levels were found in diabetic rats. In conclusion, we evidenced that adenosine signaling at the onset of diabetic kidney disease is a pathogenic event that promotes VEGF induction.

Prevalence of chronic kidney disease and progression of disease over time among patients enrolled in the Houston West Nile virus cohort.

IntroductionIn experimental models of West Nile virus (WNV) infection, animals develop chronic kidney infection with histopathological changes in the kidney up to 8-months post-infection. However, the long term pathologic effects of acute infection in humans are largely unknown. The purpose of this study was to assess renal outcomes following WNV infection, specifically the development of chronic kidney disease (CKD).MethodsIn a cohort of 139 study participants with a previous diagnosis of WNV infection, we investigated the prevalence of CKD using the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria based on the Modification of Diet in Renal Disease (MDRD) formula and urinary abnormalities, and assessed various risk factors and biomarkers.ResultsStudy participants were primarily male (60%) and non-Hispanic white (86%) with a mean age of 57 years. Most (83%) were four to nine years post-infection at the time of this study. Based on the KDOQI definition, 40% of participants had evidence of CKD, with 10% having Stage III or greater and 30% having Stage I–II. By urinary dipstick testing, 26% of patients had proteinuria and 23% had hematuria. Plasma NGAL levels were elevated in 14% of participants while MCP-1 levels were increased in 12%. Over 1.5 years, the average change in eGFR was −3.71 mL/min/1.73 m2. Only a history of Neuroinvasive WNV disease was independently associated with CKD following multivariate analysis.DiscussionWe found a high prevalence of CKD after long term follow-up in a cohort of participants previously infected with WNV. The majority of those with CKD are in Stage I-II indicating early stages of renal disease. Traditional risk factors were not associated with the presence of CKD in this population. Therefore, clinicians should regularly evaluate all patients with a history of WNV for evidence of CKD.

Insulin Resistance in the Early Stages of Renal Failure: Implications for Cardiovascular Risk

An elevated risk of cardiovascular events is present in patients with mild-to-moderate renal function impairment. Similar to patients with end-stage renal disease, this elevated risk can be accounted for by high prevalence of classic and emergent cardiovascular risk factors and additional conditions that are more specifically related to the organ failure, such as anemia and electrolyte disturbances. Among emergent cardiovascular risk factors, insulin resistance has been demonstrated to contribute significantly to the cardiovascular risk in the general population and it is known that abnormalities of glucose metabolism and hyperinsulinemia due to insulin resistance are present in patients with renal failure. Because patients with more advanced disease stage have several abnormalities that might affect the cellular action of insulin acting as important confounders, the relationship between insulin sensitivity and renal function should be better evaluated in the early stages of renal failure. This article overviews the evidence supporting the presence of increased cardiovascular morbidity and mortality in patients with early stages of renal disease, and examines the potential for insulin resistance to contribute to cardiovascular risk in these patients.

Preclinical cardiovascular abnormalities in patients in early stages of renal disease without nephrotic syndrome

Preclinical cardiovascular abnormalities in patients in early stages of renal disease without nephrotic syndrome

Insulin resistance in diabetic nephropathy — cause or consequence?

Insulin resistance (IR) is associated with multiple risk factors for cardiovascular disease. Many studies have shown that IR is present in chronic renal failure (CRF), and recent evidence suggests that IR can also occur in the early stages of renal disease. Patients with diabetic nephropathy (DN) have an increase in cardiovascular mortality, and since IR may be a contributing factor, this emphasizes the importance of a detailed understanding of the mechanisms linking IR and renal dysfunction at different stages of DN. IR can be detected early on in DN, e.g. at the stage of microalbuminuria (MA) and this could indicate a common genetic trait for IR and DN. As DN progresses further, IR is aggravated and it may, in addition to other factors, possibly accelerate the decline in renal function toward end-stage renal disease (ESRD). Several potentially modifiable mechanisms including circulating hormones, neuroendocrine pathways and chronic inflammation, are said to contribute to the worsening of IR. In ESRD, uremic toxins are of major importance. In this review article, we address the association between different stages of DN and IR and attempt to summarize major findings on potential mechanisms linking DN and IR. We conclude that IR is a consequence, and potentially also a cause of DN. In addition, there are probably genetic and environmental background factors that predispose to both IR and DN.